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The following is a summary of “Ocular features of VEXAS syndrome: a systematic review and meta-analysis,” published in the March 2025 issue of American Journal of Ophthalmology by Quigley et al. 

Researchers conducted a retrospective study to identify and analyze ocular features observed in Vacuoles, E1-ligase, X-linked Auto-inflammatory, and Somatic (VEXAS) syndrome.  

They followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: ID 566167) to analyze studies on VEXAS syndrome with genetically confirmed cases and documented eye involvement. Studies without genetic testing or ocular feature reporting were excluded. A comprehensive search of PubMed/MEDLINE, Embase, and CENTRAL databases covered January 2020 to September 2024. Data collection and bias assessment followed the PRISMA guidelines. The meta-analysis included ubiquitin-activating enzyme 1 (UBA1) mutation and systemic feature data. Kruskal-Wallis rank sum testing and Fisher’s exact test, using R, assessed associations between ocular severity, systemic or ophthalmic features, age, and causative mutation.  

The results showed that 52 articles included 204 individuals (1 female), with a mean VEXAS symptom onset age of 67 ± 5 years (range: 46-87). Orbital inflammation was the most common ocular manifestation, including periorbital edema (n=83, 40.7%), orbital myositis (n=14, 6.9%), dacryoadenitis (n=6, 2.9%), and orbital compartment syndrome (n=1, 0.5%). Other findings included episcleritis (n=28, 13.7%), scleritis (n=28, 13.7%), uveitis (n=25, 12.3%), and retinal vasculitis (n=2, 1%). Visual acuity data were reported in 4 cases (2%). Meta-analysis of 32 articles (n=48) with genotype and ocular data identified p.Met41Thr (n=24, 50%) as the most common UBA1 mutation, followed by p.Met41Val (n=17, 35%), p.Met41Leu (n=4, 8%), and splice site mutations or deletions (n=3, 6%). More severe ophthalmic features were associated with splice site mutations compared to methionine 41 missense mutations (P =0.04). Common systemic features included dermatologic manifestations (n=41, 85%), recurrent fever (n=38, 79%), and pulmonary involvement (n=30, 63%).  

Investigators concluded that the ophthalmic manifestations of VEXAS varied considerably, and ophthalmic evaluation was recommended for patients with VEXAS experiencing eye symptoms due to the potential for vision-threatening conditions. 

Source: ajo.com/article/S0002-9394(25)00153-9/fulltext