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Updated: Jul 2, 2026

Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration
Published on: May 26, 2023
Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation and Loss in Eyes with Geographic Atrophy
Justis P Ehlers1, Hasan Cetin1, Reem Amine1
1The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Purpose:
Ellipsoid zone (EZ) integrity is a key biomarker and surrogate for photoreceptor health, including in age-related macular degeneration. The objectives of this study were to determine (1) the association of baseline EZ measures with geographic atrophy (GA) progression and photoreceptor loss and (2) the impact of avacincaptad pegol (ACP), a complement inhibitor, on EZ integrity over the first year of treatment.
Design:
Post hoc analysis of the phase II/III GATHER 1 and phase III GATHER 2 trials.
Participants:
Patients 50 years of age and older with non-center point-involving GA in the study eye.
Methods:
Spectral-domain OCT images were evaluated using advanced multilayer segmentation with certified reader validation for EZ integrity, measuring total EZ attenuation or loss (EZ to retinal pigment epithelium [RPE] thickness of 0 μm, i.e., total loss of EZ) and partial EZ attenuation or degradation (EZ-RPE thickness of ≤ 20 μm). Geographic atrophy lesion growth was assessed through fundus autofluorescence.
Main Outcome Measures:
A natural history assessment of progression of GA and total EZ attenuation in sham-treated eyes based on quartiles of baseline EZ measures and the impact of ACP versus sham on progression of total and partial EZ attenuation over 12 months were evaluated.
Results:
This study included 292 eyes receiving ACP 2 mg and 332 eyes receiving sham therapy. In sham-treated eyes, mean GA growth and progression of total EZ attenuation were substantially greater in higher quartiles of baseline total EZ attenuation and partial EZ attenuation measures over 12 months. ACP 2 mg significantly reduced mean growth in total EZ attenuation by 19.5% (P = .0009) and mean growth in percentage of partial EZ attenuation by 55.3% (P < .0001) versus sham over 12 months.
Conclusions:
Greater baseline total and partial EZ attenuation were associated with higher rates of GA growth and progressive EZ loss over time, establishing these EZ measures as important predictors of future GA growth and photoreceptor loss. ACP reduced EZ loss and degradation over 12 months versus sham. Ellipsoid zone measures may enhance identification of patients at high risk of disease progression who would benefit from early therapeutic intervention.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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