NAMD Patients With More Fluctuation in Retinal Thickness Have Poorer Anti-VEGF Outcomes

By David Douglas

August 31, 2020

NEW YORK (Reuters Health) - Greater fluctuation in retinal thickness in patients with neovascular age-related macular degeneration (nAMD) portends poorer outcomes of anti-vascular endothelial growth factor (VEGF) treatment, according to a post hoc analysis of data from clinical trials.

"Practitioners may want to consider variation in retinal thickness when advising patients about their prognosis," Dr. Usha Chakravarthy of Queens University of Belfast, in the U.K., and colleagues write in JAMA Ophthalmology.

The researchers examined data on more than 1,700 patients who were treated with bevacizumab or ranibizumab during clinical trials. These trials, say the researchers, "achieved excellent adherence to monthly follow-up at which disease activity was reviewed and treatment restarted if necessary."

The investigators obtained foveal-center-point thicknesses and the standard deviation was calculated and used to group eyes by quartile. At two years, eyes with greater fluctuation in retinal thickness had significantly worse best-corrected visual acuity (BCVA) and were significantly more likely to develop fibrosis and geographic atrophy in the macular lesion than eyes that had less fluctuation.

The mean difference in Early Treatment Diabetic Retinopathy Study letters was 6.27 between the first and fourth quartiles. For fibrosis risk, odds ratios ranged from 1.40 for quartile 2 to 1.95 for quartile 4. For macular atrophy, the corresponding values were 1.32 and 2.10.

"Timely treatment during the maintenance phase of anti-VEGF therapy is critically important in ensuring optimal functional and morphological outcome," Dr. Chakravarthy told Reuters Health by email

Coauthor Dr. Barnaby C. Reeves of the University of Bristol, also in the U.K., said the results "suggest increasing priority for treatments that have a longer lasting effect/potentiated time course."

He added that "the findings may lead to development of sophisticated monitoring algorithms for inclusion in OCT (optical coherence tomography) machines - so that they record/log past results and can display changes over time and one or more statistics similar to the SD of the retinal thickness variation." Such algorithms, he told Reuters Health by email, "have been built into the software for visual field analyzers . . . for some years."

Dr. Jason Hsu, co-director of retina research at Wills Eye Hospital, in Philadelphia, said the study "highlights the importance of maintaining a stable retinal thickness by ideally keeping the retina dry and avoiding situations where the edema keeps bouncing around."

"Eyes with more active disease despite anti-vascular endothelial growth factor injections would be expected to act more like a yo-yo with greater ups and downs in the amount of edema," he told Reuters Health by email. "However, eyes with less-active or better-controlled disease should be more stable and dry at each visit, leading to less variation in retinal thickness."

Dr. Robyn H. Guymer of The University of Melbourne, Australia, author of an accompanying editorial, told Reuters Health by email "Basically there is still a lot to learn about what our endpoints should be when trying to individualize treatment for nAMD."

He adds in his editorial that the authors "call for anti-VEGF agents with greater treatment durability or sustained release to overcome this issue, but in addition, it may be useful to add compounds that prevent fibrosis and atrophy to our armamentarium."

SOURCE: and JAMA Ophthalmology, online August 20, 2020.