Environmental Conditions and Tear Chemistry

Leo G. Carney

The tear film is of crucial importance in maintaining the integrity of the underlying ocular tissues. It is also directly exposed to an environment that is constantly varying. The ability of the tear fluid to contain the resultant changes in its characteristics within narrow confines contributes importantly to the health and function of those anterior ocular tissues.

One way in which the ocular environment is varied is by the application of a contact lens—tear chemistry can then certainly be affected. A second viewpoint within the present context is, however, that tear chemistry changes may produce contact lens changes. Both of these aspects will be briefly considered.

At the outset it should be said that tear changes from environmental effects are a multifaceted topic, and I will select just a few of the possible features, namely tear pH, buffering, proteins in general, and enzymes. Crucial topics such as sampling influences will be ignored.

TEAR pH

Perhaps the most distinctive feature of the literature on human tear pH is the broad spectrum of values it has come to contain. Even with the exclusions of extreme disease conditions, a span of about pH 5.2 to 8.6 remains. To account for this range, several fundamental questions might be explored: How different are individuals from one another? What variations might a given individual show? What is the effect of environmental challenges, including contact lens wear?

From many of our studies a population average of about pH 7.45 emerges. Tear pH is nevertheless a highly individualized function, both among subjects and even more particularly for a given subject at different times of the day.



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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Environmental Conditions and Tear Chemistry Leo G. Carney The tear film is of crucial importance in maintaining the integrity of the underlying ocular tissues. It is also directly exposed to an environment that is constantly varying. The ability of the tear fluid to contain the resultant changes in its characteristics within narrow confines contributes importantly to the health and function of those anterior ocular tissues. One way in which the ocular environment is varied is by the application of a contact lens—tear chemistry can then certainly be affected. A second viewpoint within the present context is, however, that tear chemistry changes may produce contact lens changes. Both of these aspects will be briefly considered. At the outset it should be said that tear changes from environmental effects are a multifaceted topic, and I will select just a few of the possible features, namely tear pH, buffering, proteins in general, and enzymes. Crucial topics such as sampling influences will be ignored. TEAR pH Perhaps the most distinctive feature of the literature on human tear pH is the broad spectrum of values it has come to contain. Even with the exclusions of extreme disease conditions, a span of about pH 5.2 to 8.6 remains. To account for this range, several fundamental questions might be explored: How different are individuals from one another? What variations might a given individual show? What is the effect of environmental challenges, including contact lens wear? From many of our studies a population average of about pH 7.45 emerges. Tear pH is nevertheless a highly individualized function, both among subjects and even more particularly for a given subject at different times of the day.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Tear pH tends to shift, on the average, in the alkaline direction as the day progresses. The slope is small, about 0.013 pH units/hour, but statistically significant. Although not perfectly reproducible from day to day, the majority do exhibit recurrent patterns of tear pH change. Such patterns differ considerably from patient to patient in their cycloid characteristics. A relevant feature here is the proneness for patients to have a more acid tear pH following prolonged eye closure, in this case at the end of a night's sleep. Since this more acid state is rarely sustained for more than an hour under normal open-eye conditions, it would appear to be related to a possible increase in acid by-products associated with the relatively anaerobic conditions during sleep. A continually shifting tear pH is thus a natural characteristic of the unfitted eye. How then does the wearing of contact lenses affect this property of tears? The possibility that contact lens might induce an acid shift in tears, say through acting as a reservoir for acid by-products of corneal metabolism, has been confirmed in some cases. However, there remains individuality in responses, and opposite pH shifts can be found. The differential long-term effects of routine hygiene and cleaning regimens are possible additional components to be considered. Lastly, does the added presence of a contact lens under prolonged eye-closure conditions (i.e., extended-wear situations) influence tear pH? Restricted periods of eye closure do have acid shifts associated with them, ultimately becoming similar in magnitude to those found during normal sleep. TEAR BUFFERING Fluctuations in normal tear pH do exist, therefore, but in a confined range. Tear fluid buffering is therefore important; this buffering is most often attributed to the bicarbonate system, but other mechanisms also likely contribute. Tear pH responses to incremental titrations with acid and base can be compared with pH responses of an unbuffered reference solution. The enhanced resistance of the nonaqueous tear components to the pH change is a measure of the magnitude of tear buffering. The buffering is more substantial in response to acid challenge than it is to challenge with base. The substantial buffering capacity indicated by the plateau in the responses in the tear pH range of 7.0 to 7.7 may be a reflection principally of the bicarbonate system. However, other buffering systems would be expected to contribute in tears just as in other biological fluids. The major nonbicarbonate buffer components would likely be the various protein fractions present in tears. These protein contributions may explain the subtle but measurable discontinuities in pH response. The pres-

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium ence of a unique pattern of protein constituents, and one that is subject to environmental influence, may be of significance in ultimately interpreting its overall pattern of pH response. Contact lens wearing can and does induce changes in this characteristic, but the considerable intersubject variations in both the form of the response curves and in the overall buffering capacity may, at this stage, be the more relevant and overriding influence. Details of the bicarbonate buffering system in tears are usually based on calculations and assumed constants. We have recently investigated this and have been able to establish the pH/pCO2 relationships for tears. This was done by equilibrating tears with gases of pCO2 tensions of 34.5, 69.0, and 82.8 mmHg and also later allowing exposure to room air. The results show that for a closed-eye tear pH value of 7.25 the pCO2 would be approximately 55 mmHg, much as would be expected. On the other hand, for an open-eye value of 7.45 the pCO2 would be approximately 25 mmHg, that is, tears in situ are not air equilibrated. This feature becomes even more relevant given the recent information on carbon dioxide accumulation beneath hydrogel contact lenses. ACID-BASE INFLUENCES ON CONTACT LENSES The role of tear fluid buffering in damping tear pH changes may also influence the success of contact lens wear. Tear fluid pH has been demonstrated to be important in protein adsorption onto hydrogel lenses. Additionally, it influences the water content and, hence, the oxygen permeability, dimensions, and fitting characteristics of some current hydrogel contact lenses. For example, the dehydration characteristics of hydrogel lenses under open- and closed-eye conditions can be used to demonstrate the effect. Medium-water-content lenses can display greater absolute decreases in water content than higher-water-content lenses, depending on the ionic nature of the polymer. This is at least in part a consequence of the pH of the environment. Diminishing the magnitude of tear pH shifts, particularly during the closed-eyelid phase of extended wear, protects the integrity of the contact lens and hence ultimately the cornea itself. TEAR ENZYMES Finally, I would like to look at quite a different aspect of tear chemistry: glycolytic enzymes and enzymes of the tricarboxylic acid cycle. These are known to be present in tear fluid. The source of these enzymes is not the lacrimal gland but rather the underlying ocular tissues. Thus, tear chemistry can reflect corneal and conjunctival biochemical responses to environmental stresses, including hypoxia and contact lens wear.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium An appropriate system to indicate the activity of the parent metabolic pathways is the determination of the ratio of two enzymes, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH), in the tears. The principal reason for monitoring the relative activities of two enzymes is to surmount the considerable variability in absolute enzyme levels resulting from the nonuiform dilution effect of reflex tears. It should in fact be possible to quantify the severity of metabolic stress by determining the magnitude of elevation in the tear LDH/MDH ratio. In the normal open-eye situation the tear LDH/MDH ratio is relatively constant. Overnight lid closure raises the ratio in an almost twofold increase. Shorter periods of lid closure (of 2, 4, and 6 hours' duration) cause an increase in the ratio that is a function of the period of stress. When various hypoxic environments are used, a significant correlation is found between the magnitude of elevation of the ratio and the severity of the hypoxia. However, environments with oxygen concentrations of 1 percent or less do cause disproportionately greater effects. Following wear of contact lenses, tear LDH and MDH activities are again altered, so the LDH/MDH ratio is elevated. The magnitude and time course of this elevation is influenced by contact lens type, fit, and duration of wear. The ratio changes in a way that would be predicted from the expected severity of hypoxic challenge. CONCLUSION In summary, the tear fluid is unique among body fluids because of its exposed situation. The subsequent environmental challenges do bring about changes in its characteristics, the tear chemistry role being to ensure that the health of the underlying tissues is sustained throughout. ACKNOWLEDGMENT Parts of the work described here were carried out with the collaboration of Richard M. Hill, Thomas F. Mauger, and Rod J. Fullard, whose contributions I am pleased to acknowledge.