262 RETINA AND VITREOUS

Metabolic and Degenerative Disease

AGE-RELATED MACULAR DEGENERATION (AMD) The major cause of irreversible, severe, central vision loss in developed countries. Affects 18% of persons >60 years old (2.2% of whom are blind), or about 10 million Americans. Disease is characterized by drusen deposits in Bruch’s membrane, RPE disturbance, and potential violation of Bruch’s with resultant CNVM.

AMD risk factors: age, Caucasian, light-colored irides, cardiovascular disease, family history of AMD (especially Malattia Leventinese or Doyne’s honeycomb retinal dystrophy; also, ATP-binding cassette rim (ABCR) gene mutation as in Stargardt’s disease is found in 8–16% of AMD), extensive light exposure, smoking, and poor nutrition.

Risk factors for vision loss: age, hyperopia, positive family history, soft confluent drusen (especially in the second eye), pigment clumping, focal hyperpigmentation, and retinal pigment epithelial detachment (PED).

Favorable prognosis: normal blood pressure, nonsmoker, and with exudative disease, blood or blocked fluorescein on foveal side (e.g., no extension of CNVM into the FAZ).

Differential diagnosis: ICSR, pattern or adult vitelliform dystrophy (yellow spot in macula), any bull’s-eye maculopathy, basal laminar drusen (good prognosis), melanoma (may look like extrafoveal disciform scar), and macroaneurysm.

‘‘DRY,’’ NONEXUDATIVE, OR ATROPHIC AMD Comprises 90% of AMD and only 10% of severe vision loss; characterized by usually mild loss of central VA that is slowly progressing from macular drusen, RPE changes, or geographic atrophy of the RPE (GARPE).

Drusen: excrescences of lipoproteins in and thickening of Bruch’s membrane: ‘‘hard’’ drusen are small <63 mm, distinct, and flat; ‘‘soft’’ drusen are larger, more diffuse or basal laminar (nodular, cuticular), and are usually found in younger patients.

RPE pigmentary changes: may be hyperfluorescent (window defect) or hypofluorescent (blocking defect) on FA; pigment clumping is a risk factor for exudative disease.

Geographic atrophy of the RPE (GARPE or areolar atrophy): central, large (>175 mm), demarcated atrophic RPE with loss of choriocapillaris and overlying photoreceptors; see large choroidal vessels underneath the GARPE lesion.

Treatment: no proven therapy for dry ARMD. Antioxidant vitamins and nutritional supplements may play preventive role. Amsler grid monitoring for development of CNVM; however, only 10% progress to exudative disease. Encourage sunglass wear, and consider low-vision aids.

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‘‘WET,’’ EXUDATIVE, OR NEOVASCULAR AMD Characterized by severely decreased central VA from CNVM, PED, disciform scars (fibrovascular wound-healing scar associated with CNVM), or rarely VH. Makes up only 10% of AMD but is responsible for 90% of severe vision loss.

RPE detachment (PED): orange-yellow dome-shaped elevation; FA shows sharp borders, with slow pooling of fluorescein (like a dimmer switch turning on), and may have a ‘‘notch’’ blocking defect. May lead to RPE tears; the free edge may roll over on itself, blocking on FA, leaving a ‘‘half moon’’ shape of early hyperfluorescence in the area devoid of RPE. One third of patients with PED develop CNVM within 5 years.

Choroidal neovascular membrane (CNVM): patient reports blurred or distorted vision (metamorphopsia) or scotoma. Exam usually shows subretinal hemorrhage and exudate with a gray-green crescent or membrane, and possible localized serous RD. May be difficult to detect clinically (17% of AMD patients with CNVM will have a ‘‘normal’’ exam by retina specialist); obtain FA to diagnose.

Classic CNVM: 13% of exudative cases, showing a well-defined CNVM on FA, with early hyperfluorescence that increases in size and intensity (unlike RPE window defects), as well as progressive leakage and late staining.

Extrafoveal: >200 mm from the center of the FAZ. Sixtythree percent of patients lose six lines of vision by 3 years.

Juxtafoveal: 1–199 mm from the center of the FAZ. Seventyone percent of patients suffer severe vision loss in 21 months.

Subfoveal: 64% of patients with initially good VA lose six lines of VA at 2 years.

Occult CNVM: also called fibrovascular PED or diffuse leakage of undetermined origin; poorly defined on FA, with speckled late hyperfluorescence. Consider indocyanine green angiography (ON looks black), which may show a ‘‘treatable’’ lesion in 40% of cases. A ‘‘hot spot’’ (well-defined small bright area within 3 to 5 minutes; lasts 20 minutes but loses definition with time) on ICG is very helpful in guiding laser treatment.

CNVM risk factors: bilateral drusen (14% risk over 4.3 years), larger more confluent drusen (30% risk to fellow eye over 5 years), extensive drusen (five or more within the central macula), RPE hyperpigmentation (alone carries a 30% risk of CNVM in the fellow eye over 5 years; if with large drusen, then 60% risk), exudative disease in fellow eye (about 10% risk per year), hypertension, low serum levels of antioxidants and micronutrients, smoking, and hyperlipidemia.

Risk of CNVM in fellow eye: 10 to 12% per year, especially if multiple, soft, confluent drusen or RPE clumping is present.

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264RETINA AND VITREOUS

Decreased CNVM risks: high carotenoids, estrogen replacement therapy

Gass classification: type 1 CNVM grows within the sub-RPE space, as in exudative AMD in older patients with a ‘‘sick’’ RPE; type 2 grows through a focal defect of Bruch’s membrane and RPE into the subretinal space and may induce reactive RPE

response, as in OHS (Submacular Surgery Trial: ongoing multicenter, randomized controlled trial).

Treatment: standard treatment is laser photocoagulation of the CNVM (see Macular Photocoagulation Study recommendations below). Technique: have a current FA; consider a retrobulbar block if necessary; adjust power to apply confluent white laser burns usually with 200 mm spot and 0.5 second; repeat angiography in 2 to 3 weeks.

Macular Photocoagulation Study: laser treatment was beneficial for classic CNVM (52% of lesions in the study were purely classic, 35% mixed, 13% occult).

Extrafoveal CNVM: laser treatment, in general, considered beneficial. Twenty-five percent of treated eyes had severe vision loss at 18 months versus 69% of untreated eyes; at 5 years, 46% of treated versus 64% of untreated eyes had severe vision loss. Recurrent CNVM found in 54% of treated eyes at 5 years.

Juxtafoveal CNVM: in general, laser treatment considered beneficial if no systemic hypertension is present. Fifty-two percent of treated eyes had lost six lines of vision loss at 5 years (average 20/200) versus 61% of untreated eyes (average 20/250). CNVM was persistent within 6 weeks after treatment in 32% (vs. 10% extrafoveal). Recurrent CNVM seen in 69% of treated patients at 3 years, 79% at 5 years. Average VA in treated eyes at 4 years was 20/80, 20/200 if persistent CNVM, and 20/250 if recurrent.

Subfoveal CNVM: only well-defined subfoveal CNVM <3.5 DD was treated in the study, and occult lesions were excluded. At 3 months, 20% of treated versus 11%

of untreated eyes lost six lines of vision, but at 24 months, 20% of treated versus 37% of untreated eyes lost six lines. Fifty-one percent of treated eyes had persistent or recurrent CNVM at 24 months. Occult lesions may be stationary.

Photodynamic therapy (PDT): The Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study (a multicenter, randomized ongoing controlled trial) showed that Visudyne safely reduces visual loss in AMD with subfoveal CNVM that is at least >50% classic for patients with VA

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20/20–400. Sixty-one percent of treated versus 46% of untreated eyes lost <15 letters on the ETDRS chart. Sixteen percent of treated versus 7% of untreated eyes had >one line increase in VA.

Age-Related Eye Disease Study (AREDS): high levels of antioxidants and zinc reduce the risk of vision loss from advanced AMD by 19%. No benefit found for minimal AMD, and does not prevent the initial development of AMD or improve vision (also showed no benefit to prevent or slow progression of cataracts). Doses used:

Vitamin C 500 mg

Vitamin E 400 IU

Beta-carotene 15 mg (avoid in smokers, as it is linked to lung cancer)

Zinc oxide 80 mg plus copper 2 mg (cupric oxide): high-dose zinc is associated with copper deficiency.

AMYLOIDOSIS Eight percent of patients with primary familial disease have ocular involvement, often with retinal hemorrhage, exudates, CWS, peripheral NV, and extracellular vitreous opacities adjacent to retinal vessels with wispy edges. Associated with polyneuropathy, skin and heart involvement.

ASTEROID HYALOSIS Unilateral vitreous opacities representing calcium soaps (calcium hydroxyapatite). Asymptomatic; may be associated with diabetes.

CHOLESTEROLOSIS BULBI, SYNCHYSIS SCINTILLANS Cholesterol crystals in liquefied vitreous that settle inferior after a large VH; seen as yellow, glistening bodies attached to the vitreous framework.

EPIRETINAL MEMBRANE (ERM), MACULAR PUCKER, CELLOPHANE MACULOPATHY, SURFACE WRINKLING Disruption of the ILM with glial proliferation and differentiation into myofibroblasts that may contract, causing retinal surface wrinkling.

Most cases are asymptomatic but may have metamorphopsia, decreased VA, diplopia, or central photopsias (especially with vitreomacular traction). Exam may show cellophane wrinkling, vessel tethering or straightening, retinal hemorrhage, CWS, macular pucker or pseudohole, and CME (if seen on preoperative FA, portends a lower prognosis for visual recovery after surgery). Eighty-five percent of patients have VA better than 20/70.

Prevalence 5% (20% by age 75). Idiopathic is leading cause (associated with PVD, 30% bilateral) but also seen with RD (examine peripheral retina for holes), vascular occlusion, inflammation, trauma, postoperative.

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266 RETINA AND VITREOUS

Treat with vitrectomy plus membrane peel if VA 20/40 or worse; 80% regain two lines of vision. Fifty to 60% of phakic patients develop cataract after surgery. Five to 7% of cases are recurrent.

HIGH MYOPIA, MYOPIC DEGENERATION Progressive thinning of the choroid and RPE in the macula that may cause loss of central VA, usually at about age 50. May be associated with posterior staphyloma, RPE atrophy, tilted disk, extensive PPA, increased IOP, RD, and the following:

Fuchs’ spot (also known as Fo¨rster-Fuchs’ spot): a raised circular pigmented lesion that represents a small, aborted CNVM.

Lacquer cracks: linear breaks in Bruch’s membrane that may present acutely as photopsias follwed by decreased VA. May have hemorrhage; CNVM in 72% of cases.

CNVM: usually close to fovea, small size, and less likely to respond to laser than in AMD. Sixty percent of patients have VA <20/200 but higher spontaneous resolution; does not behave as poorly as AMD.

IDIOPATHIC CENTRAL SEROUS RETINOPATHY (ICSR) Acquired macular disease with serous elevation of the neurosensory retina; 80% are male, usually age 20 to 60, presenting with metamorphopsia, micropsia, or mildly decreased VA that improves with pinhole. Exam shows absent foveal reflection, occasional PED or RPE clumping from prior episodes, possible subtle elevation of the retina, and document that there is no ON pit. FA shows a hyperfluorescent expanding dot in 80% of cases or the classic smokestack in 10 to 20% of cases and window defects from prior lesions. Fifty percent recover within 6 weeks but may need a temporary hyperopic correction. Sixty-six percent of patients eventually recover 20/20 VA, but up to 50% of cases recur. Laser treatment may accelerate resolution but does not improve VA or recurrence rate and carries the risk of CNVM. Corticosteroid treatment may greatly worsen the condition.

IDIOPATHIC MACULAR HOLE Tangential traction on the fovea by posterior cortical vitreous that creates a retinal dehiscence. Women 60 to 80 years old are most commonly affected. Ask about prior trauma; 25% are bilateral. Stage 3 and 4 holes are often treated with vitrectomy plus membrane peeling to relieve tangential traction; may use tissue adhesives such as autologous serum, transforming growth factor b (TGF-b), plasmin, or fibrinogen.

Stage 1: impending hole that is a foveal detachment by cortical vitreous contraction but no actual retinal break. May see a yellow spot or ring, mildly decreased VA; 50% resolve.

Differential diagnosis: vitreomacular traction, ICSR, pattern dystrophy, phototoxic maculopathy, post-traumatic, drusen, CME, and parafoveal telangiectasis.

Stage 2: hole that is <400 mm, and the posterior hyaloid is attached.

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Stage 3: hole >400 mm with an operculum; see yellow spots at the level of the RPE (macrophages with lipofuscin), and the posterior hyaloid is attached.

Stage 4: large full-thickness hole with complete separation of the posterior cortical vitreous. May have a cuff of SRF, yellow deposits within the defect, and RPE atrophy with window defects. Differential diagnosis includes ERM with pseudohole (negative Watzke-Allen test), impending macular hole, lamellar hole from aborted macular hole (hyperfluorescence on FA), and chronic CME.

PERIPAPILLARY STAPHYLOMA Unilateral deep excavation with welldefined normal disk from scleral weakness, usually in high myopes.

PERIPHERAL RETINAL DEGENERATIONS

Cystoid degeneration: small intraretinal cysts near the ora that increase with age; not associated with retinal tears.

Typical peripheral cystoid degeneration (TPCD): cystic spaces in the outer plexiform layer that may coalesce into a retinoschisis cavity (may see a gray band posterior to the ora serrata, usually temporal; may have Blessig-Iwanoff ’s cysts).

Reticular: cystic spaces in the NFL, usually more posterior than TPCD.

Lattice degeneration: equatorial band of retinal thinning (‘‘stretch marks’’) seen as a white ‘‘snail track’’ or reddish crater with overlying sclerosed retinal vessels; has an 8 to 10% prevalence, mostly in myopes. Found in association with 25% of RDs (is the cause of 30–45% of RDs in young myopes). Retinal tears usually occur at the end of or posterior to the lattice lesion. Twenty-five percent of cases have small atrophic holes within the lattice (usually does not cause RD). Lattice is usually not treated unless patient has a history of RD.

Pars plana cysts: usually normal finding, although may be associated with multiple myeloma.

Paving stone or cobblestone degeneration: round chorioretinal atrophy with pigmented borders that represent an infarction of a peripheral choroidal lobule, usually inferiorly; overall 22% prevalence, and incidence increases with age. May protect against RD because there is an adhesion between the retina and the choroid.

Retinoschisis (degenerative, acquired, or senile): splitting of the retina in the outer plexiform layer (thus predisposed by TPCD) from a partial vitreous detachment with oblique traction on the retina. Seventy percent are inferotemporal, and 66% are bilateral. The elevated inner retina may have tiny white dots (Mu¨ller foot processes) and is very translucent (can see choroidal details, unlike RRD). If a hole is present in the inner retinal layer only (often pinpoint), there is no RD risk. However, a hole in the outer layer of the schisis (usually has rolled

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268 RETINA AND VITREOUS

TABLE 7–3

Characteristics of Retinal Detachment versus

Degenerative Retinoschisis

edges) may cause RD (causes up to 3% of RD), and RD usually remains localized unless there is an inner and outer hole. Usually stable or very slowly progressive. May treat with laser photocoagulation or vitrectomy if threatening the fovea. (See Table 7–3 for a comparison of retinal detachment and degenerative retinoschisis.)

Differential diagnosis: reticular retinoschisis with involutional splitting of the NFL or secondary schisis seen with Coats’ disease, trauma, intermediate uveitis, tumors, and vitreomacular traction.

POSTERIOR VITREOUS DETACHMENT (PVD) Separation of the posterior cortical vitreous from the retina, as evidenced by a Weiss ring. Common, age-related degeneration of the vitreous as hyaluronidase is replaced by water (syneresis, also accelerated after intraocular surgery and with high myopia); 63% incidence in patients >70 years old and only 27% of patients 60 to 69 years old. Patients may complain of new-onset floaters or photopsias (from retinal traction). PVD may cause splinter hemorrhage, VH, or retinal tear. The more recent the symptoms, the more urgent the need for examination. Risk of retinal break is 10 to 15% if patient is symptomatic with photopsias, 2 to 4% if no VH, and 70% if VH is present. Seventy percent of PVD-associated tears are between 10 and 2 o’clock, usually at the vitreous base, where the vitreous attaches firmly to the retina and the pars plana epithelium. If there is a VH but no tear is seen, then reexamine within 2 weeks to look for tear.

Vitreomacular traction (VMT) syndrome: partial PVD but still attached to macula, causing edema, striae, thickening, or RD; if traction is on the disk, may cause ‘‘fleshy donut’’ sign. May need vitrectomy.

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RETINAL HOLES AND TEARS Often present with floaters and photopsias, may have Schaeffer’s sign (pigmented cells in anterior vitreous).

Atrophic retinal holes: round, often in areas of typical peripheral cystoid degeneration; seen in 5% of the population. Rarely progress to RD; thus, no laser treatment is necessary.

Dialyses: circumferential tear at the ora; accounts for 75% of traumatic tears, usually seen in young patients. Typically do well with scleral buckle.

Giant retinal tear: a tear that extends 90 degrees or more around the circumference of the fundus (usually at the posterior border of the vitreous base, compared with dialyses, which occur at the ora serrata). Usually nontraumatic (77%) and seen in young males; also carries a very high risk of RD in the fellow eye. Difficult to treat, usually with vitrectomy and unfolding the often inverted posterior retinal flap.

Horseshoe tear (HST): partially torn retinal flap; almost always points

progress to RD if left untreated; thus, treat all HST with laser. Apply hot laser at least two rows around the tear; if SRF is present, consider cryotherapy. Have patient avoid exertional activity until scar forms.

Operculated round tear: retinal hole with the operculum of the retina seen in the vitreous. If patient is asymptomatic and there is no current vitreous traction, <5% progress to RD. No treatment is usually needed unless the patient is a high myope, has a personal or family history of RD, or is aphakic or pseudophakic. Treat all symptomatic holes, as 5 to 17% will progress to RD if untreated.

Evidence-based treatment recommendations: type I strong evidence, type II substantial, type III consensus. Always treat symptomatic HST

(I). Almost always treat all dialysis (III). Sometimes treat symptomatic operculated tear (II), lattice in fellow eye of tear (II), and all asymptomatic HST (III). Rarely treat asymptomatic hole (II), symptomatic hole or lattice (II), asymptomatic holes or operculated tear in myope/fellow eye of tear/aphakic patient (III). No treatment needed for asymptomatic operculated tear or asymptomatic lattice in phakic or myopic eye (II).

RHEGMATOGENOUS RETINAL DETACHMENT (RRD) Most common type of RD, occurring from a break in the retina and often causing photopsias or loss of vision, like a curtain, veil, or shade coming across the vision. Retina often maintains its viability if it is repaired in a timely fashion. If chronic, the retina becomes macrocystic and often inoperable, as fixed cysts form between Mu¨ller’s cells.

Evaluation: perform history, and ask about symptom duration, trauma, family history, and previous surgery. Do full eye exam and obtain the BCVA; check IOP (usually low), APD, EOM (prior to buckle), and

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270 RETINA AND VITREOUS

note lens status, then do careful DFE (find the tear; always presume that there are other tears).

RRD etiology: myopia (40–55%), aphakia (30–40%), trauma (10– 15%), genetic predisposition (family history and certain races, e.g., Egyptian ancestry), PVD, pseudophakia/other intraocular surgery, scleral perforation, intraocular inflammation (ARN 75% have RD, CMV 25%, etc.), and inherited disease (Wagner syndrome, Jansen’s disease, Stickler’s syndrome, Goldmann-Favre syndrome). One third of RD is believed to be from myopia, one third from trauma, and one third from other causes.

RRD prevalence: 1 in 15,000 overall; high myopes (5%, mainly from lattice degeneration), aphakic patients (2%), vitreous loss after ECCE (10%; 50% are within the first year).

RRD personal risk factors (in order): RD in fellow eye (15%), myopia (7–8%), family history, lattice degeneration

Anatomical risks: meridional complex or tufts (fold in the retina up to a dentate process or oral tooth), lattice degeneration (tears begin at edge of lattice; tears within lattice are usually atrophic), degenerative retinoschisis and cystoid degeneration, retinal break (full thickness, 5–18% prevalence), retinal tear (traction present), retinal hole (operculated with no traction and low risk of RD), giant retinal tear (>90% have RD)

Pathology: early in the course, inner retinal edema is seen, followed by photoreceptor disruption and outer layer degeneration by 4 weeks; cysts are present by 10 weeks, then fixed retinal, folds. May also see proliferative vitreoretinopathy, pathologic drusen, and hyperplasia of RPE, often seen as a diffuse pigment proliferation or demarcation line (pigment line at the ora serrata is called ringschweile).

Treatment: surgical options should be considered in light of whether the patient is symptomatic or asymptomatic, presence of a tear or a hole, whether the patient is high myope, pseudophakic or phakic, or needs cataract extraction or not; also, whether there is a history of RD in the other eye, RD location (superior location has risk of macular detachment, vs. inferior location, which is usually harder to treat), and, patient reliability and access to care. Final vision is determined by duration of RD and whether the macula is ‘‘on’’ or ‘‘off.’’ Treatment options include observation, retinopexy alone (with cryotherapy or laser), scleral buckle procedure (SBP), pneumatic retinopexy, temporary buckle (Lincoff balloon, gelatin, etc.), and vitrectomy with or without lensectomy, membrane peel (MP), perfluorocarbon (PFC), retinotomy, fluid–gas exchange (FGX), and SiO.

SEROUS, EXUDATIVE RD Characterized by bullous, shifting, subretinal fluid. Usually from breakdown of the blood–retinal barrier, RPE disturbance or disturbance of the subretinal pump. Determine and treat etiology.

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