Prevalence of ocular and visual abnormalities following symptomatic and asymptomatic congenital CMV infection: a systematic review and meta-analysis

Background: Cytomegalovirus (CMV), the most common congenitally acquired infection, can result in visual disability in affected children. We aimed to estimate the burden of eye and vision disorders amongst children with symptomatic and asymptomatic congenital cytomegalovirus infection (cCMV), to inform the development of guidance for the provision of care. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, and CINAHL databases up to 6th Feb 2025 for studies reporting ocular disorders or visual impairment (VI) outcomes following cCMV diagnosis. We included longitudinal or cross-sectional studies which reported the frequency of visual or ophthalmic outcomes following an initial diagnosis of symptomatic or asymptomatic cCMV. Summary data, and individual patient level data where available, on the proportions of children noted to have visual impairment or ophthalmic disorders and the manifestation of these disorders, were extracted from published reports. Pooled prevalence of eye and vision outcomes were estimated through random effects models computed using Restricted Maximum Likelihood (REML) estimation. We included studies at lower risk of bias (assessed using the Joanna Briggs Institute tool) in meta-analyses of prevalence (random-effect models) and undertook subgroup analyses. The review protocol was registered with PROSPERO, CRD42021284678. Findings: We identified 4488 articles of which 28 were eligible for inclusion. Of these, 15 studies (total 858 children with symptomatic, 1176 with asymptomatic cCMV) were eligible for meta-analyses. Median follow up time from diagnosis of cCMV ranged from 6 to 156 months. Estimated pooled prevalence in symptomatic cCMV of visual impairment (VI) and ocular disorders 9% (95% CI, 5–14%, I² = 51.09%) and 14% (95% confidence interval, CI, 5–31%, I² = 93.2%) respectively. Cerebral visual impairment (i.e. VI due to neurological insult rather than ocular disease) was the most commonly reported visual disability, with an estimated pooled prevalence of 10% (95% CI, 6–15%, I² = 24.9). Prevalence of ocular disorders (most commonly chorioretinitis, and optic nerve and anterior segment anomalies) was higher in studies with greater proportions of pre-term birth, hearing impairment, and those undertaken prior to 2017. Estimated pooled prevalence of VI and ocular disorders was 1% and <1% (95% CI, 0–2%, I² = 0%) respectively in asymptomatic cCMV. Interpretation: Visual disability in cCMV is a strong marker of the broader neurological insult. Ocular disorders are prevalent in symptomatic disease, with consequent need for ongoing ophthalmic care. The low prevalence of sight-impactful disorders in asymptomatic disease suggests little benefit for ongoing ophthalmic surveillance, particularly in health settings with established programmes for whole population childhood eye and vision screening. This review is limited by the absence of information on the timing of diagnosis of the eye and vision disorders, data which would support the development of timeline pathways for ophthalmic surveillance. Funding: Wellcome Trust, National Institute for Health and Care Research (NIHR).<p></p>