Baseline vision influences role of submacular surgery in NIH-sponsored trial

June 1, 2005

Baltimore—Results from the Group H Submacular Surgery Trial (SST), sponsored by the National Eye Institute of the National Institutes of Health (NIH), support consideration of surgical removal of subfoveal choroidal neovascularization (CNV) in eyes with poorer vision as measured in the SST and vessel growth that is idiopathic or associated with the ocular histoplasmosis syndrome, said Neil M. Bressler, MD, at the Current Concepts in Ophthalmology meeting.

The 21-center trial randomly assigned 225 patients with new or recurrent subfoveal CNV to surgery (112 eyes) or observation (113 eyes). The proportion of successes at 24 months, defined as eyes with best-corrected visual acuity (BCVA) that was better or no more than 1 line worse than baseline, was the primary efficacy endpoint.

Early benefit In the overall analysis, surgery was associated with a large early benefit, but it diminished over time. At 24 months, the success rate was still higher in the surgical group (55%) versus observation (46%), but the approximately 20% difference between groups was not statistically significant, said Dr. Bressler, professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, and Study Chair of the SST. He spoke during the conference, sponsored by Johns Hopkins University School of Medicine and Ophthalmology Times.

Surgery was not innocuous. In the surgery group, five eyes (4%) developed rhegmatogenous retinal detachment and 27 (24%) of initially phakic eyes went on to need cataract surgery compared with no eyes in the control group. The development of cataracts occurred almost entirely among patients aged 50 years and older. One patient who had cataract surgery developed endophthalmitis and there was one vitreous hemorrhage.

The benefit of surgery in the overall study group was smaller than the trial was designed to detect, and the failure to show a benefit in the eyes with better vision at baseline was somewhat disappointing based on an expectation that eyes caught earlier might fare even better from surgery compared with those having greater vision loss. These findings do support consideration of surgery for eyes with poorer BCVA. However, that decision needs to take into account the risks for retinal detachment, cataract, and recurrent neovascularization, Dr. Bressler said.

The SST was undertaken based on results from retrospective investigations and pilot randomized clinical trials showing submacular surgery might stabilize or even improve vision in eyes with subfoveal CNV. While those prior studies largely included patients with poorer vision, their positive findings motivated interest in operating on eyes with better vision with the hope of achieving even better results, he explained.

Criteria To be eligible for participation in the Group H SST, patients needed to be at least 18 years old, have a classic component of CNV based on fluorescein angiography, and BCVA of 20/50 to 20/800 in one eye. Designers of the trial aimed to detect a treatment benefit of at least 50% in the primary efficacy analysis because that magnitude of difference was judged necessary to justify this surgery with its associated risks.

Of the patients in the Group H SST, 85% had CNV due to ocular histoplasmosis. Median lesion size was 2 to 3.5 disc areas, which Dr. Bressler noted is much smaller than the average lesion size in eyes with CNV due to age-related macular degeneration. About one-third of the patients had evidence of occult neovascularization on fluorescein angiography, and nearly one-third had previous extrafoveal laser photocoagulation. Baseline median acuity was 20/100 in each eye.

Findings from follow-up fluorescein angiography studies suggested that the development of recurrent CNV may have accounted for the declining benefit of surgery in the overall group. Leakage was noted at 6 weeks in about 40% of eyes that had undergone surgery, in about 50% of eyes by 1 year, and in 58% of eyes at 2 years.