Intravitreal faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration: short and long-term outcomes and assessment of volume dynamics using an artificial intelligence-based tool

TL;DR

This study shows that faricimab can improve retinal health and allow longer treatment intervals in patients with nAMD who did not respond well to aflibercept.

Contribution

The study introduces an AI-based tool to assess retinal fluid dynamics and evaluates faricimab's efficacy in aflibercept-refractory nAMD patients.

Findings

Faricimab significantly reduced retinal thickness and fluid volumes in patients with refractory nAMD.

Treatment intervals increased from 4.4 weeks to 6.5 weeks after switching to faricimab.

Visual acuity remained stable over 12 months despite reduced treatment frequency.

Abstract

This study assessed the short- and long-term outcomes of intravitreal (IVT) faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. The main aim was to investigate whether faricimab might enable longer treatment intervals versus aflibercept through improved fluid control, evaluated through use of an artificial intelligence-based quantification tool to evaluate retinal fluid dynamics.

This observational cohort study involved patients with refractory nAMD who received at least three consecutive IVT aflibercept 2.0 mg injections before switching to IVT faricimab (with a four-month loading phase followed by a treat-and-extend regimen) due to persistent or recurrent disease despite 4–8-week treatment intervals. Functional and anatomical outcome measures were recorded, and fluid volume dynamics were quantified, at baseline, monthly to Month 4, and at Months 6, 9, and 12.

Seventy-four eyes from 60 patients were included, with a mean ± standard deviation duration of prior aflibercept therapy of 24 ± 17 months. Fifty-two eyes completed 12-month follow-up. At Month 12, mean best-corrected visual acuity showed no significant change from baseline (+ 0.01 Early Treatment of Diabetic Retinopathy Study letters, p = 0.64). Significant reductions in mean central retinal thickness (− 80.8 μm, p = 0.0001) and maximal pigment epithelium detachment (PED) height (− 28.2 μm, p = 0.011), were observed at Month 4 and maintained to Month 12. Mean fluid volumes (intraretinal fluid [IRF], subretinal fluid [SRF]), and PED decreased significantly at Month 4 (− 26.3 nL, p = 0.007; −41.5 nL, p = 0.0001; and − 175.4 nL, p = 0.0001, respectively). At Month 12, reductions in IRF and PED volumes were sustained. The maximal fluid-free interval increased from 4.4 weeks, prior to switching to faricimab, to 6.5 weeks (p = 0.001) after switching, while mean last treatment interval improved from 5.0 ± 1.4 weeks at baseline to 7.3 ± 2.6 weeks at month 12 (p < 0.0001).

Faricimab may offer a valuable alternative for patients with refractory nAMD. The use of four loading injections administered monthly, followed by a treat-and-extend regimen can result in maintenance of visual acuity and improve anatomical parameters and retinal fluid activity, allowing for longer treatment intervals.

The online version contains supplementary material available at 10.1186/s40942-025-00751-9.

The current standard of care for neovascular age-related macular degeneration (nAMD) involves intravitreal injection of vascular endothelial growth factor inhibitors, which have proven effective. However, substantial unmet needs remain, particularly for improved efficacy and longer duration of action, especially in patients with refractory disease.

In patients with refractory nAMD, mean best-corrected visual acuity showed no significant change from baseline following switch from aflibercept 2.0 mg to faricimab. However, there were reductions from baseline to Month 12 in mean central retinal thickness and maximal pigment epithelium detachment (PED) height. A novel artificial intelligence-based automated quantification tool was used to assess fluid volume dynamics and determined a decrease in mean IRF, SRF and PED volumes from baseline to Month 4.

The most significant anatomical effect of faricimab on IRF and SRF volumes was achieved after the first injection. However, a continuous decrease in PED volume was observed during the loading phase, suggesting that the four monthly loading dose injections may be necessary for patients with refractory nAMD.

The online version contains supplementary material available at 10.1186/s40942-025-00751-9.

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