Biomarkers associated with early onset of large submacular hemorrhage secondary to neovascular age-related macular degeneration after anti-VEGF intravitreal injection

Abstract

Objectives: To identify clinical and morphological biomarkers associated with early onset of large submacular hemorrhage (SMH) secondary to neovascular age-related degeneration (nAMD) after anti-vascular endothelial endothelial growth factor (anti-VEGF) intravitreal injection (IVI). Methods: We retrospectively included patients presenting large SMH secondary to treated nAMD, for which at least 2 examinations, including spectral-domain optical coherence tomography (SD-OCT), were available prior to the onset of the SMH. Clinical characteristics, cardiovascular risk factors and treatment, as well as SD-OCT qualitative and quantitative variables were extracted at the 2 last examinations before SMH onset. History of previous SMH on the fellow eye was also documented. Early SMH onset at defined as <45 days versus > 45 days since last IVI were compared. Results: Forty-six eyes of 46 patients were included in this study, of which 93% were undergoing pro-re-nata regimen with a monthly follow-up. Onion sign, persistence of exudative signs and increasing height of PED between the two last SD-OCT were associated with early SMH onset following last IVI. SMH was bilateral for 41% patients (19/46). In case of history of SMH on the fellow eye, the pre-existence of a RPE-tear before second SMH was significantly higher (p=0.029) in comparison to unilateral SMH. Conclusion: Persistence of exudative signs,, onion sign and increasing PED height despite anti-VEGF intravitreal injections between the two last examination, as well presence of RPE tear in case of history of an SMH on the fellow eye, should be considered as warning signs for SMH.