Advanced Diagnosis of Corneal Endothelial Dysfunction

Abstract

The corneal endothelium plays a vital role in maintaining corneal transparency through fluid homeostasis, which is regulated by the tight junctions and the activity of the Na⁺/K⁺-ATPase pump. As the endothelium is not regenerable, the loss of endothelial cells due to aging, trauma or dystrophies such as Fuchs’ endothelial corneal dystrophy (FECD) can lead to corneal edema and progressive visual impairment. Conventional methods such as slit-lamp biomicroscopy and clinical grading remain essential in advanced stages, but are limited in early detection. This review emphasizes the value of multimodal imaging in the detection of subclinical dysfunction. Specular and confocal microscopy allow quantitative assessment of endothelial cell density and morphology. Spatial thickness measurements, such as corneal thickness spatial profile (CTSP) and percent thickness increase (PTI), raise diagnostic specificity beyond traditional central corneal thickness (CCT). Scheimpflug tomography enables early detection of subtle morphologic changes, such as isopachal irregularities, posterior surface depressions, and the “camel sign” in densitometry. Optical coherence tomography of the anterior segment (AS-OCT) refines the diagnosis by correlating the reflectance patterns with the integrity of the endothelium. Biomechanical evaluation of the cornea with Corvis ST adds dynamic parameters such as applanation times, deformation amplitude and concavity radius, which vary depending on the stage of the disease. The genetic basis of endothelial dystrophies is also addressed, highlighting important loci and genes such as TCF4, COL8A2 and SLC4A11, which have been implicated in autosomal dominant and complex inheritance patterns. These findings emphasize the importance of molecular diagnostics and point to future therapeutic targets. In summary, a comprehensive diagnostic strategy that combines structural imaging, functional assessment and genetic analysis supports early detection, improves preoperative risk assessment — especially in cataract and keratoplasty planning — and could benefit from integration with artificial intelligence for predictive modelling and clinical decision making in the future.