Anti-vascular endothelial growth factor monotherapy useful option in patients with retinal angiomatous proliferation, study finds

September 1, 2009

Anti-vascular endothelial growth factor monotherapy appears to be an effective treatment for retinal angiomatous proliferation, according to results of a small, retrospective chart review. Although the results indicate that in most cases repeated injections would be needed to achieve improvement or stable vision, treatment based on ocular coherence tomography-confirmed presence of fluid could achieve outcomes similar to monthly injections.

Key Points

"Our long-term results suggest that this entity behaves very similarly to age-related macular degeneration (AMD)," said Amani A. Fawzi, MD, assistant professor of ophthalmology at the Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles.

The results also are similar to those found in a recent short-term study. Meyerle and colleagues published results (Retina. 2007; 27:451–457) of a retrospective review in which 23 eyes of 23 patients in whom RAP had been diagnosed were treated with 1.25 mg of intravitreal bevacizumab (Avastin, Genentech). This therapy resulted in a significant decrease in macular thickness and improvement or stabilization of visual acuity after 3 months.

Several earlier studies of RAP, a variant of AMD, suggested that it was not responsive to photodynamic therapy and that the prognosis for RAP might be much worse, Dr. Fawzi said. The recent studies, however, seem to suggest that similar responses might be achieved with anti-VEGF therapy.

Dr. Fawzi was the senior author of the study. Her colleague Tarek S. Hemeida, MD, an international research fellow at the Doheny Eye Institute, described the work at ARVO.

20 eyes, 15 patients

The review included 20 eyes of 15 patients aged 50 years or more who had RAP. They had been treated exclusively with intravitreal anti-VEGF therapies from 2005 to 2009 and had at least 6 months of follow-up.

Best-corrected visual acuity and optical coherence tomography (OCT) were recorded at baseline and at each follow-up visit. Fluorescein angiography was performed at baseline and as required on subsequent visits. The need for re-treatment was determined primarily by OCT-related criteria such as persistence or recurrence of intraretinal or subretinal fluid accumulation or increases in retinal thickness.

Results were reported for nine females and six males who met inclusion criteria; their mean age was 85.8 years. Five eyes were in stage II RAP, and 15 eyes were in stage III. The mean follow-up was 19.8 months (range, 9 to 42 months).

Nine eyes had been treated with ranibizumab 0.5 mg (Lucentis, Genentech); eight eyes were treated with bevacizumab; and three eyes were treated with both. There was no loading dose regimen, and re-treatment was given in response to OCT criteria rather than on a monthly schedule. Repeated injections were given to 15 eyes (75%), and five eyes (25%) received only a single injection.

"The group of patients who required a single injection over this long-term study was quite notable. It may indicate a subset of eyes with RAP that are quite responsive and sensitive to anti-VEGF therapy," Dr. Fawzi said. "The frequency of re-injection was 3 to 45 months, with a range of two to 35 injections. In all, improvement or stable vision was found in 62.5% of the cases in our study."

OCT comparison showed that at baseline, 90% of the cohort had intraretinal fluid (IRF), 75% had intraretinal cystoid spaces (ICS), and 65% had subretinal fluid (SRF). At the last visit, 60% of eyes had IRF, 55% had ICS, and 20% had SRF. Minimal improvement of pigment epithelial detachment was noted, with a decrease from 85% at baseline to 75% at the last visit.

Larger trials needed

Although the results of this retrospective review were promising, larger clinical trials are needed, Dr. Fawzi said. It is unknown whether any of the patients had been undertreated or whether results would have been different if the patients had been treated at an earlier stage of RAP. Further studies could evaluate treatment approaches not used in this study, including monthly re-injection, combination therapies, and comparison of the safety and effectiveness of different anti-VEGF agents, she said.

The National Institutes of Health is sponsoring a large-scale prospective randomized controlled clinical trial (Comparison of AMD Treatments Trials [CATT]: Lucentis-Avastin Trial) that aims to answer some of these questions in patients with AMD, Dr. Fawzi said.