Phenylalanine-associated ocular risk stratification in early-treated children with phenylketonuria: a cross-sectional study

Purpose Although phenylketonuria (PKU) is primarily recognized for its neurological sequelae, the extent and metabolic correlates of ocular involvement in early-treated pediatric patients remain insufficiently characterized. This study aimed to evaluate ocular findings in children with PKU and to examine their association with serum phenylalanine levels, with particular focus on quantitative risk stratification. Methods This cross-sectional study included 33 children less than 18 years diagnosed with phenylketonuria (PKU) by neonatal or selective screening and receiving regular follow-up at the Metabolic unit of Mansoura University Children’s Hospital, after obtaining informed parental consent. All participants underwent a comprehensive ophthalmological evaluation, including visual acuity assessment, cycloplegic refraction, anterior segment examination, fundus evaluation, intraocular pressure measurement, and ocular motility assessment. Serum phenylalanine levels were recorded, and receiver operating characteristic (ROC) curve analyses were performed to explore phenylalanine thresholds associated with ocular abnormalities. Results Ocular abnormalities were observed in a substantial proportion of participants and involved both anterior and posterior segments. Higher serum phenylalanine levels were significantly associated with increased likelihood of ocular involvement. ROC analysis identified phenylalanine ranges associated with elevated ocular risk, providing a quantitative framework for metabolic risk stratification.. Conclusion Ocular abnormalities may occur in early-treated children with PKU and appear to be associated with phenylalanine control. Quantitative phenylalanine thresholds identified through ROC analysis may support risk-stratified ophthalmic surveillance strategies in pediatric PKU.