Normative database for corneal backscatter analysis by in vivo confocal microscopy

Toine Hillenaar, Roger H H Cals, Paul H C Eilers, René J Wubbels, Hugo van Cleynenbreugel, Lies Remeijer

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: To ascertain the sex and age relatedness, diurnal variation, and repeatability of backscatter measurement in the normal human cornea.

METHODS: Seven corneal backscatter variants were measured by in vivo confocal microscopy (IVCM) in both normal eyes (n = 314) of 157 healthy subjects. These subjects were assigned to one or more of three groups. The sex and age relatedness of corneal backscatter were assessed in group 1 (n = 300), which comprised 75 men and 75 women evenly distributed over five age categories. To assess diurnal variation, eyes in group 2 (n = 40) were measured four times a day, at 3-hour intervals. The eyes in group 3 (n = 50) were examined four times a year to determine intersession repeatability. Intrasession repeatability was determined by performing all IVCM examinations in duplicate. Linear mixed models were used to assess the effects of sex, age, and time of measurement on corneal backscatter.

RESULTS: Mean corneal backscatter was 3.5% higher in men (P = 0.003). From the age of 50 years, backscatter increased significantly in the anterior stroma (P = 0.0003). A small but statistically significant diurnal variation was found in all seven backscatter variants (P < 0.01). The test-retest coefficient of variation of mean corneal backscatter was 5.3%, comprising intra- and intersession repeatability.

CONCLUSIONS: Sex and time of measurement significantly affect corneal backscatter measured by IVCM, whereas age affects only backscatter in the anterior stroma. All three factors should be taken into account when conducting scientific research. For ophthalmic practice, the authors suggest ignoring these factors and propose a generalized normal range and minimum detectable change for each backscatter variant.

Original languageEnglish
Pages (from-to)7274-81
Number of pages8
JournalInvestigative ophthalmology & visual science
Issue number10
Publication statusPublished - 21 Sept 2011


  • Adult
  • Age Factors
  • Aged
  • Circadian Rhythm/physiology
  • Cornea/chemistry
  • Cross-Sectional Studies
  • Databases, Factual
  • Female
  • Humans
  • Light
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Reference Values
  • Reproducibility of Results
  • Scattering, Radiation
  • Sex Factors
  • Time Factors
  • Young Adult


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