Impact of an Ophthalmic Cooling Device on Corneal Immune and Sensory Nerve Features in Chronic Ocular Surface Pain: A Prospective, Feasibility Study

INTRODUCTION: A safe and effective treatment for chronic ocular surface pain (COSP) remains an unmet need. This prospective feasibility study investigated the impact of an ophthalmic cooling device (ETX-4143) on ocular pain, as well as corneal nerve and immune cell features, in individuals with COSP. METHODS: For this clinical trial (Clinicaltrials.gov:NCT07059754), the more symptomatic (study) eye was treated with the ETX-4143 device, involving two metallic probes, internally cooled by a -20 °C fluid, applied to the bulbar conjunctiva posterior to the limbus at 3 and 9 o'clock for 4 min, with a fellow (untreated) eye control. Ocular pain, best-corrected visual acuity (BCVA), tear osmolarity, corneal sensitivity, slit lamp biomicroscopy, ocular surface staining, and static and functional in vivo confocal microscopy (Fun-IVCM) were conducted at baseline and 2-, 6-, and 12-weeks posttreatment. Corneal nerve and immune cell parameters were quantified. RESULTS: Five eligible participants were enrolled and completed the study (mean age 66.4 ± 9.9 years, 60% female/40% male). Relative to baseline, ocular pain, measured with the Chronic Ocular Pain Questionnaire (COP-Q) Eye Pain Severity Module, was significantly lower at 2 weeks (mean change -4.4 units, 95% CI -7.4 to -1.4, P = 0.02), 6 weeks (-5.0 units, 95% CI -7.0 to -3.0, P = 0.002), and 12 weeks posttreatment (-5.8 units, 95% CI -7.8 to -3.8, P = 0.001); benefit progressed with time. Clinical ocular surface signs, BCVA, and corneal nerve morphology remained stable. In the study eye, corneal Fun-IVCM showed an increase in putative intraepithelial T-cell motility up to 6 weeks posttreatment (P < 0.001), followed by a reduction at 12 weeks (P = 0.03) that was accompanied by reduced probing of putative dendritic cells (P = 0.049), relative to baseline. CONCLUSIONS: The ETX-4143 device showed a favorable safety profile, including preserved corneal nerve morphology, while improving pain outcomes and modulating corneal immune dynamics up to 12 weeks posttreatment, acknowledging these findings are exploratory. Randomized controlled trials are warranted to evaluate treatment efficacy and mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT07059754.