Nadia Waheed, MD, MPH: Transforming retinal disease imaging and clinical trials

Nadia Wahid, MD, a professor of ophthalmology at Tufts University, discussed the advancements in ultra-high-resolution OCT technology with Modern Retina during the 2025 European Society of Retina Specialists (EURETINA) annual meeting held September 4-7 in Paris, France.

She highlighted its ability to visualize structural elements in diseases like age-related macular degeneration (AMD) and Stargardt's disease, enabling better monitoring of disease progression and therapeutic effects.

Wahid emphasized the importance of both structural and functional endpoints in clinical trials, noting that while the FDA accepts structural endpoints, European agencies require functional ones.

Editor's note: This transcript has been lightly edited for clarity.

Nadia Waheed, MD, MPH: I'm Nadia Waheed. I'm a professor in ophthalmology at the Tufts University School of Medicine. So I think imaging is really blossoming this year at EURETINA. So we have a session on the technology of OCT and especially talking about ultra high resolution OCT that I'm really excited about. Today, we're going to talk about how, across the various different talks, about how ultra high resolution OCT is able to visualize structural elements to disease that we may not traditionally be able to see as well in standard resolution OCT, and some dips into what we're seeing in terms of age-related macular degeneration and basal laminar deposits, and how those can be quantified over time on high resolution OCT.

A lot of our work is on ultra high resolution OCT in the lab, and these are not commercial devices, but of course, other groups have worked with commercial devices, and I think one of the big things that ultra high resolution OCT provides you in age-related macula degeneration is a better ability to visualize structures in the outer retinal area, and especially structures that are correlated to progression. So looking at the ellipsoid zone, looking at what we call the zone 6, which is basal laminar deposits that are deposited in advance of developing progression of age-related macular degeneration or of atrophy. I think that, at this point, we have the ability to quantify these basal laminar deposits and see how they impact progression of AMD, which to me, is a really, really exciting place to monitor, both for looking at disease progression, but also for looking at therapeutic effects of various different interventions. So I think that's one is AMD. I also think ultra high resolution OCT will be very important in other macular diseases, specifically, if we look at, for example, Stargardt disease right that are associated with deposition in that outer retinal area, as well as atrophy in the outer retinal area, as well as diseases like A-linked retinitis pigmentosa, or retinitis pigmentosa in general, as it starts encroaching towards the center of the macula to monitor progression over there with with ultra high resolution OCT. Then to look at the effect of interventions such as gene therapy. Is there recapitulation of some of the outer retinal layers that that are getting lost as a result of disease progression? Are you seeing the ellipsoid zone better? Are you seeing the outer segments of the photoreceptors recapitulate? So I think all of those are exciting areas where ultra high resolution OCT will be really, really important.

I think one of the nice pieces about imaging, we've often called OCT, kind of histopathology of the eye, and one of the great pieces about imaging is that that it bridges that bench to bedside piece. It bridges that gap. So what I'm hoping is that we'll be able to take away from here, for our clinic, is how to monitor patients more effectively, and how to better be able to look at images and be able to prognosticate our patients.

I think from the clinical trial realm, what is it that progresses and what is it that we can monitor over time to be surrogate endpoints, perhaps not for our registration trials, but obviously we need to learn to succeed or fail early, and some of these biomarkers may help us understand whether our mechanisms of action are working and enable us to fail things that don't work early, so that we can be more intentional about therapeutics and interventions that we're bringing into the later phase clinical trials. Structure and function is really, really interesting, because it doesn't always go hand in hand, right? But to be able to interrogate these end points in clinical trials, and especially, the way clinical trials are being run at this point, where a lot of the structural endpoints are accepted by the FDA, but the European agencies require functional endpoints as being very important in registrational clinical trials, it's very important to be able to put those two together, and to be able to design clinical trials that are powered to both elicit a functional benefit as well as elicit the structural benefit, or lack of progression that we're hoping to demonstrate. I think this particular symposium is is trying to better delineate what strategies of functional testing correlate best with what we're seeing in structural progression, so that we can design clinical trials that are able to interrogate both the structural and the functional element of disease progression, and are able to join those 2 hand-in-hand and show a reduction in growth or a reduction in progression or an improvement across these structural and functional endpoints. I think what's really interesting in this particular symposium is that we're exploring different strategies, not just of traditional things like visual acuity and low limit visual acuity, but also new techniques of applying microperimetry as an endpoint to clinical trials, or applying feild of vision and looking at the whole volumetric, functional feild of vision, as opposed to looking at just flat, 2-dimensional demonstrations of a visual function. So I'm really excited about about what this symposium is going to show us.