Diagnostic age- and sex-adjusted reference intervals of Meibomian gland morphological features

To establish reference intervals of Meibomian gland (MG) characteristics in healthy participants, and to classify meibography images of evaporative type dry eye disease (DED) subjects according to the determined reference intervals.

Prospective study including healthy and evaporative type DED subjects. Upper eyelid meibography images were analyzed to evaluate: MG length, minimal distance between endpoints, tortuosity, width, MG shortening area, deviation from a vertical orientation, number of linear segments, MG global area, and number of MGs. Reference intervals for MG characteristics were determined using generalized additive models for location, scale, and shape (GAMLSS). Participants with evaporative type DED were classified as normal or non-normal based on the reference intervals. Clinical features were compared between groups using Student's t test or Mann-Whitney U test.

Participants were 156 healthy individuals (50.6 % males; mean age 44 years) and 39 individuals with evaporative type DED (74.4 % women; mean age 62 years). MG length, minimal distance between endpoints, tortuosity, and width, depended on age but not on sex. MG shortening area depended on age and sex. Neither age nor sex affected the deviation from a vertical orientation, number of linear segments, MG global area, and number of MGs. Furthermore, 66.7 % of the participants in the evaporative type DED group were classified as normal (all the MG characteristics fell within the corresponding reference intervals). A significantly higher value was observed in the non-normal group in OSDI (P = 0.034) and meibum expressibility (P = 0.041, indicative of poor expressibility).

Reference intervals values may be useful in classifying meibography images as normal or non-normal, thus aiding in the objective diagnosis of morphological alterations of MGs.