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Six clinical subtypes of NCL, of which SVBM is the juvenile form (defect on chromosome 16p).

Vitamin A and zinc deficiency: vitamin A deficiency may be caused by chronic pancreatitis, cirrhosis, or bowel resection. Insufficient zinc may cause abnormal dark adaptation because it is needed for synthesis of retinal binding protein (RBP).

Stationary Tapetoretinal Disorders

ACHROMATOPSIA, ROD MONOCHROMATISM Autosomal recessive disorder characterized by a total lack of cones. Patients have a complete red- green-blue defect, severe photophobia, and nystagmus from birth with decreased VA 20/200; usually have a normal fundus with paradoxical pupils. Flat photopic ERG (no cone response); EOG is normal.

Two genetic mutations identified: CNGA3 (cyclic ganglioside alpha-3) chromosome 3 and CNGB3 chromosome 8 (Pingelap Island in the Marshall Islands has a 5% prevalence of CNGB3 achromats). CNG alphaand beta-1 is in rods, -2 in olfactory nerves, and -3 is in

cones. It is an outer plasma membrane cGMP-binding channel to exchange Caþþ/Kþ that regulates voltage of photoreceptor, and a mutated CNG keeps the channel open.

CONGENITAL COLOR BLINDNESS 8% of males are affected. Red and green disorders are X-linked. Blue defects are autosomal dominant on chromosome 7. Disease spectrum from achromatopsia, monochromat (rare, autosomal recessive, consanguinity), dichromat (protanope, deutanope, and tritanope are missing red, green, and blue pigment, respectively), trichromat (normal or protanomalous, deutanomalous, and tritanomalous have color confusion for red, green, and blue, respectively).

Deuteranomaly (5%) and protanomaly (1%) have mild red-green confusion. Deuteranopia (1%) and protanopia (1%) have severe redgreen confusion. Tritanopia (0.2%) has blue-yellow confusion, and tritanomaly is not yet reported.

Blue cone monochromatopsia: autosomal dominant disorder that is difficult to distinguish from rod monochromat (both have flat ERG flicker response, but achromatopsia is autosomal recessive). Demonstrates a reverse Purkinje shift (instead of dark adapting at 500 nm, then shifting forward to light adapt at 570 nm; instead, it shifts backward in light to 480 nm).

CONGENITAL STATIONARY NIGHT BLINDNESS (CSNB) Infantile onset of night blindness with nonprogressive nyctalopia, normal fundus, paradoxical pupils, normal VF, but a nearly nonrecordable scotopic ERG. X-linked form is the most common and has high myopia. Also autosomal recessive form with an abnormal fundus and autosomal dominant variants.

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Oguchi’s disease: autosomal recessive CSNB from chromosome 2q arrestin and other gene defects. Shows the Mizuo-Nakamura phenomenon, where the fundus has a golden-brown metallic sheen in light that disappears and normalizes 6 to 8 hours after it is dark adapted.

Fundus albipunctatus: autosomal recessive CSNB from chromosome 12q defect in 11-cis-retinol dehydrogenase; characterized by whiteyellow, round flecks radially scattered but sparing the macula.

LEBER’S CONGENITAL AMAUROSIS Profound retinal blindness from birth, presenting with nystagmus within the first few months, poor pupillary reflexes, oculodigital reflex (unlike achromats), and normal fundus initially, with late pigmentary changes (one third of cases have a normal retina, one third a salt and pepper appearance, and one third atrophic macular coloboma). Also associated with hyperopia, keratoconus, cataract, strabismus, and enophthalmos. Causes 10 to 25% of all congenital blindness. Do not confuse with Leber’s optic atrophy. Shows absent ERG amplitudes. Six known gene defects (AIPL1, GUC24D, RPE5, RPE6, CRX, RETGC-1) account for only 45% of cases (all involved in the visual transduction cycle); will end up with probably 20 or more responsible genes.

NORTH CAROLINA MACULAR DYSTROPHY Autosomal dominant chromosome 6 completely penetrant disorder present at birth with lesions ranging from few macular drusen to severe macular coloboma, well-delineated subretinal scar tissue, and risk for CNVM, although most patients have good VA.

Congenital and Genetic Vitreoretinopathies

AUTOSOMAL DOMINANT VITREORETINOCHOROIDOPATHY (ADVIRC) 360 degrees of coarse peripheral pigmentatary degeneration posterior to the equator with a discrete border. Associated with retinal and vitreous opacities, cataract, NV, and choroidal atrophy.

FAMILIAL EXUDATIVE VITREORETINOPATHY (FEVR) Autosomal dominant 11q13 defect causing the failure of the temporal retina to vascularize, leading to peripheral ischemia and neovascularization that resembles retinopathy of prematurity. Patients also may have cataract or tractional RD; 73% are asymptomatic.

GOLDMANN-FAVRE SYNDROME Rare, autosomal recessive disorder with varied presentation of RP-like peripheral degeneration, liquefied vitreous with traction bands and PVD, central or peripheral retinoschisis with inner

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246 RETINA AND VITREOUS

holes, beaten copper macula, progressive cataract, myopia, AC cell, late optic atrophy, and CME that does not leak on FA. ERG is nonrecordable late; abnormal EOG (unlike X-linked retinoschisis). M ¼ F.

JANSEN’S SYNDROME Optically empty vitreous, like Stickler’s syndrome, but no systemic manifestations.

KNIEST SYNDROME Collagen mutation that presents like Stickler’s syndrome. Characterized by RD in 50% of cases, ectopia lentis, bone dysplasia, short stature, stiff joints, cleft palate, and deafness.

KNOBLOCH’S SYNDROME Autosomal recessive chromosome 21q22.3 defect (may be seen with Down syndrome) of collagen 18 gene that causes vitreoretinal degeneration, similar to Stickler’s syndrome, with high myopia, RD, nystagmus, cataract, ectopia lentis, occipital scalp defect, or encephalocele.

NORRIE’S DISEASE X-linked (Xp11) disease of abnormal ectoderm and disorganized retina; patients are usually blind from birth and have delayedonset deafness and mental retardation in 50%. Often presents with leukocoria; differential diagnosis includes RB. Milder phenotype is like X-linked FEVR.

SNOWFLAKE DEGENERATION Autosomal dominant, rare disorder causing fibrillar degeneration of the vitreous with small yellow-white opacities in the peripheral retina, with white without pressure (WWP) and potential RD.

STICKLER’S SYNDROME, HEREDITARY ARTHRO-OPHTHALMOPATHY Autosomal dominant abnormality of type II collagen (COL2A1 gene on chromosome 12), presenting by the second decade with optically empty vitreous, lattice retinal degeneration (often radial), high myopia, retinoschisis, and RD in 35% of cases that is difficult to treat. Also associated with cataract, glaucoma, optic atrophy, orofacial and basilar skull abnormalities (flat facies, cleft palate and uvula, Pierre Robin sequence), hearing loss and frequent otitis media, tall stature, and joint hyperextensibility (marfanoid habitus). ERG is depressed. Poor long-term visual prognosis.

WAGNER’S VITREORETINAL DYSTROPHY No systemic manifestations; chromosome 5q defect with optically empty vitreous, vitreous membranes that drape over retina, moderate myopia, atrophy of choroidal vessels, and typical peripheral cystoid degeneration (TPCD). RD is unusual, but cataract is common.

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Infectious Disease

AIDS RETINOPATHY, HIV MICROANGIOPATHY Background microvasculopathy that is noninfectious but is the most common intraocular manifestation of AIDS. Mainly presents with CWS but also may have hard exudate (HE) and vessel sheathing. Correlates with the patient’s immune status; is nonprogressive and resolves.

ACUTE RETINAL NECROSIS (ARN) Rapid, painful vision loss from HSV or HZV with signs and symptoms of acute anterior uveitis, severe vitritis (unlike PORN), and retinal arteritis with multiple focal white peripheral lesions (usually spares the posterior pole). Starts slow and becomes confluent in 2 to 3 weeks, resolving in 3 to 4 weeks with hemorrhages, sheathing, capillary dropout (unlike CMV and PORN), and optic neuritis. One third of cases are bilateral (called BARN) and spread via the chiasm; with second eye infected usually within 6 weeks.

Pathology shows necrosis of the retina with strictly intranuclear inclusions (unlike CMV). M ¼ F; patients are usually 30 to 70 years old and in good health unless the ARN is central, which is usually seen in immunosuppressed patients (compare with CMV and PORN in which most patients have AIDS).

Seventy-five percent of patients develop RRD, generally within 2 years, which is difficult to repair. Retinal detachment should be anticipated and prevented if possible with extensive retinopexy. Treat with IV acyclovir 1.5 g/kg/day. Poor visual prognosis; only 30% are better than 20/200.

CANDIDIASIS Vitrial or subretinal yellow-white fluffy infiltrates that cause floaters or decreased VA usually in immunosuppressed patients, patients on hyperalimentation, or those with a history of IV drug abuse. Blood cultures are usually positive; ocular infection found in 30% of systemically positive patients. Treat with IV and intraocular amphotericin B or ketoconazole, and consider vitrectomy to debulk vitritis.

COCCIDIOIDES IMMITIS Choroiditis present in 10% of disseminated cases; pulmonary is usually the primary site (95% resolve). Fungus is inhaled as a mold and becomes a spherule, which ruptures, releasing endospores.

CYSTICERCOSIS Cysticercus cellulosae is larval form of pork tapeworm Taenia solium; 13 to 46% of infected patients have ocular involvement after ingestion of eggs, usually in pork meat. Larvae then invade the intestinal walls and migrate to the CNS, eye, skeletal muscle, and heart and grow into a cystic structure that is usually well tolerated by the body until the parasite dies, causing marked inflammation. Predilection for the macula; may see

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248 RETINA AND VITREOUS

translucent white cysts with dense white spot formed by invaginated scolex. Serologic tests help if positive (but negative result does not rule out disease); eosinophilia is uncommon, and stool samples may be negative. No effective drug treatment available; may laser the larvae, but death will produce inflammation. Surgical removal of cyst may be possible.

CYTOMEGALOVIRUS (CMV) RETINITIS Most common ocular opportunistic infection in AIDS, although relatively rare now. Usually seen when the CD4 count is <50 (otherwise, think about other causes of retinitis, e.g., toxoplasmosis) or in neonates, malignancy, or other immunocompromised states. May also be congenitally aquired, causing systemic infection with fever, hepatosplenomegaly, anemia, thrombocytopenia, and cataract, peripheral retinal lesions, and optic atrophy. Is a clinical diagnosis, as most individuals are already serologically positive.

Usually asymptomatic, but may have floaters, photopsias, or decreased VA, without redness or pain. Hemorrhagic necrotizing retintis of all layers with CWS in vascular distribution (‘‘cottage cheese and ketchup,’’ ‘‘pizza pie’’ fundus) with only mild vitritis (unlike toxoplasmosis), and rarely frosted branch angiitis. Significant retinal atrophy may lead to multiple small holes and RD in 25% of cases (difficult to treat; usually needs vitrectomy with silicone oil). May also have brushfire variant with slowly advancing white lesion at border of atrophic retina or granular variant without significant hemorrhage, usually in partially treated cases.

Pathology: ‘‘owl’s eye’’ intranuclear and intracytoplasmic DNApositive viral inclusion bodies (unlike herpes virus, which has intranuclear inclusions).

Treatment: 40% of patients lose central VA in both eyes by time of death (blindness was leading cause of suicide in AIDS patients).

Gancyclovir used IV, PO, vitreous injection or Vitrasert implant (controls CMV better than other modes but does not protect other eye and requires signficiant surgery with a 6 mm sclerotomy). Can stop gancyclovir when CD4 count rises above 50 and continue highly active antiretroviral therapy (HAART).

Can also use foscarnet (good response but needs slow infusion; use limited by nephrotoxicity), cidofavir (monthly intravitreal injection; may cause hypotony, uveitis), and Famvir, all of which are virostatic, not virocidal. Isis is an intravitreal reverse transcriptase CMV drug.

Highly active antiretroviral therapy (HAART): fewer opportunistic infections (CMV, PORN, etc.), but more atypical presentations, such as immune recovery vitritis (symptomatic vitritis with CME, seen with inactive CMV retinitis and increased CD4 from HAART).

DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS (DUSN) See Chapter 5.

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FUNGAL Insidious onset with localized vitreous abcess ‘‘snowballs’’ or choroidal granuloma. See candidiasis above.

HISTOPLASMOSIS, OCULAR HISTOPLASMOSIS SYNDROME (OHS) Histoplasma capsulatum, endemic in the Ohio/Mississippi River valleys, causes a systemic fungal infection that is usually asymptomatic. Most patients are 20 to 45 years old and may have pulmonary scars; >90% have positive histoplasmin skin test. May have choroid involvement with a classic triad of peripapillary atrophy, ‘‘histo’’ spots, and juxtapapillary CNVM; may also have linear chorioretinal scars, but no vitreous cell. Treat with Amsler grid monitoring.

CNVM: usually classic lacy ‘‘cartwheel’’ or ‘‘seafan’’ appearance. Risk of second eye developing CNVM is 1% if normal fundus and 25% over 3 years if there is a macular disciform scar.

Macular Photocoagulation Study, a multicenter, randomized controlled trial (1990–1995), showed benefit to treat juxtafoveal and extrafoveal CNVM; patients tend to do better than CNVM related to AMD. Ten percent of treated extrafoveal CNVM lost >6 lines at 3 years (compared with 47% AMD) versus 45% of untreated patients (62% of AMD). May also respond to sub-Tenon’s Kenalog (STK); submacular surgery gives better results in OHS than AMD.

NOCARDIA ASTEROIDES Acid-fast bacteria that may cause panuveitis, choroiditis, retinitis, or vitritis with abcess formation.

PNEUMOCYSTIS CARINII CHOROIDITIS Rare protozoan infection typically unique to AIDS patients, with multiple creamy-yellow, round, plaquelike, choroidal lesions with sharp borders in the posterior pole, with no vitritis. Treat with Bactrim or equivalent.

PROGRESSIVE OUTER RETINAL NECROSIS (PORN) Rare, necrotizing retinitis, usually from HZV (two thirds of patients have antecedent cutaneous zoster) and in AIDS patients (second most common retinal infection in AIDS), characterized by multifocal, full-thickness, deep (outer) retinal lesions (see retinal vessels overlying the lesion), with minimal intraocular inflammation that is rapidly progressive, with a predilection for the ON and macula. One quarter of cases are bilateral, and 70% of patients have RD. NLP in two thirds of patients by 4 weeks. No established therapy; usually try intravitreal antiviral injections at high concentrations.

RUBELLA, GERMAN MEASLES With active maternal rubella infection, 25 to 50% of exposed infants will have retinitis with a salt and pepper fundus and optic atrophy; also associated with cataract, esotropia, mental retardation, congenital heart disease, and deafness. Often also have signs of

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