Symptom-based stratification of heterogeneous symptoms of dry eye disease in patients with Sjögren's syndrome.

Objective: We aimed to use symptom-based stratification to identify the subtype-specific pathophysiology of dry eye disease (DED) in Sjögren's syndrome (SS).

Methods: We retrospectively enrolled patients with SS who visited Juntendo University Hospital between October 2017 and July 2023 and were diagnosed with DED (2016 Asia Dry Eye Society guideline). The DED subtype and pathophysiology were classified under five distinct tear film breakup patterns: area, line, spot, dimple, and random breaks. Based on responses to the Japanese version of the Ocular Surface Disease Index (J-OSDI), spectral clustering was used to stratify participants; inter-cluster comparison of J-OSDI total scores and key DED-related objective findings was undertaken.

Results: Among the 239 participants, DED prevalence was the highest in Cluster 3 (98.2%), followed by clusters 2 (83.4%) and 1 (4.1%). J-OSDI total scores were the highest in Cluster 3 (64.6 points) and lowest in Cluster 1 (2.1 points) (P < 0.001). Prevalence of line and area breaks (aqueous-deficient type) was highest in Cluster 1 (81.6%) whereas dimple and spot breaks (decreased-wettability type) were most prevalent in Cluster 2 (21.0%). Random breaks (increased evaporation) were observed most frequently in Cluster 1 (8.2%). Median MBI was shortest in Cluster 3 (7.1 s), followed by Cluster 2 (8.6 s) (P = 0.003). The median serum anti-SS-A/Ro concentration was highest in Cluster 3 (32.0 U/mL; P = 0.018). Cluster 2 showed a notable discrepancy between subjective symptoms and CFS scores.

Conclusions: Using symptom-based DED severity of SS, we successfully stratified patients into three clusters to potentially facilitate type-customised interventions to improve treatment efficacy.