Corneal epithelial dendritic cell density in the healthy human cornea: A meta-analysis of in-vivo confocal microscopy data

Purpose: Numerous studies have reported a wide range of corneal epithelial dendritic cells (CEDC) density using in-vivo confocal microscopy in healthy participants. It is necessary to establish normal CEDC values for healthy corneas to enable differentiation from pathological corneas. This meta-analysis aimed to establish CEDC density and distribution and examine their relationship with age and sex. Methods: A systematic review of the literature of studies using the Heidelberg Retinal Tomograph with Rostock Corneal Module and reporting CEDC density in healthy subjects up to December 2018 was conducted via Medline, Google Scholar, Scopus, PubMed, Embase and Cochrane library. A random effect modeling approach was used to obtain the results of meta-analysis and meta-regression was conducted to estimate the effect of age and sex. Results: 38 studies reported central and 9 reported peripheral inferior CEDC density of 1203 participants (mean age 46.0 +/- 12.2, range 18-81 years). CEDC density in the central and peripheral inferior cornea was 26.4 +/- 13.6 cells/mm(2) (95% CI:22.5-26.8) and 74.9 +/- 22.7 cells/mm(2) (95%CI:59.8-90.0), respectively. No effect of age was found on central CEDC density (p = 0.63); whereas peripheral CEDC density decreased with increasing age (p = 0.02). CEDC density was not influenced by sex at either location (p > 0.48). Conclusion: This study established that the density at the peripheral inferior cornea is three-fold higher than at the central cornea. Peripheral but not central CEDC density decreased with increasing age. There are limited studies in youth (< 18 years), precluding a more detailed analysis. Sex does not appear to be a significant factor in CEDC density.