Corneal Sensory Changes and Nerve Plexus Abnormalities in Chronic Neuropathic Ocular Pain and Dry Eye Post-Refractive Surgery.

Abstract

PURPOSE Chronic neuropathic ocular pain (NOP) can develop alongside chronic dry eye (DE) post-laser-assisted in-situ keratomileusis (LASIK), yet its specific characteristics remain poorly understood. This study aims to compare the clinical characteristics of patients who developed both DE and NOP after LASIK to those with only DE and to asymptomatic LASIK patients, to facilitate the diagnosis of NOP. METHODS Prospective, cross-sectional "case-control" comparison study. An 89-subject post-LASIK study comprised three groups: 34 patients developing NOP and DE (NOP-DE group), 25 patients developing only DE (DE group), and 30 asymptomatic subjects (control group). Assessments included clinical history and symptom questionnaires (OSDI, mSIDEQ, NRS, WFPRS), anxiety and depression evaluation (HADS), tear film stability (osmolarity and TBUT) and production (Schirmer), and ocular surface integrity. Corneal mechanical and thermal sensitivity thresholds were measured using Belmonte's non-contact esthesiometer, whereas tactile sensitivity threshold was assessed pre/post-topical anesthesia using the Cochet-Bonnet esthesiometer. In vivo confocal microscopy (IVCM) was used to evaluate the sub-basal nerve plexus characteristics and dendritic cell density in the central cornea. Group comparisons and correlations were conducted. RESULTS Compared with DE group, patients in the NOP-DE group exhibited significantly more DE symptoms with mSIDEQ (p=0.019) higher level of pain with NRS and WFPRS, increased use of ocular lubrication (p=0.003), greater frequency of patients with pathological results on anxiety and depression questionnaires (p<0.001), and a higher prevalence of central sensitization syndromes (p<0.001). Additionally, NOP-DE patients demonstrated higher tactile corneal sensitivity post-topical anesthesia (p=0.002). IVCM revealed lower nerve density (p=0.049) and higher microneuroma density (p=0.008) in the sub-basal nerve plexus of NOP-DE patients compared to DE patients without NOP (p=0.008). Most nerve metrics correlated moderately to strongly with clinical parameters. CONCLUSIONS Persistent high corneal tactile sensitivity post-anesthesia, reduced nerve density and increased microneuroma density in the central cornea may serve as diagnostic indicators for confirming NOP in patients experiencing chronic DE post-LASIK. These findings underscore the potential utility of incorporating these measures into clinical assessments to improve diagnostic accuracy and guide management strategies in this patient population.