March 2015
Volume 56, Issue 3
Free
Letters to the Editor  |   March 2015
Author Response: More to Stable Tears Than Thickness of the Lipid Layer
Author Affiliations & Notes
  • P. Ewen King-Smith
    College of Optometry, The Ohio State University, Columbus, Ohio, United States; and
  • Richard J. Braun
    Department of Mathematical Sciences, University of Delaware, Newark, Delaware, United States.
Investigative Ophthalmology & Visual Science March 2015, Vol.56, 1602. doi:10.1167/iovs.15-16607
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      P. Ewen King-Smith, Richard J. Braun; Author Response: More to Stable Tears Than Thickness of the Lipid Layer. Invest. Ophthalmol. Vis. Sci. 2015;56(3):1602. doi: 10.1167/iovs.15-16607.

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      © ARVO (1962-2015); The Authors (2016-present)

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We are in general agreement with the thoughtful discussion of Fenner and Tong1 about how tear film breakup is dependent on factors other than reduced thickness of the lipid layer. Our paper2 showed that while breakup patterns are usually associated with corresponding patterns in the lipid layer, the lipid was sometimes not obviously thinner in the breakup region (Fig. 8) or may even have appeared to be thicker (Fig. 9). An interpretation of these results is that the structure and/or composition of the local lipid layer was defective, causing excessive evaporation and rapid tear film thinning and breakup. However, it should be noted that breakup was sometimes associated with regions of thin lipid—Figures 6 and 7. Thus our findings indicate that breakup is sometimes associated with thin lipid and sometimes with abnormal lipid that is not particularly thin. 
We note that Fenner and Tong1 found no significant correlation between tear film breakup time and lipid thickness in their study. We have performed a similar study on 95 subjects, 42 of whom were classified as dry eye by the Ocular Surface Disease Index questionnaire. Central lipid thickness was determined using a previously described method3 followed by fluorescein breakup time measurement. We found a significant but weak correlation, Spearman R = 0.233, P = 0.025. The difference in statistical significance between Fenner and Tong's result and ours may be related to a difference in the study population and also to sampling variance. The two studies are in agreement that the correlation between breakup time and lipid thickness is weak at best. 
Despite this poor correlation, we would still maintain that a major factor in tear film breakup is increased evaporation through a defective lipid layer, either because the layer is too thin or because of abnormal structure and composition. We have summarized evidence that the normal lipid layer is a good barrier to evaporation, and that a defective lipid layer causes increased evaporation leading to rapid tear film thinning between blinks and contributing to breakup.4 
To understand the role of the lipid layer in reducing evaporation, two types of study deserve emphasizing. First, La Mer and colleagues5,6 have shown that high evaporation resistance in monolayers of lipids such as fatty acids, alcohols, and esters requires very long, saturated hydrocarbon chains. Second, X-ray studies of meibum show the presence of multiple (stacked) lamellae of thickness approximately either 5 or 11 nm.7 Based on these and other studies, we have proposed a model of the tear film lipid layer containing lamellae having cores of very long, saturated chains that are the basis of evaporation resistance.8 In evaporative dry eye, we propose that excessive evaporation will occur when these lamellae are disrupted and not continuous. This disruption could be caused by abnormal composition of the lipid layer, but would also be more likely to occur when the lipid layer is thin so that there may be insufficient lipid in some areas to form at least one continuous lamella. Measurements of tear film thinning rate (largely due to evaporation) as a function of lipid thickness are consistent with these ideas. When the lipid layer was very thin, for example, less than 24 nm, the thinning rate was usually found to be rapid, but the thinning rate was usually slow for relatively thick lipid layers, for example, over 30 nm.3 However, it is notable that one subject with a relatively thick lipid layer of 85 nm also had a rapid thinning rate, probably indicating a defect in lipid layer composition and/or structure. 
In conclusion, there are number of possible reasons why the correlation between breakup time and lipid thickness is poor. As discussed above, evaporation rate may depend not only on lipid thickness but also on lipid composition and/or structure. Additionally, tear film breakup is a subjective (and poorly defined) measure that does not take into account the area of breakup and its development.9 The lipid thickness and breakup measurements were performed at different times and may correspond to different areas of the tear film. Apart from evaporation, other factors may contribute to breakup, including thinning at the black line near the meniscus,10 elevations on the corneal surface, and droplets in the lipid layer.11 
References
Fenner BJ Tong L. More to stable tears than thickness of the tear film lipid layer. Invest Ophthalmol Vis Sci. 2015; 56: 1601. [CrossRef] [PubMed]
King-Smith PE Reuter KS Braun RJ Nichols JJ Nichols KK. Tear film breakup and structure studied by simultaneous video recording of fluorescence and tear film lipid layer images. Invest Ophthalmol Vis Sci. 2013; 54: 4900–4909. [CrossRef] [PubMed]
King-Smith PE Hinel EA Nichols JJ. Application of a novel interferometric method to investigate the relation between lipid layer thickness and tear film thinning. Invest Ophthalmol Vis Sci. 2010; 51: 2418–2423. [CrossRef] [PubMed]
Braun RJ King-Smith PE Begley CG Li L Gewecke NR. Dynamics and function of the tear film in relation to the blink cycle. Prog Retin Eye Res. 2015; 45: 132–164. [CrossRef]
Archer RJ La Mer VK. The rate of evaporation of water through fatty acid monolayers. J Phys Chem. 1955; 59: 200–208. [CrossRef]
Rosano HL La Mer VK. The rate of evaporation of water through monolayers of esters, acids and alcohols. J Phys Chem. 1956; 60: 348–353. [CrossRef]
Leiske DL Leiske CI Leiske DR Temperature-induced transitions in the structure and interfacial rheology of human meibum. Biophys J. 2012; 102: 369–376. [CrossRef] [PubMed]
King-Smith PE Bailey MD Braun RJ. Four characteristics and a model of an effective tear film lipid layer (TFLL). Ocul Surf. 2013; 11: 236–245. [CrossRef] [PubMed]
Liu H Begley CG Chalmers R Wilson G Srinivas SP Wilkinson JA. Temporal progression and spatial repeatability of tear breakup. Optom Vis Sci. 2006; 83: 723–730. [CrossRef] [PubMed]
Korb DR Herman JP. Corneal staining subsequent to sequential fluorescein instillations. J Am Optom Assoc. 979; 50: 361–367.
King-Smith PE Nichols JJ Nichols KK Fink BA Braun RJ. Contributions of evaporation and other mechanisms to tear film thinning and break-up. Optom Vis Sci. 2008; 85: 623–630. [CrossRef]
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