Prevalence of Ophthalmological Manifestations in Patients With Inborn Errors of Immunity: A Systematic Review and Meta-Analysis

The objective of this systematic review and meta-analysis was to examine the clinical features and prevalence of ophthalmological manifestations in patients with inborn errors of immunity (IEI).The study population consisted of a pool of 7555 patients with IEI, inclusive of all ages and ethnicities, aggregated from 62 qualifying studies.This systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines across Embase, PubMed, and Lilacs. The review included observational studies, case series, case-control studies, cohort studies, cross-sectional studies, and clinical trials, and all of which were required to have no fewer than 10 patients described with IEI.After a systematic review of the available literature from 1968 to 2022, there were 7555 patients from 62 observational studies included. The patients had a mean age of presentation of 11.1 years (±7.8 years). Ophthalmic manifestations were slightly more likely to occur in male individuals (59%; 95% CI = 55-63, I2 = 35%, P = .05), especially during childhood. Ocular manifestations were identified in 54% of the patients in this meta-analysis (95% CI = 39-69, I2 = 94%, P < .01). The most commonly reported ophthalmological conditions were impaired ocular motility (nystagmus, strabismus, and oculomotor apraxia), followed by anterior segment abnormalities (cataracts, ocular telangiectasia, and corneal opacity) and that of the posterior segment (optic nerve disorders, chorioretinal scars, retinitis, and macular edema). The most identified IEI classification with ocular manifestations was combined immunodeficiencies with associated or syndromic features (82%), followed by diseases of immune dysregulation (73%), then autoinflammatory disorders (48%).Ophthalmological manifestations are prevalent in patients with IEI, especially during childhood, so pediatric clinicians need to be aware of the potential for ocular manifestations in patients with IEI to prevent delays in detection.This meta-analysis is the largest examination of ophthalmological manifestations in patients with IEI to date. There was a male predominance of ocular manifestations, which is not unexpected given the higher prevalence of IEI in male individuals due to X-linked inheritance pattern. It should be noted that this meta-analysis had robust inclusion criteria; there were a wide variety of study types included. This likely contributes to the large CI regarding the prevalence of ocular conditions and expressions of disease (54%, 95% CI = 39%–69%). Despite this, it is clear that for certain IEI classifications, such as combined immunodeficiencies with associated or syndromic features, ocular manifestations occur in more than half of the population (82%, 95% CI = 66%–91%). Unfortunately, the spectrum of ophthalmic manifestations included in this systematic review was broad and no attempt was made to define specific prevalences or comparisons with those found in healthy populations. As the authors recommended, further studies that may lend to specific guidance on when and how to screen for ocular manifestations in specific classifications of IEI would be beneficial. The study results emphasize the need for increased awareness by pediatricians, ophthalmologists, and immunologists that patients with IEIs have higher rates of ocular manifestations. Early ophthalmologic evaluation may help prevent ocular complications later in life, such as amblyopia, and improve patients’ quality of life.