In a randomized clinical trial conducted by DRCR.net of more than 300 participants, researchers have found that ranibizumab is an effective alternative to Panretinal photocoagulation (PRP) (laser therapy for treating diabetic retinopathy). Results also show that the drug therapy carries fewer side effects than the currently used laser treatment.
Since the 1970’s, ophthalmologists have successfully used PRP as the gold-standard treatment for proliferative diabetic retinopathy, a disease that causes extensive harm to the blood vessels that nourish the light-sensitive tissue (the retina) that lines the inside back of the eye. The laser therapy usually preserves central vision in the retina’s macula, but often damages night and side vision.
In a report on the research, published online November 13, 2015, by the Journal of the American Medical Association (click here for the full article), the researchers say ranibizumab is one of several drugs that block the effects of vascular endothelial growth factor (VEGF), a substance long known to spur the development of excessive and abnormal blood vessels in the eyes of some people with diabetes.
About 7.7 million people in the United States have some form of diabetic retinopathy, a frequent complication of diabetes, and, when left untreated, one of the leading causes of blindness. Of those with the condition, an estimated 1.5 percent suffer from proliferative diabetic retinopathy, in which lack of blood flow increases production of VEGF, which stimulates the growth of new, fragile blood vessels. The new vessels are prone to bleeding into the center of the eye. This can cause scarring on the surface of the retina, which can detach the retina off the back wall of the eye.
This noninferiority study was conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for diabetic macular edema (DME).
Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, −0.5 to +5.0; P < .001 for noninferiority). Mean peripheral visual field sensitivity loss was worse, vitrectomy was more frequent, and DME development was more frequent in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different.
About half of the eyes assigned to the laser group required more than one round of laser treatment. In the other group, ranibizumab (at a standardized dose) was injected into the eye once per month for three consecutive months, and then as needed until the condition resolved or stabilized.
Tests after two years showed that vision in the ranibizumab group improved by about half a line on an eye chart compared with virtually no change in the laser group. There was little change in side vision with injection, but a substantial loss of side vision with laser. Decibels, although commonly known as a measurement of sound, are also used to measure the sensitivity of the retina to light. The greater the worsening, the greater the loss of retinal sensitivity.
The research term reported that rates of serious adverse events, including cardiac arrest and stroke, were similar in the two groups. Among the 216 study participants with only one study eye, 3 percent had a heart attack in the ranibizumab group compared with 2 percent in the laser group, while 2 percent had a stroke in the ranibizumab group compared with 4 percent in the laser group. The rate of vitrectomy, a surgical procedure that clears the middle cavity of the eye of blood or scar tissue causing retinal detachment, was lower in the ranibizumab group (8 of 191 eyes) than in the laser group (30 of 203 eyes). One patient in the ranibizumab group developed endophthalmitis, a serious infection in the eye as a result of an injection. Rates of other side effects, such as retinal detachment, neovascular glaucoma, iris neovascularization and ocular inflammation, were low, with little difference between treatment groups, Bressler says.
The research team also reported that their data suggest ranibizumab may help prevent diabetic macular edema from occurring. Among people without diabetic macular edema at the start of the study, only 9 percent of ranibizumab-treated eyes developed diabetic macular edema during the study, compared with 28 percent in the laser group.
Although promising as an alternative to laser therapy, the researchers note that ranibizumab can cost an estimated $2,000 per dose, although most insurances will cover the treatment for diabetic macular edema. The researchers also caution that they did not assess two other anti-VEGF drugs, aflibercept and bevacizumab, because when the study was designed, there was little data supporting the potential effectiveness of those two drugs in treating proliferative diabetic retinopathy compared with ranibizumab.
The study was funded by the National Institutes of Health National Eye Institute’s under grant numbers EY14231, EY23207 and EY18817. Ranibizumab was provided by Genentech. Additional research funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, also a part of the National Institutes of Health.