Q&A: Rachel Downes, MD, provides highlights from the GATHER1 and GATHER2 clinical trials for GA

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At the 2025 Retina World Congress meeting, held in Fort Lauderdale, Florida from May 8-11, 2025, Rachel Downes, MD, a Vitreoretinal Surgery Fellow at Cleveland Clinic Cole Eye Institute, presented data from the GATHER1 and GATHER2 clinical trials.

Ophthalmology Times connected with Downes to learn more about this presentation and the key takeaways.

Note: This Q&A has been lightly edited for clarity.

Ophthalmology Times: Can you summarize the key points from your presentation titled “Ellipsoid zone integrity features linked to differential shifts in geographic atrophy growth rate in the GATHER1 and GATHER2 clinical trials”?

Rachel Downes, MD: A previous analysis by Dr. Glenn Jaffe demonstrated that predicting future geographic atrophy, or GA, lesion growth rate in eyes with initial moderate growth is challenging. The ellipsoid zone, which is a hyperreflective outer retinal band observed on spectral-domain optical coherence tomography, or SD-OCT, is considered a biomarker of photoreceptor health, and the integrity of the ellipsoid zone has been previously linked to GA growth rate.

In this presentation, we performed a post hoc analysis of sham-treated eyes from the pooled GATHER1 and GATHER2 trials to explore whether ellipsoid zone integrity metrics were linked to subsequent GA growth rate changes for eyes with initial moderate growth

Sham-treated eyes were classified into 4 quartiles of GA growth rate based on the first 6-month period (ie, very slow, slow, fast, or very fast).

Using SD-OCT images, ellipsoid zone integrity features at baseline for eyes with initial moderate growth (slow or fast quartiles) were compared between eyes that were fast-lane switchers (ie, eyes that moved from ‘moderate’ to ‘very fast’ growth) and slow-lane switchers (ie, eyes that moved from ‘moderate’ to ‘very slow’ growth). Results showed that fast-lane switchers had greater total ellipsoid zone loss (ie, area of 0 μm ellipsoid zone-retinal pigment epithelium, or EZ-RPE, thickness) and partial ellipsoid zone loss (ie, area of ≤20 μm EZ-RPE thickness) at baseline than slow-lane switchers. In addition, eyes with greater ellipsoid zone loss excess, which represents ellipsoid zone loss in areas of the retina that have not yet developed GA, were more likely to be fast-lane switchers

Therefore, this pooled post hoc analysis of GATHER1 and GATHER2 suggests that ellipsoid zone integrity measures can be used to identify patients who may be at risk of rapidly progressing GA.

Ophthalmology Times: What does this result tell us about the photoreceptors of patients in these clinical trials?

Downes: In this presentation, we used the ellipsoid zone metrics of partial ellipsoid zone attenuation, which represents early photoreceptor degradation, and total ellipsoid zone attenuation, which represents photoreceptor loss.

Therefore, our results suggest that patients with GA who have signs of photoreceptor degradation or loss based on ellipsoid zone metrics may be at risk of rapidly progressing GA. The same is true for patients with greater ellipsoid zone loss in areas of the retina that have not yet developed GA.

Ophthalmology Times: In the GATHER1 and GATHER2 clinical trials, we saw the benefit of avacincaptad pegol for the treatment of GA. How might this influence you use of the treatment in practice after you complete your fellowship?

Downes: I am currently in the final months of my fellowship, so I have yet to be the decision-maker around the choice to start treatment with avacincaptad pegol

Initiating treatment for GA is a big decision for a patient, and I am grateful to have had the chance to participate in research projects such as this one, which will provide me with additional context and nuance when discussing GA therapy with my patients next year.

Ophthalmology Times: As we continue to learn about GA and its progress, where do you see the future of GA treatment(s) going?

Downes: Our results show that initial GA lesion growth rates and ellipsoid zone integrity features are important measures to help predict GA progression that can be applied to clinical practice and inform treatment decision-making.

Ophthalmology Times: Is there any additional information you would like to add about the GATHER1/GATHER2 trials, avacincaptad pegol, or GA?

Downes: In addition to this presentation, there have been several exciting analyses related to the ellipsoid zone and the GATHER trials that have either been previously presented or are currently ongoing, so please be on the lookout!