Researchers at the Cleveland Clinic's Cole Eye Institute have uncovered a significant correlation between ellipsoid zone (EZ) integrity and visual function in patients with geographic atrophy (GA), a finding that could improve early identification of patients at risk for vision loss.
The findings, presented at the Association for Research in Vision and Ophthalmology 2025 annual meeting in Salt Lake City, came from a post-hoc analysis of pooled data from the GATHER1 and GATHER2 clinical trials, which originally evaluated avacincaptad pegol (Izervay) for GA treatment.
Photoreceptor Health Linked to Visual Function
The research team, led by Karen Matar, MD, and Reem Amine, MD, from the Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research at Cleveland Clinic, focused on the ellipsoid zone—a biomarker of photoreceptor integrity visible on spectral-domain optical coherence tomography (SD-OCT).
"This post hoc analysis showed the clear structure-function link in GA between the photoreceptor health, measured by the EZ integrity, and visual function, measured by the BCVA," the investigators concluded.
In their analysis, eyes were divided into quartiles based on baseline best-corrected visual acuity (BCVA), with Q1 representing poorer vision (67 letters or less, equivalent to 20/50 or worse) and Q4 representing better vision (over 77 letters, equivalent to 20/32 or better).
Key Findings on EZ Integrity and Vision
The analysis revealed several important correlations:
- Eyes with better vision (Q4) showed significantly greater preservation of EZ integrity compared to those with poorer vision (Q1)
- Mean partial EZ attenuation in the central 1-mm subfield was 86.6% in Q1 versus 57.7% in Q4
- Mean total EZ attenuation/loss in the central 1-mm subfield was 63.6% in Q1 versus 34.3% in Q4
- The mean EZ-retinal pigment epithelial central subfield thickness (EZ-RPE CST) was significantly greater in eyes with better vision (16.3 microns in Q4 versus 6.7 microns in Q1)
Predictive Value for Future Vision Loss
Further analysis of the sham-treated eyes from the clinical trials demonstrated that baseline EZ-RPE CST could predict future visual outcomes:
- Eyes with EZ-RPE CST exceeding 20 microns had a baseline BCVA of approximately 75.1 letters (20/32) and maintained stable vision over time
- Eyes with EZ-RPE CST between 0-20 microns had a baseline BCVA of 69.7 letters (20/40) and showed gradual vision decline
- Eyes with EZ-RPE CST of 0 microns had a baseline BCVA of 67.5 letters (20/50) and experienced pronounced vision deterioration
Most eyes in the study (73.5%) fell into the middle range of EZ-RPE CST measurements.
Clinical Implications for GA Management
The findings suggest that EZ loss may be a critical component of vision loss in dry age-related macular degeneration (AMD). The researchers emphasized that EZ-RPE CST measurements could serve as an early marker to identify patients at risk for GA progression and vision loss.
"Early identification of these patients may be an opportunity to preserve the EZ and future vision," noted Dr. Amine and colleagues.
The researchers suggested that incorporating these EZ integrity measurements into clinical practice could help guide treatment decisions for patients with GA. Additionally, these biomarkers might inform future clinical trial designs for dry AMD treatments.
Future Research Directions
Looking ahead, the research team plans to explore connections between EZ measurements and other functional outcomes, such as low-luminance BCVA and low-luminance deficit.
These findings highlight the importance of photoreceptor preservation in managing GA and dry AMD, potentially opening new avenues for monitoring disease progression and evaluating treatment efficacy in clinical settings.
