Does Residual Fluid Matter in Wet AMD?

Most retina specialists use a treat-and-extend approach for wet age-related macular degeneration (AMD), whereby anti–vascular endothelial growth factor (VEGF) injections are performed until the retina is dry and then the treatment interval between injections is gradually prolonged, with the goal of maintaining this effect. However, we know from clinical trials that achieving a retina with no macular fluid is not possible in all patients. The proportion of patients with no fluid at 2 years was 45.5% and 60.3% with monthly ranibizumab in the CATT and VIEW studies, respectively, and 80.3% with monthly aflibercept in the VIEW study.

Thus, there is increasing discussion about whether residual fluid matters in AMD. And there are also questions about which of the various subtypes of retinal fluid — intraretinal fluid or cysts, subretinal fluid, and subretinal pigment epithelium fluid — are the most likely to negatively affect visual acuity outcomes.

Subanalyses from both the CATT and HARBOR^[1] studies found that patients with intraretinal fluid, especially if located in the fovea, had worse visual acuity than those with subretinal or subretinal pigment epithelium fluid. Conversely, patients with subretinal fluid in the fovea had better visual acuity than those without.

The prospective, randomized FLUID study provided additional information of value by assessing whether subretinal fluid can be safely tolerated in patients with exudative AMD being treated with anti-VEGF therapy. In the intensive arm of the study, no subretinal or intraretinal fluid was tolerated. In the relaxed arm, subretinal fluid < 200 μm at the fovea was tolerated, but intraretinal fluid was not. Patients received three monthly loading doses followed by a treat-and-extend anti-VEGF regimen based on disease activity, which was a combination endpoint of visual acuity, presence of hemorrhage in the macula, and optical coherence tomography findings.

At 24 months, visual acuity was noninferior in the relaxed arm compared with the intensive arm, with a mean change in vision of three letters. The total number of injections at month 24 was significantly lower in the relaxed arm than in the intensive arm (15.8 vs 17, respectively). However, significantly more patients in the intensive arm never extended beyond monthly injections (13.5% vs 2.8%, respectively), whereas 29.6% in the relaxed group vs 15.0% in the intensive group were able to extend injections to every 12 weeks.

Taken together, these studies indicate that patients with intraretinal fluid at the fovea appear to have worse vision than those without intraretinal fluid, and those with subretinal fluid have better vision than those without.

However, we have to be careful how we draw conclusions, given that these results are in patients continually being treated with anti-VEGF therapy. The takeaway should be that in patients on a treatment regimen for anti-VEGF therapy, a small amount of residual subretinal fluid does not matter, whereas intraretinal fluid does. This can help guide our clinical decision-making to either switch therapies or continue with the current therapy.

Sophie J. Bakri, MD, a long-time contributor to Medscape, specializes in diseases and surgery of the retina and vitreous, including age-related macular degeneration. She also undertakes both clinical and translational research in the pathogenesis and treatment of retinal diseases.

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