Abstract
BACKGROUND: Nanophthalmos, a rare ocular condition characterized by small but structurally normal eyes, presents a high risk for developing angle-closure glaucoma and related complications. Accurate estimation of glaucoma prevalence and identification of predictive risk factors are essential for guiding early diagnosis and tailored interventions in this anatomically vulnerable population. Therefore, the current systematic review and meta-analysis synthesizes existing evidence on the associated clinical and biometric risk factors for glaucoma in nanophthalmic eyes. METHODS: Following PRISMA guidelines, we conducted a comprehensive literature search in PubMed and the Cochrane Library for studies published between January 2000 and December 2023. Eligible studies included investigations reporting biometric data in nanophthalmic eyes. Data were extracted on demographics, clinical parameters, and risk factors. Meta-analyses using random-effects models were conducted to estimate pooled prevalence and assess heterogeneity. Subgroup analyses and meta-regression explored sources of variability. The risk of bias was assessed using NIH quality tools. RESULTS: A total of 44 studies involving 1,397 eyes from 1,078 patients were included. The pooled prevalence of glaucoma in nanophthalmos was estimated at 51.88% (95% CI: 33.33-70.43; I² = 88.57%). Meta-regression revealed that higher intraocular pressure (IOP) at presentation was significantly associated with increased glaucoma prevalence, while shorter axial length (AL) was inversely associated. Other biometric factors, such as anterior chamber depth, lens thickness, and spherical equivalent, were variably reported but commonly showed anatomical crowding. Acute angle-closure glaucoma emerged as the most frequently observed complication. No publication bias was detected. CONCLUSION: Over half of the eyes with nanophthalmos are affected by glaucoma, with elevated IOP and short axial length serving as major risk factors. These findings emphasize the need for early biometric screening, vigilant monitoring, and individualized anatomy-based management strategies to prevent irreversible vision loss among nanophthalmic patients. TRIAL REGISTRATION: International prospective register of systematic reviews (PROSPERO) - CRD42024522578.