Best combination of MG criteria was the combination of UL and LL MG loss (AUC = 0.929, p = 0.001). The observed power calculated after study completion was (1 − β > 80%).
The area of dropped-out glands was significantly smaller in the UL than of the LL. This is in accordance to the findings of McCann et al.5 However, this group did not found these differences being significant when counting the number of dropped-out glands. Because the number of glands are different between the lids even in normal subjects,19 the computerized measurement of the area of MG drop out might be the better approach as it takes into account the area measured and density of gland within that area.
The MG of the LL was significantly wider than of the UL, which might be due to having less physical space because number of glands is higher in the UL. Interestingly, this is represented by a sketch of MG of Heinrich Meibom in the year 1666, shown in a publication of Knop and coworkers.20 The glands of the UL were more bent than those of the LL, which might be a more anatomical issue than a consequence of any dysfunction of these glands.
However, even though MG morphology between lids were significant different, there was significant relations between the lids in MG loss and bent angle but not in MG thickness. So any change in MG loss and bent angle of one lid should be recognizable in other lid too (LL <> UL).
MG loss of both lids is significantly correlated to lipid layer thickness and NIBUT, but only bent angle and width of the UL glands were significantly correlated to NIBUT. However, correlations between MG morphology and the tear film appears to be reasonable because MGD results in quantitative and/or qualitative changes of the lipid layer.1 The lipid layer protects the tear film aqueous against evaporation and helps stabilize the entire tear film.21
Loss of MGs was moderately related to age, which is assumed to be a risk factor for MGD.13,22–25 MG loss observed by meibography might indicate gland atrophy.1,26 Gland atrophy is assumed to be the result of long-term effects of MGD.1,26 As MGD progresses, increased viscosity of the meibomian oil in the gland and/or hyperkeratinization of the gland ductus and orifices results in gland obstruction, stasis, and increased pressure in the gland, with dilation of glands followed by an atrophy of the gland acini.1,26 However, in terms of age, MG loss might be a result of chronic MGD and/or be secondary to other age-related biological effects such as the well-known decline in production of sex-steroid hormones or some other mechanism, all of which have to be determined in larger epidemiological studies.23
Significant correlations between MG morphology and dry eye scores were shown in this study. Additional to the correlations between MG loss of both lids and the OSDI, the LL's MG bent angle and the UL's MG thickness were significantly correlated to OSDI scores.
To assess the ability of the MG morphology to discriminate between normal and dry eye, this cohort of subjects were grouped into OSDI±. Even though some relations between MG morphology and tear film or OSDI were analyzed in this study, only MG loss was able to discriminate between normal and dry eye, when grouped by the OSDI. The median OSDI scores of the dry eye group of 22.5 represents a moderate to severe dry eye.18
Analyzing the best MG morphology criteria combination by regression analysis of the UL or LL always resulted in the need for all criteria (MG loss, bent angle, and thickness). However, the predictive ability of the OSDI was better when using MG loss of the UL or LL or combining both.
Even though it might be obvious to consider gland thickness, gland bending, and changes in the tear film as obvious MGD signs, the greatest association with dry eye was drop out of MG in this cohort. Only a minimal loss of 16.9% of the UL MG and 28.7% of the LL was the threshold to predict dry eye. According to Nichols et al.,10 the cutoff value of 16.9% would be a grade 2, 28.7%, a grade 3 (grade 1 = no partial glands; grade 2 = <25% partial glands; grade 3 = between 25 and 75% partial glands; and grade 4 = >75% partial glands). Transforming our data to the Arita scale9 both 16.9 and 28.7% would be a grade 1 (grade 0 = no loss of MG; grade 1 = area loss was less than one third of the MG area; grade 2 = area loss between one third and two thirds; and grade 3 = area loss more than two thirds). This might signal the importance of computerized grading, because these cutoff values might be not detectable in subjective grading using the published four-grade grading scales.9,10
MG morphology between UL and LL are significantly different but correlated, except MG thickness. The cutoff value of MGD loss to discriminate between OSDI+ and OSDI− was 16.9% at the UL and 28.7% at the LL. The additional MG criteria bent angle and thickness showed only some relations to symptoms and tear film and even though they might be caused by stasis in the MG, the impact on tear film and dry eye appears to be negligible. MG loss showed significant correlation to the tear film, whereas these correlations were better for the UL's MG loss than for the LL. Combining MG loss of the UL and LL improves predictive ability of dry eye.
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