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  • Cornea/External Disease

    An analysis of corneal epithelial cell and nerve fiber images identified possible age-related degenerative trends that could be useful in building a framework for differentiating pathologic changes from normal age-related ones.

    Study Design

    This cross-sectional, observational study reviewed corneal images from 281 eyes of 143 healthy participants in Singapore to investigate the effects of age on various corneal features. Individuals were divided into 6 age groups (20–29 years, 30–39 years, 40–49 years, 50–59 years, 60–69 years, and 70 years or older). Corneal nerves and epithelial cells were imaged using in vivo confocal microscopy (Heidelberg Engineering GmbH, Heidelberg, Germany). The mean values of 7 different corneal nerve parameters were calculated from the 25 best nerve images per eye, with means similarly calculated for 3 epithelial parameters using the 15 best epithelial images per eye.


    The mean age of the patients was 49.1 years, and 53.1% of these individuals were female. As age increased, corneal nerve fiber density and length decreased significantly, with a general declining trend seen across all parameters. Furthermore, increasing age was associated with a reduction in epithelial cell circularity, density, and size.


    Limitations of this study include an absence of data on the underlying mechanism for these age-associated findings. Secondly, the authors did not assess clinical features associated with these age-related changes. Finally, there was no investigation into other races or ethnicities for the possible effect of these parameters on the observed associations.

    Clinical Significance

    Age-related changes in corneal nerves and epithelial cells should be taken into consideration when managing patients with corneal neuropathy or epithelial disease. With validation, especially among larger and more diverse cohorts, these findings may allow clinicians to better differentiate the effects of aging from pathological changes. Defining age-adjusted cutoffs for corneal nerve and epithelial metrics will help delineate screening protocols.

    Financial Disclosures: Dr. Zeba Syed discloses financial relationships with Bio-Tissue, Recordati Rare Diseases (Consultant/Advisor, Lecture Fees/Speakers Bureau); Dompe, Glaukos Corporation (Grant Support); Tarsus Pharmaceuticals (Lecture Fees/Speakers Bureau).