corneal collagen cross - linking ( cxl ) with riboflavin and ultraviolet - a ( uv - a ) is currently the only treatment that can halt or delay the progression of keratoconus . in this technique
, the combined action of riboflavin and uv - a rays is utilized to increase the corneal strength and integrity by polymerization of the stromal fibers.12 with the widespread adoption of this technique , reports of side - effects and complications are increasing.34567 in this case report , we present two patients who developed clinically diagnosed herpetic keratitis in the early postoperative period after cxl .
there was no previous history of intraocular or corneal surgery , herpetic keratitis , autoimmune disease or systemic connective tissue disease .
the uncorrected visual acuity ( ucva ) was 20/100 in the right eye and 20/70 in the left eye .
the best spectacle - corrected visual acuity ( bscva ) was 20/40 in the right eye and 20/25 in the left eye .
the central pachymetry was 436 m oculus dexter ( od ) and 457 m oculus sinister ( os ) .
topography after 6 months showed the progression of keratoconus ( defined as either an increase in the manifest cylinder of 1 d or greater or an increase in the steepest keratometry by 1 d or greater ) .
the recommended treatment was cxl with riboflavin and uv - a to stabilize the cornea .
the patient underwent a thorough discussion of the risks and benefits of cxl with the surgeon and signed a written informed consent in accordance with institutional guidelines based on the declaration of helsinki .
a 9.0 mm diameter of the corneal epithelium was mechanically removed using a surgical blade , and riboflavin 0.1% solution was instilled repeatedly for approximately 30 min .
penetration of the cornea and presence of riboflavin in the anterior chamber ( riboflavin shielding ) was confirmed by slitlamp examination .
uv - a irradiation was performed using an optical system ( uv - x illumination system version 1000 ; avedro inc . ,
waltham , ma , usa ) with a light source consisting of an array of uv diodes ( 365 nm ) with a potentiometer in series to allow regulation of voltage .
irradiance of the cornea with 3 mw / cm was performed for 30 min . during treatment ,
the riboflavin solution was applied every 2 min and drops of the physiological saline solution were instilled in between to moisten the cornea . after treatment ,
postoperative medication included predinsolone acetate 1% ( pred forte ; allergan inc . , irvine , ca , usa )
four times daily tapered over 4 weeks , ofloxacin 0.3% ( optiflox ; jamjoom pharma , oman ) four times daily for 2 weeks , and cyclopentolate 1% tid for 1-week .
the patients were also advised to instill preservative free artificial tears ( tears natural free ; alcon inc . , hnenberg , switzerland ) .
on the 7 postoperative day , the patient presented with a geographic epithelial defect with dendritic edges without iritis .
topical corticosteroid was discontinued , and the patient was started on ganciclovir ( virgan gel , 1.5 mg / g ; thea pharma , wetteren , belgium ) five times daily for 2 weeks then three times daily for 2 weeks .
after 2 days of initiation of topical antiviral therapy , the geographic ulcer dramatically improved and re - epithelialized [ figure 1 ] .
four months later , a mild central corneal opacity remained but the ucva recovered to preoperative levels without any recurrence of keratitis [ figure 2 ] .
corneal dendrite stained with fluorescein after 2 days of treatment ( photo was not taken at the beginning of the treatment ) mild corneal haze after 4 months of treatment a 21-year - old male presented with progressive bilateral keratoconus . the patient was healthy without any history of systemic diseases or previous ocular surgery .
the patient underwent a thorough discussion of the risks and benefits of cxl with the surgeon and signed a written informed consent in accordance with institutional guidelines based on the declaration of helsinki .
corneal crosslinking of the right eye was performed under sterile conditions using the same technique and the same postoperative medication that was described above .
on the 6 day , slow re - epithelialization was observed . on the ninth postoperative day ,
topical corticosteroids were discontinued , and the patient was started on ganciclovir virgan ( ( ganciclovir 0.15% ) eye gel , thea pharmaceuticals ltd , newcastle , uk ) eye gel five times daily .
dendritic epithelial keratitis ( on the 9 day postcorneal collagen cross - linking ) mild corneal haze after 4 months of treatment
there was no previous history of intraocular or corneal surgery , herpetic keratitis , autoimmune disease or systemic connective tissue disease .
the uncorrected visual acuity ( ucva ) was 20/100 in the right eye and 20/70 in the left eye .
the best spectacle - corrected visual acuity ( bscva ) was 20/40 in the right eye and 20/25 in the left eye .
the central pachymetry was 436 m oculus dexter ( od ) and 457 m oculus sinister ( os ) .
topography after 6 months showed the progression of keratoconus ( defined as either an increase in the manifest cylinder of 1 d or greater or an increase in the steepest keratometry by 1 d or greater ) .
the recommended treatment was cxl with riboflavin and uv - a to stabilize the cornea .
the patient underwent a thorough discussion of the risks and benefits of cxl with the surgeon and signed a written informed consent in accordance with institutional guidelines based on the declaration of helsinki .
a 9.0 mm diameter of the corneal epithelium was mechanically removed using a surgical blade , and riboflavin 0.1% solution was instilled repeatedly for approximately 30 min .
penetration of the cornea and presence of riboflavin in the anterior chamber ( riboflavin shielding ) was confirmed by slitlamp examination .
uv - a irradiation was performed using an optical system ( uv - x illumination system version 1000 ; avedro inc . ,
waltham , ma , usa ) with a light source consisting of an array of uv diodes ( 365 nm ) with a potentiometer in series to allow regulation of voltage .
irradiance of the cornea with 3 mw / cm was performed for 30 min . during treatment ,
the riboflavin solution was applied every 2 min and drops of the physiological saline solution were instilled in between to moisten the cornea . after treatment ,
postoperative medication included predinsolone acetate 1% ( pred forte ; allergan inc . , irvine , ca , usa )
four times daily tapered over 4 weeks , ofloxacin 0.3% ( optiflox ; jamjoom pharma , oman ) four times daily for 2 weeks , and cyclopentolate 1% tid for 1-week .
the patients were also advised to instill preservative free artificial tears ( tears natural free ; alcon inc . , hnenberg , switzerland ) .
on the 7 postoperative day , the patient presented with a geographic epithelial defect with dendritic edges without iritis .
topical corticosteroid was discontinued , and the patient was started on ganciclovir ( virgan gel , 1.5 mg / g ; thea pharma , wetteren , belgium ) five times daily for 2 weeks then three times daily for 2 weeks .
after 2 days of initiation of topical antiviral therapy , the geographic ulcer dramatically improved and re - epithelialized [ figure 1 ] .
four months later , a mild central corneal opacity remained but the ucva recovered to preoperative levels without any recurrence of keratitis [ figure 2 ] .
corneal dendrite stained with fluorescein after 2 days of treatment ( photo was not taken at the beginning of the treatment ) mild corneal haze after 4 months of treatment
a 21-year - old male presented with progressive bilateral keratoconus . the patient was healthy without any history of systemic diseases or previous ocular surgery .
the patient underwent a thorough discussion of the risks and benefits of cxl with the surgeon and signed a written informed consent in accordance with institutional guidelines based on the declaration of helsinki .
corneal crosslinking of the right eye was performed under sterile conditions using the same technique and the same postoperative medication that was described above .
on the 6 day , slow re - epithelialization was observed . on the ninth postoperative day ,
topical corticosteroids were discontinued , and the patient was started on ganciclovir virgan ( ( ganciclovir 0.15% ) eye gel , thea pharmaceuticals ltd , newcastle , uk ) eye gel five times daily .
dendritic epithelial keratitis ( on the 9 day postcorneal collagen cross - linking ) mild corneal haze after 4 months of treatment
corneal collagen cross - linking with riboflavin and uv - a is becoming the accepted method for the treatment of progressive keratoconus.3 it has been shown to increase effectively the biomechanical strength of the cornea and halt the progression of keratoconus .
reactivation of herpes simplex virus ( hsv ) has been reported after emotional stress , trauma , fever , and laser surgery.4 these established clinical triggers are thought to be mediated by the adrenergic and sensory nervous systems .
exposure to uv light can also induce oral and genital herpes in humans and ocular herpes in animal models.568 the herpetic eye study group9 studied many triggers including , psychological stress , systemic infection , sunlight exposure , menstrual cycle , and contact lens wear .
none of these factors were significantly associated with recurrence of herpetic keratitis . in this case report , we describe two patients who developed typical dendritic herpetic epithelial keratitis after cxl treatment . in our cases , the presumed clinical diagnosis of herpetic keratitis was supported by the clinical appearance of the lesions , delayed epithelial healing , decreased corneal sensation and the rapid response to antiviral treatment . in our cases , we typically follow the patient carefully until the epithelium is intact ; delayed healing raises the suspicion of secondary infective keratitis .
therefore , we propose that it is important to closely monitor the patient until there is complete reepithelialization . also , in cases of delayed healing secondary infective keratitis should be ruled out .
uv - a light may be a potent stimulus to trigger reactivation of latent hsv infections , even in patients with no history of clinical ocular herpes infection .
significant corneal epithelial / stromal trauma or actual damage of the corneal nerves could be the mechanism for hsv reactivation .
the use of topical corticosteroids with an epithelial defect is an additional risk factor for infectious keratitis of any etiology . in our cases , both patients did not have a history of previous herpetic eye disease or cold sores , which concur with kyminonis 's et al
yuksel et al.10 also reported a no previous history of herpetic keratitis or cold sores .
primary hsv keratitis frequently manifests as a nonspecific upper respiratory tract infection and is recognized as hsv < 5% of the time .
latent infection of the trigeminal ganglion may occur in the absence of recognized primary infection , with reactivation occurring later as recurrent hsv infection in any branch of the trigeminal nerve .
secondary hsv infection can affect almost any ocular tissue including : the eyelid , conjunctiva , cornea , iris , trabecular meshwork , and retina .
secondary hsv can occur as a self - limited disease , and patients may not seek medical advice in some episodes .
our patients presented later than in previous reports.710 there were no recurrences in both patients for 4 months , which was not been documented in previous case reports.710 their diagnosis was confirmed with polymerase chain reaction tear analysis for hsv . despite the rapid closure of the epithelium within 2 days and initiation of topical steroids
, they also noted a mild central corneal scar at 2 months which were similar to our patients .
as cxl is becoming increasingly popular for the treatment of progressive keratoconus , new side - effects and complications are emerging .
herpetic keratitis may be triggered by cxl , even in cases with no history of the disease .
close follow - up of patients after cxl appears to be important , as early diagnosis and proper treatment can facilitate the successful management of herpetic epithelial keratitis and prevent further potential sequelae .
the retrospective nature of this case report is a limitation . whenever there is a question regarding the etiology of an infectious keratitis
, we recommend laboratory analysis to support the clinical diagnosis of hsv keratitis and rule out similar herpes zoster virus keratitis . the prompt response to antiviral therapy
supports a herpes virus as the cause of keratitis in these cases but does not exclude the possibility of herpes zoster keratitis . in conclusion , cxl with riboflavin and uv - a can induce herpes keratitis with or without iritis .
prophylactic systemic antiviral treatment in patients with a history of the herpetic disease after cxl with uv - a might decrease the possibility of recurrence .
 to describe two cases of herpetic keratitis after corneal collagen cross - linking ( cxl ) for progressive keratoconus . an 18-year - old male and a 21-year - old male with rapidly progressive keratoconus 
 were treated with cxl . 
 postoperatively , on the 6th and 9th days respectively , a dendritic ulcer was observed in the treated eye . 
 the corneal sensation was significantly diminished compared to the fellow eye . 
 both patients had no prior history of herpetic eye disease or cold sores . 
 the keratitis improved dramatically over the following days after initiation of antiviral therapy . at 4 months , 
 the visual acuity was stable without corneal scarring . 
 herpetic keratitis could be induced by cxl even in patients with no history of previous herpetic eye disease . 
 early diagnosis and proper treatment can facilitate the successful management of this rare but important complication . 