Primary intraocular lens implantation and secondary glaucoma after congenital and infantile cataract surgery: a systematic review of randomized and observational evidence

Background The association between primary intraocular lens (IOL) implantation and glaucoma after congenital or infantile cataract surgery remains uncertain. In this study, we compared randomized and observational evidence to assess glaucoma outcomes after primary IOL implantation vs. initial aphakia. Methods Five databases were searched for studies published from January 1999 to 8 August 2026. Randomized trials formed the primary synthesis, taking into account one eye per child; observational cohorts and matched case–control evidence were evaluated separately. Random-effects odds ratios (ORs) were estimated via Paule–Mandel variance estimation and Hartung–Knapp confidence intervals (CIs). The risk of bias and evidence certainty were assessed based on the study design. Exploratory analyses examined baseline comparability, follow-up, and outcome definitions. Results Twenty-one studies were included: three randomized trials, 17 cohort studies, and one nested case–control study. The trials included 228 children and yielded an OR of 1.01 (95% CI, 0.31–3.24; low-certainty evidence). Fifteen cohort studies with events yielded an unadjusted OR of 0.15 (95% CI, 0.06–0.36; I 2 = 73.4%; very-low-certainty evidence). Two additional cohort studies reported no glaucoma events in either group. A five-study analysis combining the trials with observational comparisons selected for greater baseline comparability yielded an OR of 1.09 (95% CI, 0.69–1.74). Confounding by surgical age, ocular anatomy, and treatment selection was a major limitation of the observational evidence. Conclusions Randomized evidence remains compatible with clinically important benefit or harm from primary IOL implantation. The lower glaucoma odds observed in cohorts differ from the randomized findings and require interpretation in the context of baseline imbalance and heterogeneous follow-up. Therefore, glaucoma prevention alone is an insufficient basis for selecting primary IOL implantation. Systematic Review Registration https://osf.io/r86hv/ , Identifier: 10.17605/OSF.IO/R86HV