Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration from a Phase III Clinical Trial.

ABSTRACT

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.