Quigley Clare, Pietris James, Ang Terence, Zgaga Lina, Selva Dinesh
From the Department of Ophthalmology, Royal Adelaide Hospital (C.Q., J.P., T.A., D.S.), Adelaide, South Australia, Australia.
From the Department of Ophthalmology, Royal Adelaide Hospital (C.Q., J.P., T.A., D.S.), Adelaide, South Australia, Australia.
Am J Ophthalmol. 2025 Aug;276:50-63. doi: 10.1016/j.ajo.2025.03.036. Epub 2025 Mar 27.
To identify and analyze ocular features seen in Vacuoles, E1-ligase, X-linked Auto-inflammatory, Somatic (VEXAS) syndrome.
A systematic literature review was performed following PRISMA guidelines (PROSPERO registration number: ID 566167).
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.
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).
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.
识别和分析空泡、E1连接酶、X连锁自身炎症性体细胞（VEXAS）综合征中的眼部特征。
按照PRISMA指南（PROSPERO注册号：ID 566167）进行系统的文献综述。
文章纳入标准包括基因确诊的VEXAS综合征且有眼部受累情况。排除标准包括缺乏基因检测或眼部特征报告。于2020年1月至2024年9月对PubMed/MEDLINE、Embase和CENTRAL数据库进行系统检索。根据系统评价和Meta分析的首选报告项目（PRISMA）指南收集数据并评估偏倚风险。对于Meta分析，还纳入了特定的UBA1突变和全身特征数据。分别使用R软件中的Kruskal-Wallis秩和检验和Fisher确切检验研究眼部特征严重程度、特定眼科或全身特征的存在与年龄或致病突变之间的关联。
纳入52篇文章，共204例个体（1例女性）。VEXAS症状发作的平均年龄为67±5岁（范围：46 - 87岁）。眼眶炎症是最常见的眼部表现，包括眶周水肿（n = 83，40.7%）、眼眶肌炎（n = 14，6.9%）、泪腺炎（n = 6，2.9%）和眼眶间隔综合征（n = 1，0.5%）。其他特征包括表层巩膜炎（n = 28，13.7%）、巩膜炎（n = 28，13.7%）、葡萄膜炎（n = 25，12.3%）和视网膜血管炎（n = 2，1%）等。视力报告有限（n = 4，2%）。对32篇有基因型和眼部特征数据的文章（n = 48）进行了Meta分析。最常报道的UBA1突变是错义突变p.Met41Thr（n = 24，50%），其次是p.Met41Val（n = 17，35%）、p.Met41Leu（n = 4，8%）以及剪接位点突变或缺失（n = 3，6%）。剪接位点突变组与甲硫氨酸41错义突变组相比，眼部特征更严重（P = 0.04）。最常相关的全身特征包括皮肤表现（n = 41，85%）、反复发热（n = 38，79%）和肺部受累（n = 30，63）。
VEXAS的眼科特征存在显著差异。鉴于有视力威胁性疾病的风险，建议对出现眼部症状的VEXAS患者进行眼科检查。
