Macular Diseases

Age-related macular degeneration (AMD) is the leading cause of legal blindness in people aged 65 years or older in the United States. Approximately 90% of individuals with AMD have the nonexudative or “dry” form of the disease. Types of nonexudative AMD include drusen, retinal pigment epithelial alterations, and geographic atrophy. Risk factors for AMD include age, family history of AMD, and cardiovascular factors including hypertension and a history of cigarette smoking.

Symptoms

The majority of people with nonexudative AMD are asymptomatic. Individuals with drusen may complain of mild distortion or visual loss. Individuals with more extensive retinal pigment epithelial alterations or geographic atrophy complain of difficulty reading or recognizing details, and have paracentral or central scotomas. Visual loss associated with geographic atrophy is slow; abrupt changes in vision suggest the possibility of choroidal neovascularization (CNV).

Clinical Features

The characteristic finding in AMD is drusen. Drusen are small, discrete yellowish white deposits. They are observed most commonly in the macula but may be found in every area of the fundus. Drusen tend to be bilateral and symmetric. Several types of drusen have been observed: hard, soft, calcified, and basal laminar/cuticular (see “Drusen” in Chapter 3). Retinal pigment epithelial (RPE) alterations include atrophy and hyperpigmentation. Geographic atrophy is characterized by well-demarcated round or oval patches of atrophy in the parafoveal/foveal region. The atrophic patches may enlarge or coalesce over years. In general, the center of the fovea is involved late in the disease process.

Ancillary Testing

Fluorescein angiography may be performed to examine for evidence of CNV or progression of geographic atrophy. This evaluation is particularly important for patients with sudden alterations in vision. Drusen appear as focal areas of hyperfluorescence that are not associated with late leakage. Geographic atrophy demonstrates a classic transmission or “window” defect as a result of RPE loss.

Pathology/Pathogenesis

Drusen are localized deposits found between the basement membrane of the RPE and the remainder of Bruch’s membrane. Two types of deposits have been identified: basal laminar and basal linear. Basal laminar

deposit is composed of wide-spaced collagen located between the plasma membrane and the basement membrane of the RPE. Basal linear deposit consists of granular and vesicular, electron-dense, lipid-rich material located external to the basement membrane of the RPE in the inner collagenous zone of Bruch’s membrane. Geographic atrophy is characterized by well-demarcated areas of RPE atrophy with sclerosis of the underlying choriocapillaris.

The pathogenesis of AMD is not completely understood. Twin and family studies suggest genetics may have a significant influence on the development and progression of AMD. Alterations in choroidal blood flow also may play a role.

Treatment/Prognosis

There is no known treatment for nonexudative AMD. The Age-Related Eye Disease Study (AREDS) demonstrated a reduction in the progression of AMD in patients taking zinc, beta-carotene, vitamin C, and vitamin E. Laser-induced drusen reduction is associated with improved visual acuity and contrast sensitivity in eyes at 1 year. The long-term effects of laser-induced drusen reduction on visual function require additional observation, and several studies are investigating the role of grid laser treatment for the prevention of CNV in patients with drusen.

The majority of individuals with nonexudative AMD do very well with excellent visual function. Visual loss is the result of progressive geographic atrophy or CNV. The estimated risk for the development of CNV in patients with bilateral drusen is 10% to 15% over

5 years. Clinical features associated with an increased risk of CNV are soft drusen, areas of focal hyperpigmentation, and CNV in the fellow eye.

Systemic Evaluation

Age-related macular degeneration may be associated with cardiovascular risk factors including hypertension and a history of cigarette smoking. A general physical examination and smoking cessation are strongly recommended.

A variety of different types of drusen may be observed in patients with age-related macular degeneration. “Soft” drusen are larger, yellowish deposits with slightly ill-defined borders. “Hard” drusen are small, discrete deposits located at the level of the retinal pigment epithelium.

The risk of developing exudative age-related macular degeneration is greater in patients with soft, confluent drusen and focal areas of hyperpigmentation.

Patients with drusen are usually asymptomatic; rarely, patients may complain of reduced or distorted vision.

Geographic atrophy is responsible for most cases of visual loss in patients with nonexudative age-related macular degeneration. The atrophic patches may enlarge or coalesce over years. In general, the center of the fovea is involved late in the disease process.

Early-phase fluorescein angiogram of a patient with age-related macular degeneration demonstrates variable hyperfluorescence of the soft drusen.

Late-phase fluorescein angiogram of the same patient in the previous figure reveals late staining of the drusen material. Note the linear streaks of hypofluorescence corresponding to areas of focal hyperpigmentation.

This patient has numerous hard drusen located in the temporal macula of each eye. Hard drusen have not been associated with an increased risk of choroidal neovascularization.

This patient has a few soft, confluent drusen located near the fovea. She was asymptomatic.

Over time, soft drusen may coalesce to form larger deposits, simulating a pigment epithelial detachment. Patients may experience a hyperopic shift in their refractive error.

This 64-year-old man had numerous soft drusen with areas of focal hyperpigmentation. He subsequently experienced visual loss related to the development of occult choroidal neovascularization.

Calcific drusen are usually observed in the setting of geographic atrophy. Calcific drusen are highly refractile and represent dystrophic calcification of the drusen material.

This 90-year-old man had visual loss related to agerelated macular degeneration with geographic atrophy. Note the presence of calcific drusen. Also note the absence of drusen in the region of atrophy.

This pair of fundus photographs demonstrates the progression of age-related macular degeneration. Note the soft, coalescent drusen.

This patient had age-related macular degeneration with geographic atrophy that was most notable in the temporal macula.

Over a 5-year period, the macular degeneration progresses with the development of geographic atrophy and calcific drusen.

Three years later, the same patient presented with sudden vision loss. The patient had subretinal blood and fluid consistent with choroidal neovascularization. Approximately 20% of patients with geographic atrophy develop choroidal neovascularization.

The extent of geographic atrophy is unclear on this fundus photograph of a 68-year-old woman with agerelated macular degeneration.

A fluorescein angiogram of the same patient highlights the transmission or “window” defect corresponding to the extensive area of retinal pigment epithelial atrophy.