New Orleans is known as the birthplace of jazz, and Derek S. Welsbie, MD, kicked off Glaucoma Subspecialty Day at the 2026 AAO meeting in the "Big Easy" Friday with a session titled, “The Metabolic Jazz of Neuroprotection.”Just as jazz brings together different instruments and rhythms, protecting the optic nerve may require targeting multiple mechanisms of disease.
Dr. Welsbie’s presentation focused on 2 metabolic approaches, nicotinamide supplementation and glucagon-like peptide-1 (GLP-1) receptor agonists, that have shown potential for protecting retinal ganglion cells. However, questions remain about their effectiveness and safety, said Dr. Welsbie, a glaucoma specialist and associate professor of ophthalmology at the Shiley Eye Institute, University of California San Diego.
Interest in nicotinamide, a form of vitamin B3, emerged from preclinical studies showing that nicotinamide adenine dinucleotide (NAD) levels decline in experimental glaucoma, Dr. Welsbie explained. Nicotinamide supplementation has been seen to increase NAD levels and prevent glaucomatous damage in mice, and early human studies suggested functional benefits, including improvements in the photopic negative response, an electroretinographic measure of retinal ganglion cell function. However, Dr. Welsbie cautioned that the photopic negative response (PhNR) is a notoriously variable measurement, making it difficult to determine whether the small improvements observed in these studies reflected a meaningful treatment effect.
Another short-term study evaluated nicotinamide combined with pyruvate and found improvements at more visual field locations than placebo. However, Dr. Welsbie noted that individual test locations on the Humphrey 24-2 visual field, like the photopic negative response, are subject to considerable measurement variability.
Evidence for slowing disease progression is less convincing. A prospective Hong Kong trial evaluating nicotinamide riboside, another NAD precursor, found no protective effect against glaucoma progression, with potentially worse outcomes among older participants.
Safety also remains a concern. High-dose nicotinamide has been associated with hepatotoxicity. Dr. Welsbie emphasized the importance of distinguishing nicotinamide from niacin, another form of vitamin B3 with a worse toxicity profile.
He mentioned that several clinical trials are currently investigating whether nicotinamide can slow glaucoma progression, including the phase 3 NAMinG trial in the United Kingdom. “I don’t routinely recommend nicotinamide,” he commented. “In my mind, the risks and benefits are rather equal, and I’m waiting for the results of the randomized controlled trial.”
GLP-1 receptor agonists represent another potential neuroprotective strategy, with preclinical evidence suggesting they may reduce neuroinflammation associated with retinal ganglion cell injury.
Retrospective studies have reported lower glaucoma rates among patients with diabetes receiving GLP-1 receptor agonists compared with other medications. A Danish registry analysis found that longer treatment duration was associated with greater apparent protection. Similar findings emerged among patients using GLP-1 receptor agonists for weight management, including reduced rates of glaucoma and ocular hypertension.
However, these observational studies cannot establish causality or demonstrate protection against progression in established glaucoma, cautioned Dr. Welsbie. Evidence for neuroprotection in other neurologic diseases has also been mixed, with negative findings in Alzheimer's disease, he said. Safety concerns include an association with nonarteritic anterior ischemic optic neuropathy (NAION), although the condition is rare.
Dr. Welsbie said a randomized controlled trial is needed to determine whether GLP-1 receptor agonists can prevent glaucoma or slow disease progression.
“I don’t routinely recommend the GLP-1s yet,” he said, “but at least in my mind, the evidence is more favorable in terms of risk-benefits that these could be something to use in our arsenal.” GP