Maternal Ocular Immunometabolism during Pregnancy: A Systematic Review of Metabolic-immune Reprogramming and Its Translational Implications for Ophthalmic Disease

Abstract

Pregnancy represents a uniquely dynamic biological state characterized by extensive immune adaptation and metabolic restructuring, processes that are essential for maternal–fetal tolerance and successful gestation. Although these systemic changes have traditionally been examined within obstetric and immunologic contexts, their potential implications for ocular physiology and disease behavior have received comparatively limited attention. In clinical practice, this disconnect is not uncommon; ocular manifestations are often interpreted as isolated events even when they emerge in the setting of profound systemic change. The present systematic review aimed to examine the emerging concept of maternal ocular immunometabolism and to synthesize current evidence linking pregnancy-associated metabolic–immune reprogramming with ophthalmic alterations and disease outcomes. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations using major electronic databases and predefined eligibility criteria. Thirty-one studies were ultimately included for qualitative synthesis following structured screening, full-text assessment, and risk-of-bias evaluation. Available evidence suggests that pregnancy-induced immunometabolic adaptation may influence several ophthalmic pathways through coordinated alterations in cytokine signaling, immune-cell phenotypes, glucose metabolism, oxidative stress, and endothelial function. These changes appear to contribute to variations in uveitis activity, diabetic retinopathy progression, retinal vascular instability, and neuroinflammatory responses, although the strength and consistency of evidence remain variable across disease categories. Taken together, the literature suggests that the eye may reflect broader maternal biological adaptation during pregnancy rather than function as an isolated organ system. Further prospective studies integrating immunologic, metabolic, and ophthalmic biomarkers are needed to establish clinically applicable predictive frameworks for maternal–fetal care.