Retinal metabolic and structural alterations in response to aflibercept treatment in neovascular age-related macular degeneration

Abstract

Purpose: Non-invasive retinal markers of disease activity could pave the way for individualized treatment in neovascular age-related macular degeneration (nAMD). We aimed to evaluate if retinal vascular oxygen saturation and calibres could predict the initial treatment response after a loading phase of intravitreal aflibercept in nAMD.

Method: A total of 149 eyes were included (nAMD, n = 76; dry AMD, n = 30; normal eyes n = 43). Of these, 57 treatment-naïve eyes with nAMD received three monthly injections with 2.0 mg aflibercept and were subsequently stratified according to functional and structural response according to development in best-corrected visual acuity and macular retinal thickness. The retinal vascular oxygen saturation and calibres were measured prior to treatment and 1 month after the third injection.

Results: Patients with nAMD and dry AMD had higher retinal arteriolar oxygen saturation as compared to normal eyes (94.3% versus 95.2% versus 92.6%, p = 0.04). Thirty-nine (68.4%) and 12 (21.1%) eyes with nAMD were functional and structural responders. After the loading phase, structural nonresponders developed a higher retinal arteriolar (95.3% versus 93.3%, p = 0.03) and venular (64.7% versus 59.4%, p = 0.02) oxygen saturation, and responders developed a lower retinal arteriolar calibre (118.0 versus 114.3 μm, p < 0.01). In a multiple logistic regression model, increasing retinal venular oxygen saturation associated with a negative structural treatment outcome (odds ratio 1.17 for each 1% increment after the loading phase, 95% confidence interval 1.01-1.36, p = 0.03).

Conclusion: Changes in the retinal venular oxygen saturation associate independently with initial treatment response in nAMD, but functional and structural retinal measurements prior to treatment could not predict the treatment response.

Keywords: aflibercept; choroidal neovascularization; disease activity; neovascular age-related macular degeneration; retinal oximetry; retinal vascular calibre.