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A previously healthy 46-year-old man presented with a 7-day history of fever, dry cough, and mild dyspnea. On examination, he was febrile, mildly tachypneic, tachycardic, but maintained oxygen saturation on room air. His chest X-ray revealed consolidation involving the left mid and lower zones. SARS-CoV-2 PCR tested positive, and he was started on COVID-19 management for pneumonia following local protocols. The repeated PCR tests were persistently positive for 47 days. The patient was discharged home, asymptomatic after negative PCR.

A healthy 19-year-old man presented with a short history of fever and sore throat. The examination was remarkable for low-grade fever and tachycardia, and laboratory investigations and chest X-ray were unremarkable. He was diagnosed as a case of COVID-19 mild URTI and did not require hospital admission but transited through quarantine. His PCR swab remained positive for 48 days.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

A 53-year-old man, known to have HTN, DM, and end-stage renal disease (ESRD), presented with fever, abdominal pain, diarrhea, nausea, and vomiting. Physical examination revealed a tired-looking man with mild abdominal tenderness but was otherwise unremarkable. Abdominal computed tomography (CT) scan was performed to rule out causes of acute abdomen. It showed no abdominal pathology but numerous bilateral lungs’ basal patchy consolidations and ground-glass opacities. Subsequently, nasopharyngeal PCR confirmed COVID-19. He received the treatment guided by the local protocol, and he became symptom-free and was discharged home following negative swab PCR after 28 days. Eighteen days later, he again presented with fever, chest pain, and mild dyspnea. The chest X-ray showed bilateral lung infiltrates increasing compared with the previous Images. The initial test for COVID-19 was inconclusive; then, the repeat test was positive 2 days after the second hospital admission. He was restarted on the treatment protocol and continued to improve with an unremarkable hospital stay. The repeated test was negative after 1 week from the second presentation. The patient had 48 days elapsing from the first positive PCR result until the last positive sample.

A previously healthy 46-year-old man presented with a 7-day history of fever, dry cough, and mild dyspnea. On examination, he was febrile, mildly tachypneic, tachycardic, but maintained oxygen saturation on room air. His chest X-ray revealed consolidation involving the left mid and lower zones. SARS-CoV-2 PCR tested positive, and he was started on COVID-19 management for pneumonia following local protocols. The repeated PCR tests were persistently positive for 47 days. The patient was discharged home, asymptomatic after negative PCR.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

A 35-year-old man presented with a 10-day history of fever, headache, and dry cough. Physical examination was unremarkable. His baseline blood investigation was remarkable for high inflammatory markers and mild transaminitis. Chest X-ray revealed left mid-zone consolidation with a cavitary lesion. He was found to be positive for SARS-CoV-2 from nasopharyngeal swab PCR. Given the cavitary lesion, tuberculosis (TB) was suspected, and sputum smear acid-fast bacilli confirmed the presence of mycobacterial infection. Thus, the patient was treated as a case of COVID-19 pneumonia and active pulmonary TB. TB culture showed Mycobacterium tuberculosis sensitive for first-line anti-TB drugs. He later developed a rise in liver enzymes suspected to be either secondary to TB drugs versus COVID-19–related hepatitis. Subsequently, he was shifted temporarily to second-line antituberculosis therapy until improvement in his liver enzymes. Re-swabbing was performed as per the protocol, and the patient tested persistently positive for a total of 62 days.

A previously healthy 46-year-old man presented with a 7-day history of fever, dry cough, and mild dyspnea. On examination, he was febrile, mildly tachypneic, tachycardic, but maintained oxygen saturation on room air. His chest X-ray revealed consolidation involving the left mid and lower zones. SARS-CoV-2 PCR tested positive, and he was started on COVID-19 management for pneumonia following local protocols. The repeated PCR tests were persistently positive for 47 days. The patient was discharged home, asymptomatic after negative PCR.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

A 53-year-old man, known to have HTN, DM, and end-stage renal disease (ESRD), presented with fever, abdominal pain, diarrhea, nausea, and vomiting. Physical examination revealed a tired-looking man with mild abdominal tenderness but was otherwise unremarkable. Abdominal computed tomography (CT) scan was performed to rule out causes of acute abdomen. It showed no abdominal pathology but numerous bilateral lungs’ basal patchy consolidations and ground-glass opacities. Subsequently, nasopharyngeal PCR confirmed COVID-19. He received the treatment guided by the local protocol, and he became symptom-free and was discharged home following negative swab PCR after 28 days. Eighteen days later, he again presented with fever, chest pain, and mild dyspnea. The chest X-ray showed bilateral lung infiltrates increasing compared with the previous Images. The initial test for COVID-19 was inconclusive; then, the repeat test was positive 2 days after the second hospital admission. He was restarted on the treatment protocol and continued to improve with an unremarkable hospital stay. The repeated test was negative after 1 week from the second presentation. The patient had 48 days elapsing from the first positive PCR result until the last positive sample.

A healthy 19-year-old man presented with a short history of fever and sore throat. The examination was remarkable for low-grade fever and tachycardia, and laboratory investigations and chest X-ray were unremarkable. He was diagnosed as a case of COVID-19 mild URTI and did not require hospital admission but transited through quarantine. His PCR swab remained positive for 48 days.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

A 35-year-old man presented with a 10-day history of fever, headache, and dry cough. Physical examination was unremarkable. His baseline blood investigation was remarkable for high inflammatory markers and mild transaminitis. Chest X-ray revealed left mid-zone consolidation with a cavitary lesion. He was found to be positive for SARS-CoV-2 from nasopharyngeal swab PCR. Given the cavitary lesion, tuberculosis (TB) was suspected, and sputum smear acid-fast bacilli confirmed the presence of mycobacterial infection. Thus, the patient was treated as a case of COVID-19 pneumonia and active pulmonary TB. TB culture showed Mycobacterium tuberculosis sensitive for first-line anti-TB drugs. He later developed a rise in liver enzymes suspected to be either secondary to TB drugs versus COVID-19–related hepatitis. Subsequently, he was shifted temporarily to second-line antituberculosis therapy until improvement in his liver enzymes. Re-swabbing was performed as per the protocol, and the patient tested persistently positive for a total of 62 days.

A healthy 19-year-old man presented with a short history of fever and sore throat. The examination was remarkable for low-grade fever and tachycardia, and laboratory investigations and chest X-ray were unremarkable. He was diagnosed as a case of COVID-19 mild URTI and did not require hospital admission but transited through quarantine. His PCR swab remained positive for 48 days.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

A 35-year-old man presented with a 10-day history of fever, headache, and dry cough. Physical examination was unremarkable. His baseline blood investigation was remarkable for high inflammatory markers and mild transaminitis. Chest X-ray revealed left mid-zone consolidation with a cavitary lesion. He was found to be positive for SARS-CoV-2 from nasopharyngeal swab PCR. Given the cavitary lesion, tuberculosis (TB) was suspected, and sputum smear acid-fast bacilli confirmed the presence of mycobacterial infection. Thus, the patient was treated as a case of COVID-19 pneumonia and active pulmonary TB. TB culture showed Mycobacterium tuberculosis sensitive for first-line anti-TB drugs. He later developed a rise in liver enzymes suspected to be either secondary to TB drugs versus COVID-19–related hepatitis. Subsequently, he was shifted temporarily to second-line antituberculosis therapy until improvement in his liver enzymes. Re-swabbing was performed as per the protocol, and the patient tested persistently positive for a total of 62 days.

A 53-year-old man, known to have HTN, DM, and end-stage renal disease (ESRD), presented with fever, abdominal pain, diarrhea, nausea, and vomiting. Physical examination revealed a tired-looking man with mild abdominal tenderness but was otherwise unremarkable. Abdominal computed tomography (CT) scan was performed to rule out causes of acute abdomen. It showed no abdominal pathology but numerous bilateral lungs’ basal patchy consolidations and ground-glass opacities. Subsequently, nasopharyngeal PCR confirmed COVID-19. He received the treatment guided by the local protocol, and he became symptom-free and was discharged home following negative swab PCR after 28 days. Eighteen days later, he again presented with fever, chest pain, and mild dyspnea. The chest X-ray showed bilateral lung infiltrates increasing compared with the previous Images. The initial test for COVID-19 was inconclusive; then, the repeat test was positive 2 days after the second hospital admission. He was restarted on the treatment protocol and continued to improve with an unremarkable hospital stay. The repeated test was negative after 1 week from the second presentation. The patient had 48 days elapsing from the first positive PCR result until the last positive sample.

Write a detailed clinical case vignette based on the following key phrases: COVID-19, Prolonged PCR positivity, Recovery and discharge

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian female was referred with an IOP of 48 mmHg on maximal medications and corneal edema after phacoemulsification. LPIs had been done in the past for PAC glaucoma (PACG). The AC was moderately shallow. An urgent trabeculectomy with intraoperative mitomycin C (MMC) application was done. The following morning, the IOP was 24 mmHg with a flat AC. Malignant glaucoma was suspected, and the patient started on atropine and topical steroids. Nd: YAG laser posterior capsulotomy and hyloidotomy were done, but the AC remained very shallow and the IOP increased to over 40 mmHg. The following week, a ZHV was performed, and the AC deepened intraoperatively []. Postoperatively, while the AC was deep, the IOP remained high and on gonioscopy, the angle was almost completely closed. She was started on dorzolamide-timolol fixed combination eyes drops. On her last visit, 32 months after ZHV, VA was 20/60 and IOP 14 mmHg on medications. There was corneal edema, and the AC remained deep.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 83-year-old lady of Indian origin with PAC, bilateral pseudophakia and IOP of 35 mmHg on maximal medical therapy underwent an augmented trabeculectomy with MMC in the right eye. Preoperatively, the AC was moderately shallow in the right eye, and gonioscopy showed a closed angle. The left eye AC was shallow with some peripheral anterior synechiae. A month later, the AC remained shallow, and IOP was 15–20 mmHg on 3 topical glaucoma medications. The patient was referred to the glaucoma clinic where malignant glaucoma was diagnosed, and ZHV preformed. The AC deepened; IOP settled at 15 mmHg and VA was 20/30. 6 months later, she presented with blurred vision for 3 months in the same eye. Her IOP was 23 in the left eye, and the AC was shallow with peripheral irido-corneal touch. Malignant glaucoma was suspected, and she was treated with Atropine 1% drops in that eye. The vision improved to 20/30, the AC deepened, and the IOP was 19 mmHg at 7 days follow-up. However, on a routine follow-up visit 15 months after ZHV, IOP was raised at 34 mmHg and peripheral AC was shallow once more with iridocorneal touch. A repeat ZHV was performed after which the AC deepened []. 2 years after the second ZHV, the IOP was stable at 17 mmHg without medication.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 81-year-old Caucasian lady with PACG was referred to the glaucoma clinic for raised IOP and blurred vision in the right eye. She had LPI and trabeculectomy 15 years ago and phacoemulsification with anterior vitrectomy 8 years ago. Her left eye had no vision due to complicated extracapsular cataract extraction, bullous keratopathy, and possible advanced glaucomatous optic atrophy. The IOP in the right eye was 22 mmHg on oral acetazolamide, topical pilocarpine 2%, latanoprost, and apraclonidine 1%. The VA was 20/40 with peripheral corneal edema and a shallow AC. Malignant glaucoma was thought to be the cause. Pilocarpine drops were stopped, and atropine started. However, the AC remained shallow. A ZHV was performed, and the AC deepened on the table. She subsequently underwent a penetrating keratoplasty for the preexisting pseudophakic bullous keratopathy. There has been no recurrence of malignant glaucoma for the last 7 years. On her last visit, the VA was 20/60 and IOP 18 mmHg without medications.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 63-year-old Caucasian gentleman with schizophrenia was referred to the glaucoma clinic by his optician with bilateral pale optic discs, IOPs over 60 mmHg and vision of counting fingers in both eyes. In both eyes, AC was shallow; the angle completely closed, and the optic discs cupped and pale. A diagnosis of chronic angle closure was made, and bilateral LPIs done. The patient was started on oral acetazolamide and 3 topical glaucoma medications. A month later, the IOP had reduced to 21 mmHg in the right eye. Right eye phacotrabeculectomy under general anesthesia was done with prior explanation of the poor prognosis for visual recovery to the relatives. Intraoperatively, a floppy iris was noted which responded to intracameral phenylephrine. Postoperatively, the AC was shallow and IOP 16 mmHg. A week later, the IOP crept to 23 mmHg, the AC remained shallow with a fibrinous deposit over the pupil. Malignant glaucoma was considered to be the cause and ZHV performed. The AC deepened on the table, but the next morning, the AC was shallow with fibrin covering the pupil and the PI. Nd: YAG laser lysis of the fibrin and anterior hyaloidotomy through the PI was done. The AC deepened immediately. The IOP has been stable over the next 4 years at 18 mmHg without glaucoma medications. However, VA was counting fingers.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 75-year-old woman was referred for further treatment for uncontrolled intraocular hypertension following trabeculectomy. The patient had a past medical history significant for hypertension. Her family history was negative for glaucoma. She had a past ocular history significant for cataract in both eyes and lens zonular laxity in right eye. She underwent right phacoemulsification with intraocular lens (IOL) and CTR (Holland, OPHTEC B.V., 13.0 mm in noncompressed diameters) implantation in November of 2017. Following surgery, the best corrected visual acuity (BCVA) was 20/22 and IOP was 11.1 mmHg in the right eye. The slit-lamp examination showed that anterior segment examination was unremarkable. Twelve days after cataract surgery, elevated IOP of 41.2 mmHg in the right eye was noted and she underwent laser peripheral iridotomy and was placed on medical therapy for intraocular hypertension.\nSeveral months with treatment of maximal medical therapy, right IOP remained uncontrolled. She presented with complaints of pain on March 20, 2018. On examination, visual acuity (VA) was 20/200 in the right eye and 20/33 in the left eye. IOPs were 39.5 mmHg in the right and 15.6 mmHg in the left eyes on fixed combination brimonidine 0.2%/timolol 0.5%/brinzolamide 1% bid and bimatoprost 0.03% qn in the right eye, respectively. Slit-lamp examination revealed peripheral AC <1/4 corneal thickness in both eyes, patent peripheral iris incisions (PIs) and narrow closed angles in the right eye, narrow open angles in the left eye, and cup to disc ratios of 0.3 in both eyes. Posterior chamber IOL was in good position in the right eye and early senile cataract was present in the left eye. Axial length is 20.72 mm in the right eye and 20.69 mm in the left eye. Len-star showed that white to white is 11.6 mm in the right eye and 10.4 mm in the left eye. UBM showed shallowing of the AC in both eyes and angle closure in the right eye (Fig. A–D). A diagnosis of secondary angle-closure glaucoma was made. Given her pain and uncontrolled IOP, she underwent trabeculectomy on March 21, 2018.\nThe surgery was uneventful except the presenting of shallow AC of Shaffer grade 1 and relieved by tropicamide. However, the IOP quickly increased to 43.5 mmHg during the first hour after the operation. The slit-lamp examination was significant for 2+ corneal edema. In an effort to reduce her IOP, the filtering bleb was massaged. On postoperative day 1, the patient presented as shallow AC of Shaffer grade 1, uncorrected VA was counting fingers and an elevated IOP of 51.0 mmHg in the right eye. UBM showed ciliary block between CTR and ciliary body (Fig. A and B). Since there were no signs of choroidal detachment or suprachoroidal hemorrhage, a diagnosis of MG was made. Subsequently, the patient underwent posterior capsulotomy by Nd: YAG and accepted oral acetazolamide and maximum topical medical therapy (atropine 1%, prostaglandin analog, timolol, bromonidine, brinzolamide) for 4 days. However, AC remained shallow and IOP was uncontrolled. UBM was done again on March 20, 2018 and high attenuation shadow of CTR was noticed (Fig. C and D).\nGiven presence of unacceptable IOP, it was considered to surgically manage her ciliary block glaucoma. However, whether to remove the CTR was a problem. It seemed that removal of CTR was the most effective way to relive ciliary block as well as the most difficult procedure. Given our personal successful experience with the CP in patients with refractory glaucoma in shallow AC, we decided on performing LDCP first. Pars plana vitrectomy and CTR removal was also prepared in case of the failure of LDCP.\nThe Ethics committee of the eye hospital of Wenzhou Medical University approved the conduct of LDCP as a new therapy for MG (YX2018-015). An informed consent was obtained from the patient.\nLDCP was performed under retrobulbar anesthesia with OcuLight SLx semiconductor diode 810 nm laser and the contact G-probe on March 27, 2018. The ciliary body was identified by transillumination and the contact G-probe was placed at the anterior aspect of the ciliary body which approximately 1.8 mm posterior to the limbus. The treatment consisted of 15 applications of 2.0 W energy applied for 2 seconds over 6 to 9 o’clock (avoiding the 9 o’clock position, 90° total) of the ciliary body. Upon termination of the procedure, atropine and dexamethasone ointments were placed on the eye to reduce the postoperative inflammation.\nThree hours after LDCP treatment, IOP in the right eye decreased to 24.9 mmHg with the ease of corneal edema and improvement of transparency, and uncorrected VA was 20/250 in the right eye. She was treated with atropine, dexamethasone ointments, timolol, and brinzolamide. On postoperative day 2, the IOP was 22.7 mmHg with a clear cornea and 20/167 vision, and bimatoprost 0.03% qn was added. UBM showed the relief of inferior ciliary block (Fig. ) and a suspect communication from the posterior space of the lens to the posterior chamber. On the day 7 visit, the IOP was 15.9 mmHg on 5 medications and 3 medications was reduced. The patient was seen at the 1-month postoperative visit with an IOP of 17.0 mmHg on atropine bid/bimatoprost 0.03% qn, and her uncorrected visual acuity (UCVA) in the right eye improved to 20/100. UBM confirmed a well-relief of ciliary block with an anterior chamber depth (ACD) of 1.70 mm. At 3 months, IOP measured 17.5 mmHg on atropine bid/bimatoprost 0.03% qn. The patient discontinued topical atropine and bimatoprost 4 months postoperatively. During her 6 months of follow-up, her IOP was 18.9 mmHg and ACD was 2.09 mm without any medication. At her last visit on March 29, 2019, VA remained 20/167, IOP measured 16.5 mmHg in the right eye. Slit-lamp examination and UBM showed the depth of central AC in the right eye (Fig. A and B). There was no significant uveitis and other complications observed during 1-year follow-up.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 77-year-old Caucasian male who had a routine extracapsular cataract extraction with a surgical PI in his right eye 15 years ago, was seen with complaints of blurred vision. His BCVA was 20/30. Nd: YAG laser posterior capsulotomy was done twice. It was repeated after a year as he was still complaining of blurred vision, and the ophthalmologist thought that the central capsular clearance was inadequate. A month later, he had no improvement, and his VA was 20/60. The AC was deep, and some vitreous was herniating though the inferotemporal pupillary margin. He was managed conservatively. A further 6 months later his VA had decreased to 20/200 and IOP was 32 mmHg. He was started on topical beta-blockers, but the IOP remained high. He was referred to the glaucoma clinic where a shallow AC with peripheral iris-cornea touch and vitreous herniation through the inferotemporal pupillary margin was noted. Malignant glaucoma was diagnosed, and ZHV performed. By the 6th postoperative week, the IOP increased to 40 mmHg. It was controlled on topical travoprost and brinzolamide. Gonioscopy showed that the angle was >270° closed. He also developed nonresponsive cystoid macular edema (CMO). On the last visit, 67 months after ZHV, his IOP was 14 mmHg on the aforementioned medications and BCVA was 20/120.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

An 89-year-old lady with high hypermetropia was referred by her optician for raised IOPs of 49 and 40 mmHg in the right and left eye, respectively. She had bilateral cataracts reducing VAs to 20/60 right and 20/30 in left eye. The optic discs were healthy. She was commenced on topical prostaglandin analogs and subsequently had phacotrabeculectomy with MMC in the right eye. On the first postoperative visit, the AC was very shallow with iridocorneal touch and IOP 24 mmHg. Malignant glaucoma was suspected and topical atropine 1% was started. An air bubble was injected to reform the AC. The AC remained shallow. On the advice from one of us (NA), the surgeon performed a ZHV and noted that the AC had deepened intraoperatively. However, the AC was shallow and IOP 35 mmHg the following day. She was then referred to the glaucoma clinic, and a repeat ZHV was done. The emphasis was to remove the anterior vitreous. Following the procedure, her AC deepened, and IOP was 22 mmHg. A month later, her vision improved to 20/60 but her IOP was raised at 40 mmHg with a moderately shallow AC. It was felt that the PI was blocked by vitreous and Nd: YAG laser hyaloidotomy was done through the PI. The AC deepened immediately after the laser. The IOP was initially controlled on 3 topical medications. Two years later, VA was 20/40, the IOP 23 mmHg on a timolol-dorzolamide fixed combination and AC deep. In the interim, her left eye which had raised IOP and >180° of iridotrabecular contact underwent a routine phacoemulsification with no subsequent complications.

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

A 77-year-old lady with PAC and an IOP of 34 mmHg without medication underwent a phacoemulsification in her right eye. The procedure was difficult with positive pressure and iris prolapsed through the temporal corneal section. 2 weeks postoperatively, IOP rose to 44 mmHg and AC shallowed significantly []. Nd: YAG laser anterior and posterior capsulotomy and hyaloidotomy were done through an inadvertent temporal PI. The AC deepened immediately after the procedure, and the IOP dropped to 34 mmHg. Over the next 2 weeks, the AC was deep, and IOP stabilized at 15 mmHg on topical latanoprost. In the meantime, she also underwent a routine phacoemulsification in the fellow eye. 4 months after her phacoemulsification, the right eye IOP had crept up to 32 mmHg on maximal tolerated medications and AC shallowed. ZHV was performed. Postoperatively, the AC deepened but the IOP control was inadequate, and CMO was noted. The CMO resolved on oral acetazolamide, topical prednisolone 1%, and ketorolac eye drops. However, gradually she developed intolerance to most topical medications. A year after ZHV, she noted blurred vision in the right eye. The IOP was over 30 mmHg, the AC moderately shallow and CMO had recurred. This time 270° cyclodiode laser was done, leading to resolution of the malignant glaucoma. The CMO partially resolved on oral acetazolamide. 2 years after the ZHV, her VA was 20/60 and IOP 22 mmHg without medication.

An 86-year-old Caucasian female was referred to the VR specialist for deteriorating vision in her right eye (2/200) due to a macular hole. The diagnosis was confirmed on optical coherence tomography, and she underwent a phacovitrectomy with internal limiting membrane peel, posterior chamber IOL implantation and gas tamponade with C2F6. On the first postoperative day, her AC was shallow and IOP 66 mmHg. This was thought to be because of gas overfill as the lower edge of the gas bubble was not visualized. The gas was released on 2 separate occasions by the VR surgeon. Laser and surgical PIs were done, but IOP remained extremely high on maximal medication, oral and intravenous hyperosmotic agents. B-scan ultrasonography ruled out suprachoroidal hemorrhage. Malignant glaucoma was diagnosed and 2 weeks after the VR surgery a ZHV was done. The rationale was that the remaining anterior vitreous was probably blocking communication between the anterior and posterior segments. Postoperatively, the AC deepened, and IOP decreased to 4 mmHg. However, there was no visual recovery, and the eye became phthisical over the next few months.

Write a detailed clinical case vignette based on the following key phrases: Malignant Glaucoma, Shallow Anterior Chamber, Intraocular Pressure

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Woman, 65-year-old, with sensory-motor polyneuropathy for 15 years, worsening in the\nprevious 6 months. The patient had diffuse hyperpigmentation, dry skin and hemangiomas\n( and ). She reported hypertrichosis, edema of the legs, facial lipoatrophy,\nleukonychia and weight loss ( and ). Analytically, she presented polyglobulia,\nthrombocytosis, hypotestosteronemia, hyperalbuminemia and elevation of IgG in the\nliquor. The immunochemical study emphasized IgG monoclonal gammopathy of lambda\nchains.\nInvestigations showed small adenopathies, cardiomegaly, hepatosplenomegaly, generalized\nedema and extensive lytic lesion of L5. A biopsy of this lesion showed a lytic\nproliferation of plasma cells, CD138 +, К chains - chains λ +. The myelogram showed\nhypercellularity and eosinophilia. The electromyogram showed slowing of motor and\nsensory nerve conduction of several nerves. An excision of the right breast angioma was\nperformed and was compatible with capillary hemangioma. The patient has begun treatment\nwith dexamethasone, radiotherapy, bortezomib and is waiting for a bone marrow\ntransplant.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.

The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.

Write a detailed clinical case vignette based on the following key phrases: POEMS syndrome, polyneuropathy, monoclonal gammopathy

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 2 is a 68-year-old male who was initially diagnosed with a well-differentiated G2 (Ki-67 10%) metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles (Fig. a). A subsequent biopsy confirmed metastatic NET. To manage his acute periorbital swelling, he was first treated with corticosteroids and later completed image-guided radiation therapy (IGRT) to 44 Gy to bilateral orbits in December 2017. The patient had a post-treatment MRI scan which demonstrated a decrease in signal abnormality and enhancement in the previously visualized lesions (Fig. b). Post-radiation, patient continued octreotide until his death in February 2018 due to progressive disease.

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 5 is a 61-year-old female who was diagnosed with a well differentiated G2 (Ki-67 5%) metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. a). She was then started on capecitabine in January 2017 on a two week on, one week off regimen schedule. Patient also established care with ophthalmology at this time. She achieved stable disease in her orbits with symptomatic improvement and did not demonstrate any evidence of visual field deficits. She continues capecitabine and her last MRI in July 2018 revealed ongoing shrinkage of her right lateral rectus mass (Fig. b); her recent 68Ga-DOTATATE PET/CT from October 2018 shows residual SSTR avidity within her bilateral recti muscles (Fig. c and d).

A 45-year-old female patient presented with weight loss, mild proptosis, and decreased vision in both the eyes. She was evaluated to have multiple lymphnodes and biopsy from mediastinal lymphnode showed metastatic neuroendocrine tumour. She was referred for whole body Ga-68 DOTANOC PET/CT for detection of primary site. Whole body PET/CT showed an intense uptake in the left lung nodule, mediastinal, and retroperitoneal lymph nodes and also uptake in the EOM lesions (arrows) []. A diagnosis of primary carcinoid lung with nodal and extrocular muscle metastasis was made and she was treated with Lu-177 DOTATATE (7.4GBq). Whole body Lu-177 images [] showed intense uptake in lymphnodes and bilateral EOM metastasis (arrows). Symptomatically, she had improvement with weight gain and normal vision in both eyes on clinical examination.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Patient 2 is a 68-year-old male who was initially diagnosed with a well-differentiated G2 (Ki-67 10%) metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles (Fig. a). A subsequent biopsy confirmed metastatic NET. To manage his acute periorbital swelling, he was first treated with corticosteroids and later completed image-guided radiation therapy (IGRT) to 44 Gy to bilateral orbits in December 2017. The patient had a post-treatment MRI scan which demonstrated a decrease in signal abnormality and enhancement in the previously visualized lesions (Fig. b). Post-radiation, patient continued octreotide until his death in February 2018 due to progressive disease.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 5 is a 61-year-old female who was diagnosed with a well differentiated G2 (Ki-67 5%) metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. a). She was then started on capecitabine in January 2017 on a two week on, one week off regimen schedule. Patient also established care with ophthalmology at this time. She achieved stable disease in her orbits with symptomatic improvement and did not demonstrate any evidence of visual field deficits. She continues capecitabine and her last MRI in July 2018 revealed ongoing shrinkage of her right lateral rectus mass (Fig. b); her recent 68Ga-DOTATATE PET/CT from October 2018 shows residual SSTR avidity within her bilateral recti muscles (Fig. c and d).

Patient 3 is a 63-year-old female who was initially diagnosed with a well differentiated metastatic ileal NET in 1994. She was found to have G3 (Ki-67 22%) disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions (Fig. a and b). Although she was planned for earlier, in the setting of disease-related complications, her anticipated start date for 177Lu-DOTATATE PRRT is December 2018.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Patient 2 is a 68-year-old male who was initially diagnosed with a well-differentiated G2 (Ki-67 10%) metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles (Fig. a). A subsequent biopsy confirmed metastatic NET. To manage his acute periorbital swelling, he was first treated with corticosteroids and later completed image-guided radiation therapy (IGRT) to 44 Gy to bilateral orbits in December 2017. The patient had a post-treatment MRI scan which demonstrated a decrease in signal abnormality and enhancement in the previously visualized lesions (Fig. b). Post-radiation, patient continued octreotide until his death in February 2018 due to progressive disease.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI []. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figures and ]. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.\nThe clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in .

Patient 5 is a 61-year-old female who was diagnosed with a well differentiated G2 (Ki-67 5%) metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. a). She was then started on capecitabine in January 2017 on a two week on, one week off regimen schedule. Patient also established care with ophthalmology at this time. She achieved stable disease in her orbits with symptomatic improvement and did not demonstrate any evidence of visual field deficits. She continues capecitabine and her last MRI in July 2018 revealed ongoing shrinkage of her right lateral rectus mass (Fig. b); her recent 68Ga-DOTATATE PET/CT from October 2018 shows residual SSTR avidity within her bilateral recti muscles (Fig. c and d).

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 2 is a 68-year-old male who was initially diagnosed with a well-differentiated G2 (Ki-67 10%) metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles (Fig. a). A subsequent biopsy confirmed metastatic NET. To manage his acute periorbital swelling, he was first treated with corticosteroids and later completed image-guided radiation therapy (IGRT) to 44 Gy to bilateral orbits in December 2017. The patient had a post-treatment MRI scan which demonstrated a decrease in signal abnormality and enhancement in the previously visualized lesions (Fig. b). Post-radiation, patient continued octreotide until his death in February 2018 due to progressive disease.

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 5 is a 61-year-old female who was diagnosed with a well differentiated G2 (Ki-67 5%) metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. a). She was then started on capecitabine in January 2017 on a two week on, one week off regimen schedule. Patient also established care with ophthalmology at this time. She achieved stable disease in her orbits with symptomatic improvement and did not demonstrate any evidence of visual field deficits. She continues capecitabine and her last MRI in July 2018 revealed ongoing shrinkage of her right lateral rectus mass (Fig. b); her recent 68Ga-DOTATATE PET/CT from October 2018 shows residual SSTR avidity within her bilateral recti muscles (Fig. c and d).

Patient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint (Fig. a and b). In March 2018, the patient was hospitalized for preseptal cellulitis. During the hospitalization, she underwent a CT scan which revealed focal thickening of the right medial rectus and left lateral rectus muscles. Opthalmology evaluated her and felt the cellulitis was unrelated to her orbital masses. Once her infection resolved she underwent biopsy of a rectus muscles mass which confirmed orbital metastases from her NET primary. Patient did not have any worsening visual symptoms or signs (limited extraocular motility, visual field deficits or proptosis).\n177Lu-DOTATATE PRRT was initially recommended; however, this was not pursued due to the patient’s poor renal function. Radiation therapy was then considered but given the proximity of the lesions to other critical structures and her lack of symptoms, this too was deferred in favor of close surveillance. In July 2018, she started on capecitabine and temozolomide for better systemic control of her NET, which also involved her liver, pancreas, bone and intra-abdominal lymph nodes. On a follow-up orbital MRI in July 2018, her lesions were noted to be stable.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 2 is a 68-year-old male who was initially diagnosed with a well-differentiated G2 (Ki-67 10%) metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles (Fig. a). A subsequent biopsy confirmed metastatic NET. To manage his acute periorbital swelling, he was first treated with corticosteroids and later completed image-guided radiation therapy (IGRT) to 44 Gy to bilateral orbits in December 2017. The patient had a post-treatment MRI scan which demonstrated a decrease in signal abnormality and enhancement in the previously visualized lesions (Fig. b). Post-radiation, patient continued octreotide until his death in February 2018 due to progressive disease.

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

Patient 5 is a 61-year-old female who was diagnosed with a well differentiated G2 (Ki-67 5%) metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. a). She was then started on capecitabine in January 2017 on a two week on, one week off regimen schedule. Patient also established care with ophthalmology at this time. She achieved stable disease in her orbits with symptomatic improvement and did not demonstrate any evidence of visual field deficits. She continues capecitabine and her last MRI in July 2018 revealed ongoing shrinkage of her right lateral rectus mass (Fig. b); her recent 68Ga-DOTATATE PET/CT from October 2018 shows residual SSTR avidity within her bilateral recti muscles (Fig. c and d).

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.\nVisual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland []. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2–6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [].

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

Patient 4 is a 72-year-old gentleman who was diagnosed with a well differentiated G2 metastatic ileal NET in 2006. He started monthly octreotide shortly thereafter in 2007. He was incidentally noted to have a left lateral rectus mass in March 2007 during a brain MRI. This lesion was monitored with serial MRI and remained stable until 2015 when it began to grow (Fig. c). The patient developed progressive diplopia and proptosis in 2015 which prompted an evaluation by radiation oncology. He received stereotactic radiosurgery (SRS) administered over 5 fractions to the site in February 2015 at VUMC and his diplopia and proptosis resolved within several months of treatment completion. He has unfortunately developed complications from his other sites of metastatic involvement including right sided nephrostomy tube placement from ureteral obstruction and an end colostomy due to recurrent small bowel obstructions from mesenteric tethering. His disease remains radiographically stable on his 68Ga-DOTATATE PET-CT from August 2018 (Fig. a and b).

Write a detailed clinical case vignette based on the following key phrases: Neuroendocrine Tumor, Orbital Metastasis, Carcinoid Syndrome