The Ocular Manifestations of Individuals With Down Syndrome: A Systematic Review and Meta-Analysis

Background: Down syndrome (DS) is the most common genetic cause of intellectual disability. Ocular manifestations occur frequently in people with DS (pwDS) but to date, there is no systematic review or meta-analysis of these conditions across the lifespan. Methods: PubMed, Medline, Embase, Web of Science and Scopus were searched for observational studies reporting ocular manifestations in pwDS, without limiting publication date. The proportion of pwDS with specific ocular manifestations were meta-analysed to obtain a pooled incidence using a random effects model. Sources of heterogeneity were assessed using a meta-regression analysis. For manifestations reported, but without sufficient prevalence data available, a narrative approach was adopted. Results: The search identified 1208 papers. Reviewers independently screened the abstracts, and 54 studies were found to fit the criteria. The age range of the individuals was birth to 88.7 years. Ocular manifestations from highest to lowest prevalence included refractive errors (69.97%, 95% CI 59.95%-79.13%), strabismus (31.41%, 95% CI 24.66%-38.57%), lens opacities (13.79%, 95% CI 8.61%-19.86%), nystagmus (12.72%, 95% CI 9.02%-16.92%) and keratoconus (9.34%, 95% CI 2.47%-19.26%). Alterations of lens and corneal morphology, posterior segment anomalies (including glaucoma) and Brushfield spots were also identified. Conclusions: The ocular manifestations of pwDS are common but varied. Age and/or ethnicity may influence the prevalence of certain ocular manifestations. The level of intellectual disability may also affect the prevalence of ocular manifestations as the prevalence of ocular disorders is known to increase with the severity of intellectual disability in pwDS.