We thank Dr Wong and associates for their interest in our recent article demonstrating the rapid effect of intravitreal pegaptanib sodium for macular edema (ME) secondary to branch retinal vein occlusion (BRVO).
With regard to the observation window, 10 eyes with BRVO of 1 to 3 months’ duration and 10 eyes with BRVO of 3 to 6 months’ duration were enrolled. Of the first 10 eyes, 5 needed additional anti–vascular endothelial growth factor (VEGF) treatment, macular photocoagulation, or both in year 2. Of the remaining 5 eyes, 2 patients treated 2 months after symptom onset theoretically could have improved spontaneously within 3 months. Notably, other recent studies evaluating pharmacologic treatments for ME of BRVO have enrolled eyes with ME of fewer than 3 months’ duration; these have included 37% of eyes in the SCORE Study and more than 50% of eyes in the BRAVO Study (Campochiaro PA, et al. Safety and efficacy of intravitreous ranibizumab [Lucentis] in patients with macular edema secondary to branch retinal vein occlusion: the BRAVO Study. Paper presented at the Retina Congress. October 4, 2009; New York, New York).
Dr Wong and associates suggest that eyes receiving laser should have been excluded from the analysis to obviate their potential confounding effects. Only 1 eye received laser before enrollment, and 2 received laser during the study; neither had visual improvement at week 54. Therefore, in our 20-eye cohort, laser did not seem to influence the visual acuity findings. However, to address their request, we performed a post hoc analysis of eyes receiving pegaptanib monotherapy, excluding the 2 eyes that could have resolved spontaneously and the 3 eyes receiving photocoagulation. Taken together, the remaining 15 eyes at week 54 had an average visual acuity gain of 15.7 letters and center point thickness reduction of 235 μm, suggesting greater pegaptanib efficacy than reported for the original 20 patients.
Finally, our proposal that pegaptanib may have a theoretical advantage over nonselective anti-VEGF agents was in reference to the potential safety benefit of VEGF 165 selective inhibition. VEGF-A is a neuronal survival factor, and based on experimental evidence, the overuse of nonselective anti-VEGF agents to treat wet age-related macular degeneration may lead to retinal ganglion cell, photoreceptor cell, and choriocapillaris toxicity in rodents. Furthermore, patients who have retinal vein occlusion are at a 2-fold risk for stroke (Holecamp NM, et al. Myocardial infarction and cerebrovascular accidents in patients with retinal vein occlusion. Paper presented at the Retina Congress. October 4, 2009; New York, New York). Theoretically, chronic intraocular pan-VEGF inhibition could heighten that risk.
It is our belief that pegaptanib monotherapy leads to rapid foveal microarchitectural deturgescence often achieved within 24 to 36 hours after initial injection and sustained for at least 3 to 4 weeks. Although findings of post hoc analyses should be viewed with healthy skepticism because of the potential for bias, when assessing outcomes for the 15 eyes in our cohort that met Dr Wong and associates’ criteria, visual acuity gains and center point thickness reductions were even greater than those reported for the full cohort. As such, we continue to be convinced that pegaptanib may provide a clinically important treatment option for patients with ME after BRVO. A larger randomized clinical trial to confirm this hypothesis is warranted.