Age-related macular degeneration is the deterioration of the central part of the retina. It is the primary cause of irreversible vision loss in patients living in developed countries. Unfortunately, effective treatments are unavailable for most patients with this condition; therefore, patients often resort to experimental or unproven therapies. Currently, several clinical trials are evaluating prophylactic and therapeutic treatments. Fine and colleagues provide an update on the status of existing, investigational and unevaluated therapies for the treatment of patients with age-related macular degeneration.
The macula is the central, posterior part of the retina and contains the largest concentration of photoreceptors. It is typically 5 to 6 mm in diameter, and its central portion is known as the fovea. The macula serves to facilitate central vision and allows for high-resolution visual acuity.
Age-related macular degeneration can be classified into early and late stages. Patients with early-stage, age-related macular degeneration usually experience minimal vision loss. In the early stage, the macula contains large drusen and pigmentary abnormalities. Drusen are accumulations of acellular, amorphous debris subjacent to the basement of the retinal pigment epithelium. Most persons older than 50 years have at least one small druse. Eyes with large and numerous drusen (more than 63 μm) are at risk for one of the two forms of late-stage, age-related macular degeneration—the atrophic form and the neovascular, exudative form. Both forms affect the various tissue layers of the retina. However, the neovascular, exudative form results in serous or hemorrhagic detachment of retinal pigment epithelium and choroidal neovascularization. This leads to leakage and fibrovascular scarring; thus, it is called “wet” age-related macular degeneration. Patients with the atrophic form may sustain good central vision for a longer period of time but have substantial functional limitations (e.g., fluctuating vision, difficulty reading). As the atrophy continues, reading vision decreases, and patients must use magnification to read. Eventually, both forms lead to irreversible loss of the ability to read, recognize faces or drive. Most patients maintain enough peripheral vision to walk unaided.
The prevalence of macular degeneration increases with age. In one population-based study, macular degeneration occurred in only 0.1 percent of persons 43 to 54 years of age but increased to 7.1 percent in persons 75 years or older. Risk factors (see accompanying table) identified from case-control studies include a family history of the disorder, cigarette smoking, low dietary intake or plasma concentrations of antioxidant vitamins and zinc, and white race (in the case of age-related macular degeneration).
The progression of macular degeneration can be variable and quite insidious. Some patients do not notice the visual fluctuations associated with age-related macular degeneration. Thus, routine eye examinations remain an important part of follow-up in elderly patients. However, once neovascularization occurs, leakage of blood may result in dramatic and abrupt loss or distortion of vision.
Laser photocoagulation remains the standard treatment in patients with age-related macular degeneration, based on the results of a 15-year clinical trial. Eligible patients must undergo fluorescein angiography, which delineates well-circumscribed, new blood vessels in the macula that are then treated with laser photocoagulation. Limitations of this therapy include the fact that only 10 to 15 percent of neovascular lesions can be identified by fluorescein angiography, there is at least a 50 percent chance that leakage will recur during the two years following treatment, and about one half of treated patients will experience some initial leakage beneath the center of the fovea. Laser photo-coagulation treatment results in an immediate reduction in central vision. Nonetheless, patients treated with laser photocoagulation experience less vision loss than untreated patients.
A newer and potentially effective treatment is photodynamic therapy. This nonthermal process mediates local vascular injury and results in partial destruction of new blood vessels. One large clinical trial revealed that only 33 percent of patients experienced vision loss with this therapy compared with 61 percent in the placebo group. However, treatment was beneficial to those patients with predominantly classic choroidal neovascularization. Ongoing trials should better define the role of photodynamic therapy.
The authors discuss several investigational approaches that are currently being studied in clinical trials. These include submacular surgery, external-beam radiation therapy and thalidomide therapy. Treatments yet to be evaluated through clinical trials include indocyanine green–guided laser therapy, retinal transplantation, transplantation of retinal pigment epithelium, retinal translocation, retinal prosthesis and gene therapy. The authors also discuss the potential role for laser treatment, antioxidant vitamins, and zinc and nutritional supplements in the treatment of patients with age-related macular degeneration.
The authors conclude that genetic mutations may be discovered in patients with this condition and that perhaps environmental factors can be modified (i.e., diet) before macular degeneration develops. Delaying the onset of macular degeneration by five to 10 years could significantly decrease the rate of blindness because some elderly patients would not live long enough to lose their vision.