PAIN PHENOTYPES IN OCULAR INVOLVEMENT OF RHEUMATOID ARTHRITIS: A CLINICAL-INFLAMMATORY MODEL

R. Usatii¹, E. Russu², E. Bendelic³, A. Corduneanu³, O. Tagadiuc³, L. Groppa³ | ¹Timofei Mosneaga Republican Clinical Hospital, Chisinau, Republic of Moldova; ²Timofei Mosneaga Republican Clinical Hospital, Chisinau, Republic of Moldova; Nicolae Testemitanu State Medical and Pharmaceutical University, Chisinau, Republic of Moldova; ³Nicolae Testemitanu State Medical and Pharmaceutical University, Chisinau, Republic of Moldova

Abstract

Background and Aims. Ocular manifestations in rheumatoid arthritis (RA) are heterogeneous and may contribute significantly to the overall pain burden. The variability of pain expression suggests the presence of distinct clinical phenotypes driven by inflammatory and structural mechanisms. This study aimed to identify and characterize pain phenotypes associated with ocular involvement in RA.
Methods. A cohort of 54 patients with RA underwent comprehensive ophthalmologic and clinical evaluation. Pain intensity was assessed using the visual analog scale. Disease activity was evaluated using the Disease Activity Score 28 (DAS28) and inflammatory status by C-reactive protein (CRP). Cluster analysis and multivariate modeling were applied.
Results. Three distinct pain phenotypes were identified: 1. Inflammatory ocular pain phenotype (31%): predominantly associated with scleritis, characterized by high pain intensity (7.1±0.9), elevated CRP (13.2±5.8 mg/L), and high DAS28 (5.6±0.7). 2. Surface-related pain phenotype (41%): mainly keratoconjunctivitis sicca, with moderate pain (6.1±1.0) and intermediate inflammatory levels (3). Low-pain phenotype (28%): minimal ocular involvement, lower pain (4.3 ± 1.2), and low inflammatory markers Pain intensity correlated significantly with CRP (r=0.36; p=0.008) and DAS28 (r=0.41; p=0.003), indicating inflammation-driven pain mechanisms. Patients in the inflammatory phenotype had longer disease duration (10.4±4.1 years vs. 6.2±3.5; p=0.01) and significantly lower functional scores (p=0.002), reflecting cumulative disease burden. Cluster discrimination showed excellent performance (accuracy 82%; area under the curve 0.85).
Conclusions. Ocular involvement in RA is associated with distinct pain phenotypes driven by systemic inflammation. Identification of these patterns may facilitate early recognition of severe disease and enable personalized management strategies.