RESUMEN
PURPOSE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity. DESIGN: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial. PARTICIPANTS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial. METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes. MAIN OUTCOME MEASURES: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA). RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 ≤ r ≤ 0.47; EZ-RPE central subfield thickness: 0.22 ≤ r ≤ 0.41; SHRM volume: -0.33 ≤ r ≤ -0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters. CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMEN
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.