Nonexudative (Dry) Age-Related Macular Degeneration (AMD) Treatment & Management

No approved medications for the treatment of dry age-related macular degeneration (AMD or ARMD) are available.

Role of vitamins, antioxidants, risk of smoking, and hypertension  ^{[6, 7, 8, 25]}

Evidence shows that patients with early or moderate dry age-related macular degeneration (AMD or ARMD) should consume adequate quantities of antioxidants, including vitamin A, vitamin E, zinc, and lutein. Prevention is the best treatment in this case because no satisfactory method exists to treat dry AMD. Accumulated evidence suggests that AMD is a genetic disease. Therefore, children of patients who have lost vision to AMD are the best candidates for a primary prevention trial.

The first Age-Related Eye Diseases Study (AREDS) has concluded, and its results are illuminating. In this study, patients with very mild or moderate forms of dry AMD were given antioxidant supplementation (15 mg of beta-carotene, 500 mg of vitamin C, 400 IU of vitamin E, 80 mg of zinc, plus 2 mg of copper). These patients had a small but definite decrease in their progression to advanced AMD. Interestingly, the data showed benefit in preventing the conversion of dry AMD to neovascular AMD.

A study by Millen et al examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and the prevalence of AMD. ^[26] The study determined that high concentrations of 25(OH)D protected against early AMD in women younger than 75 years.

The Rotterdam Study (1990–1993) investigated whether regular dietary intake of antioxidants was associated with a lower risk of developing AMD in more than 4000 persons aged 55 years or older in The Netherlands. In this study, a high dietary intake of beta-carotene, vitamins C and E, and zinc was also associated with a substantially reduced risk of AMD in elderly persons.

Some evidence indicates that multivitamins with antioxidants and lutein may be of benefit. Clear evidence shows that smoking accelerates the disease process. It is recommended that patients who have a family history of AMD, and specifically those patients whose first-degree relative has lost vision due to AMD, should take a multivitamin with lutein each day. It is advised that patients stop smoking and consider supplemental oral antioxidants if they are unable to stop smoking.

Controversy exists over the exact vitamin combination that may be beneficial. Zinc and vitamin E are commonly touted as providing the best benefits. One study reports the beneficial effects of zinc, while another study shows a worse outcome with large doses of zinc. Therefore, it would be prudent to take a multivitamin containing a moderate dose of these vitamins.

To further refine the specific benefits of antioxidants, a randomized controlled clinical trial, Age-Related Eye Disease Study 2 (AREDS2), was performed. This study determined that oral supplementation with macular xanthophylls (lutein at 10 mg/d plus zeaxanthin at 2 mg/d) was superior to lutein alone at slowing dry AMD progression, while omega-3 long-chain polyunsaturated fatty acids (LCPUFAs; DHA plus eicosapentaenoic acid at a total of 1 g/d) did not decrease the risk of progression to advanced AMD, as compared with placebo.

Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of AMD. The objective of the Women’s Antioxidant and Folic Acid Cardiovascular Study was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride, and cyanocobalamin. ^[9] The trial included 5442 female healthcare professionals aged 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. The randomized trial data for the large cohort of women at high risk of cardiovascular disease indicated that daily supplementation with folic acid (2.5 mg/d), pyridoxine 50 mg/d) and cyanocobalamin (1 mg/d) may reduce the risk of AMD.

The purpose of the Cardiovascular Health and its Association with Prevalence and Progression of Age-Related Macular Degeneration (CHARM) study was to determine if cardiovascular health, as determined by novel noninvasive techniques, was associated with prevalent AMD or AMD progression. ^[27] The results were unexpected in that better cardiovascular health was associated with increased risk for prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these noninvasive methods of characterizing the cardiovascular system should be undertaken because they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.

Epidemiologic studies using a computer database previously indicated that the use of statins was protective against the development of AMD. However, a 2007 study, using rigorous systems and graded macular photographs, confirmed that the use of statins was not correlated with AMD incidence or progression. ^[28]

Early symptoms

Prolonged darkness (delayed dark adaptation) upon entering a restaurant from bright sunlight is one of the earliest symptoms, with patients noting this phenomenon prior to the presence of any significant atrophy. One effective suggestion for patients with this symptom is to use wrap-around shades. Some low-vision specialists suggest the use of orange-tinted, blue-blocker lenses.

Patients with dry AMD often have a visual function that is much poorer than suggested by their Snellen acuity. The presence of large areas of atrophy, usually in a perifoveal zone, results in large scotomas near the center of the visual field. These scotomas prevent patients from performing simple tasks (eg, recognizing faces, reading). Low-vision specialists often prescribe magnifiers with a line marker so that patients do not lose their place while reading.

Family members of patients with AMD

While it would seem logical that the same vitamins used to treat patients with AMD would be of benefit prior to the development of AMD in family members, in the AREDS, supplements did not show any significant benefit with treatment over the 7-year follow-up when the disease was very mild. Additionally, many risks are associated with long-term zinc, vitamin A, and vitamin E supplementation. Instead, family members of patients with AMD should do the following:

• Do not smoke and avoid second-hand smoke.
• Protect eyes from direct sunlight using either dark glasses or a wide-brimmed hat.
• Eat a well-balanced diet high in natural antioxidants.
• Eat fresh baked fish (1-2 servings) daily.
• Eat green leafy vegetables (eg, spinach, kale) daily.
• Consider a supplement consisting of folic acid (2.5 mg/d), pyridoxine (50 mg/d), and cyanocobalamin (1 mg/d). ^[9]

Family members should be specifically requested NOT to take the AREDS supplement vitamins because the risk associated with long-term supplementation with these vitamins may not overcome the benefits of taking them. For example, in subjects with 1 risk factor in the AREDS, the race of progression of disease at 5 years was minimally different from that of the placebo-treated subjects. This also held true at 10 years. Subjects with more risk factors (2-4) had progressively increased levels of benefit with supplementation.

Clinical guideline summaries

American Academy of Ophthalmology Retina/Vitreous Panel - Age-related Macular Degeneration

US Preventive Services Task Force - Screening for impaired visual acuity in older adults: U.S. Preventive Services Task Force recommendation statement

National Institute for Health and Clinical Excellence (NICE) - Ranibizumab and pegaptanib for the treatment of age-related macular degeneration

No accepted surgical alternative to dry age-related macular degeneration (AMD or ARMD) is available.

It is possible that the drusen present in dry AMD can be ameliorated by the performance of a very light grid laser therapy. ^[29] The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT), a National Eye Institute–sponsored study examining the visual benefit from such treatment, has concluded. Preliminary results indicate that focal laser therapy in a light grid pattern causes drusen resorption and improved visual acuity in the short term. However, the procedure was associated with a slightly higher risk of developing choroidal neovascularization in the short term compared with no laser treatment. Additionally, at the end of the study, no significant visual benefit was observed in those who were treated compared with those who did not receive laser treatment.

More recently, a few patients underwent retinal translocation surgery during which the retina is rotated. Many of these patients developed accelerated dry macular degeneration with retinal pigment epithelium (RPE) atrophy at the site of the new macula. Interestingly, the area of atrophy that developed at the new site resembled almost identically the area of atrophy that was preexistent prior to the translocation. This provides clinical evidence that the RPE layer is the source of disease pathophysiology and that the retinal atrophy that results is a response to diseased RPE.

A phase II study using encapsulated, genetically modified cells that secrete ciliary neurotrophic factor indicated the retinal thickening occurred in a dose-dependent, statistically significant manner. Treated subjects also had a higher percentage of preserved vision. Additional studies are required prior to approval by the US Food and Drug Administration (FDA).

Isolated reports of both embryonic and adult-derived stem cells being placed in the subretinal space have been noted. These are small reports whose primary purpose was to determine the feasibility of such an endeavor. In the near future, RPE cell repair via external transplantation of stem cells may provide a reasonable method of treatment for those patients with severe disease.

Serial general ophthalmologic examination, on a nonemergent basis, is indicated for patients with dry age-related macular degeneration (AMD or ARMD). If these patients have an acute loss of vision, retina consultation with fluorescein angiography is indicated in a timely manner to rule out the possibility of conversion to wet AMD.

Patients who have significant AMD changes, with or without vision loss, may wish to have their children evaluated by an ophthalmologist once the children reach age 50 years.

A neurologist should be consulted for patients with AMD who exhibit signs of cognitive dysfunction, since an association with Alzheimer disease has been found. ^[18]

Evidence suggests that diet plays an important role in the prevention of dry age-related macular degeneration (AMD or ARMD). ^[30] Epidemiologic studies suggest that a diet containing green leafy vegetables is of benefit. Smoking cessation is of significant benefit. Consumption of baked fresh fish also is beneficial, owing to the fatty acids provided; 1-2 servings a week are adequate.

No limitations are noted for age-related macular degeneration (AMD or ARMD). Each state has specific visual-acuity criteria for driving with a private license. Commercial driving licenses typically require at least 20/40 vision in the worse eye and have other typical requirements for side vision.

Patients with dry age-related macular degeneration (AMD or ARMD) should be observed frequently. Their follow-up care should be determined by the extent of disease and by the ophthalmologist's assessment of risk of conversion to wet AMD.

Daily Amsler grid evaluation is necessary, with immediate reports to the ophthalmologist of any changes are noted.

Recently, an alternate home visual field monitoring device to detect metamorphopsia (ForeseeHome device, Notal Vision Ltd, Tel Aviv, Israel) has been developed and demonstrated to provide earlier detection of wet AMD development.