TRP with Ranibizumab Fails Improve DME Visual Outcome, Treatment Burden

David M. Brown, MD, FACS

In a recent study of 40 eyes with diabetic macular edema (DME), researchers found no evidence that adding targeted retinal photocoagulation (TRP) to ranibizumab treatment improved visual outcomes, decreased treatment burden, or reduced demand for anti-VEGF therapy.

“Many retina physicians assume that laser photocoagulation to the peripheral retina would decrease VEGF production and therefore decrease the amount of intravitreal anti-VEGF injections needed to control DME,” study author David M. Brown, MD, FACS, a clinical professor of ophthalmology at Baylor College of Medicine in Houston, Texas, told MD Magazine.

The 3-year, phase 1/2 prospective, randomized, controlled trial, dubbed DAVE, examined eyes from 29 patients with center-involved macular edema secondary to type 1 or 2 diabetes mellitus. Each patient’s best-corrected visual acuity (BCVA) was between 24 and 78 letters (Snellen equivalent, 20/320 and 20/32), according to the Early Treatment Diabetic Retinopathy Study (ETDRS). Patients were randomized to either 0.3 mg ranibizumab monotherapy, or 0.3 mg ranibizumab plus TRP with wide-field fluorescein angiography.

All patients were injected with ranibizumab 4 times per month, and then received monthly exams and pro re nata (PRN) re-treatment over the next 3 years. The TRP patients received TRP in areas of retinal capillary nonperfusion outside the macula, as well as in a 1-disc area margin after a week, and additional treatment, if needed, at 6, 18, and 25 months.

The study’s main outcome measures were mean changes in the patients’ ETDRS BCVA, along with the number of injections patients needed.

Patients’ mean BCVA at baseline was 20/63. A total of 34 eyes progressed to the study’s 36-month mark, and the mean BCVA had improved 13.9 letters in the ranibizumab monotherapy group and 8.2 letters (P = .20) in the combination therapy group. Over the course of the study, a mean of 24.4 injections was administered in the ranibizumab monotherapy group, and 27.1 to the combination therapy patients. The authors reported a visual field area (Goldmann visual field isopter III-4e area) decrease of 2% in the monotherapy group and 18% in therapy combination therapy group (P = .30).

“The DAVE trial demonstrates that there was no benefit from peripheral laser photocoagulation in decreasing treatment burden for DME,” Brown said. “While pan-retinal photocoagulation has a role in the management of proliferative diabetic retinopathy, it should not be recommended for diabetic macular edema.”

Adverse events observed in the monotherapy group included 2 instances of neovascularization of the iris with neovascular glaucoma requiring surgical treatment. One of these eyes also experienced neovascularization of the disc and of the mid-periphery. Posterior neovascularization (of the mid-periphery, disc, or both) was reported in 3 eyes.

Five eyes in the monotherapy group had new PDR-associated neovascularization; no eyes in the combination therapy group were observed to have this effect.

In the combination therapy group, the research team reported 1 instance of acute vision loss secondary to vitreous hemorrhage, with no fluorescein evidence of posterior neovascularization.

The study, “Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion,” was published in Ophthalmology.