Humanistic Burden of Non-Infectious Uveitis: A Systematic Review and Meta-Analysis: Short Title: Humanistic Burden Non-Infectious Uveitis.

Purpose: This study aimed to evaluate the humanistic burden of non-infectious uveitis (NIU).

Design: Systematic review and meta-analysis.

Methods: A comprehensive search was conducted across Medline, Embase, and Scopus databases from inception to March 2023. Studies pertaining to the health-related quality of life (HRQoL) of patients with NIU in both adult and pediatric populations were included. Identified studies were critically appraised and assessed for bias using the Joanna Briggs Institute Critical Appraisal tools.

Results: A total of 68 studies involving 8,403 participants met the inclusion criteria, and 10 studies were included in the meta-analysis. Across 14 HRQoL instruments used across the studies, Visual Function Questionnaire 25 (VFQ-25) was the most frequently used (n=35), followed by the 36-Item Short Form Survey (SF-36) and 8-Item Short Form Survey (SF-8) (n=30), EuroQol 5-Dimensions (EQ-5D) (n=8) and Pediatric Quality of Life (PedsQL) (n=8). Thirteen studies assessed pediatric populations (19%), 12 studies compared NIU and systemic disease (18%), 14 studies assessed QoL outcomes with different treatment modalities (21%), and 4 studies explored QoL outcomes through qualitative exploratory methods (6%). Patients with JIA-U had poorer HRQoL scores than non-uveitic JIA by 5.26 (95% CI -7.24, -3.28; P < .05) on the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) questionnaire and the Childhood Health Assessment Questionnaire (CHAQ). Adults with NIU with systemic disease scored notably lower on both Mental Component Summary (MCS) (mean difference (MD): -5.63; 95% CI -9.37, -1.88; P < .01) and Physical Component Summary (PCS) (MD: -4.99; 95% CI -11.71, 1.73; P < .01) segments of the 36-Item Short Form Survey (SF-36) compared to healthy controls. Overall, the studies were of moderate to high quality.

Conclusion: NIU poses a significant QoL impact from a physical health, mental health, daily functioning, and caregiving perspective. Patients with NIU experience significant declines in QoL, particularly those with comorbid conditions and systemic diseases, highlighting the need for validation of uveitis-specific patient-reported outcome measures(PROMs). Future studies should develop interventions and explore QoL impacts on diverse geographic regions.