Reduced Retinal Fluid Linked to Better nAMD Visual Improvements

David A. Eichenbaum, MD

Improved best corrected visual acuity (BCVA) gains from anti-VEGF therapy are associated with instances of lesser post-loading retinal fluid in patients with neovascular age-related macular degeneration (AMD), according to new findings.

In new post hoc analysis data from the HAWK and HARRIER trials, presented at the American Academy of Ophthalmology (AAO) 2021 Meeting in New Orleans, a team of investigators observed that greater BCVA gains from anti-VEGF treatment were more frequent among patients with a greater rate of fluid-free visits through week 96 of the original phase 3 trials.

Presented by David Eichenbaum, MD, of the Retina Vitreous Associates of Florida, the Novartis-supported assessment sought to observe the influence of retinal fluid-free status post-treatment loading phase on critical outcomes of vision care in patients with wet AMD.

“Retinal fluid is an important biomarker of disease activity and a key morphologic feature used to guide treatment decisions in nAMD,” Eichenbaum and colleagues wrote.

The phase 3 HAWK and HARRIER trials were randomized clinical studies of patients aged ≥50 years old with choroidal neovascularization (CNV) lesions secondary to wet AMD, with a presence of subfoveal fluid. The patients were treatment-naïve to anti-VEGF and were randomized 1:1 to either brolucizumab 6 mg (n = 360 in HAWK, n = 370 in HARRIER) or aflibercept 2 mg (n = 360 in HAWK, n = 369 in HARRIER).

Eichenbaum and colleague’s pooled cohort for their assessment included 1459 patients. They sought a primary endpoint of total number of retinal fluid-free visits after treatment loading phase (from baseline to week 8), with fluid-free status defined as the absence of intraretinal fluid (IRF), subretinal fluid (SRF), or both.

The team used data from weeks 12 to 96 in HAWK and HARRIER, identifying 22 weeks of assessment to observe rates of retinal fluid in treated patients.

The investigators categorized total fluid-free visits on a 1-5 scale—with 0 visits indicating “never dry” in a patient and 22 visits indicating “always dry”—and stratified each category by no presence of IRF, SRF, or both.

Categories 4 and 5—defined as “almost always dry” or “always dry”—were associated with greater gains in treated patients’ BCVA, regardless of retinal fluid cohort stratification, than the other categories. Patients in category 5 reported a mean 7.2 difference in BCVA change to patients in category 1 (“never dry”) at week 48 (95% CI, 3.9 – 10.5), then a mean 8.1 difference at week 96 (95% CI, 4.4 – 11.9).

Investigators additionally observed lower mean rates of central subfield thickness (CST) variability among the higher categories of fluid-free retinas (8.9 mean CST variability in category 5; 33.1 mean CST variability in category 1). Such an observation comes after HAWK/HARRIER data has shown correlates between greater CST variability and worse BCVA outcomes in patients with wet AMD.

In a comparison of the treatment arms, Eichenbaum and colleagues observed a greater proportion of patients treated with brolucizumab were in categories 4 or 5 for both all fluid and SRF versus patients on aflibercept.

The team concluded that the post hoc data supported an association between long-term “always dry” or “almost always dry” retina fluid status and improved BCVA gains in patients treating wet AMD with anti-VEGF.

The study, “A treatment-agnostic analysis of the long-term impact of IRF and SRF on vision and anatomy in nAMD in the HAWK and HARRIER studies,” was presented at AAO 2021.