Update on branch retinal vein occlusion primary outcomes

Editor's Note: From February through April, the health-care publications of Advanstar Communications-parent company of Ophthalmology Times-will unite in an interdisciplinary effort to investigate and address vascular conditions. This three-month series begins with a look at SCORE study data and primary outcomes with regard to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO).

In future installments, we will explore the efficacy and safety of ranibizumab (Lucentis, Genentech) for the treatment of macular edema (ME) secondary to BRVO and CRVO, as well as studies about vascular endothelial growth factors for neovascular age-related macular degeneration.

Like the Cardiometabolic Disorders and Weight series that ran in the September, October, and November 2009 issues of Ophthalmology Times, this series is part of Advanstar Communications' Action for Outcomes interdisciplinary health-care initiative.

In the SCORE-BRVO study, similar efficacy results were seen in the standard care (laser) group and the two triamcinolone (Allergan) treatment groups in visual acuity (VA), the safety profile of the standard care group was superior to that of the triamcinolone groups, and the reduction in the retinal thickness was greatest in the standard care group, according to Dr. Scott, who reported the BRVO data for the SCORE Study Research Group during retina subspecialty day at the annual meeting of the American Academy of Ophthalmology.

The SCORE Study, sponsored by the National Eye Institute (NEI), is composed of two randomized, controlled, multicenter clinical trials, one in patients with BRVO and the other in patients with central retinal vein occlusion (CRVO).

In the BRVO trial, standard care was grid laser photocoagulation in eyes without dense macular hemorrhage and deferral of laser treatment until the hemorrhage cleared in eyes with dense macular hemorrhage; in the CRVO trial, standard care was observation.

In each trial, patients were randomly assigned to receive standard care or one of two doses of intravitreally administered triamcinolone acetonide (1 or 4 mg). The protocol allowed re-treatment as often as every 4 months. In each trial, the primary outcome was the proportion of patients who gained 15 or more letters of visual acuity at 1 year, said Dr. Scott, professor of ophthalmology and public health sciences at Penn State College of Medicine, Hershey, PA.

The results of both studies were published last year (Archives of Ophthalmology. 2009;127:1101-1114 and 1115-1128).

BRVO study results

A total of 137 patients were randomly assigned to standard care, 136 to the 1-mg triamcinolone group, and 138 to the 4-mg triamcinolone group. The mean patient age was 67 years and 88% were Caucasian. The mean VA was about 20/80 (57 letters). Patients had ME for a mean of 4 months, and the mean center point thickness was 525 µm. A dense macular hemorrhage was present in 29% of patients at baseline, Dr. Scott said.

"For eyes with a dense macular hemorrhage at baseline and [randomly assigned] to the standard care group, the mean number of treatments with grid laser photocoagulation before 12 months was 0.7; for eyes without a dense macular hemorrhage, the mean number of laser treatments before 12 months was 1.8; 27% of these eyes received the maximum number of three treatments during the first year of the study," she added.

In the patients assigned to intravitreal injections of triamcinolone, the mean number of treatments before the 12-month time point in the eyes in the 1-mg group was 2.2 and 2.1 for those assigned to the 4-mg group. In the 1-mg group, 46% of patients received the maximum three treatments, as did 34% in the 4-mg group.

"The primary outcome of the trial, which was the proportion of patients with a gain in VA letter score of 15 or more from baseline to month 12, was 29% in the standard care group, 26% in the 1-mg triamcinolone group, and 27% in the 4-mg triamcinolone group," Dr. Scott said.

All three groups had a similar gain of about 4 to 6 in the mean VA letter score from baseline to month 12. After month 12, the mean change from baseline in the mean VA letter score was greater in the standard care group compared with the triamcinolone groups, she pointed out.

The retinal center point thickness decreased compared with baseline throughout follow-up in all groups. At 12 months, the decrease was similar in the three groups.

"After month 12 and through month 36, the center point thickness was lowest in the standard care group," Dr. Scott said.

The standard care group had a better safety profile than the two triamcinolone groups. One case of infectious endophthalmitis developed in the 4-mg triamcinolone group. The rate of infectious endophthalmitis considering 914 injections in the SCORE-BRVO trial was 0.1% per injection. The proportion of eyes that were treated with medication to lower IOP during the first year of the study was 41% in the 4-mg triamcinolone group, 8% in the 1-mg triamcinolone group, and 2% in the standard care group.

The difference in the rates of initiation of IOP-lowering medication was significant among the groups (p = 0.03 for the standard care group versus the 1-mg group; p <0.001 for the standard care group versus the 4-mg group; and p <0.001 for the 1-mg group versus the 4-mg group). One patient in the 4-mg group required a laser peripheral iridotomy for angle-closure glaucoma.

Lens opacity

During the first year of the study, the rates of onset or progression of lens opacity were also higher in the 1-mg and 4-mg group compared with the standard of care group (35%, 25%, and 13%, respectively).

The difference in the rates of lens opacity onset or progression was significant among the groups (p = 0.03 for the standard care group versus the 1-mg group; p <0.001 for the standard care group versus the 4-mg group; and p = 0.10 for the 1-mg versus the 4-mg group). During the first year of the study, four, zero, and three patients, respectively, underwent cataract surgery. Between 12 and 24 months, 35, eight, and six patients, respectively, underwent cataract surgery.

At 12 months, there were no significant differences in the VA levels among the three groups. From 12 to 36 months, the mean improvement in the VA letter score was greatest in the standard care group. At 12 months, all groups had a decrease in the center point thickness; afterward and out to 36 months the standard care group had the greatest decrease in the center point thickness compared with baseline.

"The SCORE-BRVO results support grid laser as the continued standard of care treatment for ME secondary to BRVO because of the similar efficacy in all treatment arms, the superior safety profile of the standard care group over the two triamcinolone groups, the fact that the safety profile of the standard care does not include the potential for injection-related complications, and after month 12 the improvement in VA and the reduction in central retinal thickness was greatest in the standard care group," Dr. Scott concluded. "The SCORE Study results indicate that grid laser should remain the benchmark against which other treatments are compared in future clinical trials for eyes with vision loss associated with ME secondary to BRVO."