Bacillary Layer Detachment in Neovascular Age-related Macular Degeneration From a Phase 3 Clinical Trial

Objective To evaluate the incidence of bacillary layer detachment in patients with neovascular age-related macular degeneration (nAMD) and their response to anti–vascular endothelial growth factor (VEGF) therapy Design Post-hoc analysis of the brolucizumab 6-mg and aflibercept 2-mg arms from the HAWK clinical trial, a 48-week, prospective, double-masked, phase 3 trial Participants Participants (n=652 and 652 eyes) randomized to brolucizumab 6-mg and aflibercept 2-mg arms from HAWK (NCT02307682) Methods SD-OCT scans were obtained at 4-week intervals throughout HAWK trial and segmented automatically using a proprietary, machine learning–enabled, higher-order feature extraction platform Main Outcome Measures The incidence of bacillary layer detachment and effect of anti-VEGF therapy in these eyes on best corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid volumes, subretinal hyperreflective material (SHRM) volume, and ellipsoid zone (EZ) integrity from baseline to week 48 Results Classic bacillary layer detachment was identified in 7.2% (47/652) of eyes, demonstrating worse BCVA and higher CST, EZ total attenuation, subretinal fluid (SRF), and SHRM volume at baseline than eyes without bacillary layer detachment. Anti-VEGF treatment resulted in resolution of bacillary layer detachment in 97.9% of eyes by week 48. In eyes with bacillary layer detachment, anti-VEGF treatment improved BCVA and decreased SRF and SHRM volume; however, eyes with bacillary layer detachment never reached the level of BCVA improvement as eyes without bacillary layer detachment. A greater proportion of eyes with bacillary layer detachment had high exudative volatility (increased mean SD after loading dose) of CST, SRF, and total fluid than eyes without bacillary layer detachment (P < .05 for each comparison) Conclusion Bacillary layer detachment an OCT signature representing photoreceptor schisis is identifiable in a notable proportion of eyes with nAMD. Anti-VEGF therapy resulted in a very high proportion of bacillary layer detachment resolution with significantly decreased SRF and SHRM volumes. The majority of eyes with bacillary layer detachment have high exudative volatility, which may be associated with lower BCVA outcomes. The presence of bacillary layer detachment may provide an important imaging biomarker to be considered for clinical trial inclusion/exclusion based on trial design and therapeutic goals due to its unique behavior