Short-term Response to Anti-VEGF as Indicator of Visual Prognosis in Refractory Age-Related Macular Degeneration

Abstract Background: Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis. Subjects/Methods: Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD, evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence. Results: A significant improvement was found at week 1 in terms of CRT (p<0.0001), intraretinal (IRF) (p=0.007), subretinal fluid (SRF) (p<0.0001), and pigment epithelium detachment (PED) volume (p50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF+SRF) (p=0.003), larger PED (p=0.007), lower visual acuity (p=0.004) and less anatomic changes at treatment initiation (p<0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p=0.005), with the presence of atrophy (p=0.01) and larger PED volumes (p=0.002). Conclusions: Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.