Q&A: Dilraj S. Grewal, MD, FASRS, on therapeutics for non-infectious uveitis

Photo taken of Dilraj S. Grewal, MD, FASRS, at Retina World Congress 2025

Dilraj S. Grewal, MD, FASRS, an associate professor of ophthalmology at Duke Eye Center, spoke with Ophthalmology Times at the 2025 Retina World Congress meeting held in Fort Lauderdale, Florida. At this meeting, Grewal gave a presentation entitled, "New therapeutics for non-infectious uveitis in 2025," which provided an in-depth overview of the current state of research and treatment innovations.

Note: This conversation has been lightly edited for clarity.

Ophthalmology Times: What is new in the world of uveitis?

Dilraj S. Grewal, MD, FASRS: It's an exciting time to be in uveitis. We've always seen our colleagues getting exciting clinical trial data for macular degeneration and diabetes, and yet, uveitis remains 10% of all blindness in the United States, even today. So there's a large unmet need to have therapies that go just beyond steroids or beyond what we have in our systemic armamentarium currently, which is mainly anti-metabolites and biologics.

So we're very fortunate to have a spectrum of clinical trials that are currently under various stages. We're looking at systemic therapies, looking at local therapies, intravitreal, as well as looking at topical therapies. The unifying theme here is to provide control of disease activity without having the associated side effects that steroids bring with them.

OT: Is there anything that you wish your fellow ophthalmologists, those who do not specialize in uveitis, knew about this condition?

Grewal: It's extremely important, because in the midst of a busy retina clinic, we often tend to ignore subtle signs of inflammation, or we don't fully evaluate inflammation in our patients that have uveitis. We learn a lot from clinical trial design, as well, the importance of, for example, wide-field fluorescein angiography to fully characterize the extent of leakage, because leakage is a very defining marker of intraocular inflammation. If you look at some of the trials that are out there right now, for example, brepocitinib, which is an oral JAK1 TYK2, small molecule inhibitor, and has shown positive results in the phase 2 NEPTUNE study.

But in addition to controlling intraocular inflammation, there's been robust data on reduction in angiographic leakage, and I think that really speaks to the underlying efficacy of any new drug that is being evaluated for uveitis, because once you have reduction in angiographic leakage, you will get subsequent improvement in intraocular inflammation, as well as sequelae like macular edema.

The other thing that's important to recognize is for the presence of uveitic macular edema, which could be cystoid spaces, intraretinal fluid, subretinal fluid, or even noncystic thickening. And there's a IL-6 molecule, vamikibart, which is now being tested in a phase 3 program, MEERKAT and SANDCAT studies. These are global studies that are fully enrolled, and we should get the data later this year. This is specifically looking at intravitreal IL-6 dosing for uveitic macular edema. What's unique about this approach is that it's focused on uveitic macular edema, not per se intraocular inflammation. So patients in this trial could still be receiving antimetabolites. They could still be receiving biologics for control of intraocular inflammation. Yet if they have uveitic macular edema (UME), they would be eligible to receive IL-6.

This has shown good data in the phase 1/2 DOVETAIL study, again indicating IL-6 being a good target. We know IL-6 works, for example, in other diseases that have an inflammatory component, like diabetes and Kodiak [Sciences] is now looking at a molecule that inhibits both IL-6 and VEGF, and is going to look at that in uveitic macular edema.

We've also known about other pathways, for example, the Wnt-signaling pathway. that is being investigated in again, neovascular AMD and diabetes. And there's a company Surrozen, that is looking at a tri-specific antibody, where you combine VEGF with IL-6 inhibition and fCD4 inhibition to target the Wnt pathway.

So again, very exciting times in terms of approaches that are available for our patients. And again, underscores the importance that as we see these patients, we want to fully characterize their extent of inflammation. We want to characterize their uveitic macular edema, so that we can then scientifically approach each of these targets.