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

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 nervous system (PNS) or central nervous system (CNS), rather than a problem with the eye itself. The extent of and evidence for therapeutic interventions targeting pain in the PNS and CNS among patients suffering from COP are unknown.

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 nonpharmacologic interventions (e.g., vagal nerve stimulation) used in adults 18 years or older with COP for at least 3 months. Studies were included if the impact on pain intensity, functioning, or quality of life was measured as primary, secondary, or exploratory outcomes. All articles were independently screened by 2 team members for inclusion. Data extraction was performed independently by 2 team members. Any disagreements during the screening and data extraction processes were adjudicated by a third team member and discussed as a group.

Our search identified 9,656 studies from 2015 to 2026. Of those, 21 met our inclusion/exclusion criteria. The study designs were mostly retrospective: 5 case reports, 9 observational, and 1 case-control study; 3 prospective studies were nonrandomized, observational studies. Three studies were randomized clinical trials, but one did not have published results. Most of the studies (67%, n = 14) were on pharmacologic interventions including all 3 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 6 studies including nonpharmacologic interventions used transcutaneous electrical nerve stimulation, trigeminal ganglion stimulation, and pulsed radiofrequency procedures. The 3 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 the studies were pain intensity scales (range 0-10), such as the numeric rating scale. Improvements in COP were reported for most studies. The reporting of adverse events occurred in 8 studies (43%).

Although COP is a common symptom, we found few studies on pharmacologic and nonpharmacologic 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 the current approach to COP treatment.