CHRONIC ocular surface pain may reflect nociplastic CNS dysfunction and will be phenotyped using comprehensive characterization.
Why Chronic Ocular Surface Pain Persists
Chronic ocular surface pain (COSP) remains a common driver of U.S. eye care visits, yet many patients experience limited relief from therapies aimed only at the ocular surface. The study team proposes that, for a subset of individuals, pain may be sustained by altered central nervous system (CNS) processing rather than active pathology confined to the eye. This framework mirrors chronic overlapping pain conditions, where amplified sensory signaling contributes to persistent symptoms.
Chronic Ocular Surface Pain and Symptom Discordance
A key concept in this protocol is sign and symptom discordance. Some patients report severe pain despite minimal objective ocular surface findings, while others show surface changes with lower pain intensity. The investigators hypothesize that as discordance increases, indicators of nociplastic pain will also increase, suggesting a greater contribution from CNS dysfunction.
Mapping Nociplastic Features Beyond the Eye
The observational study aims to enroll 200 participants with COSP. Participants will undergo clinical phenotyping using validated patient-reported outcome measures alongside standard ocular examinations, including presentations linked to conditions such as dry eye syndrome.
In a subset of participants, the protocol includes multimodal evoked sensory testing across pressure, thermal, and visual domains, performed both near the eye and at remote body sites. This approach is designed to detect broader sensory amplification patterns consistent with nociplastic pain mechanisms, similar to those described in conditions such as fibromyalgia.
Testing Treatment Response with Topical Anesthetic
To clarify pain origination, the study will also evaluate predictors of pain response before and after applying a topical ocular anesthetic. Because topical anesthesia is expected to block peripherally induced discomfort, changes in pain intensity may help distinguish predominantly peripheral drivers from centrally mediated pain patterns, with implications for future CNS-directed treatment strategies.
Funding was awarded in August 2024, with recruitment beginning in January 2025. As of January 2026, 59 participants had enrolled and 51 had completed study visits. The authors conclude that this work could reshape how COSP is conceptualized, diagnosed, and treated, particularly for patients unlikely to respond to surface-focused therapies.
Reference: De Lott LB et al. Central nervous system mechanisms and treatment response in chronic ocular surface pain: protocol for a cross-sectional observational phenotyping study. JMIR Res Protoc. 2026;15:e84240.
