To date, this is the only study that reports on the relationship between clinical signs, subjective symptoms, and the conformational state of lysozyme deposited on contact lenses. These results clearly suggest that there is a linear correlation between lysozyme activity recovered from contact lenses and subjective comfort, even over short periods of lens wear. Previous studies have shown that tolerant contact lens wearers have fewer symptoms of discomfort and a more stable tear film (as measured by a higher maximum forced interval between blinks, tear meniscus height and volume, and NITBUT).71 In the past, studies have also shown that the tear film of tolerant lens wearers showed lower levels and activity of secretory phospholipase A2, lower concentration of lipocalin, and lower levels of peroxidized lipids.47 It has also been shown that in the absence of lens wear, there were no differences between tolerant and intolerant lens wearers in conjunctival or limbal redness, lipid layer appearance, tear flow rate, tear film osmolality, and total protein, lactoferrin, lysozyme, or secretory immunoglobulin A concentrations in the tear film.71
A previous study by Lever et al. that investigated the relationship between total protein deposition and patient-rated lens comfort found that there was no statistical correlation between these two factors.62 This was the only study that attempted to determine the relationship between protein deposition on contact lenses and subjective comfort by quantifying the total protein deposited on lenses using biochemical techniques62; other studies estimated the relationship by evaluating the visible deposition/video image analysis of deposits on the lenses.4,63 – 66 Most studies that used visible deposition/video image analysis showed that there was an association between visible deposition and comfort4,64 – 66; however, one study that surveyed 50 comfortable and uncomfortable contact lens wearers did not show a difference in the amount of visible deposition on the lenses between the two groups.63 A recent study that looked at correlating clinical responses during contact lens wear with the amount of protein or cholesterol extracted from lenses after wear suggested that the quantity of protein that deposits onto contact lenses during wear may have more effect on lens performance on eye94; however, this study did not look at the conformational state of the protein deposited on these contact lenses. Furthermore, protein deposition has a significant potential to cause problems, as these deposits do play a significant role in modulating microbial adherence to lens materials.95,96 Therefore, it is important that practitioners advise their patients regarding the importance of lens disinfection and cleaning and appropriate lens replacement schedules.
This study is the first to demonstrate that a significant correlation exists between subjective comfort and active lysozyme recovered from etafilcon lens materials, even over short periods of lens wear. However, these results should be interpreted with caution, as it would be erroneous to conclude that denatured lysozyme on contact lenses is solely responsible for the symptoms experienced by symptomatic contact lens wearers. Rather, they should be interpreted as lysozyme deposited on the contact lenses of symptomatic lens wearers tends to denature more than that seen in asymptomatic lens wearers. This is likely to happen because of the biochemical changes that occur in the tear film of symptomatic lens wearers,71,76 resulting in altered properties of the lens material, potentially leading to a change in the conformational state of the deposited lysozyme. Therefore, in addition to the other factors mentioned earlier, the conformational state of the deposited protein, inflammatory and subinflammatory mediators, and the secretomotor response of the lacrimal system could also be significant factors in contact lens-induced dry eye, reiterating that this condition is multifactorial.
In conclusion, the results from this study suggest that even over a short period of contact lens wear, a significant correlation exists between subjective symptoms of comfort and dryness and the activity of lysozyme recovered from etafilcon contact lenses, with little correlation being shown with total amounts of either total protein or total lysozyme. Therefore, in addition to investigating the total quantity of the deposited protein, it is of significant clinical relevance to study the conformational state of the deposited protein. These results have tremendous implications, in that the novel contact lens materials that are being developed should possess properties that can retain the activity of the deposited protein, in addition to being deposit resistant. Care regimens and multipurpose solutions should be capable of removing denatured proteins that are deposited on the lens materials or be manufactured to maintain protein activity at the material surface.
Further work is required to determine whether this important clinical finding is transferable to those patients who use silicone hydrogel lens materials. It would also be of interest to determine whether there is a difference in the activity of lysozyme recovered from the tears of symptomatic and asymptomatic contact lens wearers. Although it is interesting to note that a significant correlation exists between the conformational state of the deposited protein and clinical symptoms, further studies with a better sample size and validated instruments that clearly identify symptomatic and asymptomatic groups are warranted. In addition to determining the activity of lysozyme, it would also be of interest to determine the activity of lactoferrin and other tear proteins with high cationicity, such as the defensin peptides.
Lakshman N. Subbaraman
This work was funded by a Collaborative Research and Development Grant from Natural Sciences and Engineering Research Council of Canada (NSERC) and Alcon Research Limited, U.S.
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