Discordant dry eye disease and chronic pain: A systematic review and meta-analysis.

Purpose: To evaluate the relative contributions of objective and subjective indicators of dry eye disease (DED) in individuals with chronic pain conditions compared with controls.

Methods: A systematic review and meta-analysis was conducted of studies that reported the signs and symptoms of DED and/or their prevalence in individuals with chronic pain compared with controls. International Association for the Study of Pain (IASP) International Classification of Diseases (ICD)-11 codes for chronic pain conditions were applied, and outcomes defined as DED signs and symptoms. A search strategy utilised the EMBASE, Web of Science, Cochrane Library and MEDLINE databases. Risk of bias assessment was performed with the Newcastle-Ottawa scale. Random effects meta-analysis calculated mean differences (MD) and odds ratios (OR), while subgroup analysis of different chronic pain conditions explored their relative association with the signs and symptoms of DED. Evidence certainty was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE).

Results: Fourteen observational studies comprising 3,281,882 individuals were included. Meta-analysis found high quality evidence that individuals with chronic pain were more likely to experience symptoms of DED than controls (OR = 3.51 [95 %CI: 3.45,3.57]). These symptoms were more severe (MD = 18.53 [95 %CI: 11.90, 25.15]) than controls with a clinically meaningful effect size. Individuals with chronic pain had more rapid tear film disruption (MD = -2.45 [95 %CI: -4.20, -0.70]) and reduced tear production (MD = -5.57 [95 %CI: -9.56, -1.57]) compared with controls (with moderate evidence quality). High quality evidence revealed individuals with chronic pain had lower basal tear production (anaesthetised) than controls (MD = -2.59 [95 %CI: -3.60, -1.58]). Tear film osmolarity showed no significant differences between the chronic pain and pain-free groups. Group differences for DED signs were not considered clinically meaningful.

Conclusion: More severe, clinically meaningful symptoms of DED were reported in individuals with chronic pain than controls, however group differences for the signs of DED were typically of limited or questionable clinical relevance. This ocular phenotype where DED is felt more than it is seen in chronic pain may reflect underlying sensory hypersensitivity, shared by both conditions and contributing to their frequent comorbidity. Advancing understanding of this potential pathophysiological mechanism may guide clinical management.