JMIR Publications

ABSTRACT

Background:

Chronic ocular surface pain (COSP) is a leading cause of eye care visits in the US, occurring either in isolation or as part of numerous ocular conditions, such as dry eye syndrome. Conventional treatments directed at the ocular surface – the perceived pain source – are often inadequate for pain relief. We hypothesize that some individuals with COSP are experiencing symptoms driven by central nervous system (CNS) dysfunction, similar to chronic overlapping pain conditions (COPCs), rather than solely pathological problems in the eye. Some individuals with COPCs (example: fibromyalgia) show evidence of nociplastic pain mechanisms, where the pain results from amplified and/or dysregulated CNS signaling and sensory processing. Although, data exist suggesting the presence of nociplastic pain features in COSP, there is a need for comprehensive studies.

Objective:

Our aim is to rigorously define the role of nociplastic pain in COSP with a large, representative cohort of patients (n=200 COSP participants) using established clinical, neurobiological, and treatment response features. We propose that as sign/symptom discordance increases so will features indicative of nociplastic pain.

Methods:

In Aim 1, we will clinically phenotype COSP participants using validated patient-reported outcome measures and standard ocular exams. In Aim 2, we will compare the neurobiological features of nociplastic pain across the discordance spectrum among a subset of Aim 1 participants using multimodal evoked sensory testing (pressure, thermal, and visual testing) at sites local and remote from the eye. Participants will also complete structural/functional brain MRI to assess regions important for pain perception and modulation. In Aim 3, we will examine and validate predictors of COSP pain responses before and after application of a topical anesthetic to the ocular surface which should block peripherally induced discomfort to allow for clarification of pain origination.

Results:

We received funding for this project in August 2024. Recruitment and enrollment began in January 2025 after protocol development and piloting was completed. The study is ongoing with 49 participants enrolled as of September 2025.

Conclusions:

Findings from the study have the potential to fundamentally change the way ocular pain syndromes are conceptualized, diagnosed, and treated. This work will not only help identify new CNS-directed pain treatments for a subset of patients with COSP, but also help us better understand why many peripherally directed therapies are destined to be ineffective in a subset of individuals experiencing COSP Clinical Trial: None