Study identifies macular atrophy in AMD patients undergoing anti-VEGF therapy

There is no clear evidence that anti-VEGF therapy itself causes the development or progression of atrophy.

Issue: April 25, 2015

Macular atrophy occurred in a significant percentage of patients receiving anti-VEGF therapy for exudative age-related macular degeneration, according to one clinician.

At the Angiogenesis, Exudation, and Degeneration 2015 meeting in Miami, SriniVas R. Sadda, MD, presented findings related to macular atrophy culled from the HARBOR study. The multicenter, randomized 2-year trial focused on the safety and efficacy of monthly vs. as-needed 0.5 mg and 2 mg injections of Lucentis (ranibizumab, Genentech) in the treatment of subfoveal neovascular AMD.

“Even with highly effective anti-VEGF therapies, atrophy or the non-neovascular end stage of macular degeneration still occurs in a substantial percentage of patients,” Sadda said in a subsequent interview with Ocular Surgery News. “These treatments are phenomenal and they can make the wet macular degeneration, the neovascularization, go away, but they don’t stop the fact that patients can have this underlying progression of dry degeneration or atrophy.”

SriniVas R. Sadda

However, patients gained vision despite the presence of atrophy, Sadda said.

“The development of atrophy did not prevent patients from gaining vision, at least at 2 years,” Sadda said. “The reason that’s very important is that you don’t want people to stop treating patients for fear of atrophy. We know from previous studies that the natural history of untreated wet macular degeneration is worse. Patients lose vision. That’s probably the key message because the great fear is that people will start to undertreat patients or be worried about treating them for fear of atrophy.”

Analysis and results

In the retrospective analysis of data from the HARBOR study, masked graders re-read more than 17,000 images using fluorescein angiography and color fundus photography.

Macular atrophy was defined as clearly visible areas of depigmentation with increased visibility of choroidal vessels at least 250 µm in diameter. Lesions corresponded with flat areas of well-demarcated staining on fluorescein angiography. The definition did not include retinal pigment epithelium tears, Sadda said.

At 24 months, in the 0.5 mg ranibizumab group, macular atrophy was found in 23% of eyes in the as-needed subgroup and 34% of eyes in the monthly subgroup. In the 2 mg ranibizumab group, atrophy was found in 27% of eyes in the as-needed subgroup and 34% of eyes in the monthly subgroup.

Limitations of the analysis included its retrospective design, small subgroups, lack of controls, lack of optimal detection methods, lack of consensus on diagnostic criteria and lack of quantitative data on atrophic progression, Sadda said.

Sadda also noted that the HARBOR study and similar trials were not designed to explore the potential relationship between anti-VEGF dosing strategies and the development or progression of macular atrophy.

Does treatment cause atrophy?

“We don’t know why atrophy develops in these patients. There are three potential reasons why atrophy could be occurring,” Sadda said.

The first reason is that atrophy may result from underlying dry macular degeneration.

“This is sort of the expected end stage of macular degeneration, and the treatment just can’t stop it,” he said.

Secondly, atrophy may be a consequence or sequelae of the exudative process, related to the damaging effects of hemorrhage or chronic fluid.

“The CNV may cause some initial active destruction of the retina, which the treatment is not able to entirely prevent, and hence, that could be a cause of the atrophy,” Sadda said.

Lastly, it is unknown whether anti-VEGF treatment itself induces macular atrophy.

“We don’t know that. We don’t have evidence that it’s causing more atrophy so far,” Sadda said.

Sadda said that patients in the as-needed group who received the highest number of injections had less atrophy than those who received fewer injections.

“The connection between frequency of therapy and atrophy is still somewhat muddled because of this interesting contrary kind of finding that in the patients who were treated as needed, the ones who got the most injections actually seemed to develop less atrophy,” Sadda said. – by Matt Hasson

For more information:

SriniVas R. Sadda, MD, can be reached at Keck School of Medicine, University of Southern California, 10 Congress St., Pasadena, CA 91105; email: ssadda@doheny.org.
Disclosure: Sadda reports he is a consultant for Allergan and Genentech, receives research support from Allergan and Genentech, and has served as a consultant for Alcon, Novartis, Regeneron and Roche.