Refining How We Diagnose and Classify Limbal Stem Cell deficiency

Refining how we diagnose and classify limbal stem cell deficiency.

With the development of multimodal anterior segment imaging modalities and molecular diagnostic tests for the diagnosis and staging of limbal stem cell deficiency (LSCD), and better understanding of LSCD presentation and pathophysiology, a comprehensive step-by-step algorithm is established to more precisely evaluate the ocular surface environment and stage the disease.

This is a review of the most relevant publications on the method of diagnosing and staging LSCD. Clinical presentation and pathophysiology of LSCD were reviewed. Factors that impact LSC function and survival were discussed and outlined.

The International LSCD Working Group has put forth the first guidelines on the definition, classification, diagnosis, staging, and management of LSCD. Precise diagnosis and staging of LSCD is limited by subjective nature of the fluorescein staining test. As other comorbidities negatively impact the function of both corneal epithelial cells and LSCs, assessment of these comorbidities such as dry eye disease, ocular surface inflammation, corneal innervation, conjunctival health, medication toxicity, and eyelid abnormalities should be included in the initial evaluation of LSC function. Advances in anterior segment imaging, including anterior segment optical coherence tomography and in vivo confocal microscopy allow objective evaluation of epithelial phenotype, cellular morphology, basal cell density, corneal innervation, and inflammatory cell infiltration in both the cornea and limbus. The knowledge of ocular surface microstructure provides important information regarding the corneal and limbal epithelial cell function, remaining LSC reserve, and factors associated with LSCD improvement after all comorbidities are treated. Impression cytology remains a valuable tool for objectively confirming conjunctivalization through assessment of epithelial phenotype.

LSCD diagnosis and classification have advanced beyond the simple fluorescein staining test for the detection of abnormal epithelial cells on the corneal surface. A comprehensive assessment of the LSC function and the ocular surface environment by integrating multimodal imaging and molecular testing enables precise staging of LSC function and identification of factors that influence LSCD reversibility. Adoption of a standardized multimodal diagnostic framework will improve diagnostic accuracy, guide the management of the disease, facilitate comparisons across clinical studies, and support the development and evaluation of emerging cell-based and cell-free regenerative therapies for LSCD.