Ophthalmology
June 30, 2026 · via Europe PMC
Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation and Loss in Eyes with Geographic Atrophy.
Ehlers JP, Cetin H, Amine R, +8 more, Talcott KE.
AI summary — for doctors, generated from the abstract only
Avacincaptad pegol slowed ellipsoid zone loss over 12 months in geographic atrophy, and baseline EZ damage predicted faster lesion growth.
What was studied
Post hoc OCT analysis comparing 292 eyes on avacincaptad pegol 2 mg with 332 sham eyes, using multilayer segmentation to quantify total and partial EZ attenuation and fundus autofluorescence for GA growth.
Key findings
- In sham eyes, higher baseline EZ attenuation was linked to faster GA growth and EZ loss
- ACP 2 mg reduced growth of total EZ attenuation by 19.5% (P = .0009)
- ACP 2 mg reduced growth of partial EZ attenuation by 55.3%
Clinical relevance
EZ measures on OCT may identify GA patients at highest progression risk and show treatment effects on photoreceptors.
Who should care
Limitations
Secondary imaging analysis of 12-month data with industry-related context, and the link between EZ preservation and visual function is not shown in the abstract.
Consider EZ integrity on OCT when assessing GA progression risk and when discussing early complement inhibition.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
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.
DOI
10.1016/j.ophtha.2026.06.023
PMID
42379522
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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