Glaucoma Has a Silent Partner

HOT TOPIC

FDA Accepts Aldeyra’s Resubmitted NDA for Reproxalap

Aldeyra Therapeutics recently announced that the FDA has accepted for review the resubmitted New Drug Application (NDA) for topical ocular reproxalap, a first-in-class investigational new drug candidate for the treatment of the signs and symptoms of dry eye disease. Reproxalap is a small molecule modulator of reactive aldehyde species (RASP) that cause inflammation by damaging the tear lipids that maintain the eye moisture barrier-tear film. When this barrier is damaged, the eyes become dry, leading to various forms of ocular surface disease.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of April 2, 2025. In conjunction with the acceptance of the NDA for review, Aldeyra also announced the expansion of its exclusive option agreement with AbbVie. Under the modified agreement's terms, AbbVie can obtain a co-exclusive license to develop, manufacture, and commercialize reproxalap in the United States. Upon exercise of this option, AbbVie would pay Aldeyra a $100 million upfront cash payment, minus any option fees already paid. In addition, Aldeyra would be eligible to receive up to $300 million in regulatory and commercial milestone payments. The profits and losses from Aldeyra would be split 60/40 between the two companies, with AbbVie getting 60%.

My Two Cents

Fingers crossed that Aldeyra will finally get reproxalap across the finish line! I’ve taken a look at some of their data, and it looks like this wonderful little RASP inhibitor might be just what many of us dry eye doctors have ordered. Personally, I always get a little excited when a PDUFA date gets issued, as it seems like the medication just “got real” and will hopefully be something we can soon get into the hands of our patients. I’m incredibly excited to see what Aldeyra and AbbVie have up their sleeves with this one!

OUTSIDE THE LANE

High Blood Pressure, Faster VF Progression in Glaucoma

LA new study has found higher blood pressure linked to faster visual field progression in glaucoma. The retrospective cohort study of 985 patients was conducted at the University of California San Diego and was published in JAMA Ophthalmology. According to the chief researcher, the findings suggest that long-term blood pressure variability may be a modifier of IOP as a risk factor for glaucomatous progression.

Angelo P. Tanna, MD, from the Northwestern University Feinberg School of Medicine in Chicago, wasn’t directly involved in the study, but believes there is a connection between hypertension and glaucoma. He states, “We believe that hypertension and abnormally low blood pressure leads to impaired blood flow to the optic nerve, making that tissue more susceptible to glaucoma damage.” He adds, “Early in the hypertensive disease process, high blood pressure may cause [more] blood flow to the optic nerve. As the nerve advances, blood vessel damage may result in impaired optic nerve blood flow in those same patients.”

For the study, researchers used longitudinal data on patients with suspected or confirmed glaucoma from November 2000 to December 2022 and underwent blood pressure and visual field testing. Of the 985 adult patients, the mean visual field mean deviation change rate was -0.13 dB/year over a mean follow-up of 8 years. (Read more here.)

My Two Cents

I see a surprising number of patients with glaucoma each day, many of whom have been or had been on glaucoma drops for many years, causing substantial disruption to their ocular surface, and I’m often asked if there is a connection between high blood pressure and glaucoma. I’ve always answered that I don’t believe there is a definitive relationship; however, at some point, I wouldn’t be surprised if there is. Well, it looks like it’s time for me to change that answer of mine. This study connects these two disease processes eloquently, and I now have an answer that I believe will satisfy my understanding of glaucoma and my patient’s natural curiosity. Well done to the study coordinators!

CAN YOU RELATE

As I get closer to my 40th birthday, I seem to be experiencing more and more “firsts.” Difficulty reading when my son, Brooks, shoves something in my face closer than 6 inches, the first gray hairs in my beard, and now my first external hordeolum. I know hordeola aren’t exactly correlated with age, but I will definitely add it to the list of observations I’ve noted as I inch closer to the big four-oh.

Also, let me tell you something: I see multiple patients in my clinic each week with complaints of a “bump in/on their eyelid,” and I have a brand-new sense of respect for their level of discomfort. My “stye” has made me highly uncomfortable for nearly 2 weeks. Not only that, but I felt like a mutant when talking to people in public and was highly self-conscious with this large bump protruding from my left lower lid. And, of course, I had to give two presentations to a couple of wonderful groups of doctors in Lafayette, Louisiana, and Starkville, Mississippi!

So, what did I use to treat this hordeolum? A heavy dose of hypochlorous acid spray, two to three Eyedration Air-Activated Moist Heat Eye Masks (Bruder) daily, and a dose of cephalexin 500 mg twice daily. As with many things, the hordeolum seemed to get worse before it got better (just like I tell all my patients), but now it’s barely noticeable.

Before this experience, I often let patients choose how “aggressive” they wanted to be with their treatment. But after experiencing this nuisance, I will push all of them to follow the same regimen I successfully followed.

What a friendly, not-so-subtle reminder to prescribe and treat your patients just as you would yourself!