Status of baseline central subfield ellipsoid zone predictive of future visual loss

(Image credit: ©kwanchaift/AdobeStock)

A post hoc analysis of the GATHER1 and GATHER2 clinical trial^1,2 data showed that the ellipsoidal zone-retinal pigment epithelial (EZ-RPE) central subfield thickness (CST) is a precursor of greater future visual loss.

Early identification of these patients may be an opportunity to preserve the EZ and future vision, according to Reem Amine, MD, and colleagues. She is from theTony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland.

 The investigators described their study at the Association for Research in Vision and Ophthalmology 2025 annual meeting in Salt Lake City.

Previous studies have already reported that the integrity of the photoreceptors is reflected in the EZ,^3-6 and the EZ integrity was previously found to be associated with visual function in retinal diseases that included age-related macular degeneration.^3-7

Based on the previous research, the investigators theorized that the EZ-RPE CST may be an early marker of the risk of progression of geographic atrophy (GA) and an indicator of future functional outcomes.

They investigated an association between the baseline EZ integrity features, as measured based on the mean EZ-RPE CST, with the baseline visual acuity (VA) and visual changes over time in patients with GA from the sham-treated group of the GATHER1 and GATHER2 clinical trials. GATHER1 (phase 2/3: NCT02686658) and GATHER2 (phase 3: NCT04435366) were multicenter, randomized, double-masked, sham-controlled trials that investigated the efficacy and safety of avacincaptad pegol 2 mg (Izervay, Astellas Pharma, Inc.) in patients with GA not involving the foveal center. The EZ was studied on spectral-domain optic coherence tomography images.

Key findings

Amine and colleagues reported that the mean baseline best-corrected visual acuity (BCVA) differed in the sham-treated eyes depending on theextent of the baseline EZ integrity. 

In eyes with a mean EZ-RPE CST exceeding 20 microns (20/32), the mean best-corrected VA (BCVA) at baseline was 75.1 letters; in those with a mean EZ-RPE CST of greater than 0 but 20 microns or less, the BCVA was 69.7 letters (20/40); and in those with a mean EZ-RPE CST of 0 microns, the BCVA was 67.5 letters (20/50). Most of the sham eyes (73.5%) had a mean EZ-RPE in the middle range.

Considering the three groups, those eyes with the thickest CST had a stable BCVA over time; those in the middle range showed decreases in the BCVA over time; and those with the 0-micron CST had pronounced decreases in the VA over time.

The rates of future visual loss over time differed with the degree of thinning of the EZ-RPE CST at baseline, according to the investigators.

When the investigators evaluated the sham eyes with a mean EZ-RPE CST between >0 and ≤20 µm at baselinebased on the degree of EZ degradation with the goal of further characterizing the changes in the BCVA over time, they found that thoseeyes with more severe thinning at baseline showednumerically larger decreases in the BCVA over time.

The conclusions that Amine and colleagues reached were as follows:

This post hoc analysis demonstrated differences in the central subfield EZ integrity andBCVA at baseline.

• Eyes with thinner mean EZ-RPE CSTs at baseline exhibited greater future VA loss.
• Eyes with more severe central subfield EZ-RPE degradation had greater VA loss compared with eyes with less severe central subfield EZ-RPE degradation.
• The EZ-RPE CST value can be used for early identification of patients with GA who may be at risk for losing vision, which may lead to preservation of the EZ and vision over time.

The authors said, “Future directions include linking these EZ measures to other functional outcomes, such as the the low-luminance BCVA and low-luminance deficit, and potentially incorporating these measures into a clinical trial design.”

References

1. Litts KM, Zhang Y, Freund KB, Curcio CA. Optical coherence tomography and histology of age-related macular degeneration support mitochondria as reflectivity sources. Retina. 2018;38:445-461.

2. Acharya S, Sitaula RK, Karki P, Mishra SK, Dahal HN, Poudel A. Does outer retinal layer thickness correlate with the central visual field indices in early dry age-related macular degeneration?Taiwan J Ophthalmol. 2022;12:437-443.

3. Gong Y, Chen LJ, Pang CP, Chen H. Ellipsoid zone optical intensity reduction as an early biomarker for retinitis pigmentosa.Acta Ophthalmol. 2021;99:e215-e221.

4. Yordi S, Cakir Y, Kalra G, et al. Ellipsoid zone integrity and visual function in dry age-related macular degeneration. J Pers Med. 2024;14:543; 10.3390/jpm14050543 

5. Riedl S, Cooney L, Grechenig C, et al. Topographic analysis of photoreceptor loss correlated with disease morphology in neovascular age-related macular degeneration. Retina. 2020;40:2148-2157.

6. Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 2/3 trial. Ophthalmology. 2021;128:576-586. doi: 10.1016/j.ophtha.2020.08.027

7. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023;402(10411):1449-1458.doi: 10.1016/S0140-6736(23)01583-0.