How normal is the transparent cornea? Effects of aging on corneal morphology

Toine Hillenaar, Hugo van Cleynenbreugel, Lies Remeijer

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: To ascertain the effects of aging on corneal morphology and to illustrate the morphologic diversity of the different layers in the normal cornea as seen by in vivo confocal microscopy (IVCM).

DESIGN: Observational cross-sectional study.

PARTICIPANTS: A total of 150 healthy subjects, evenly distributed over 5 age categories, comprising 75 men and 75 women.

METHODS: Both transparent corneas (n = 300) of all subjects were examined in duplicate by white light IVCM (Confoscan 4, NIDEK Technologies, Albignasego, Padova, Italy). After reviewing the IVCM examinations for morphologic variations of the corneal layers, we selected the 8 most common features to illustrate the morphologic diversity. Subsequently, all 600 IVCM examinations were assessed for the presence of these features. We used binary logistic regression analyses to assess the age-relatedness of each feature.

MAIN OUTCOME MEASURES: Age distribution of bright superficial epithelial cells, dendriform cells, alterations characteristic of epithelial basement membrane dystrophy (EBMD), tortuous stromal nerves, stromal microdots in the anterior stroma, folds in the posterior stroma, opacification of Descemet's membrane, and corneal guttae.

RESULTS: Four features were found characteristic of the aging cornea: stromal microdots in the anterior stroma (P<0.0001), folds in the posterior stroma (P<0.0001), opacification of Descemet's membrane (P<0.0001), and corneal guttae (P<0.0001). Alterations characteristic of EBMD were found in 3% of all eyes and only detected in subjects aged ≥40 years, suggesting age-relatedness (P = 0.09). Other features, such as bright superficial epithelial cells (n = 38, 13%), dendriform cells (n = 42, 14%), and tortuous stromal nerves (n = 115, 38%), were age-independent. We also found a novel phenotype of corneal endothelium in 4 normal eyes of 2 subjects, which we coined "salt and pepper endothelium." We could not establish whether this novel phenotype represented a morphologic variant of normal endothelium, an early stage of a known corneal endothelial disorder, or a completely new disease entity.

CONCLUSIONS: Knowledge of the common morphologic variations of the corneal layers and the effects of aging on corneal morphology as seen by IVCM increases our understanding of corneal degenerative disorders and is essential to detect corneal pathology. Our finding of a novel phenotype of corneal endothelium emphasizes the morphologic diversity of this optically transparent tissue.

Original languageEnglish
Pages (from-to)241-8
Number of pages8
Issue number2
Publication statusPublished - Feb 2012


  • Adult
  • Aged
  • Aging/physiology
  • Cell Shape
  • Cell Size
  • Cornea/anatomy & histology
  • Corneal Stroma/anatomy & histology
  • Cross-Sectional Studies
  • Descemet Membrane/anatomy & histology
  • Female
  • Humans
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Ophthalmic Nerve/anatomy & histology
  • Young Adult


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