Ranibizumab (Lucentis) Found Noninferior to Panretinal Photocoagulation for Treatment of Proliferative Diabetic Retinopathy
Commentary by Paul A. Sieving, MD, PhD; Lee M. Jampol, MD; Jeffrey G. Gross, MD; and, Timothy W. Olsen, MD
Ranibizumab (Lucentis) was noninferior to panretinal photocoagulation at treating proliferative diabetic retinopathy in a 2-year randomized noninferiority trial. Ranibizumab blocks the effects of vascular endothelial growth factor (VEGF) and is indicated for the treatment of wet age-related macular degeneration, macular edema following retinal vein occlusion, and diabetic macular edema.
Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can cause permanent peripheral visual field loss and decreased night vision and may exacerbate diabetic macular edema, which makes alternative treatments desirable, according to the study background.
“These latest results from the DRCR Network [Diabetic Retinopathy Clinical Research Network] provide crucial evidence for a safe and effective alternative to laser therapy against proliferative diabetic retinopathy,” said Paul A. Sieving, MD, PhD, Director of the National Institutes of Health’s National Eye Institute, which funded the trial. The findings were published in the November 13 Journal of the American Medical Association.
Randomized Noninferiority Trial
The study included 305 participants (394 eyes) with proliferative diabetic retinopathy in one or both eyes at 55 clinical sites across the country. Individual eyes were randomized to treatment with ranibizumab or PRP. For participants with both eyes affected by the disease, one eye was assigned to the PRP group, and the other was assigned to the ranibizumab group.
Approximately half of the eyes assigned to the PRP group required more than 1 round of laser treatment (39% required 2 rounds, and 7% required 3 rounds). Ranibizumab (0.5 mg) was administered via injection into the eye once per month for 3 consecutive months, and then as needed until the disease resolved or stabilized.
The study permitted the use of ranibizumab for the treatment of diabetic macular edema (one of its indications) in both groups, if necessary. Slightly more than half (53%) of eyes in the laser group received ranibizumab injections to treat diabetic macular edema. About 6% of eyes in the ranibizumab group received PRP therapy, mostly to treat retinal detachment or bleeding.
Injection Treatment Deemed Noninferior to Standard of Care
Over the course of two years, mean visual acuity improved +2.8 in the ranibizumab and by +0.2 in the PRP group (difference, +2.2; P<0.001 for noninferiority). The loss of peripheral visual field sensitivity was greater in the PRP group than in the ranibizumab group (-422 vs -23 dB; P<0.001). In addition, the PRP group had a higher rate of vitrectomy (15% vs 4%; P<0.001) and diabetic macular edema development (28% vs 9%; P<0.001) than the ranibizumab group.
Rates of serious systemic adverse events, including major cardiovascular events, were similar between the 2 groups. One patient in the ranibizumab group developed endophthalmitis. The rate of other side effects was low, with little difference between treatment groups.
“After 2 years, we have shown that ranibizumab was noninferior to PRP and in many aspects was superior to PRP,” noted coauthor Lee M. Jampol, MD, Professor of Ophthalmology at Northwestern University and Chair of the Diabetic Retinopathy Clinical Research Network. “Although the 2-year endpoint was not statistically significant, when we looked at visual acuity over the 2 years (area under the curve), we found that the injections were statistically better than the standard of care. In addition, we found that the injection group had almost no loss of peripheral vision.”
“This is a 5-year study, and we will see if the benefit of the injections persists or improves over the next 3 years,” Dr. Jampol said in a statement to the press. “In addition, we are planning a study where we give less frequent injections to see if we can maintain or prevent the development of proliferative diabetic retinopathy. Patients at an earlier stage [of proliferative diabetic retinopathy] will receive a diminished number of injections, and we will see if they are protected against the more severe complications.”
Ranibizumab May Be a Viable Alternative Therapy
“Lucentis should be considered a viable treatment option for people with proliferative diabetic retinopathy, especially for individuals needing anti-VEGF for diabetic macular edema,” said lead author Jeffrey G. Gross, MD, Ophthalmologist and Founder of the Carolina Retina Center in Columbia, South Carolina.
“The short-term role (2 years) for using anti-VEGF agents seems to represent a viable alternative therapy for adherent patients with high-risk PDR [proliferative diabetic retinopathy],” noted Timothy W. Olsen, MD, of Emory University, Atlanta, in an accompanying editorial. “Nevertheless, PRP represents the standard of care for PDR and may represent the best long-term treatment option for high-risk PDR. It is certainly not time to abandon PRP in favor of exclusively treating patients with PDR using only intravitreal antiVEGF injections. Clinical judgment and timing of initiation of either therapy are viable options, and the findings reported by the DRCR Network researchers provide clinicians with evidence to support the alternative option of anti-VEGF pharmacotherapy for high-risk PDR. Further advances in pharmacologic management and sustained delivery systems will help expand this alternative therapy for PDR.”
November 25, 2015