Eyeworld

C OCTOBER 2025 | EYEWORLD BONUS ISSUE | 27 Relevant disclosures Donnenfeld: AbbVie, Alcon, Azura, Bausch + Lomb, Nordic Pharma, Tarsus Epitropoulos: AbbVie, Aerie Pharmaceuticals, Alcon, Aldeyra, Bausch + Lomb, BioTissue, Bruder Healthcare, Dompe, EyeCool Therapeutics, Harrow, Hilco Vision, Horizon, Johnson & Johnson Vision, OTX, Physician Recommended Nutriceuticals, Sun Ophthalmics, Tarsus, Trukera, Viatris Contact Donnenfeld: ericdonnenfeld@gmail.com Epitropoulos: eyesmd33@gmail.com defects. "For many patients with severe dry eyes, putting an amniotic membrane on for 3 or 4 days stabilizes the ocular surface, and that allows the other therapies to contribute to man- aging the dry eye," he said. Amniotic membrane is not only a short-term treatment for dry eye but can be a long term as well. Dr. Donnenfeld also thinks there is a signif- icant role for oral doxycycline. A lot of doctors use too high a dose, he said. "All you need is 50 mg or less a day. I'll keep them on that for sometimes months at a time." Dr. Epitropoulos said she will use a tiered approach to treatment in these patients. If a patient is not improving with baseline therapy (artificial tears, lid hygiene, prescription drops like cyclosporine or lifitegrast), she'll consider: • In-office procedures: Thermal pulsation (LipiFlow, Johnson & Johnson Vision, and iLux, Alcon) for MGD or intense pulsed light, especially for patients with rosacea • Anti-inflammatory strategies: Short courses of corticosteroids or add-on agents like Tyrvaya (varenicline nasal spray, Viatris) or punctal occlusion (Lacrifill) can be used in aqueous deficient disease, she said. • Autologous serum tears: These are especial- ly helpful in severe or post-surgical dry eye and in cases of neurotrophic or neuropathic pathology. • Amniotic membranes: These can be used for patients with epithelial compromise or severe keratitis, Dr. Epitropoulos said. • Oxervate: This can be used in patients with NK. • Neuropathic treatment: Gabapentin, pregab- alin, or low-dose antidepressants can be used in select cases, Dr. Epitropoulos said, adding that a pain specialist referral is sometimes necessary. Dr. Epitropoulos has found the Cedars Dry Eye Algorithm helpful for guiding treatment es- calation in non-responders. "It incorporates the use of compounded medications, such as topical tacrolimus, doxycycline, testosterone drops, N-acetylcysteine drops, topical metronidazole, tailored to specific inflammatory or meibomian gland dysfunction," she said. "These alternative therapies can be invaluable when conventional therapies have been exhausted." What's next Dr. Donnenfeld is excited for the develop- ments being made in dry eye options. "Just like glaucoma, I think we're going to have multiple therapies for dry eye that will work on different pathways," he said. He noted acoltremon ophthalmic solution 0.003% (TRYPTYR, Alcon), which works on the TRPM8 pathway to stimulate tear secretion, adding that trials were promising and showed rapid improvement in Schirmer scores and im- provement in corneal staining. Dr. Epitropoulos also noted several promis- ing developments in this arena. One of the most exciting is the development of reactive alde- hyde species (RASP) inhibitors like reproxalap (Aldeyra Therapeutics), she said, which target oxidative stress and inflammation high up on the inflammatory cascade. Data has shown promise in reducing both signs and symptoms of dry eye, particularly in patients with high inflammatory burden. She also noted AZR-MD-001 (a selenium sulfide ophthalmic ointment, Azura Ophthal- mics) as a novel therapeutic for MGD using a first-in-class ophthalmic keratolytic aimed at normalizing keratinization and lipid composi- tion at the gland level by breaking apart disul- fide bonds that bind keratin, addressing MGD more upstream than traditional therapies. Dr. Epitropoulos stressed that managing non-responsive dry eye often requires a multi- disciplinary, holistic approach. "In addition to pharmaceutical and procedural interventions, counseling on behavior modification—like blink training, ergonomic changes, diet, hydration, and sleep—is key," she said. "Also, we should never underestimate the psychological impact of chronic ocular discomfort. Empathy and education go a long way in maintaining patient engagement and adherence." " Empathy and education go a long way in maintaining patient engagement and adherence." —Alice Epitropoulos, MD

• Cover