Ranibizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF), which promotes angiogenesis. The purpose of this prospective, interventional, multicenter follow-up study was to evaluate the benefit of increased follow-up and treatment with ranibizumab between months 24 and 36 in the Ranibizumab for Edema of the Macula in Diabetes (READ-2) Study.
Senior author Peter A. Campochiaro, MD, the George and Dolores Eccles Professor of Ophthalmology and Neuroscience at Johns Hopkins University School of Medicine in Baltimore, Maryland stated that, "These data demonstrate that many patients with [DME] require very frequent (in many cases every month) intraocular injections of an anti-VEGF agent to control the edema and maximize visual acuity." "Many DME patients currently being managed with as-needed injection protocols are being undertreated and have chronic edema. Over time, this chronic edema is likely to lead to permanent loss of vision."
The study sample consisted of patients enrolled in READ-2 who agreed to participate between months 24 and 36. There were 28 patients receiving ranibizumab treatment alone, 22 receiving laser therapy alone, and 24 receiving ranibizumab plus laser therapy. From months 24 to 36, these participants received ranibizumab, 0.5 mg, at monthly follow-up if foveal thickness (FTH, center subfield thickness) was at least 250 μm.
"In several large studies, the mean number of injections of anti-VEGF injections went down in year 2 and beyond when injections are given on an as-needed basis, but when one examines the mean central foveal thickness or percentage of patients with foveal thickness less than 250 μm with time domain optical coherence tomography, it is clear that many of the patients have substantial residual edema," Dr. Campochiaro said.
In the present analysis, the primary study endpoints were improvement in best-corrected visual acuity (BCVA) and reduction in FTH between months 24 and 36.
In the ranibizumab group, BCVA improved by a mean of 10.3 letters from baseline at month 36 compared with 7.2 letters at month 24 (change in BCVA letters, 3.1 letters; P = .009). At month 36, mean FTH was 282 μm compared with 352 μm at month 24 (change in FTH, 70 μm; P = .006).
Changes between months 24 and 36 in BCVA and FTH were not statistically significant in the laser group (−1.6 letters and −36 μm, respectively) or in the ranibizumab plus laser group (+2.0 letters and −24 μm, respectively).
The ranibizumab group had a significantly greater mean number of ranibizumab injections than the laser group (5.4 vs 2.3 injections; P = .008), but not compared with the ranibizumab plus laser group (3.3 injections; P = .11).
Lead author Diana V. Do, MD, associate professor of ophthalmology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine in Baltimore, Maryland added that, "This multicenter study demonstrated that ranibizumab was effective and safe for the treatment of DME." "In fact, ranibizumab was more effective than laser photocoagulation, which used to be the standard of care. The READ-2 study was one of the first studies to prove that intravitreal VEGF blockade is the most effective treatment for DME, and currently VEGF blockade is the new standard of care when treating patients with vision loss due to DME."
Abdhish R. Bhavsar, MD, clinical correspondent, American Academy of Ophthalmology, and managing partner and director of clinical research, Retina Center of Minnesota, Minneapolis, stated that, "The strengths of the study include that it is a prospective follow-up of a randomized clinical trial." "The weaknesses of the study include that it is not masked, which introduces bias; that the primary outcome was at 6 months in the original study, and that is too short in DME studies; that the follow-up from 24 to 36 months does not seem to have been prospectively planned; and that the study involves relatively small numbers of subjects."
When asked about the clinical implications of this study, Dr. Bhavsar, who was not involved in the work, noted that "DME can be treated successfully with ranibizumab alone or ranibizumab plus focal laser, but focal laser appears to reduce the number of ranibizumab injections needed. The bottom line is that this adds to the evidence that anti-VEGF agents such as ranibizumab are useful in the treatment of DME."
In terms of additional research, Dr. Bhavsar recommends clinical trials with larger numbers of subjects, such as the Diabetic Retinopathy Clinical Research (DRCR) Laser-Ranibizumab-Triamcinolone trials.
Arch Ophthalmol. Published online October 8, 2012. Abstract