CHOROIDAL NEOVASCULARIZATION

Clinical Features

Choroidal neovascularization (CNV) may be observed in a variety of common and unusual conditions. The unifying feature is a disruption of the Bruch’s membrane/retinal pigment epithelial complex, which allows vessels from the choriocapillaris to grow into the subretinal pigment epithelial and/or subneurosensory retinal space. CNV is observed clinically as a grayish green subretinal lesion. The lesion is usually associated with subretinal fluid, hemorrhage, and lipid exudation.

Fluorescein angiography is used to distinguish between classic and occult CNV. Classic CNV consists of a lacy vascular network with well-defined borders during the early transit phase of the angiogram. In contrast, occult CNV is characterized by ill-defined hyperfluorescence with poorly demarcated borders. Symptoms associated with CNV include blurred vision, distortion, and central scotoma.

Differential Diagnosis

Age-related macular degeneration (AMD) is the most common condition associated with CNV. The development of CNV is responsible for the vast majority of cases of significant visual loss in individuals with AMD. Other conditions include degenerative myopia; angioid streaks; pattern dystrophies; polypoidal choroidal vasculopathy; presumed ocular histoplasmosis syndrome; multifocal choroiditis; serpiginous choroiditis; Best’s disease; Stargardt disease; gyrate atrophy; retinitis pigmentosa; choroidal nevus; choroidal osteoma; choroidal rupture/trauma; status post laser photocoagulation; optic disc drusen; and idiopathic choroidal neovascularization.

Diabetic retinopathy

Human immunodeficiency virus retinopathy

Branch retinal vein occlusion

Purtscher’s-like retinopathy

Clinical Features

A cotton wool spot is a small area of superficial retinal whitening located in the posterior fundus (often in the macula, with a perivascular and peripapillary distribution). It results from an ischemic insult to the nerve fiber layer and represents interruption of axoplasmic flow. Histologically, cotton wool spots are characterized by thickening of the ganglion cell and nerve fiber layers and the presence of cystoid bodies, which are globular structures within the nerve fiber layer.

Differential Diagnosis

Cotton wool spots are observed most commonly in retinal vascular diseases such as diabetic retinopathy, hypertensive retinopathy, and vascular occlusions. They have been seen in association with anemia, leukemia, and multiple myeloma, and following bone marrow transplantation and radiation therapy of the head and orbits.

Cotton wool spots may be observed in individuals with human immunodeficiency virus. They may be seen in various inflammatory disorders including systemic lupus erythematosus, polyarteritis nodosa, giant cell arteritis, scleroderma, dermatomyositis, cat scratch neuroretinitis, cytomegalovirus retinitis, and Behçet’s disease. They have been described in association with interferon therapy.

A variant of the cotton wool spot is seen in Purtscher’s-like retinopathy. Purtscher’s-like retinopathy is characterized by prominent peripapillary superficial white patches and retinal hemorrhages surrounding a normal optic disc. It was originally described after head trauma but since has been observed in childbirth, pancreatitis, chest compression injuries, renal failure, and connective tissue disorders (dermatomyositis, scleroderma). The pathogenesis remains unclear; however, complement activation with occlusion of the superficial retinal capillaries has been proposed.

Post-cataract surgery cystoid macular edema (fluorescein angiogram)

Retinitis pigmentosa

Clinical Features

Cystoid macular edema (CME) is characterized by a stellate or honeycomb pattern of retinal thickening in the fovea and parafoveal region. It is visualized most efficiently with the use of a fundus contact lens; often, the cyst-like lesions are seen best with retroillumination. Fluorescein angiography reveals a classic “petaloid” pattern of hyperfluorescence as the dye accumulates in the cystoid spaces. A central yellow spot may be observed in some cases of CME. This feature likely results from the loss of the normal foveal depression and the anterior displacement of xanthophyll pigment.

Histologically, CME is characterized by large cystic spaces containing serous exudate in the outer plexiform layer and small spaces with exudate in the inner nuclear layer. Although the pathogenesis is not completely understood, inflammation likely plays a significant role in the development of CME.

Differential Diagnosis

Cystoid macular edema may develop after any intraocular surgery—particularly cataract surgery. Clinically

Epiretinal membrane

Birdshot chorioretinopathy

significant post-cataract surgery CME occurs in approximately 1% of patients; it is more common in cases of vitreous loss and vitreous incarceration.

CME may be observed in a variety of other conditions including exudative age-related macular degeneration (AMD), epiretinal membrane contraction, and chronic vitreoretinal traction syndromes. CME may be associated with retinal vascular disorders such as diabetic retinopathy and retinal vein occlusions. The condition may result in central visual loss in patients with retinitis pigmentosa as well as inflammatory diseases including birdshot chorioretinopathy, pars planitis, and idiopathic vitritis. CME also has been described in patients with choroidal tumors including choroidal melanomas. CME may develop in individuals with rhegmatogenous retinal detachment. Nicotinic acid toxicity may be associated with a CME-like condition distinguished by the absence of leakage on fluorescein angiography. Latanoprost has been implicated as a cause of CME in pseudophakic and aphakic individuals. X-linked juvenile retinoschisis is characterized by a stellate foveal appearance similar to that of CME. In contrast to CME, the schisis occurs in the nerve fiber layer.

Hard drusen

Calcific drusen

Clinical Features

Drusen are small, yellowish white, round or oval deposits located between the basement membrane of the retinal pigment epithelium (RPE) and the remainder of Bruch’s membrane. They are found most commonly in the macula but may be present in any area of the fundus including the periphery. Drusen are usually bilateral and symmetric. Most individuals with drusen are asymptomatic, although some may complain of blurred vision or distortion. Significant visual loss is associated with the development of choroidal neovascularization (CNV) or atrophy.

Several types of drusen have been described: hard, soft, calcified, and basal laminar/cuticular. Hard drusen are small, yellowish white, discrete deposits. Hard drusen are not associated with the development of advanced age-related macular degeneration (AMD) and are considered by many to be a “normal” aging phenomenon. Soft drusen are larger yellowish deposits with less distinct borders. They may coalesce and become confluent in the foveal/parafoveal region. Soft drusen may be associated with alterations of the RPE, including atrophy and focal hyperpigmentation. Soft drusen and focal hyperpigmentation are associated with an increased risk for the development of CNV. Calcified drusen are small,

Soft, confluent drusen

Basal laminar drusen

refractile deposits associated with AMD and geographic atrophy. They represent dystrophic calcification of drusen. Basal laminar or cuticular drusen are innumerable small, round, discrete nodular deposits that are more apparent on fluorescein angiography. Fluorescein angiography reveals numerous hyperfluorescent pinpoint spots described as having a “stars-in-the-sky” or “Milky Way” appearance. Basal laminar drusen may be associated with vitelliform-like detachments of the RPE and geographic atrophy in the end stage of the disease.

Differential Diagnosis

Drusen are usually observed in the setting of AMD. Occasionally, drusen may be observed in younger individuals (familial or dominant drusen). Basal laminar drusen have been described in patients with type II glomerulonephritis and as a dominantly inherited disorder characterized by a radial pattern of drusen deposition (Malattia levantinese). Unilateral drusen may be associated with an underlying choroidal nevus.

Drusen must be distinguished from Stargardt disease and other fleck dystrophies, the inflammatory white dot syndromes, and fundus albipunctatus.