A Scoping Review of Pharmacologic and Non-Pharmacologic Interventions to Treat Chronic Ocular Pain

Abstract

Background: Chronic Ocular Pain (COP) is disabling and a common reason for referral to neuro-ophthalmologists. Many patients with COP suffer from amplified or dysfunctional pain processing in the peripheral or central nervous system, rather than a problem with the eye itself. The extent and evidence for therapeutic interventions targeting pain in the peripheral and central nervous system among patients suffering from COP is unknown. Evidence Acquisition: We performed a search of Ovid MEDLINE, Embase.com, Scopus.com, and Clinicaltrials.gov. We limited our search to English language articles published since 2015. We included observational and experimental studies of pharmacologic and non-pharmacologic interventions (e.g., vagal nerve stimulation) used in adults 18 years or older with COP for at least 3 months. Studies were included if impact on pain intensity, functioning, or quality of life were measured as primary, secondary, or exploratory outcomes. All articles were independently screened by two team members for inclusion. Data extraction was performed independently by two team members. Any disagreements during the screening and data extraction process were adjudicated by a third team member and discussed as a group. Results: Our search identified 9656 studies from 2015 to 2026. Of those, 21 met our inclusion/ exclusion criteria. The study designs were mostly retrospective: five case reports, nine observational, one case-control study; three prospective studies were non-randomized, observational studies. three studies were randomized clinical trials, but one did not have published results. Most (67%, n=14) were studies of pharmacologic interventions including all three completed prospective studies. Pharmacologic interventions included gabapentin, cryosim-3 applied to the eyelids, autologous serum tears, botulinum toxin type A injections, and nerve blocks. The six studies including non-pharmacologic interventions used transcutaneous electrical nerve stimulation, trigeminal ganglion stimulation, and pulsed radiofrequency procedures. The three randomized controlled clinical trials were of transcutaneous electrical nerve stimulation, topical ocular cooling device, and topical OK-101 ophthalmic solutions at different concentrations. The most common pain measures used across studies were pain intensity scales (range 0–10), such as the numeric rating scale. Improvements in COP were reported for most studies. Reporting of adverse events occurred in eight (43%) studies. Conclusions: Although COP is a common symptom, we found few studies of pharmacologic and non-pharmacologic treatment interventions with a few randomized controlled trials. Rigorous studies of treatment interventions aimed at reducing COP are needed. We provide recommendations for both the conduct of future studies and a current approach to COP treatment.