Pediatric phenylketonuria and the eye: Unveiling subclinical anterior segment changes

Phenylketonuria (PKU) is a rare autosomal recessive metabolic disorder classically associated with neurocognitive impairment if left untreated. Although the systemic effects of hyperphenylalaninemia are well-characterized, the ophthalmic implications, particularly anterior segment alterations in pediatric patients, have not been comprehensively addressed in recent literature. Earlier reports on ocular findings in PKU primarily focused on advanced complications such as cataracts, strabismus, or corneal opacities in adult or poorly managed cases.[1,2] However, little is known about subclinical anterior segment changes in children with early diagnosis and proper dietary control. This knowledge gap is increasingly important as these patients now live longer and may present for ocular interventions such as cataract or refractive surgery later in life. Emerging clinical observations suggest that pediatric patients with PKU may exhibit subtle but measurable alterations in corneal curvature and endothelial morphology.[3] Flatter keratometric values and lower hexagonality of corneal endothelial cells have been reported in this population, raising questions about the role of systemic oxidative stress and disrupted dopamine metabolism in ocular development.[3–5] Dopamine, synthesized from phenylalanine-derived tyrosine, is a key modulator of eye growth and emmetropization.[6] Altered dopaminergic signaling has been linked to both myopia and impaired visual function in PKU models, suggesting a plausible mechanistic pathway.[7] Oxidative stress, which is elevated in PKU due to impaired antioxidant defenses, may also contribute to endothelial cell damage, leading to morphological irregularities that are detectable through specular microscopy.[8,9] While these changes may not currently affect visual acuity or function, they might increase susceptibility to surgical complications or delayed corneal healing. The clinical relevance of such findings is underscored by the increasing life expectancy of individuals with PKU. As these patients age, ophthalmologists must be prepared to evaluate and manage anterior segment conditions with a tailored understanding of PKU-specific anatomical and biochemical alterations. Routine anterior segment imaging—such as corneal topography and specular microscopy—could be beneficial in long-term follow-up, especially for those being considered for intraocular procedures. Despite these observations, large-scale, prospective studies are needed to confirm whether these findings are disease-specific or incidental. The small sample sizes and variability in metabolic control among patients further complicate interpretation. Nonetheless, the convergence of metabolic, neurochemical, and structural changes in PKU presents a compelling area for interdisciplinary research. In conclusion, PKU may subtly affect anterior segment anatomy in pediatric patients, even under appropriate metabolic control. These ocular clues should prompt clinicians to adopt a more vigilant approach in long-term eye care for this unique population. Author contribution Manuscript editing and research were performed by Sevim Ayça Seyyar, Gizem Gürbostan Soysal. Data acquisition and research were performed by Duhan Hopurcuoğlu. Study design, research, and manuscript were performed by Sevim Ayça Seyyar. All authors read and approved the final manuscript.