Abstract
Purpose :
Dry eye disease (DED) represents a heterogeneous group of conditions with tear film instability and ocular surface irritation. While DED is traditionally classified as aqueous tear deficient vs evaporative, the full spectrum of DED subtypes is poorly characterized. Different etiological subtypes are hypothesized to respond to treatments differently. The DREAM study was a large multi-center randomized clinical trial that did not find omega-3 to be more effective than placebo in treating a broad spectrum of patients with symptomatic DED. We performed secondary analysis of the DREAM data to characterize DED subtypes and their response to omega-3.
Methods :
535 patients with moderate-to-severe DED were 2:1 randomized to receive omega-3 or placebo over one year. We used latent profile analysis to identify subtypes based on baseline DED symptoms, measured via the Ocular Surface Disease Index (OSDI), and 5 DED signs: tear break-up time (TBUT), anesthetized Schirmer’s test, corneal staining, conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated the effect of omega-3 on symptom improvement for each subtype using generalized linear regression with false discovery rate (FDR)-adjustment for multiple comparisons.
Results :
We identified 5 DED subtypes considered clinically meaningful by dry eye experts (Table 1, Figure 1). Sex (p<.001) and race (p=0.02) differed significantly among subtypes. Class 1, characterized by the most severe DED signs yet relatively milder symptoms, was significantly associated with a higher proportion of Sjögren’s syndrome patients (21%, p<.001). Class 5, characterized by severe MGD and TBUT, was significantly associated with rosacea (29%, p=0.04). For Class 1 only, the mean OSDI change over one year was greater in patients receiving omega-3 (n=60, -12.2±1.9) than placebo (n=29, -5.3±1.7) (95% CI for difference: [-11.9, -1.9], FDR-adjusted p=0.03). However, this was not significant after adjustment for baseline OSDI (-11.3±1.7 vs -7.1±1.9, 95% CI: [-9.2, 0.8], FDR-adjusted p=0.54).
Conclusions :
Five clinically meaningful DED subtypes identified in the DREAM study differed significantly in demographics, symptoms, signs, and systemic disease associations. Understanding DED subtypes can improve DED classification and targeted management. We did not find omega-3 to be significantly beneficial for the five DED subtypes.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.