Uveitis characteristics and multiple sclerosis phenotype of patients with multiple sclerosis-associated uveitis: A systematic review and meta-analysis
Authors: Saboya-Galindo Paola , Mejía-Salgado Germán , Cifuentes-González Carlos , Rodríguez-Rodríguez Camilo Andrés , Boada-Robayo Laura , Méndez-Marulanda Rafael , Varela Joan Sebastián , Riveros-Sierra Laura , Gaviria-Carrillo Mariana , de-la-Torre Alejandra 
Published: October 2024

Purpose
To summarize and meta-analyze uveitis characteristics and multiple sclerosis (MS) phenotype of patients with multiple sclerosis-associated uveitis (MSAU) within a systematic review and meta-analysis.

Methods
A comprehensive literature search was performed on January 25, 2023, utilizing PubMed, Embase, and Virtual Health Library (VHL) databases. We included studies involving patients with MSAU, such as case series with over 10 patients, cross-sectional, case-control, and cohort studies. Quality and risk of bias were assessed using CLARITY tools and validated metrics like the Hoy et al. and Hassan Murad et al. tools. The pooled analysis focused on 1) uveitis characteristics, 2) ocular complications, 3) MS phenotype, and 3) administered treatments for uveitis and MS. Gender-based subgroup analysis was conducted across continents; heterogeneity was measured using the I2 statistic. Statistical analysis was performed using R software version 4.3.1. The study was registered in PROSPERO with CRD42023453495 number.

Results
Thirty-six studies were analyzed (24 with a low risk of bias, 8 with some concerns, and 4 with a high risk of bias), including 1,257 patients and 2,034 eyes with MSAU. The pooled analysis showed a mean age of 38.2 ± 12.1 years with a notable female predominance (67%, 95% CI [59%-73%]). MS before uveitis was seen in 59% of the cases (95% CI [48%-69%]), while uveitis was present before MS in 38% (95% CI [30%-48%]). The mean age for the first uveitis episode was 35.7 ± 8.3 years, predominantly affecting both eyes (77%, 95% CI [69%-83%], from 23 studies involving 452 patients). Intermediate uveitis was the most frequent anatomical location (68%, 95% CI [49%-82%], from 22 studies involving 530 patients), often following a recurrent course (63%, 95% CI [38%-83%]). Key complications included vision reduction (42%, 95% CI [19%-70%], from five articles involving 90 eyes), macular compromise (45%, 95% CI [20%-73%], from 4 studies involving 95 eyes), and cataracts (46%, 95% CI [32%-61%], from eight articles involving 230 eyes). Concerning MS phenotype, relapsing-remitting MS (RRMS) was the most common subtype (74%, 95% CI [64%-82%], from eight articles involving 134 patients), followed by secondary progressive MS (24%, 95% CI [18%-33%], from eight articles involving 125 patients). The most frequently occurring central nervous lesions were supratentorial (95%, 95% CI [70%-99%], from two articles involving 17 patients) and spinal cord (39%, 95% CI [16%-68%], from two articles involving 29 patients). The mean Expanded Disability Status Scale (EDSS) score and annual recurrence rates were 2.9 ± 0.6 and 1.07 ± 0.56, respectively. Treatment trends showed the prevalent use of Fingolimod (96%, 95% CI [17%-100%], from two articles involving 196 patients), Mycophenolate (48%, 95% CI [11%-87%], from four articles involving 51 patients), and Interferon-beta (43%, 95% CI [24%-65%], from 11 articles involving 325 patients).

Conclusion
MSAU primarily affects young adult females, typically presenting as bilateral intermediate uveitis with vision-related complications. The most common MS phenotype is RRMS, often associated with supratentorial and spinal cord lesions on imaging. These findings give ophthalmologists and neurologists a comprehensive clinical picture of MSAU, facilitating prompt diagnosis.