Key points are not available for this paper at this time.
OBJECTIVE: To evaluate symptom-sign discordance in dry eye disease (DED) using 3 distinct analytical frameworks in a large prospective cohort and to identify associated systemic risk factors. DESIGN: Secondary analysis of a multicenter randomized clinical trial. PARTICIPANTS: A total of 535 participants enrolled in the Dry Eye Assessment and Management (DREAM) study with moderate to severe DED. METHODS: Discordance was assessed at baseline using 3 approaches: (1) a rank-based comparison of symptom-sign severity; (2) a discomfort-based classification using Brief Ocular Discomfort Inventory (BODI) questionnaire; and (3) a novel temporal method evaluating symptom-sign changes between months 3 and 12. Patients were categorized as concordant, symptom-dominant, or sign-dominant discordant using each method. Multivariable regression models were used to identify predictors of discordance. MAIN OUTCOME MEASURES: Prevalence and characteristics of symptom-sign discordance across methods; strength of associations between symptoms, discomfort, and clinical signs; and clinical and systemic predictors of discordance. RESULTS: Using the rank-based method, 77% of patients were discordant. Symptom-dominant discordance (37.8%) was associated with younger age and greater ocular discomfort, while sign-dominant discordance (39.3%) was more common in patients with Sjögren's syndrome and was associated with greater relief from treatment. Discomfort-based analysis showed strong correlations between ocular discomfort and subjective symptoms (ρ = 0.47, p < .001), but weak associations with clinical signs. Temporal analysis revealed 46% of patients had discordant symptom-sign trajectories over 9 months, while 54% demonstrated concordance. Concordance was highest for TBUT (47.5%) and lowest for Schirmer's test (32.7%). Antidepressant use was associated with concordance, while female sex and higher bodily pain scores were associated with symptom-dominant discordance. CONCLUSIONS: Symptom-sign discordance in DED is common, multifactorial, and persists over time. This is the first study to apply and compare 3 discordance classification methods in a single cohort. Each offers distinct clinical utility, allowing clinicians to better stratify DED patients and enabling more targeted treatment and referral strategies, thus improving outcomes.
Matar et al. (Tue,) studied this question.