ARVO 2024: What retinal specialists can learn about DRIL from the POINT study

Amitha Domalpally, MD, PhD, sat down with Modern Retina to discuss how disorganization of retinal inner layers affects OCT outcomes in cases of uveitic macular edema. Domalpally shares some of the research highlights here with Group Editorial Director Sheryl Stevenson.

Video Transcript

Editor’s note - The following transcript has been lightly edited for clarity.

Sheryl Stevenson: We are here today with Dr. Amitha Domalpally. And we'd love to talk more about ARVO and the presentations that are coming up here very quickly. One in particular is regarding the POINT [PeriOcular vs INTravitreal corticosteroids for uveitic macular edema] study.

What can you tell us about the association of DRIL—disorganization of retinal inner layers—with OCT outcomes in uveitic macular edema?

Amitha Domalpally, MD, PhD: Thank you, Sheryl. Thanks for introducing me. I am the Research Director of the Wisconsin Reading Center [Department of Ophthalmology and Visual Sciences, University of Wisconsin System, Madison, Wisconsin]. The Wisconsin Reading Center was the image analysis center for the POINT study, which is a periocular versus intravitreal corticosteroids for uveitis. It's a National Eye Institute-sponsored study. It's a grant looking at treatments for uveitic macular edema, a disease that is not studied so much. We are grateful that NIH sponsored the study and were able to look at treatments.

This study was completed about a year ago and the publications on primary results are out. Essentially, steroids work great for uveitis. They do improve vision...and this was all kinds of uveitis was studied in this POINT study and steroids work well for uveitis and retinal thickness as measured by OCT was also reduced. We had both anatomical and visual benefits with steroid treatment. The safety was also assessed as part of the study.

Now, because there was this rich collection of images collected as part of the clinical trial, including OCT scans on a monthly basis, we sought to understand are there other markers that can help us identify patients who improve and those who don't early on, because the treatment works but not in everybody as always. We wanted to see are there other imaging biomarkers that can help us identify these.

So that's kind of how we undertook this whole DRIL analysis and everything which is been done in diabetic macular edema, in retinal vein occlusion, and has been shown to be associated with visual recovery. If you have DRIL, it's a poor prognosis for vision recovery. It's a bad biomarker. We wanted to see if in uveitis the same thing holds because uveitis is a different disease as we know. Anti-VEGFs don't work for uveitis just like everything else. We know the macular edema has a different physiology. It's inflammation related. We wanted to know: does it work at all?

Stevenson: It's fascinating research. Can we take a deeper dive in terms of the outcomes and what these mean for retina specialists and their patients?

Domalpally: Yeah, so DRIL is a difficult biomarker. It requires one to look at the OCT scans carefully, because it is those specific layers that we need to look at between the ganglion cell layer and the outer plexiform layer. Those are not easy to figure out, especially in uveitis when there's so much inflammation and there are cysts and there's edema and thickness and the anatomy of the eye is distorted. It's hard to see. We had our reading center graders, who are trained in this, look at this carefully. What they found was that DRIL is very, very common. In uveitis, we found almost 80% of the eyes had DRIL so this biomarker was present. In a lot of the eyes, these eyes had a lot of edema, so there were cysts in the eye and the cysts can be a little bit of a confounder and make real assessment a little difficult. Nevertheless, we said okay we did our best and we found that yes, 80% of the time you have DRIL. Then we wanted to see in eyes with DRIL what happens over time.

One, overtime does this DRIL stay the same or does it change? does it go away? Because in diabetes and vein occlusion, it doesn't go away. Once you have DRIL, it's forever. We wanted to see in uveitis what happens. Does it go away? Or does it stay?

The second thing we wanted to see is how does DRIL correlate with OCT thickness. Does it come down or not? And what we found is that, yes, high rate of DRIL 80% have DRIL. DRIL was associated. So when you had DRIL you had a very thick retina. Most of these eyes were 500 microns, which is a very thick retina. Most of them had cysts, most of them. We even looked at the photoreceptor status in these eyes and most eyes, which had DRIL also had this photoreceptor disruption and ellipsoids own disruption, which is a new biomarker that everyone's interested in. So eyes with DRIL overall were more diseased than eyes without so that was the baseline.

And then we looked at what happens over time. Interestingly, what we found was if you don't have DRIL in the beginning, at baseline, you don't have DRIL throughout. We followed these eyes for nearly 4 months (12 weeks) and 3 months and they don't have DRIL. If you don't have DRIL, you're good. You don't have DRIL forever. But if you have DRIL, nearly half the eyes seemed to recover from the DRIL. So it disappeared over time. All was not lost if you had DRIL in the beginning. What we think is the reason is because the eyes in the beginning are a little more diseased. If you wait a little, maybe a month, and then assess DRIL it might give you a better understanding of how severe the eye is anatomically affected. That's what we thought. So about half the time DRIL goes away. So that was longitudinal.

The third thing we looked at was thickness. With thickness, what we found was that because these eyes with DRIL were very thick in their central subfield thickness, about 500 microns, they seem to come down much more. They became flatter, so they had much more to lose in terms of thickness. We had about 35% improvement in the central subfield thickness in eyes with DRIL compared to about 15%. So about half of that in eyes without DRIL. Those were our three major findings. Lots of eyes with DRIL. If it's not there, it's not there, but if it's there, it goes away 50% of the time, and thickness does come down even in eyes with DRIL.

Stevenson: That's certainly fascinating research. Is there anything else that you'd like to add that we haven't touched upon

Domalpally: I think one of the things we want to continue to do is DRIL, what does it do for vision and that is upcoming. For ARVO all we focused on was the OCT. We are going to go ahead and do vision correlations and extend this into an upcoming publication.