CATT at 5 years: Visual acuity gains not maintained

Issue: September 10, 2016

SAN FRANCISCO — Regardless of treatment drug, either bevacizumab or ranibizumab, visual acuity gains seen in the first 2 years of the CATT study were not maintained at year 5, study chair Daniel F. Martin, MD, reported here.

Perspective from John A. Wells III, MD, FACS

Speaking at the American Society of Retina Specialists annual meeting, Martin said, “Between year 2 and year 5, there was a mean 11-letter decrease, such that at 5 years, the average patient was three letters worse than they were at baseline.”

In the National Eye Institute-funded follow-up study, CATT patients who were alive at the end of the initial 2-year clinical trial were invited to return for a follow-up visit that included assessment of visual acuity, a review of records, and imaging studies with color fundus photographs, fluorescein angiography and SD-OCT. Data were available for 647 patients (71% of those eligible), mean age was 83 years, and follow-up ranged from 4.3 years to 7.1 years.

“This was an elderly population,” Martin said. “Between the end of CATT and 3-1/2 years later – 5.5 years – over 200 of them had died.”

Another approximately 200 patients were unable to participate for age-related reasons, such as moving to an assisted living facility. Of those who could participate, 91% (591 patients) were continuing their care at a CATT center, although only 25% of patients continued treatment exclusively with their CATT-assigned drug, making comparisons between the two drugs irrelevant in this follow-up.

“The thrust of this was no longer a comparison of Lucentis to Avastin, monthly vs. PRN,” Martin said. “The primary interest here was to assess the global effect of anti-VEGF therapy on 5-year outcomes, specifically visual acuity and anatomical results.”

Reference:

Martin DF. 5-Year outcomes after initiating anti-VEGF therapy for neovascular AMD in the Comparison of AMD Treatments Trials (CATT). Presented at: American Society of Retina Specialists 34th Annual Meeting, Aug. 9-14, 2016; San Francisco, Calif.

Disclosure: Martin reports no relevant financial interests.

Perspective

John A. Wells III, MD, FACS

I think the most remarkable thing about the 5-year results from the CATT study is that 50% of eyes had 20/40 or better vision at the 5-year endpoint, which is much better than you would expect from natural history and much better than in prior therapy like photodynamic therapy or macular laser, like we used to do. It is further evidence that anti-VEGF is a very effective therapy.

There is no way to make a comparison between Lucentis and Avastin at the 5-year endpoint because after the 2 years of the study, over the next 3 years, patients got a variety of things. Only 20% of the original Lucentis group got Lucentis only in the next 3 years and 31% of the Avastin group got only Avastin for the next 3 years.

The study did report a mean loss of 11 letters across all the patients who were re-evaluated at the 5-year point. Why did people lose vision after they left the study? To me, it is pretty obvious that they were no longer following a structured re-treatment protocol that was mandated by the study, and they were undertreated for the last 3 years. These patients received a mean of 4.5 injections each year in the third, fourth and fifth years after they left the study.

On fluorescein angiography there was an increase in the lesion size from the second year to the fifth year. It was an increase of about 50% at 3 years after the study ended. That is a huge increase, and I am sure that is responsible for some of the vision loss. This data also suggest there was undertreatment.

There was less foveal geographic atrophy than I would have thought. I would have suspected GA to have been one of the major causes of vision loss, but only about 17% of the patients had subfoveal GA at the 5-year point. A large majority of patients, 83%, had persistent fluid on their OCT, again possibly suggesting some other marker of undertreatment. So, to me, that is the big take-home message.

We need to learn from these outcomes so in our clinical practice we stay on top of this and make sure our patients are examined and treated more frequently. As a CATT investigator, I found the potential that these patients were undertreated somewhat surprising. Most of these patients remained in the care of their original CATT ophthalmologists who are very good retina specialists. Maybe we need to re-examine what we are doing.

John A. Wells III, MD, FACS

Palmetto Health-USC Medical Group, Columbia, S.C.

Disclosures: Wells reports he is an investigator for Genentech and Regeneron and was protocol chairman for the DRCR.net Protocol T study and an investigator in the CATT study.