Ocular Features of VEXAS Syndrome: A Systematic Review and Meta-analysis

PURPOSE

To identify and analyze ocular features seen in Vacuoles, E1-ligase, X-linked Auto-inflammatory, Somatic (VEXAS) syndrome.

DESIGN

A systematic literature review was performed following PRISMA guidelines (PROSPERO registration number: ID 566167).

METHODS

Article inclusion criteria comprised genetic confirmation VEXAS syndrome that included eye involvement. Exclusion criteria included lack of genetic testing, or ocular feature reporting. A systematic search of the PubMed/MEDLINE, Embase, and CENTRAL databases was performed from January 2020 to September 2024. Data were collected and risk of bias assessed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. For the meta-analysis, specific UBA1 mutation and systemic feature data were also included. An association between severity of ocular features, presence of specific ophthalmic or systemic features, with age or causative mutation was investigated using Kruskal-Wallis rank sum testing and Fisher exact test, respectively, using R.

RESULTS

Fifty-two articles were included, amounting to 204 individuals (1 female). Mean age of VEXAS symptom onset was 67 ± 5 years (range: 46-87). Orbital inflammation was the most common ocular manifestation, comprising 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 features included episcleritis (n = 28, 13.7%), scleritis (n = 28, 13.7%), uveitis (n = 25, 12.3%), and retinal vasculitis (n = 2, 1%), among others. Visual acuity reporting was limited (n = 4, 2%). Meta-analysis was conducted on 32 articles (n = 48) with genotype and ocular feature data. The most commonly reported UBA1 mutation was the missense mutation p.Met41Thr (n = 24, 50%), followed by p.Met41Val (n = 17, 35%), p.Met41Leu (n = 4, 8%), and splice site mutations or deletions (n = 3, 6%). There was an association for more severe ophthalmic features in the splice site mutation group vs methionine 41 missense mutations (P = .04). The most commonly associated systemic features included dermatologic manifestations (n = 41, 85%), recurrent fever (n = 38, 79%), and pulmonary involvement (n = 30, 63).

CONCLUSION

There is notable variation in the ophthalmic features of VEXAS. Ophthalmic review is advised for VEXAS patients who develop eye symptoms, given the risk of sight-threatening disease.