Ocular surface pathology and the liver‑eye axis; ophthalmological manifestations as early potential clinical indicators of chronic liver disease: A scoping review

Dry eye disease (DED) has traditionally been considered a local disorder of the ocular surface. However, accumulated evidence indicates that DED often reflects systemic metabolic, immune and neurosensory disorders. In recent years, interest has grown in interorgan interactions, particularly the ‘liver‑ocular surface’ axis, given the central role of the liver in regulating lipid metabolism, vitamin metabolism, systemic inflammation and immune tolerance. The aim of the present scoping review was to summarize and structure published data on ocular manifestations of various forms of chronic liver disease, analyze key pathogenetic mechanisms of the ‘liver‑ocular surface’ axis, identify gaps in the evidence base, and evaluate the clinically oriented ‘ophthalmology‑first’ concept, wherein atypical or refractory DED may precede the diagnosis of liver pathology. The present scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses extension for Scoping Reviews recommendations. Only peer‑reviewed publications from ophthalmology, hepatology and interdisciplinary journals addressing the epidemiology, pathogenesis and clinical phenotypes of DED in liver diseases were included. A meta‑analysis was not planned due to significant heterogeneity in study designs, populations and ophthalmological outcomes. It was established that chronic liver diseases can affect the ocular surface through several interconnected pathogenetic mechanisms, including impaired vitamin A metabolism, systemic inflammation and immune dysregulation, dyslipidemia with meibomian gland dysfunction, and neurosensory disorders. These mechanisms are closely associated with specific clinical phenotypes of DED, often characterized by atypical or refractory course, the disproportionate severity of objective changes and reduced corneal sensitivity. DED should be viewed not only as a local ophthalmological pathology, but also as a potential indicator of systemic disorders, including subclinical liver dysfunction. The ‘ophthalmology‑first’ concept emphasizes the diagnostic role of the ophthalmologist in the early detection of chronic liver diseases and justifies the need for an interdisciplinary approach in managing patients with severe and atypical forms of DED.