Laser still useful diabetic eye disease tool in anti-VEGF era

Although clinical trial results have advanced anti-VEGF injections to the forefront of treatment for diabetic eye disease, laser photocoagulation continues to be an important modality for the management of diabetic macular edema (DME) and diabetic retinopathy (DR), said Elias Reichel, MD, at the inaugural Retina World Congress.

“Laser for treatment of DME and DR is not dead," said Dr. Reichel, professor and vice chairman, Department of Ophthalmology, Tufts University School of Medicine.

"It still has an important place for treating noncenter-involving DME, and several studies provide support for focal/grid laser in eyes with center-involving DME," he said. "In particular, patients with mild to moderate DME may respond very nicely to laser, and micropulse technology may even allow treatment of patients with fovea-involving disease.”

While panretinal photocoagulation (PRP) may ultimately be supplanted by anti-VEGF therapy for proliferative DR (PDR), data from clinical trials show PRP may still be needed for its treatment in some patients despite their having received aggressive anti-VEGF therapy, he added.

Reviewing the literature relevant to the role of laser in management of diabetic eye disease, Dr. Reichel cited four studies providing evidence supporting its place for treatment of DME:

DRCR.net Protocol I randomly assigned patients to ranibizumab (Lucentis, Genentech) plus deferred laser (beginning after 6 months), ranibizumab plus prompt laser, sham injection plus prompt laser, and triamcinolone plus prompt laser. Results from the analysis of mean change in visual acuity from baseline to 2 years showed the greatest improvement occurred among patients who received ranibizumab plus deferred laser, Dr. Reichel said.

DRCR.net Protocol T was designed to compare the three anti-VEGF agents, ranibizumab, aflibercept (Eylea, Regeneron), and bevacizumab (Avastin, Genentech) for the treatment of DME. Laser treatment was also part of the treatment protocol, being allowed beginning at 6 months for eyes with central subfield thickness exceeding the eligibility criteria or with edema threatening the fovea and that failed to achieve a ≥10% decrease in central subfield thickness and a ≥5-letter BCVA gain despite receiving at least two anti-VEGF injections. By 12 months, between 37% and 56% of eyes across the three anti-VEGF treatment groups received laser treatment.

“Use of laser in Protocol T is somewhat analogous to the deferred laser plus ranibizumab arm in Protocol I,” Dr. Reichel said.

“The data from Protocol T show that there is still a very significant percentage of patients being treated with anti-VEGF therapy for DME who are considered to need laser photocoagulation.”

Results of RESTORE, a smaller scale randomized trial, showed that laser treatment worked well in the setting of relatively minimal to moderate amounts of macular edema. At month 12, visual acuity results for patients fitting that description were similar across the study’s three treatment groups that were represented by ranibizumab alone, laser alone, or ranibizumab plus laser.

READ-2 also compared ranibizumab, laser, and ranibizumab plus laser and found no significant difference in visual acuity outcomes after 2 years across the three study arms. Patients in the combination group, however, required fewer ranibizumab injections than their counterparts treated with ranibizumab monotherapy.

Dr. Reichel noted that subthreshold laser technologies have not been evaluated in combination with anti-VEGF agents in a rigorous fashion, but these alternative approaches to laser therapy of the retina, which are marketed by several manufacturers, have the advantage of limiting photoreceptor damage and may also increase the area of retina that is positively affected by the laser.

“The subthreshold technologies minimize tissue thermal elevation by chopping the continuous-wave laser beam into a series of repetitive short pulses," he said. "Therefore, they are gentler to the retina and retinal pigment epithelium but still effective.” 

Role for diabetic retinopathy

Benefits of anti-VEGF therapy for limiting progression of DR and reducing its severity were identified in the context of the pivotal trials leading to the approval of ranibizumab and aflibercept for the treatment of DME.

“Although it was exciting to see that anti-VEGF therapy could reverse the severity level of DR in eyes with DME, some patients still required laser photocoagulation for PDR despite receipt of chronic anti-VEGF injections,” Dr. Reichel said.

Treatment of PDR was the focus of DRCR.net Protocol S that compared prompt panretinal photocoagulation (PRP) with ranibizumab plus deferred PRP. The study met its primary endpoint, demonstrating that ranibizumab was non-inferior to PRP in its effect on visual acuity, but favored the anti-VEGF treatment in analyses of visual field loss, incidence of vitrectomy, and development of DME.

Nevertheless, the data collected in Protocol S also showed that 6% of patients receiving ranibizumab required PRP.

“Furthermore, with one or just a few treatments, PRP can be a very durable treatment for PDR," Dr. Reichel said. "For that reason, it is something to consider instead of anti-VEGF therapy for patients who are unable or not expected to be compliant with frequent follow-up visits.” 

Dr. Reichel receives fees for being a consultant or lecturer for Iridex, Lutronic, and Regeneron.