Ocular manifestations of expanded dengue syndrome: a systematic review with meta-analysis

Abstract

Ocular manifestations are under-recognized complications of expanded dengue syndrome, with no robust frequency estimates available. A systematic review was conducted following PRISMA guidelines. Primary studies reporting the frequency of ocular manifestations consistent with expanded dengue syndrome (uveitis, maculopathy, retinal hemorrhage, retinal vasculitis, and optic neuropathy) in patients with confirmed dengue diagnosis were included. Six databases were searched (PubMed, Scopus, Embase, WoS, BIREME–BVS, and SciELO), supplemented by manual searching of reference lists and gray literature, with no date, language, or geographic restrictions. Risk of bias was assessed using the JBI critical appraisal checklist for prevalence studies. Pooled frequency estimates were calculated using a random-effects model with Freeman–Tukey double arcsine transformation. Heterogeneity was evaluated using Cochran's Q, I 2 , and Tau 2 . Subgroup analyses were performed based on time of onset of ocular manifestations relative to dengue symptom onset (early < 7 days vs. late ≥ 7 days). Funnel plot asymmetry and Egger's test were used to assess reporting bias in analyses, including ≥ 10 studies. Eight studies ( n = 1,394 patients) were included. Pooled frequency estimates were maculopathy 6% (95% CI 3–10%; I 2 = 28.9%, τ 2 = < 0.01) and retinal hemorrhage 8% (95% CI 3–14%; I 2 = 55.9%, τ 2 = < 0.01). Maculopathy frequency was higher beyond 7 days from symptom onset (10% vs. 5%), a pattern consistent with, but not confirmatory of, an immune-mediated pathophysiology. Maculopathy, retinal hemorrhage, and optic neuropathy are relevant complications of expanded dengue syndrome. Clinicians should maintain a high index of suspicion for these ocular manifestations, particularly during the recovery phase.