Anti-VEGF drugs are the go-to treatment for wet AMD, but patients sometimes have poor or no response to this therapy option. New research aiming to establish the cause behind negative outcomes found that choroidal neovascularization and pigment epithelial detachment (PED) may be at the root of the problem.

The investigation included 235 treatment-naïve eyes of 202 patients. All eyes were treated with IV ranibizumab in intervals of four-to-six weeks. Poor response was defined as recurring, persistent or worsening signs and symptoms of wet AMD despite treatment activity. These findings were recorded based on clinical exams or SD-OCT performed one month after six doses of IV ranibizumab.

Out of the 235 eyes, 67% responded well to treatment. Out of 33 bilateral patients, 17 had a good response to anti-VEGF vs. seven that had an adverse response, while nine patients experienced both results in either eye. Increased central retinal thickness and the presence of intraretinal cysts were significantly more common among good responders, while the groups showed no difference in subretinal fluid presence.

The investigators noted a significant difference between good and poor responder eyes in terms of baseline PED (47% and 89%, respectively). Additionally, the prevalence of fibrovascular PED was significantly higher in poor responders (77%) compared with good responders (about 40%).

The researchers also found five distinct subgroups in the poor responders:

• True non-responders: eyes with no change in activity (subretinal fluid, intraretinal fluid, sub-RPE fluid, fresh hemorrhage) during treatment.
• Partial non-responders: eyes exhibiting partial improvement (e.g., minimal regression in subretinal fluid, intraretinal fluid) during treatment.
• Anti-VEGF dependents: eyes that showed complete regression in activity with treatment but were unable to tolerate intervals longer than four-to-six weeks between injections without showing recurrence (increase in subretinal fluid, intraretinal fluid, sub-RPE fluid, PED size).
• Worsening: eyes with progression of anatomic findings, with exudate or hemorrhage, despite treatment.
• Nonresponse over time: eyes that initially responded well to treatment but became unresponsive over time due to a reduction in drug effectiveness with continued treatment.