240 RETINA AND VITREOUS

RPE cells with collagenous periodic acid–Schiff positive deposits between the RPE and Bruch’s membrane with no drusen.

Adult-onset foveomacular dystrophy: solitary, round, yellow spots in the fovea seen in middle-aged patients; may have central pigment with atrophy later, rarely CNVM. Usually unilateral with good prognosis; also called adult Best’s disease. Autosomal dominant defect of the retinal degeneration slow (RDS)/peripherin gene that codes for a photoreceptor structural protein.

Butterfly dystrophy: most common pattern dystrophy that shows bilaterally symmetric ‘‘winged’’ pigmented foveal lesions. Autosomal dominant of the RDS/peripherin gene.

Reticular dystrophy: coarse, knotted ‘‘fishnet’’ or ‘‘chicken wire’’ pattern in fovea extending to the periphery and later fades. Autosomal recessive.

Fundus pulverulentus: prominent, coarse, punctate RPE mottling. Autosomal dominant.

SORSBY’S FUNDUS DYSTROPHY Drusen along the arcades; may lead to CNVM. Defect is problem remodeling Bruch’s membrane from TIMP-3 gene, chromosome 22q.

STARGARDT’S DISEASE Bilateral progressive macular dystrophy with yellow flecks in the posterior pole. Macula has a ‘‘beaten metal’’ or bronze appearance with pigmentary granularity or bull’s-eye appearance that is progressive to atrophy. Patients may be asymptomatic or have central vision loss, but no night blindness or photophobia. All races and both sexes are affected. Same disease but different manifestation as fundus flavimaculatus, which is more peripheral.

FA shows a silent choroid (lipofuscin in enlarged RPE cells blocks transmittance), and multiple window defects are seen as a mottled hyperfluorescence.

Fundus flavimaculatus: soft, yellow-white, subretinal, pisciform (‘‘fishlike’’) flecks surrounding the macula.

Multiple gene defects identified, including, most commonly, an autosomal recessive form from the ABCR (now ABC4A) gene on chromosome 1p whose product is expressed in rods and cones. Autosomal dominant form has no silent choroid, and mitochondrial DNA inheritence is also reported.

No treatment has been proven beneficial, including vitamin A supplementation.

Progressive Tapetoretinal Disorders

BIETTI’S CRYSTALLINE DYSTROPHY White crystals in the retina and cornea (crystalline corneal dystrophy); most patients are blind by age 30; most prevalent in China.

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CHOROIDEREMIA Pale, peripheral fundus from loss of RPE with islands of pigment. Patients are night blind but usually have 20/20 VA with RP symptoms. Onset: age 6 to 15; M >F, with poor visual prognosis. X-linked recessive disorder of choroidal vasculature with absence of RPE and choriocapillaris except in the macula. CHM gene causes abnormal enzyme-generating protein that cannot anchor fatty acids in the RPE cell membrane. Carriers are asymptomatic, with mottled midperipheral retinal and choroidal atrophy and normal ERG. No treatment effective.

COCKAYNE’S SYNDROME Autosomal recessive defect in DNA repair, with congenital cataract, neurodevelopmental delay, failure to thrive, club feet, poor bony development, dwarfism, progeria, deafness, mental retardation, skin photosensitivity, ocular and orbital degeneration, and usually death before teenage years. Ophthalmic findings include enophthalmos, poor dilation, and pigmentary retinopathy.

GYRATE ATROPHY OF THE CHOROID RPE degeneration beginning in the periphery, with scalloped areas of wiped-out RPE and eventually choriocapillaris with abrupt transition to normal areas. Patients have RP-like symptoms (night blindness, ring scotoma) and progressive myopia in the first decade. From an autosomal recessive chromosome 10q defect in the urea cycle enzyme ornithine aminotransferase (OAT) with elevated serum ornithine. Highest prevalence in Scandinavian Laplanders, with onset at age 10 to 40 and abnormal EOG. Carriers have decreased OAT in skin fibroblasts. Treat with low protein/arginine diet (vegetarian) with creatine supplementation; there is a vitamin B6 responsive subgroup.

RETINITIS PIGMENTOSA (RP), PIGMENTARY RETINAL DYSTROPHY

Diseases characterized by abnormal dark adaptation and night blindness from midperipheral RPE degeneration (bone spicules in the zone of maximum rod concentration) leading to photoreceptor degeneration ! decreased NFL and arteriolar diameter ! waxy pallor of the disk. May also have ERM and pigment cells in vitreous (differential diagnosis includes uveitis), ON drusen, myopia, glaucoma, and keratoconus. Patients have decreased VF with early inferotemporal scotoma leading to ring scotoma (do not confuse with arcuate defects seen with glaucoma or uncorrected hyperope). The central VA is preserved until late in the disease (usually from atrophic macular degeneration, CME in 50%, or PSC cataract). 1:3500 incidence in the United States. Histopathology shows all retinal layers lost except the ILM.

ERG: abnormalities precede signs and symptoms, with increased rod threshold with normal cone response and decreased scotopic amplitude and delayed cone B-wave implicit time. Conventional ERG typically ‘‘flat,’’ as it cannot detect <10 mV. However, computer averaged ERG can detect down to 0.05 mV. RP averages 1.3 mV at age 32, and

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242 RETINA AND VITREOUS

although the conventional ERG looks flat, even that low voltage can often carry patients into their 60s.

Genetics: autosomal dominant in 43% of cases (least severe, varying penetrance), autosomal recessive (20%), X-linked (8%), and isolated (2%). (Older literature still quotes 50% sporadic, 16% autosomal recessive, 22% autosomal dominant, and 9% X-linked recessive.) X-linked is the most rapidly progressive and disabling type, whereas autosomal dominant is least disabling. X-linked carriers have salt and pepper fundus and bronze macular sheen.

Rhodopsin gene: first identified RP defect and most common RP mutation, on chromosome 3q, but over 100 other gene defects have been identified. Protein is folded in rod outer segment membrane to create a pocket to hold vitamin A. Pro23his rhodopsin mutation seen in 12% of cases, with average age of RP onset at 37 and average voltage 14.4 mV (thus, patients usually are not blind until age 70).

RPGR: X-linked

RPE65: autosomal recessive, RPE protein; gene defect also involved in Leber’s congenital amaurosis, chromosome 1p.

ABCA4 (previously called ABCR): cone and rod degeneration and Stargardt’s disease, chromosome 1p defect; unable to pump vitamin A out of RPE (do not give vitamin A).

Arrestin: autosomal recessive, chromosome 2q; also in involved in Oguchi’s disease.

Types of RP: most are rod degenerations.

Type 1 (rod–cone): primarily rod degeneration, ‘‘classic RP;’’ 20% sine pigmento (no pigmentary changes). Abnormal scotopic ERG.

Type 2 (cone–rod): less pigment than type 1 (50% sine pigmento), abnormal photopic ERG.

Pigmented paravenous variant: RP along vessels.

Differential diagnosis: pigmented paravenous retinochoroidal atrophy (PPRCA) in young males; may be degenerative disorder that is asymptomatic, not progressive, but with ON pallor, attenuated vessels late, and normal ERG.

Sector RP: autosomal dominant or recessive, inferior retina, stationary and with a good prognosis. Decreased ERG amplitudes and normal implicit time. Pro-23-his rhodopsin mutation; also with X-linked variant with lyonization.

Usher’s syndrome: RP associated with sensorineural hearing loss and vestibular dysfunction.

Type I: RP, deafness, but no vestibular function.

Type II: RP, partial deafness, and normal vestibular function.

Type III: RP, progressive hearing loss, and vestibular dysfunction. Several genes are implicated, most commonly myosin VII expressed in photoreceptors and cochlea.

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Treatment of RP: vitamin A palmitate 15,000 IU/day; check fasting serum vitamin A and liver function tests. Avoid vitamin A if serum retinol >100 mg/dL, patient is pregnant or <fifth percentile of body weight. Encourage a well-balanced diet; avoid high-dose vitamin E (>400 IU/day). CME often responds to Diamox. Recommend annual exam and ERG every 2 years. Low vision aids: night-vision pocketscope provides best monocular daylight vision at night.

SECONDARY RETINITIS PIGMENTOSA Diseases that present with RP-like signs and symptoms but not true dystrophy like RP. Pigmentary retinal degenerations often seen after trauma or inflammation, especially syphilis.

Abetalipoproteinemia, Bassen-Kornzweig syndrome: rare autosomal recessive disorder, usually presenting in teenage Ashkenazi Jews, with malabsorption and steatorrhea leading to vitamin A deficiency (decreased chylomicrons), acanthocytosis (RBC ‘‘burr cells’’), ataxic neuropathy, growth retardation, and tiny specks in peripheral retina but usually no bone spicules. Treat with low-fat diet, and replenish vitamins A, E, and K (ERG may reverse).

Bardet-Biedl syndrome: autosomal recessive, developmental abnormality, characterized by polydactyly, obesity, mental retardation, hypogenitalism (delayed puberty, undescended testes), short stature, and RP, with progressive cone dysfunction early and rods later. Flat ERG. Several genes have been identified; legal blindness by age 20 to 30.

Friedreich-like ataxia and RP: rare, from decreased serum vitamin E.

Kearnes-Sayre syndrome, progressive external ophthalmoplegia: mitochondrial inheritance disorder with RP-like disease if severe; associated with facial weakness, ophthalmoplegia, dysphagia, and cardiac conduction defects; usually before age 20.

Laurence-Moon syndrome: mental retardation, hypogenitalism, short stature, spastic paraplegia, and RP with rod and cone dysfunction. Legally blind usually by age 20 to 30; probably a subset of Bardet-Biedl syndrome.

Refsum’s disease: autosomal recessive disorder of lipid metabolism with decreased phytanic acid alphahydroxylase (chromosome 10p) and accumulation of phytanic acid in the RPE and serum. Patients have atypical RP (granular RPE appearance), cerebellar ataxia, peripheral neuropathy, nerve deafness, anosmia, and EKG conduction defects. Treat with a low phytol diet (no dark green vegetables), and maintain ideal body weight.

Spielmeyer-Vogt-Batten-Mayou disease (SVBM), neuronal ceroidlipofuscinosis (NCL): fatal autosomal recessive disorder of abnormal lipopigment deposition in neural tissue. Progressive blindness from RP with a bull’s-eye maculopathy; associated with seizures, progressive dementia, and ataxia; seen in very sick children with poor life prognosis. Pathology shows vacuolation of peripheral lymphocytes.

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