Anti-VEGF study shows long-term loss of initial visual acuity gains in AMD patients

Researchers saw improvement at 2 years, but regression at 5 years.

Issue: July 2016

A long-term study of anti-VEGF use in patients with wet age-related macular degeneration found an initial improvement in visual acuity in most patients, but a regression to baseline or worse at 5 years.

The Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) results were presented in May at the Association for Research in Vision and Ophthalmology meeting.

“Our primary goal of the CATT follow-up study was to assess the overall visual acuity and morphologic outcomes at 5 years of any anti-VEGF treatment,” researcher Daniel F. Martin, MD, said at the meeting, as reported by Primary Care Optometry News sister publication, Ocular Surgery News.

Martin and fellow researchers obtained visual acuity from 647 patients with wet AMD, of which 328 patients were randomized to receive Lucentis (ranibizumab, Genentech), and 319 patients were randomized to Avastin (bevacizumab, Genentech). Treatments were randomized for monthly or as-needed injections of either drug.

After 2 years, most patients were treated with a drug and dosing strategy that was different from what they were originally assigned, which compromised the researchers’ ability to assess differences between drugs and treatment strategies at 5 years, Martin explained. Mean follow-up time was 5.5 years, and mean number of visits for AMD care was 25, averaging 4.55 visits per year.

At the 5-year follow-up, 50% of patients had visual acuity of 20/40 or better, and 20% of patients had visual acuity of 20/200 or worse. Mean change in visual acuity was a loss of three letters from baseline and a loss of 11 letters over 2 years.

When discussing anti-VEGF treatment for AMD, Doug Rett, OD, FAAO, often uses the analogy of a boat with a hole, leaking water.

“When you see an OCT and you see fluid building up under the retina, the anti-VEGFs work to bail out the water, but what eye care needs is a way to fix the leak,” the PCON blogger said in an interview.

The anti-VEGF drugs do not exactly fix the leak, he explained. “In some patients, the leak stops on its own, but what we’re finding in this 5-year data is that in a large percentage of the time the leak continues,” Rett added.

“While these drugs are considered a miracle compared to what we used to have, which was essentially nothing, you cannot consider these drugs a cure,” he said.

“The results show that with wet macular degeneration ... you need to keep using anti-VEGF therapies for an extended period of time to preserve vision,” PCON Editorial Board member Michael Tolentino, MD, said in an interview. “You cannot stop treating a patient, regardless of how long they’ve been on it or improvement thus far. More injections show better results, even at 5-year time point or beyond.”

When patients average four or five injections every year, the fluid continues to build up and they receive more and more medicine into the retina, Rett said. Most of the time the leak continues.

“The study goes on to postulate what the drugs are doinRg to patients long term,” he said. “It found that the vision is not nearly as good as what we thought it was. After the 2-year data there was a vast improvement compared to the baseline, but in the 5-year data, the vision has regressed to baseline, and in some patients it’s worse than when they even began treatment.”

Tolentino, who began studying Avastin for eye disease more than 15 years ago, said the trial data shines light on what is needed for future AMD treatment. “We have to develop therapies that will minimize the size of the lesion,” he said. “Over the 5 years, the lesions of those who lost their vision enlarged. Furthermore, there was a significant number of patients who developed geographic atrophy over time.”

PAGE BREAK

Anti-VEGF therapies with an anti-geographic atrophy drug are needed, he said.

Rett noted that prior to anti-VEGF therapies patients were going blind in large-scale numbers.

“Here we are at least finding a way to relatively stabilize patients,” he said. “Fifty percent of patients had better than 20/40 at 5 years, which is a great number. But at 2 years it was 60%. So, you’ve lost 10% of patients. There is still a significant percentage of patients who go worse than 20/200.”

In the trial, abnormal retina thinning was found in 36% of eyes at the end of year 5 compared to 22% of eyes at the end of year 2. Rett looks forward to medicine that prevents retinal thinning, which could be a big step in the right direction.

“This is important data, as it’s one of the only 5-year anti-VEGF studies we have,” Rett said. A key finding was “learning that there is a regression in the mean visual acuity with a bell curve, not a slope that we thought continued.

“I was surprised that vision regressed worse than the baseline,” he continued. “If you look at the data from the 1- and 2-year studies, you get marked improvement for 3 to 4 months, and then visual acuity kind of holds its own. I figured that flat line would continue to hold. However, in these 5-year results, the vision goes back to what it was.”

Rett said there are positive and negative angles to the results.

“On the positive side, 50% of eyes had 20/40 or better at the end of year 5, which would be amazing results before anti-VEGF medications became available,” he said.

However, some patients’ vision continues to worsen, and most require multiple, regular injections over time, he noted. – by Abigail Sutton and Nhu Te

Reference:
Maguire MG, et al. Ophthalmology. 2016.doi:http://dx.doi.org/10.1016/j.ophtha.2016.03.045.

For more information:
Doug Rett, OD, FAAO, sees patients and works with students and residents at the optometry clinic for the VA Boston Healthcare System. He can be reached at doctorrett@gmail.com.
Michael Tolentino, MD, is director of clinical research at the Center for Retina and Macular Disease and associate professor of ophthalmology at the University of Central Florida. He can be reached at miket@crmd.net.

Disclosures: Rett reported no relevant financial disclosures. PCON was unable to determine if Tolentino has any relevant financial disclosures.