Optical Coherence Tomography Findings in a Variable–Dosing Regimen with Ranibizumab (LucentisTM): The PrONTO Study

Abstract

Purpose: : The Phase III clinical trial results with ranibizumab (Lucentis^TM, Genentech) for neovascular AMD showed an average visual acuity (VA) improvement after monthly injections for at least 1 year. A different treatment strategy would be to inject ranibizumab until the neovascularization resolved followed by retreatment only if the neovascularization recurred. In the Phase I/II extension study with ranibizumab at the Bascom Palmer Eye Institute, we used OCT to determine when retreatment was necessary. Using this strategy, we were able to maintain the improved VA in our patients for at least 2 years. To further investigate the role of OCT in a variable dosing regimen, we have initiated a trial known as the Prospective OCT Imaging of Patients with Neovascular AMD Treated with Intra–Ocular Lucentis (PrONTO) Study.

Methods: : Neovascular AMD patients were enrolled with VA from 20/40 to 20/400 and macular neovascularization with OCT central thickness measurements of at least 300 microns. Each patient received 3 consecutive monthly injections of ranibizumab (500µg) in their study eye given at baseline, Month 1, and Month 2. OCT measurements were obtained at baseline and on post–injection days 1, 2, 4, 7, 14, and 30 during the first 2 months then monthly thereafter. Retreatment with ranibizumab was performed only if one of the following was observed: an increase in OCT central thickness of at least 100µm, a loss of 5 letters in conjunction with recurrent fluid by OCT, new onset classic neovascularization, or a new macular hemorrhage.

Results: : Forty patients were enrolled and followed for at least 7 months. One day after the first injection, there was a decrease in the mean OCT thickness measurement (–47µm; p<0.001), and most of this decrease resulted from resolution of the retinal cysts and subretinal fluid. The proportion of eyes that showed complete resolution of retinal cysts and subretinal fluid by Month 1 was 72%, by Month 2 was 92%, and by Month 3 was 95%. The most common reason for retreatment after Month 2 was evidence of fluid detected by OCT. As the neovascularization recurred, OCT identified changes in macular anatomy prior to changes in visual acuity.

Conclusions: : OCT monitoring was able to detect resolution of macular fluid as well as the earliest manifestations of recurrent leakage even prior to changes in visual acuity. Continued follow–up is planned for 2 years.

Keywords: age-related macular degeneration • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • choroid: neovascularization