Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration from a Phase III 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-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 III trial.
Participants: Participants (n = 652 and 652 eyes) randomized to brolucizumab 6-mg and aflibercept 2-mg arms from HAWK (NCT02307682).
Methods: Spectral-domain OCT scans were obtained at 4-week intervals throughout the 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 hyper-reflective 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 standard deviation after loading dose) of CST, SRF, and total fluid than eyes without bacillary layer detachment (P < 0.05 for each comparison).
Conclusions: 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 because of its unique behavior.
Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
(Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)