CHAPTER 43 AGE-RELATED MACULAR DEGENERATION 347
15.What is the role of pharmacologic management in age-related macular degeneration?
Currently, medical management involves the inhibition of angiogenic growth factors and associated modulators. Inhibition of VEGF has assumed primary importance. These agents can cause successful regression or inhibition of neovascular membranes in selected vascular neoplasms and animal models of neovascularization. Several vascular inhibitors and their delivery systems are available.
Although Food and Drug Administration (FDA)–approved and off-label intravitreal anti-VEGF injections have assumed primary importance in the treatment of exudative ARMD, the aging of our population has increased the incidence of visual loss from nonexudative ARMD. Although AREDS2 vitamin supplements are the only available form of prophylaxis, multiple investigational protocols attacking other mechanisms of atrophic macular disease evolution are undergoing trials. These include complement inhibition, vitamin A analogs, interdiction of other inflammatory pathways, and addition of neurotrophic factors.12,13
16.Describe vascular endothelial growth factor and its role in ocular neovascularization.
VEGF is a homodimeric glycoprotein with multiple isomers, split products, and receptor sites. It is essential in the development and proper maintenance of normal body vasculature. It is influenced by multiple growth factors, cofactors, and environmental influences such as ischemia. Loss of normal VEGF homeostasis can result in its upregulation with resultant neovascularization.14
17.What are the advantages of current anti-vascular endothelial growth factor therapy in the treatment of exudative age-related macular degeneration compared to previous therapies such as thermal laser and photodynamic therapy?
Previous laser-based therapies created thermal or photodynamic tissue damage. This treatment for exudative ARMD lesions is based on either location or type. Although these treatments might slow the process, most patients progress to end-stage foveal involvement and visual decline is the rule. AntiVEGF therapies have the advantage of being effective on nearly all subtypes of ARMD especially in subfoveal lesions. Their track record for visual stability and improvement is extremely good over time and their mechanism of effect is physiologic, not tissue destructive.
18.What are disadvantages of current anti-vascular endothelial growth factor therapy for exudative age-related macular degeneration?
Unfortunately, anti-VEGF agents must currently be delivered intravitreally via pars plana injection. They are effective for approximately 1 month after injection; thus recurrence is noted in nearly all eyes over time. This necessitates the need for multiple visits both for active treatment and for surveillance. Patients are seen every 4 to 8 weeks. Intravitreal injections have secondary risks including endophthalmitis, intraocular pressure elevation, and possible progression of atrophic macular disease.15
19.Describe the role of vitamins in the treatment and prophylaxis of age-related macular degeneration.
The Age-Related Eye Disease Study (AREDS) is sponsored jointly by the National Institutes of Health and the National Eye Institute and has proved the benefit of high-dose vitamins in the prophylaxis of ARMD. Individuals with intermediate or high risk of developing ARMD had a 25% reduction in
developing visual loss from either exudative or nonexudative forms of ARMD. Theoretically, the intake of certain vitamins and trace elements acts directly or indirectly through association with certain enzymes in free radical scavenging, thereby modulating the aging process.
AREDS vitamins include high concentrations of vitamins C and E, lutein/zeoxanthine, zinc, and copper. Release of the AREDS2 study demonstrated no benefit from ω-3 fatty acids and potential increased risk of lung cancer in previous smokers taking β-carotene, prompting elimination of β-carotene from current AREDS2 formulations and replacement with lutein/zeoxanthine.16
AREDS summary: www.nei.nih.gov/amd/summary.asp.
20.What is photodynamic therapy? How does it differ from laser photocoagulation?
PDT is an FDA-approved intervention for predominantly discrete subfoveal choroidal neovascular membranes secondary to ARMD. It involves the intravenous administration of a porphyrin-based medication that is absorbed by abnormal subretinal vessels. The drug is activated by wavelength-specific, low-energy, nonthermal infrared laser exposure. Activation of the photosensitizing compounds produces localized vascular damage via generation of free radicals. Because its action is local, the overlying sensory retina is spared while abnormal neovascularization is destroyed. Because so many exudative lesions in ARMD are foveal, PDT has the ability to eliminate subfoveal choroidal neovascular changes while preserving fixation.17
