SUMMARY:
UCLA researchers in the Department of Ophthalmology have identified novel in vivo biomarkers of limbal stem cell function to accurately diagnose and stage limbal stem cell deficiency.
BACKGROUND:
The cornea, which is the main part of the eye that is responsible for the production of clear vision, is protected from microbes and fluids by the corneal epithelium. Made up of several layers of cells, the corneal epithelium is constantly renewed by limbal stem cells that regenerate every 3 to 10 days. In limbal stem cell deficiency (LSCD), these limbal stem cells have a reduced ability to repopulate. Without proper function of limbal stem cells, the corneal epithelium cannot be repaired or renewed and results in loss of corneal clarity, potential loss of vision, and chronic ocular pain. While the incidence of LSCD is not well understood, its occurrence is associated with a variety of conditions, including UV radiation, multiple surgeries, and contact lens wear. The diagnosis for LSCD has largely been made based on medical history and clinical signs, which can lead to late or inaccurate diagnoses. Currently, impression cytology is the standard diagnostic test for LSCD; however, its accuracy is sensitive to many factors during sample collection. Thus, new quantitative assessments for the diagnosis and staging of LSCD are needed to improve treatment plans and outcomes for patients.
INNOVATION:
UCLA researchers led by Dr. Sophie Deng in the Department of Opthalmology have developed a comprehensive grading formula combining in vivo biomarkers and clinical presentation to accurately diagnose LSCD and its stage of severity. The proposed staging system utilizes in vivo laser scanning confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) to evaluate corneal morphological changes in LSCD patients. Using images taken from 126 subjects with LCSD and 67 control subjects, the researchers analyzed 29 in vivo parameters and found that the clinical subscore in LCSD eyes had a very strong negative correlation with 3 parameters in particular. With further rank correlation analysis, the researchers gave each parameter a specific weight to arrive at a formula that provides more accurate and reliable staging of LSCD. They demonstrated this grading formula in two clinical cases. This novel diagnostic assessment could help guide decision making for surgical intervention and outcome measures in LSCD patients.
POTENTIAL APPLICATIONS:
• Diagnostic and grading tool for limbal stem cell deficiency
ADVANTAGES:
• Proposed quantitative assessment can measure changes in corneal epithelium parameters that precede clinical manifestations
• AS-OCT is a widely available tool used by ophthalmologists
DEVELOPMENT-TO-DATE:
The researchers have demonstrated successful use of their grading formula on 2 LSCD patients.
Related Papers (from the inventors only):
1. Chan, E. H., Chen, L., Rao, J. Y., Yu, F., & Deng, S. X. Limbal Basal Cell Density Decreases in Limbal Stem Cell Deficiency. American journal of ophthalmology, 2015. 160(4), 678–84.e4
2. Chuephanich P, Supiyaphun C, Aravena C, Bozkurt TK, Yu F, Deng SX. Characterization of the Corneal Subbasal Nerve Plexus in Limbal Stem Cell Deficiency. Cornea. 2017. 36(3):347-352.
3. Le, Q., Cordova, D., Xu, J., & Deng, S. X. In Vivo Evaluation of the Limbus Using Anterior Segment Optical Coherence Tomography. Translational vision science & technology, 2018. 7(4), 12.
4. Liang, Q., Le, Q., Cordova, D. W., Tseng, C. H., & Deng, S. X. Corneal Epithelial Thickness Measured Using Anterior Segment Optical Coherence Tomography as a Diagnostic Parameter for Limbal Stem Cell Deficiency. American journal of ophthalmology, 2020. 216, 132–139.