familial amyloid polyneuropathy ( fap ) is an inherited disorder with autosomal dominant transmission , characterized by systemic extracellular accumulation of amyloid fibrils . the most common type of fap is related to transthyretin ( ttr ) , a protein that carries thyroxine and vitamin a . plasma - circulating ttr is mainly synthesized in the liver , but there is also production in the retinal pigment epithelium and in the choroid plexus [ 3 , 4 ] . the clinical expression is variable among different mutations and different populations , and even the same population with the same mutation can present significant variability . the peripheral nerves and the heart are the organs most frequently affected . more than 100 mutations have been related to fap , but one point mutation in which a methionine residue replaces the valine residue at position 30 ( ttr val30met ) is particularly frequent and is associated with several large foci around the world , namely portugal , japan , sweden and the balearic islands [ 6 , 7 , 8 , 9 ] . this condition was first described in portugal in 1952 , when andrade   reported a peculiar neuropathy characterized by ascending sensory - motor loss and severe autonomic dysfunction , affecting patients of both genders between 25 and 35 years of age . vitreous involvement was mentioned for the first time by kantarjian and dejong   in 1953 in two siblings with fap . the first description of the swedish focus in 1968 also reported the occurrence of vitreous opacities along with the typical sensory , motor and autonomic neuropathy with onset at a later age if compared with portuguese and japanese patients . in portugal , vitreous opacities have rarely been described in patients with the natural and fatal course of the disease , but the prolonged survival after liver transplant led to a significant increase in the prevalence of this problem [ 14 , 15 ] . ocular manifestations of fap include abnormal conjunctival vessels , keratoconjunctivitis sicca , irregularities on lens surface and border of the pupil , change of pupillary shape and light reflex , vitreous opacities and glaucoma [ 16 , 17 ] . vitreous deposits of amyloid may be seen as one manifestation among other signs of the disease , but it has also been described as the earliest , isolated symptom of the disease [ 18 , 19 , 20 ] . we report a case of vitreous opacities as the initial manifestation of fap ttr val30met in a late - onset portuguese patient without a history of fap . an apparently healthy 66-year - old man , born in santa maria da feira and resident in vila nova de gaia , portugal , was first examined in march 2010 for right blurred vision and floaters . best - corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye . the anterior segment of both eyes was unremarkable , with no abnormal conjunctival vessels , no change of pupillary shape , and no amyloid deposition at pupillary border or lens surface . vitreous yellowish - white opacities precluding examination of the fundus were identified in the right eye . full clinical evaluation showed an asymptomatic first - degree atrioventricular ( av ) block in the absence of other neurologic or cardiac signs of disease . the mutation ttr val30met was identified by full sequencing of the gene , and a salivary gland biopsy was done but failed to show amyloid deposition . in november 2010 , as the right visual acuity dropped to 20/100 the patient underwent a pars plana vitrectomy . the pathological examination of the surgical specimen which included congo red stain showed material with yellowish - green birefringence consistent with amyloid . a mobitz 2 second - degree av block was demonstrated with a holter register and he was submitted to a pacemaker implantation , with complete recovery of these symptoms . in september 2012 , the right eye developed a cataract and the left eye presented vitreous opacities ( fig . 1 ) . at that time , the light pupillary reflex and the pupil shape were normal . biomicroscopy of both eyes revealed no amyloid deposits on the lens surface or at the pupillary border . he was submitted to a phacoemulsification of the cataract with intraocular lens implantation in the right eye in september 2012 . one month later , pars plana vitrectomy was performed in the left eye without complications ( fig . his best - correct visual acuity of both eyes was 20/20 , and the ophthalmological examination was normal , except for pseudophakia of the right eye . nine siblings ( 1 brother , 1 sister and 7 half - brothers and half - sisters ) , 3 sons and 7 grandsons had no symptoms suggesting onset of the disease up to the time of reporting ( fig . fap is a heterogeneous disease characterized by systemic accumulation of mutant amyloidogenic ttr in different tissues , including the eye . portugal is the largest focus of the disease in the world , and it is related almost exclusively to the same mutation , ttr val30met . the age of onset shows a wide range ( from 17 to 78 years ) , but 87% of patients developed symptoms before 40 years of age ( mean 33.5 years of age ) . ocular manifestations commonly reported in fap patients are abnormal conjunctival vessels , keratoconjunctivitis sicca , pupillary abnormalities , glaucoma and vitreous opacity . in a study with 37 japanese patients , abnormal conjunctival vessels had the highest incidence with 100% after 10 years of follow - up , followed by the other abnormalities , with vitreous opacities reaching 17% in the same follow - up . it was also demonstrated that ocular manifestations increase with time [ 16 , 21 ] . however , our patient had no other ocular manifestation except vitreous opacities , which are , when numerous , pathognomonic of the disease . in portuguese fap patients , vitreous opacities usually occur years after neurologic manifestations and are associated with other ocular changes , such as pupillary abnormalities . vitreous amyloid deposits are one of the main causes of decreased visual acuity in fap patients . although there are some reports describing isolated vitreous opacities , to the best of our knowledge , this is the first description of a similar case in a portuguese patient . at least 20 mutations of ttr have been related to vitreous deposits , including ttr val30met , ttr tyr114cys , ttr phe33val , ttr ile84ser and ttr ile84asp . in a report of swedish homozygous the only mutation identified in patients with vitreous opacities was ttr val30met , as in our patient . ideally , treatment of vitreous amyloidosis should remove the existing amyloid fibrils and prevent further amyloid deposition . vitrectomy , which can be diagnostic and therapeutic , is a safe and effective surgical treatment done when a significant visual morbidity is present . the recurrence of vitreous opacities after vitrectomy has been described in some series [ 24 , 25 ] . this should be prevented with an extraction , as complete as possible , of vitreous , particularly behind the posterior capsule of lens . suggest performing phacoemulsification and intraocular lens implantation because more extensive removal of the vitreous base is possible with lens removal . it is known that ttr , the precursor protein of amyloid , is predominantly synthesized by the liver . primarily , it has been suggested that amyloid deposits in the vitreous because ttr can cross the blood - aqueous barrier . however , there is evidence of ttr synthesis in the retinal pigment epithelium of the eye , and it has been proposed that vitreous amyloid deposition is the result of the local synthesis of the mutated ttr . in a study of kawaji , it is suggested that ciliary pigment epithelium may also synthesize ttr in addition to the retinal pigment epithelium . the frequent occurrence of ocular amyloid deposition after liver transplantation confirms the importance of persistent local synthesis of mutated ttr . patients with the val30met mutation usually present sensory - dominant polyneuropathy ( more commonly in lower limbs ) , autonomic disturbances and cardiac dysfunction . in the present case , an av block needing a pacemaker implantation was the only systemic manifestation during the follow - up . this means the vitreous amyloid can be a signal of a potential severe systemic disease despite an absence of systemic manifestations , demonstrating the importance of being alert to the whole system . this unusual presentation should not preclude the diagnosis because vitreous opacities are pathognomonic of amyloidosis . in conclusion , the ophthalmologist can have an important role as the first physician detecting typical manifestations of the disease . ocular manifestations such as vitreous opacities and glaucoma lead to visual impairment and can potentially be addressed by surgery . an accurate and frequent follow - up evaluation is needed for the detection of ocular manifestations to ensure a good vision and quality of life of fap patients .