Pharmacotherapy for Age-Related Macular Degeneration

Recent developments in pharmacotherapy for retinal disorders may be considered as a turning point in ophthalmology. The introduction of new therapies for devastating conditions such as age-related macular degeneration (AMD), the main cause of irreversible blindness in the elderly, stemmed from the tremendous work by Folkman and colleagues who identified the pivotal role of the vascular endothelial grow factor (VEGF) in angiogenesis. Later it was revealed that among the different subtypes of vascular endothelial grow factor, VEGF-A plays a key role in inducing angiogenesis in neovascular AMD. Before the era of pharmacotherapy for reti-nal disorders, no treatment modality for neo-vascular AMD could actually improve vision. Therapeutic options as thermal laser and pho-todynamic therapy (PDT) may halt disease progression in certain patients but as a rule, visual improvement cannot be expected. Even pegaptanib, an aptamer against the 165 isoform of VEGF-A which is FDA approved for intra-vitreal injection, yields comparable results to PDT. It was after the introduction of bevaci-zumab, the full length antibody against VEGF, and ranibizumab, its antibody fragment, that a "change" occurred. The results of MARINA, a randomized clinical trial comparing ranibizu-mab to placebo for occult and minimally classic CNV, showed not only preservation of vision but also improvement in visual acuity in about one third of treated cases. 1 A few months later, the beneficial short-term effects of intravitreal bevacizumab were reported by retina specialists at the Bascom Palmer Eye Institute. 2 Although various controlled clinical trials had been conducted as an obligatory process before FDA approval of ranibizumab, no clinical trial was ever performed on bevacizumab up to that time. Therefore, intravitreal injection of beva-cizumab was considered to be off-label. With the widespread use of bevacizumab as a less expensive and more readily available agent for treatment of a variety of retinal disorders, particularly AMD, various questions have arisen. The first one is whether bevacizumab is really effective in AMD. Although multiple case reports and small case series have suggested encouraging outcomes, larger and well designed studies are necessary to confirm them. The possible additive effect of intravitreal triamcinolone is another issue worth investigating. The optimal therapeutic dose for beva-cizumab also needs to be determined. Doses of up to 2.5 mg have been shown to be safe in experimental studies. 3 In clinical practice, the two commonly used doses are 1.25 mg/0.05 ml and 2.5 mg/ 0.1 ml. The current issue of this journal contains two …