Quantitative Multimodal Imaging Characterization of Intraretinal Cysts versus Degenerative Pseudocysts in Neovascular Age-Related Macular Degeneration

Objective: To differentiate intraretinal fluid (IRF) cysts from degenerative pseudocysts in neovascular age-related macular degeneration (AMD) by quantitative multimodal imaging. Design: Observational, cross-sectional. Participants: Patients affected by macular neovascularization secondary to AMD. Methods: All patients were analyzed by OCT, OCT angiography (OCTA), and dense automatic real-time (ART) OCTA. New-onset cysts were considered IRF, whereas those cysts that were found to be persistent for at least 3 months were categorized as degenerative pseudocysts. Intraretinal cysts were automatically segmented to calculate cyst circularity. Peri-cyst space was quantitatively analyzed to assess the presence of perfusion signal and hyperreflective foci (HF). Main Outcome Measures: Best-corrected visual acuity, cyst circularity, peri-cyst perfusion, peri-cyst HF, fibrosis, and outer retinal atrophy. Results: We analyzed 387 cysts collected from 35 eyes of 35 patients with neovascular AMD (14 men; mean age, 80 ± 5 years). We classified 302 IRF cysts and 85 degenerative pseudocysts. Intraretinal fluid cysts were characterized by significantly higher circularity (0.86; range, 0.81–0.91), perfusion signal in the peri-cyst space, and peri-cyst HF in 89% of cases (all P < 0.05). Degenerative pseudocysts showed significantly lower circularity (0.68; range, 0.64–0.76), no perfusion signal in the peri-cyst space, and peri-cyst HF in only 29% of cases (all P < 0.05). The adopted quantitative metrics significantly correlated with disease duration, number of injections, fibrosis, and outer retinal atrophy. Conclusions: Intraretinal fluid cysts can be discriminated from degenerative pseudocysts using a quantitative multimodal imaging approach. These findings are clinically relevant and should be included in future training models for artificial intelligence algorithms to improve the diagnostic power and fluid monitoring in neovascular AMD. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.