AMD: Baseline Vision Features May Predict Vision Loss

Larry Hand

June 09, 2014

Few patients who completed the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) experienced sustained visual acuity (VA) loss of 15 letters or more, according to an article published online May 29 in JAMA Ophthalmology. The loss primarily developed gradually during the 2-year trial period.

New treatments that target prevention of foveal scarring and geographic atrophy (GA) could help prevent VA loss, the researchers write.

Gui-shuang Ying, PhD, from the Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues conducted a cohort study and analyzed the records of CATT participants, who were randomly assigned to receive either ranibizumab or bevacizumab as antivascular endothelial growth factor (anti-VEGF) treatments for neovascular age-related macular degeneration (AMD).

Although anti-VEGF treatment has been shown to improve vision overall in patients with AMD, VA loss can still occur in some patients, the researchers write, and they sought to determine the incidence and factors that can lead to such loss. CATT results demonstrate that bevacizumab and ranibizumab "are equally effective" in improving visual acuity during a 2-year period, the authors write.

Still, 61 eyes (5.9%; 95% confidence interval, 4.6% - 7.5%) among the 1030 trial patients developed sustained VA loss of 15 letters or more, including 20 eyes (1.9%; 95% confidence interval, 1.3% - 3.0%) that lost 30 letters or more. Mean VA decreased gradually: 2 letters from baseline at 4 weeks, 19 letters at 1 year, and 33 letters at 2 years.

Researchers in this study examined images from color fundus photography, fluorescein angiography, and optical coherence tomography taken at baseline and 1- and 2-year follow-up visits. Trained readers from the Reading Center at the University of Pennsylvania who were blinded to the treatments evaluated the images for lesion characteristics and morphological characteristics. A retina specialist also examined images.

The researchers determined that the most likely causes of sustained VA loss were:

  • foveal scarring in 27 eyes (44.3%),

  • pigmentary abnormalities in 17 eyes (27.9%),

  • foveal GA in 7 eyes (11.5%),

  • retinal pigment epithelium tear in 4 eyes (6.6%),

  • active choroidal neovascularization in 3 eyes (4.9%), and

  • hemorrhage in 1 eye (1.6%).

Similar Among Regimens

The incidence of VA loss was similar among 3 treatment regimens: 4.2% in eyes treated monthly for 2 years, 7.9% in eyes with treatment switched after a year from monthly to as needed, and 5.8% in eyes treated as needed for 2 years.

Eyes treated with bevacizumab had "marginally" (~3%) higher incidence of VA loss (4.5%) compared with eyes treated with ranibizumab (7.4%; P = .06).

Of the 61 eyes that had sustained VA loss, 68.9% had VA of 20/200 or worse and 20% had VA worse than 20/800 at 2 years, the researchers write.

"Most sustained [VA] loss was due to foveal scar, pigmentary abnormalities, or GA. The presence of baseline nonfoveal GA, larger lesion size, and bevacizumab treatment are predictive of sustained visual acuity loss," the researchers conclude.

"So if new treatments could be developed to prevent or slow down scar or geographic atrophy development, we will make the anti-VEGF treatment more effective," Dr. Ying told Medscape Medical News.

Message for Ophthalmologists?

"The sustained visual acuity loss is uncommon, [occurring] in 5.9% of patients within 2 years," Dr. Ying said. "Deciding what drugs to choose and what regimen to use is a multifactorial decision. You have to consider the cost, efficacy, safety, etc. These findings alone could not tell ophthalmologists about which of these drugs to choose and what regimen to use, but it did provide ophthalmologists useful information to consider when deciding how to treat their patients."

Barney Reeves, DPhil, professorial research fellow in health services research at the University of Bristol, United Kingdom, and a coauthor of another published article that described similar results for the 2 drugs in a clinical trial, thinks more research should be done before that research may be warranted.

He said the current article is unclear about what is more important: the association between morphological features and VA loss or the baseline predictors of VA loss. "I think it is difficult to infer causality from cross-sectional data," he said to Medscape Medical News. "Both morphology and visual function may be the consequence of something else that happened earlier. So I wouldn't invest in the future research they recommend just on the basis of these data."

He added, "The prediction of poor visual function at 2 years based on baseline characteristics is potentially more useful. This is clearly useful since, if one could predict [accurately] people who were not going to benefit, then one might be able to investigate alternative treatment or, at least, stop the current treatment. It might also help to schedule follow-up."

"Very Important"

"Overall, I don't know how much this is going to change my practice," Lisa J. Faia, MD, assistant professor of ophthalmology at the Oakland University William Beaumont School of Medicine and a partner in Associated Retinal Consultants, Royal Oak, Michigan, told Medscape Medical News.

"I tell patients that it's very important that they have strict follow-up. Because if you have good follow-up, that's a good way of knowing whether the as-needed [regimen] works."

She said she prescribes both drugs mostly as needed, but in consultation with patients. "I give them all the data and we decide together from there. That's more patient-dependent at this point. I'll talk to them about the 3% difference [between the drugs], but again you have to weigh all the other factors."

The 3% difference is "nothing to sneeze at, but at the same time, it is not a large difference," she said. "The biggest takeaway from this is that macular degeneration is a very difficult disease to treat, and that's why we don't have a cure for it. Those eyes that pretty much had bad disease to begin with, whether it was larger lesions or worst vision, unfortunately were often the ones who experienced the largest loss of vision. The worst baseline characteristics were predictors of the worst vision loss."

However, she added, "It was good that the loss was gradual vs sudden, because I feel like people can adapt when they have more of a gradual loss."

Regarding the fovea scarring and the geographic atrophy, she said, "there are companies out there that are working on that, so ultimately for wet macular degeneration, the neovascular form, we probably will need to do some dual-regimen treatments."

This research was supported by the National Eye Institute. Dr. Kim has reported serving on advisory boards in 2012 for Allergan and Eyetech; a coauthor has reported serving as a consultant and on a speaker's bureau and receiving grants from Genentech and Regeneron; another coauthor has reported serving as a consultant for Ocusoft and on a speaker's bureau for Bausch & Lomb and Genentech. The other authors, Dr. Faia, and Dr. Reeves have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online May 29, 2014. Full text


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