Purpose:
The High dose ranibizumab for Pigment Epithelial Detachment (HiPED) Study enrolled wet age-related macular degeneration (AMD) patients with fibrovascular pigment epithelial detachments (PED) that remained after 6 consecutive injections of standard dose ranibizumab and/or bevacizumab. Changes in fluorescein angiographic (FA) patterns were evaluated every 6 months in these refractory patients treated with monthly 2mg ranibizumab. We hypothesized that the higher dose would more effectively reduce neovascular activity as evidenced by reduced leakage on angiography.
Methods:
The HiPED protocol was granted approval by the CPMC IRB and conducted in compliance with the Declaration of Helsinki. Consented subjects were enrolled for 24 months of follow-up. Subjects were randomized to either Group 1: 2mg ranibizumab injections monthly or Group 2: 2mg injections x 3 monthly injections followed by as needed (PRN) injections for presence of any macular fluid or PED on SDOCT. At each visit, visual acuity, dilated fundus exam, and SDOCT were performed. Fluorescein angiography was obtained at baseline, Months 6, and 12. FA images were graded by two independent readers (JK and EW) for lesion size (size of the PED and size of the area of leakage), change in lesion composition, and lesion activity.
Results:
37 patients were enrolled: 19 in Group 1, 18 in Group 2. Patients have completed 6 months (n=31), and 12 months (n=13). Of the 21 patients with angiographic data, the majority of lesions showed no worsening over the initial 6-12 months of high dose therapy. Twelve of the 21 patients (57%) had no change in lesion size (including PED size and area of choroidal neovascularization). Eight of the 21 patients (38%) showed a reduction in the area of leakage or PED size. Of these patients, all showed some component of decreased choroidal neovascularization leakage. One patient (5%) showed progression angiographically (PED enlargement). No patient developed an angiographic adverse event (RPE tear, subretinal hemorrhage, choroidal nonperfusion).
Conclusions:
High dose 2mg ranibizumab for PEDs due to AMD that persisted following standard dose Anti-VEGF therapy was able to stabilize or reduce the fluorescein angiographic neovascular activity in a majority of patients at 6 and 12 months.
Clinical Trial:
http://www.clinicaltrials.gov NCT01189019
Keywords: age-related macular degeneration • retinal pigment epithelium • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials