Eyeworld

C ORNEA 26 | EYEWORLD BONUS ISSUE | OCTOBER 2025 chronic ocular surface pain symptoms while pre- serving corneal sensitivity and the normal blink reflex. Earlier this year, the company announced positive results from a double-masked, random- ized controlled trial demonstrating a favorable safety profile and a significant reduction in patient-reported ocular pain compared to the control group. Dr. Epitropoulos said the unmet therapeutic needs of these patients underscore the critical need for ongoing research and innovation in the field of ocular surface disease, particularly for complex or treatment-resistant cases. She also shared a number of other reasons that patients may be non-responsive to dry eye treatments: • Incorrect subtype identification: For instance, Demodex blepharitis, which can contribute to meibomian gland dysfunction and patient symptoms (itching, mattering), may not improve unless specifically addressed (lotilaner). Treating evaporative dry eye with aqueous-enhancing strategies, or vice versa, will naturally yield inadequate results. • Incomplete treatment: Patients may discon- tinue medications early or use them incon- sistently, especially if symptomatic relief is delayed, she said. • Neurotrophic keratitis: This is another im- portant consideration; patients with reduced corneal sensation may exhibit advanced ocu- lar surface disease with minimal symptoms. These patients may not respond to conven- tional treatments due to impaired epithelial healing. Dr. Epitropoulos said that identifying neurotrophic components is crucial for direct- ing appropriate therapies such as cenegermin (Oxervate, Dompe), serum tears, and/or amniotic membrane. • Uncontrolled inflammation or meibomian gland dysfunction (MGD): Persistent sub- clinical inflammation, Demodex infestation, or gland dropout may not respond to conven- tional therapy. • Systemic comorbidities: Autoimmune con- ditions, hormonal changes, sleep apnea, or polypharmacy (especially anticholinergics and antihistamines) can exacerbate symptoms. • Environmental/lifestyle: Prolonged screen time, low humidity, infrequent or incomplete blinking, or poor sleep habits often play a role in treatment resistance. Dr. Donnenfeld agreed that one of the main reasons patients may not respond to treatment is because of incorrect subtype identification. "When I evaluate a patient with dry eye who's unhappy, I generally want to ascertain what the cause of the dry eye is," he said, adding that certain therapies are good for aqueous deficient dry eye, and certain drugs are better for MGD. "A lot of times, when patients are not respond- ing to one therapy, it's because you're treating the wrong disease." For example, when cyclo- sporine was first approved by the FDA, that was the only therapy that was readily available for dry eye. "When all you have is a hammer, every- thing looks like a nail, and we treated a lot of patients who were not responding because they really had MGD and not aqueous deficient dry eye," he said. "I like to find out what the cause of the problem is. Many times, patients need both treatments." Dr. Epitropoulos also noted that certain symptoms and conditions are more likely to be non-responsive to treatment. In particular, she said that neuropathic pain masquerading as dry eye tends to be especially difficult to manage. Key indicators include severe symptoms with minimal clinical signs, allodynia, and poor response to conventional treatments. More advanced options "Typically, I allow 6–8 weeks to evaluate the effectiveness of a new therapy, though some treatments, such as cyclosporine or lifitegrast, may need 3–6 months," Dr. Epitropoulos said. "If a patient's condition worsens or shows no improvement after 4 weeks, I begin adding or switching to other therapies, such as autologous serum or amniotic membrane. I also routinely reassess diagnostics, including osmolarity, MMP- 9 and meibography, to better understand the underlying disease factors." When moving on to more advanced treat- ment options, Dr. Donnenfeld said punctal occlusion may be helpful for some dry eye pa- tients. He noted Lacrifill (Nordic Pharma) being particularly effective at sealing the punctum. "The crosslinked hyaluronic acid in the punc- tum is released into the tear film and provides a sustained delivery of tears," he said. "For significant dry eye, I think that we underutilize serum tears," he continued. "These are superb treatment for patients with recalci- trant dry eye." Along a similar line, he said amniotic mem- branes are often used for persistent epithelial continued from page 24

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