Background:
Vascular endothelial growth factor (VEGF) has been shown to be capable of inducing Choroidal Neovascularization (CNV). CNV is the wet form of Macular Degeneration. Therefore, a strategy to treat the wet form of macular degeneration is to block the VEGF action by using anti-VEGF drugs.

Macugen (Pegaptanib) Clinical Trials

In 1971 Judah Folkman first proposed the targeting of a specific angiogenic factor (like VEGF) as a way to treat disease, and specifically a way to treat cancer and ophthalmic disease. VEGF which is an acronym for vascular endothelial growth factor makes blood vessels very leaky and also makes them grow. In the late stages of wet macular degeneration - the neovascular phase - abnormal new vessels begin to grow up towards the retina. These vessels leak fluid, lipid and blood, and they damage the photoreceptors which sense light. This process, the angiogenic process, is VEGF driven. Macugen (Pegaptanib) is a selective Vascular Endothelial Growth Factor (VEGF) antagonist to VEGF isoform 165. Macugen blocks VEGF actions and prevents the growth of abnormal new vessels and prevents leakage of fluid and blood in the retina. Macugen was approved by the FDA for use in wet macular degeneration in December 2004.

The recommended dose of Macugen is 0.3 mg of intravitreous injection administered once every 6 weeks. In the clinical trials, after 1 year 45% eyes developed moderate vision loss and 22% developed severe vision loss if no treatment was given. If treated with Macugen, the probability of developing moderate vision loss over a period of 1 year is reduced by about 15% and the probability of developing severe vision loss is reduced by about 50%. This implies that the rate of vision decline with Macugen treatment is slower than the rate in patients who do not receive macugen treatment. Serious adverse events related to the intravitreal injection procedure included endophthalmitis (1.3%), retinal detachment (0.7%), and traumatic cataract (0.6%). Other frequently reported adverse events in patients treated with Macugen were eye irritation, eye pain, hemorrhage under the outer membrane of the eye (conjunctiva), and blurred vision. Macugen is contraindicated in patients with ocular or periocular infections.

AgingEye Times comment: The problem in wet macular degeneration is that there is a relentless loss of vision despite treatment (even with photodynamic therapy). As with Photodynamic therapy, Macugen slows vision loss, but it is unclear whether this vision benefit is due to lessening of edema and blood in the macula or whether the degeneration process itself is halted or reversed. VEGF is required for normal functioning of neurons, therefore it remains to be seen whether there will be any long term neural toxicity due to VEGF blockage.
Even so, given the paucity of other available treatments, any treatment that preserves vision deserves to be welcomed, albeit with tempered expectations. Wet macular degeneration results in more severe vision loss than any other disease in the elderly population. These patients demand our continued efforts to find safe and effective modalities to prevent this devastating disease as well as treatments that actually improve vision.

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