Victor Hugo Gonzalez, MD (Mcallen, TX)


Preclinical data indicate that pegaptanib, an aptamer targeting VEGF165, can reverse diabetesinduced blood-retinal barrier breakdown; clinical trials demonstrate pegaptanib’s efficacy in treating choroidal neovascularization. A prospective double-masked, randomized trial was designed to evaluate treatment in DME. Effects of selective VEGF blockade were studied in associated proliferative and nonproliferative DR.


A double-masked, randomized, controlled Phase II trial enrolled 172 patients with clinically significant DME. Intravitreous injections of Macugen (0.3 mg, 1 mg, or 3 mg) or sham injections were given at study entry, week 6, and week 12, with additional injections and/or focal photocoagulation (as required) for 18 additional weeks. Final assessments were made at week 36. Pre-specified endpoints included visual acuity, retinal thickness, and need for
additional photocoagulation therapy; retrospective analyses examined the effects of pegaptanib treatment on retinal neovascularization and severity of retinopathy.


Pegaptanib was superior to sham for all endpoints. Mean change in visual acuity (VA) with a 0.3 mg dose was +4.7 vs. -0.4 letters with sham (P=0.04). Significantly more patients receiving pegaptanib maintained or gained =?5 or 10 letters. Fewer subjects receiving the 0.3 mg dose than those receiving sham required laser (25% vs. 48%; P=0.042). Of 16 subjects with retinal neovascularization in the study eye, 8/13 treated with pegaptanib and 0/3 receiving sham, as well as 0/4 in the non-study eye, had regression of neovascularization and/or reduced leakage. 28% of patients receiving pegaptanib improved from baseline ETDRS severity by at least one step vs. 13% on sham. Macular volume decreased 58 mm3 in the 0.3 mg arm but increased 12 mm3 with sham (P=0.009)


Subjects who received pegaptanib had better VA, showed more reduction in central retinal thickness, experienced regression of neovascularization and amelioration of the DR severity, and were less likely to require laser therapy. Given the possible deleterious effects of nonselective VEGF blockade in ischemic retina, selective blockade may have a primary role intreating ocular complications of diabetes.