May 08, 2020
2 min read

Anti-VEGF-resistant subretinal fluid may lead to decreased risk for macular atrophy

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Persistent subretinal fluid, or SRF, in the course of anti-VEGF treatment may operate as a compensatory mechanism that maintains the function of the degenerating macula and prevents progression to atrophy, according to one presenter at the virtual Association for Research in Vision and Ophthalmology meeting.

“Clinical trial experience suggests that the best vision outcomes in neovascular AMD are observed when steady state induced by anti-VEGF treatment includes some residual, treatment-resistant SRF. Using the HARBOR clinical trial data, we investigated the effect of SRF thickness on vision outcomes and macular atrophy incidence. It should be noted that in the study, SRF persisted in spite of aggressive therapy,” Marco Zarbin, MD, PhD, said.

In the HARBOR trial, two doses of ranibizumab and different dosing schedules were tested. Post hoc analysis was limited to 785 eyes with SRF.

“Ranibizumab-treated eyes with residual SRF had greater mean BCVA at 12 and 24 months than eyes with no SRF regardless of SRF thickness,” Zarbin said. The difference, he said, was statistically significant.

Residual SRF was also associated with a reduced risk for developing macular atrophy. Patients with no SRF at month 3 had a 26% incidence of macular atrophy at month 12 vs. 5% among those with SRF at month 3. These different outcomes persisted at 24 months.

“The presence of residual SRF is associated with a three- to fivefold reduced risk of macular atrophy,” Zarbin said.

In a hypothetical sequence of events involved in the pathogenesis of age-related macular degeneration, impaired oxygen transport to the photoreceptors, and consequent hypoxia, is the driver of increased VEGF-A expression, which stimulates choroidal neovascularization. One of the consequences may be a reduction of the hypoxic stimulus, but also the accumulation of SRF.

“If this view of the sequence is valid, we could consider SRF as a manifestation of an imperfect but perhaps critical survival mechanism that maintains the function of the degenerating macula,” Zarbin said. “The loss of SRF may be associated with a reduced choroidal vessel perfusion, which could be associated with increased hypoxia, resulting in the development of macular atrophy.” by Michela Cimberle


Zarbin M. Anti-VEGF resistant subretinal fluid is associated with reduced risk of macular atrophy and better visual acuity: Drug-induced choroidal new vessel homeostasis? Presented at: Association for Research in Vision and Ophthalmology annual meeting; May 6, 2020 (virtual meeting).

Disclosure: Zarbin reports he is a consultant to Genentech, Novartis, Iveric bio and Frequency Therapeutics and has a personal financial interest in Iveric bio, NVasc and Frequency Therapeutics.