Are new anti-VEGF agents beneficial for pigment epithelial detachment?

Key takeaways:

• One specialist proposed that new-generation anti-VEGFs show better efficacy.
• Another said there is a lack of high-level evidence in this area.

SEVILLE, Spain — Retinal pigment epithelial detachment is associated with neovascular age-related macular degeneration in 30% to 80% of cases, according to the literature.

It is often difficult to treat, requires a higher than average number of injections and can often lead to retinal pigment epithelial (RPE) tears. Are the new-generation anti-VEGF agents more specifically beneficial for pigment epithelial detachment (PED)? Two specialists at the Congress on Controversies in Ophthalmology shared their views.

For

Post hoc analyses of clinical trials and real-world studies indicate that new-generation anti-VEGFs are associated with improved structural outcomes for PED in neovascular AMD, according to Francesco Bandello, MD.

Long-term continuous suppression of VEGF allows these new drugs to have a greater impact on PED resolution, with a lower number of injections and decreased burden, according to Bandello. In a post hoc analysis of the HAWK and HARRIER trials, brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept 2 mg over 96 weeks.

“The use of brolucizumab was not associated with an increased number of RPE tears and may offer the advantages of better visual acuity and reduction of PED,” Bandello said.

Similar data emerged from a post hoc analysis of the TENAYA and LUCERNE trials of faricimab presented by Avery and colleagues at the Macula Society meeting in 2024.

“In this post hoc analysis, it was shown that using this drug we could have better anatomical and functional results in patients with PED,” Bandello said.

Faricimab was associated with a reduction in PED thickness compared with aflibercept 2 mg in the head-to-head dosing phase. The number of RPE tears was not higher compared with aflibercept 2 mg.

Data on this specific topic are not currently available for aflibercept 8 mg.

Against

According to Patricia Udaondo, MD, PhD, there is no evidence of the resolution of PED with anti-VEGFs in general, and therefore it cannot be confirmed that the new generation of these drugs is better than the previous ones.

The few data available come from subanalyses, and high-level evidence regarding the effect on PED is lacking because the major clinical trials are not focused on PED.

“They are not focused on biomarkers or on different subtype lesions,” she said.

In addition, PED is not just one entity. There are subtypes that include drusenoid, serous and fibrovascular (or hemorrhagic) PED.

“We really need to talk the same language,” she said. “What are we talking about? The serous or the fibrovascular PED? Because it makes a difference.”

There is also a lack of real-world studies, she said.

“The evidence we have comes from the industry-sponsored trials, which is fine. We need a starting point, but we don’t have real-world evidence and we don’t have meta-analysis about what is happening with PED in the real world and the use of these treatments after the clinical trials,” she said.

Papers were recently published that seem to contradict the optimistic view of a better efficacy of new-generation anti-VEGFs on PED. A retrospective study by Mukai and colleagues compared the efficacy of faricimab and aflibercept 2 mg in 41 eyes with PED.

“There were no changes in the diameter and little change in the height of the lesion, but there were no statistically significant differences when we compare the two treatments. The final visual acuity was similar in both groups,” Udaondo said.

In another study by the same author comparing brolucizumab and aflibercept 2 mg in the management or PED, results were similar.

“It was again a retrospective study, including [83] eyes, and they were measuring exactly the same biomarkers, the height and the diameter in type 1 lesions specifically. The results suggested that brolucizumab was a little bit better in controlling the height but not the diameter of the PED,” Udaondo said.

In a paper recently published by Cattaneo and colleagues, AI-assisted quantification of PED volume reduction after treatment with faricimab showed positive outcomes in treatment-naive as well as switch eyes.

“There is evidence in favor of almost every new treatment in refractory cases after a switch,” Udaondo said, but this does not mean that researchers can consistently confirm that one therapy is better than another.

She argued that there is no strong, high-level evidence supporting new-generation anti-VEGF agents in the specific parameter of PED resolution.

“We have similar changes in best corrected visual acuity and macular thickness, and the main difference is the durability of the treatments. We still cannot conclude that the new generations of anti-VEGF agents are beneficial for PED,” she said.

References:

• Avery RL, et al. Greater reduction in pigment epithelial detachment size with faricimab vs. aflibercept during head-to-head dosing in patients with nAMD. Presented at: Macula Society meeting; Feb. 7-10, 2024; Palm Springs, California.
• Cattaneo J, et al. Int J Retina Vitreous. 2025;doi:10.1186/s40942-025-00629-w.
• Clemens CR, et al. Graefes Arch Clin Exp Ophthalmol. 2020;doi:10.1007/s00417-020-04675-y.
• Dugel PU, et al. Ophthalmology. 2020;doi:10.1016/j.ophtha.2019.04.017.
• Heier JS, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)00010-1.
• Khanani AM, et al. Ophthalmol Retina. 2025;doi:10.1016/j.oret.2024.07.012.
• Khanani AM, et al. Ophthalmology. 2024;doi:10.1016/j.ophtha.2024.02.014.
• Mukai R, et al. BMC Ophthalmol. 2022;doi:10.1186/s12886-022-02617-2.
• Mukai R, et al. BMC Ophthalmol. 2024;doi:10.1186/s12886-024-03663-8.

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Sources/Disclosures

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Source:

Bandello F, et al. Debate 1: New generation anti-VEGF agents are specifically beneficial for pigment epithelial detachment. Presented at: Congress on Controversies in Ophthalmology; April 4-5, 2025; Seville, Spain.

Disclosures:
Bandello reports consulting for AbbVie, Alimera, Bayer, Boehringer Ingelheim, Breye Therapeutics, Fidia/Sooft, Hoffmann-La Roche, Novartis, NTC Pharma, Oxurion and Sifi. Udaondo reports consulting for AbbVie, Adverum, Alimera, Apellis, Bayer, Boehringer Ingelheim, Brill, EyePoint Pharmaceuticals, Janssen, Ocular Therapeutix, Outlook Therapeutics, Roche and Sandoz.

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