Anti-VEGF injections result in better visual outcomes than laser

At 1 year, patients gained nine letters on average, regardless of prompt or deferred laser treatment.

Neil M. Bressler

According to results from a large trial organized by the Diabetic Retinopathy Clinical Research Network, or DRCR.net, patients receiving anti-VEGF treatment with prompt or deferred focal/grid laser on average had greater gains in visual acuity at 1 year compared with patients receiving laser and sham or laser plus triamcinolone.

Patients in the study had a visual acuity between 20/32 and 20/320 at baseline and diabetic macular edema involving the central subfield on OCT.

“The results appear to be generalizable or apply to most people who have DME in the center of the macula with some vision loss,” Neil M. Bressler, MD, chair of the DRCR.net, said in an e-mail interview with Ocular Surgery News.

Re-treatment protocol

A central question posed in the study was whether prompt or deferred (at least 24 weeks) laser therapy in conjunction with intravitreal Lucentis (ranibizumab, Genentech) was preferable. At the 1-year primary endpoint, patients treated with either prompt or deferred laser gained on average nine letters of vision from baseline, which was significantly greater than patients treated with triamcinolone and prompt laser (average gain of four letters) and sham plus laser (average gain of three letters).

Patients in the study received an injection of ranibizumab, steroid or sham at baseline followed by drug or sham every 4 weeks. Starting at week 16, study drug or sham was administered every 4 weeks through the week 20 visit unless treatment was considered successful, in which case re-treatment was at the investigator’s discretion.

Starting at the week 24 visit, re-treatment was initiated if there was a gain of five or more letters from the last dose, a 10% or greater improvement in central subfield thickness as measured on optical coherence tomography, or both. Re-treatment was at the investigators’ discretion if the patient met criteria for success or failure. Ranibizumab re-treatment was as often as every 4 weeks; triamcinolone re-treatment was as often as every 16 weeks, with sham injections in between.

Although the re-treatment protocol appears complex, Dr. Bressler said, compliance throughout the study was good. Overall, 94% of 691 participants completed the 1-year follow-up and 87% so far who were eligible completed the 2-year visit.

“There was excellent compliance (96% of the time), with physicians providing drug or sham when required by protocol,” he said.

Through 2 years of follow-up, patients in the ranibizumab with prompt laser group received a median of 11 of 25 potential injections, and patients in the ranibizumab with deferred laser group received a median of 13 injections. Patients treated with triamcinolone with prompt laser and followed to 2 years received a median of four out of a maximum possible eight injections of the steroid.

Pseudophakic eyes

Although intravitreal corticosteroid with prompt laser was not superior to laser alone with respect to visual acuity, central subfield thickness measured on OCT was reduced compared with laser alone at the 1-year visit. Additionally, in a secondary analysis of 273 eyes pseudophakic at baseline, 62 patients treated with triamcinolone and laser demonstrated an eight-letter gain at the 1-year visit — results on par with gains in either ranibizumab group.

While visual acuity outcomes using intravitreal corticosteroid plus prompt laser in pseudophakic eyes appear similar to those attained with ranibizumab injections, “triamcinolone was associated with an increased risk of elevated eye pressure that frequently required medications to prevent vision damage from glaucoma,” Dr. Bressler said.

In the study, three cases of endophthalmitis were recorded following 3,973 total ranibizumab injections (0.08%). Final visual acuity letter score was unknown after one case was lost to follow-up, 73 (approximately 20/32) in the second and 58 (approximately 20/64) in the third. Occurrence of cataract was more common among patients treated with triamcinolone.

The study will follow patients for a total of at least 3 years to gauge long-term treatment effect, although the primary outcome was 1-year results. – by Bryan Bechtel

Reference:

• The Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema [published online ahead of print April 22, 2010]. Ophthalmology. doi:10.1016/j.ophtha.2010.02.031.

• Neil M. Bressler, MD, can be reached at the Wilmer Eye Institute, 550 N. Broadway, Suite 115, Baltimore, MD 21205; 410-955-8342; e-mail: nbressler@jhmi.edu.