Experimental and clinical evidence of multilayer retinal damage caused by subretinal hemorrhage in neovascular age-related macular degeneration.

Neovascular age-related macular degeneration (AMD) with subretinal hemorrhage (SRH) is associated with a poor visual prognosis. This study investigated the effects of SRH in neovascular AMD on visual function and retinal integrity. An SRH mouse model, established by subretinal injection of autologous blood, exhibited early apoptotic cell death across both outer and inner retinal layers, ultimately resulting in retinal ganglion cell loss and inner retinal thinning. Clinically, we retrospectively reviewed consecutive treatment-naïve neovascular AMD patients who visited Kyoto University Hospital between December 2012 and December 2013. Among 43 eyes from 43 patients, the presence of baseline SRH was independently associated with poorer best-corrected visual acuity at 1 year (β = 0.16, P = 0.03). Eyes with SRH exhibited significant thinning of the ganglion cell complex (GCC) and outer nuclear layer (ONL). Reductions in GCC and ONL thickness were significantly correlated with worse 1-year BCVA (ρ = 0.51, P = 0.02; and ρ = 0.62, P = 0.003, respectively). These findings indicate that SRH induces neuronal damage not only in the outer retina adjacent to the hemorrhage but also in the inner retinal layers, both of which contribute to sustained visual impairment in neovascular AMD.