Mechanism of Contact Lens-related Dry Eye

Because dry eye is so prevalent among contact lens wearers, eyecare practitioners must stay up to date with the latest research and the newest products. Here�s where we stand today.

By Jason J. Nichols, OD, MPH, PhD, FAAO

Dry eye disease seems ubiquitous these days. Some 12 to 15 million Americans who don�t wear contact lenses have dry eye symptoms, and as many as 50% of contact lens wearers suffer from this condition as well.¹

The scientific and clinical understanding of tear film physiology and its relationship to dry eye disease is continually changing as research into the etiology and disease course advances and as manufacturers introduce new targeted therapies. These new directions in research, understanding and product development can leave our heads spinning.

In the contact lens field, terms such as wettability, lubriciousness, friction, modulus and tribology are being used frequently to characterize new polymers and their corresponding lenses, but with little qualification or standardization of the methods for studying or interpreting each.

This article will update you on the latest information on dry eyes and contact lens wear to help you stay current when caring for your patients.

Impact of Dry Eye

Most contact lens practitioners understand the all-to-common dry eye symptoms that their patients experience. We know contact lens wearers experience ocular irritation much more frequently than non-lens wearers do.1 In a recent study¹, my colleagues and I found that 52.3% of contact lens wearers were classified as having dry eyes based on self-reporting various symptoms, while about 24% of spectacle wearers and only 7% of clinical emmetropes had the same level of symptoms. In other words, lens wearers were about 12.5 times more likely than clinical emmetropes and five times more likely than spectacle wearers to experience dry eyes.

Another important consideration is how symptoms increase in contact lens wearers during the day. This could prove to be a critical assessment in terms of prescribing a material (or material/care system combination) that improves comfort levels so patients can wear their lenses longer. Our ultimate goal is to keep patients safely and comfortably wearing contact lenses for as long as they desire, and this relates in large part to their daily comfort levels.

In another recent study,² my colleagues and I found that out of 730 subjects surveyed, more than one-half (n = 453, 62%) had some experience with wearing contact lenses. Of those with some experience, 26% (n = 119) reported that contact lenses were not the ideal form of correction for them, while another 24% (n = 109) had discontinued wearing contact lenses permanently.

When comparing the groups studied (current satisfied lens wearers, current dissatisfied lens wearers and dropouts), we learned the dissatisfied lens wearers tended to be female, while those who discontinued lens wear tended to be male. Furthermore, former lens wearers were likely to have tried both rigid and soft lens modalities and spent less total time in lenses than current lens wearers (about 3 to 4 years less on average).

The study also showed that a patient�s age when starting contact lens wear was a significant determinant of future satisfaction and continuation with lens wear. We found that the younger a patient is when first fitted with contact lenses, the more likely he is to be satisfied with them and the less likely he is to discontinue wearing them. This is critical information that we can use in practice to help keep our patients happy and successful.

Last, and not surprising, the most frequently reported reason for dissatisfaction with or discontinuation of lens wear was ocular surface-related symptoms. The two studies outlined here help to define the concern relative to improving our patients� experiences with contact lenses.

In 1993 and 1994, the National Eye Institute and key corporations sponsored workshops on dry eye syndrome. A 1995 report generated from theseworkshops indicated that contact lens-related dry eye is a subclassification of dry eye syndrome, yet the epidemiology and etiology of this condition still elude us.³ Contact lens-related dry eye was termed evaporative relative to its etiology, although no studies have directly compared evaporation rates in satisfied lens wearers to rates in patients with contact lens-related dry eyes.

The next few sections of this article will explore this evaporative mechanism as well as the characteristics of contact lens materials that may be associated with patient comfort and preference. To this point, the mechanism of contact lens-related dry eye and comfort is poorly understood and in need of further study. Knowledge of the disease mechanism may allow clinicians to offset any potential for discomfort, ocular surface desiccation and disease, which could lead to failure of contact lens wear in these patients.

It is important that we move past incremental improvements in both lens materials and care solutions; to do this, the industry must continue to fund basic, fundamental research into understanding disease mechanisms so new materials and solutions can be identified to prevent or stop the disease process.

Lens Material Considerations

There have been tremendous advances in polymer chemistry over the last 5 to 7 years, and our patients are benefiting on several fronts. Silicone hydrogels have brought much-needed increases in oxygen permeability, and other characteristics of some silicone hydrogel materials seem to improve comfort.

More recently, wetting agents have been incorporated into daily disposable materials to improve performance and comfort. To understand the interaction between contact lenses and the tear film, we must first understand the surface characteristics of polymers. Let�s review some fundamental concepts and terminology as we continue the discussion about these novel materials.

� Wettability. Wettability relates to cohesive forces (forces within a molecule of one component) and adhesive forces (forces between two different molecular components). Specifically, cohesive forces tend to keep one component together (e.g., water is attracted to itself), whereas adhesive forces must be substantial enough to overcome cohesive forces for the surface to become wetted.

Within a drop of liquid, for example, cohesive forces pull each molecule equally in all directions with little to no net force. However, the surface of the liquid has excess energy (surface energy or tension) because there is no outward force that can negate the inward pulling forces of the molecules. The stronger the cohesive forces are within the drop, the higher the surface tension. When a drop of liquid is in contact with a solid surface (which has surface energy itself), energies at the interface (interfacial tension) need to be considered as the liquid becomes attracted to the solid surface, reducing the surface tension of the liquid.

In terms of the ultimate wettability of a system, we need to consider the surface tension of the liquid, the surface tension of the solid surface and the interfacial tension. High surface tension of the liquid (due to its own high cohesive forces) and high interfacial tension (low adhesion forces) are associated with decreased wettability, whereas lowering the surface tension of the liquid or increasing the surface tension of the solid will lead to increased wettability.

We measure wettability in vitro via contact angles. Several methods exist, including the sessile drop, the captive bubble and the Wilhelmy balance methods. Contact angles can be advancing or receding, and each may give you different information about the system being evaluated. In general, lower contact angles indicate more wettability, and a contact angle of zero indicates complete wettability.

Historically, some doctors have been guarded about the clinical utility of contact lens wettability measurements, given the in vitro nature of the data obtained, particularly because there is very little information on how these measurements relate to the subjective performance of various materials. However, we are obtaining more clinically meaningful data by using newer approaches and investigations.

One alternative approach is to determine the impact of wear on wettability by measuring baseline (�out-of-the-box�) wettability followed by post-wear wettability. This gives us insight into factors that influence wettability, such as wearing time, care solutions and deposition. Figures 1, 2 and 3 are examples of surface measurements of wettability, with Figure 1 showing the process of measuring an advancing contact angle, while Figure 2 shows a very wettable silicone hydrogel surface (note that the contact angle is 0�) and Figure 3 demonstrates a very unwettable silicone hydrogel lens surface (note that the contact angle is around 90�).

Given the potential limitations of in vitro measurements, more in vivo surrogate measurements of wettability are of clinical interest, and advances have been made in this regard. Traditionally, we can approximate clinical wettability measurements by measuring tear film stability and breakup. However, even this is confusing in that we don�t really understand the outcome of the test. For instance, with fluorescein-associated tear breakup, what is not clear when one observes a �dry spot� is whether or not a tear film is present or if the dimming is associated with quenching of fluorescence. Newer, noninvasive imaging technologies, namely optical coherence tomography and interferometry, are providing even more insight into on-eye tear film distribution, especially as it relates to contact lens surfaces. While both technologies are still used mainly for research, each is capable of providing tremendous insight into tear film distribution, thickness and breakup. This information can help us understand on-eye differences in polymers, care solutions, rewetting agents and various other factors that influence the aforementioned tear-film parameters. Figures 4 to 6 show examples of a stable pre-lens tear film and images that show particularly unstable pre-lens tear films, indicating breakup that may be due to dewetting. (Note the difference in the images relative to the characteristics of the dry spots.)

� Tribology. Tribology deals with the design, friction, wear and lubrication of interacting surfaces in relative motion. It�s gaining interest among those involved in contact lens research, development and marketing. I want to emphasize that lubrication and wettability are different characteristics, although they may be related. Technically, lubrication occurs when otherwise adjacent surfaces are separated by a film. There are at least two distinct types of lubricants: so-called boundary lubricants, which offer incomplete separation of the surfaces; and hydrodynamic lubricants, which offer complete separation of the surfaces.

Lubricants are used to reduce friction between two surfaces, and traditionally they are oil-based (i.e., synthetic, mineral, natural). Clinically speaking, lubrication is relevant when considering interaction between a contact lens and the palpebral conjunctiva (say, during a blink) and also in terms of the posterior surface of the contact lens and the cornea. It seems that it should be important for lubricants to maintain wettability in order for them to coat a surface.

Kinetic friction is the energy created when two surfaces are opposed in motion, usually opposite in direction to the surface that is in motion. Friction is classified using the coefficient of friction, which is a measure of the force created between two surfaces. In general, rougher surfaces tend to have higher coefficients of friction. However, the tear film-lens surface interface is interesting relative to our understanding of friction.

Similar to the issues relating to measuring wettability in vitro, it is unclear how measures of friction relate to on-eye performance differences associated with lens surfaces. Certainly, it seems intuitive that we would want to reduce the friction of the tear film-lens surface, but it could be likely that a stable pre-lens tear film holds this responsibility. If we consider the supposedly rough corneal glycocalyx and its role in maintaining a stable precorneal tear film, we might logically surmise that a similarly structured contact lens surface, which also would be considered inherently rough, would be better than an inherently smooth surface in maintaining a stable pre-lens tear film. Many questions remain unanswered in this regard.

� Dehydration. One of the more controversial factors associated with contact lens-related dry eye is nominal water content (and refractive index) of a lens and associated lens dehydration. The refractive index of a low water-content contact lens is higher than that of a high water-content lens, and dehydration results in an increase in refractive index. Generally, low water-content lenses may lose about 1% of their water content, high water-content lenses may lose up to about 5%.^4-6 For years, clinicians have relied on the theoretical argument that a result of pre-lens tear film evaporation was lens dehydration with accompanying drying of the eye.

In a study of more than 350 contact lens wearers,⁶ my colleagues and I found that patients using lower water-content hydrogels were less likely to have contact lens-related dry eye. However, the study did not show that lens dehydration was related to contact lens-related dry eye. Several smaller-scale studies^7-10 have evaluated contact lens dehydration and patients� symptoms, with varied results.

Efron and Brennan7 found that patients wearing low water-content lenses that maintained hydration (as compared to low watercontent lenses that dehydrated) generally reported their eyes never felt dry during lens wear. Pritchard and colleagues9 examined dehydration of three different water-content hydrogel lenses and the relation of this dehydration to lens movement, diameter changes and dryness symptoms. They found no correlations between dehydration, movement, diameter and dryness symptoms.

Fonn and colleagues10 performed a similar study, but used two groups of patients � one with symptoms of dryness and the other without such symptoms � showing no relationship between lens dehydration and dryness, comfort or tear film thinning time. Thus, the evidence to date seems to suggest that although high water-content (low refractive index) lens use may be associated with contact lensrelated dry eye symptoms, dehydration of these lenses does not seem to be the mechanism associated with the dry eye symptoms.

One possible explanation for this is that the polar head groups associated with the tear film lipid molecules may be attracted to lenses of higher water content (or silicone expression), leaving their nonpolar tails extended away from the lens surface leading to evaporation and/or dewetting.

� Transmissibility. Another issue that isn�t well understood is the relationship between contact lens oxygen transmissibility and contact lens-related ocular surface symptoms (e.g., comfort, dryness). The benefits of increasing oxygen transmissibility are numerous and well-established; however, the link to improved comfort during lens wear appears to be elusive. This might not be surprising; in fact, one could argue that lenses with lower oxygen transmissibility might be more comfortable because they effectively numb the cornea, reducing its sensitivity and increasing the patient�s tolerance.

My Australian colleagues Drs. Chantal Coles and Noel Brennan have been painstakingly addressing the issue of the relationship between oxygen transmissibility and comfort.¹¹ By accumulating a large dataset composed of several completed studies, the group retrospectively evaluated seven lens materials (balafilcon A, etafilcon A, hioxyfilcon A, lotrafilcon B, omafilcon A, polymacon and senofilcon A). Subjects were asked questions about comfort, dryness and end-of-day comfort after a minimum of 1 month of wear. While senofilcon A (a silicone hydrogel, Acuvue Oasys) generally performed best in terms of overall comfort, it was not generally true that silicone hydrogels themselves provided improved comfort compared to their nonsilicone hydrogel counterparts.

Tear Film Considerations

When discussing the mechanisms of contact lens-related dry eye, it is important to consider the relationship between three key variables: the tear film; the contact lens; and the lens-care system. It is very difficult to localize problems to any one of these three components, because each must perform in concert with the others.

The tear film is a complex, thin film that protects and maintains the cornea, allowing for good vision. The �functional unit� is normally able to tolerate environmental stresses and demands, but a contact lens disrupts the tear film, dividing it into two layers � the pre- and post-lens tear film. The pre-lens tear film probably consists of the superficial lipid layer anteriorly, with a base layer that is more aqueous. The post-lens tear film likely consists of aqueous anteriorly with a mucin gradient near the corneal epithelium. Although we are just starting to unravel the mysteries associated with these complex layers, we believe they must perform the normal functions of the precorneal tear film in order for successful contact lens wear. Current investigations are examining the physical (thickness and structure) and biochemical compositions (e.g., lipid components, inflammatory mediators/proteins) of these layers during lens wear, both with and without the presence of ocular surface symptoms.

When considering the underlying causes of contact lens-related dry eye associated with the tear film, it is important to recall the components and their interaction with the lenses. If tear film evaporation is a component of contact lens-related dry eye, this certainly implicates the superficial lipid layer of the tear film, as seen in Figure 3, whose function is to prevent evaporation of the tear film.^12-14 The ionicity of the material, lipophilic surface properties (due to silicone expression), or polarity of the water within the material may be chemically attractive to tear film biomolecules, such as the lipid or protein components.

Studies suggest that contact lenses with high water content dehydrate to a greater extent than low water-content hydrogel lenses, and thinner lenses dehydrate faster than thicker lenses, and this has been implicated as a cause of lens-related dry eye.^4,16 However, recent work suggests that while high water-content lenses typically are associated with lens-related dry eye, dehydration of these lenses is not. The likely explanation for this finding is that the extra water in these materials attracts the polar components of the tears (i.e., polar lipids or proteins), altering their surface wettability and tear film evaporation (i.e., increased pre-lens tear film thinning and breakup). With altered pre-lens tear film thinning, this leads to a direct increase in osmolality (i.e., increased thinning rate reduces the volume of the solvent present, but the solutes go unchanged), and it is likely the increase in osmolality that leads to patient symptoms.⁶

However, lipid alterations or interactions with the lens may contribute only in part to tear film evaporation. Proteins are involved in the innate defense of the ocular surface, in addition to having scavenging or surfactant properties themselves. Many of the proteins known to be present in the tear film (e.g., lysozyme, lactoferrin, albumin) have protective roles, serving as antimicrobial agents. Another consideration is that increases in osmolality (as discussed above) have been shown to lead to an up regulation of the stress response in animal models.¹⁷ The stress response is usually characterized by an expression of proteins that are involved in the inflammatory response, such as interleukins, cytokines, matrix metalloproteinases and others. Thus, while likely not the direct inciting factor, inflammation is likely a result of increased evaporation/tear film thinning given the osmolality link between the two (i.e., fast evaporation/thinning leads to increased osmolality, which leads to the inflammatory response).

Ocular Surface Sensation

Ocular surface sensation is a complicated area of research. Contact lens wear is associated with alterations in corneal sensation. How much the sensation is altered relates to the oxygen transmissibility of the contact lens and the length of wear (short-term vs. long-term).

The modulus (stiffness) of the polymer material may affect a contact lens�s overall comfort. To my knowledge, the relationship between ocular surface sensation and lens material modulus is not understood, although, intuitively, one would think that a lower modulus lens might be more comfortable, while a higher modulus lens might be easier to handle. It does appear as though some of the more mechanical� contact lens complications (i.e., superior epithelial arcuate lesions, contact lens-associated papillary conjunctivitis) may be related to lens modulus and patient comfort during lens wear. One of the more controversial topics related to patient comfort during contact lens wear is corneal staining. In the general, non-lens wearing population, some degree of corneal staining is somewhat common, and it typically lasts for about a day.

Care Solution Considerations

We all acknowledge that care solutions/systems have an important role in disinfecting contact lenses. Recent events associated with product recalls remind us that we should never take the care system for granted. It is critical that the industry continue to focus on improving our understanding of disinfectants used in marketed products. It is also critical that we move past so-called incremental improvements and toward true advances and next-generation products.

Remember, too, that care systems can improve patient comfort. Manufacturers strive to improve comfort through the demulcents and surfactants (surface active agents) used in their products. Demulcents, which are water-soluble polymers such as hydroxypropyl methylcellulose, sorbitol and propylene glycol, are being included in care systems to improve lubrication. Surfactants may improve comfort on several fronts. First, they can help improve wetting by lowering the surface tension of a liquid or the surface energy of a solid. Surfactants are amphipathic (hydrophobic tails and hydrophilic heads), and because of this, many surfactants can form micelles.The shape of a micelle is related to the pH of the system. Micelles will form only when the surfactant�s concentration is greater than the critical micelle concentration (CMC). When surfactants are present above the CMC, they take on emulsification/detergent properties. In this regard, they can help clean contact lenses by incorporating poorly soluble hydrophobic material (i.e., proteins, etc.) in their core where they, in essence, surround the protein and denature it. Theoretically, a cleaner lens might be associated with improved comfort, although we do think that a biofilm is an important part of the picture as well.

Long-standing Goal

Comfortable contact lens wear is arguably one of the biggest clinical challenges facing eyecare practitioners today. While we have gained some insight into the composition of the tears and the mechanisms of dry eye disease, work is still needed to move the field ahead. We should all look forward to new products, including polymer materials, contact lens care systems and rewetting agents that will help our patients safely and successfully wear contact lenses.

REFERENCES
1. Nichols JJ, Ziegler C, Mitchell GL, Nichols KK. Self-reported dry eye disease across refractive modalities. Invest Ophthalmol Vis Sci. 2005;46:1911-1914.
2. Richdale K, Sinnott LT, Skadahl E, Nichols JJ. Frequency of and factors associated with contact lens dissatisfaction and discontinuation. Cornea. 2007;26:168-174.
3. Lemp MA. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J. 1995;21:221-232.
4. Efron N, Brennan NA, Bruce AS, et al. Dehydration of hydrogel lenses under normal wearing conditions. CLAO J. 1987;13:152-156.
5. Efron N, Young G. Dehydration of hydrogen contact lenses in vitro and in vivo. Ophthalmic Physiol Opt . 1988;8:253-256.
6. Nichols JJ, Sinnott LT. Tear film, contact lens, and patient-related factors associated with contact lensrelated dry eye. Invest Ophthalmol Vis Sci. 2006;47:1319-1328.
7. Efron N, Brennan NA. A survey of wearers of low water content hydrogel contact lenses. Clin Exp Optom. 1988;71:86-90.
8. Lowther GE. Comparison of hydrogel contact lens patients with and without the symptoms of dryness. Int Contact Lens Clin. 1993;20:191-194.
9. Pritchard N, Fonn D. Dehydration, lens movement and dryness ratings of hydrogel contact lenses. Ophthalmic Physiol Opt. 1995;15:281-286.
10. Fonn D, Situ P, Simpson T. Hydrogel lens dehydration and subjective comfort and dryness ratings in symptomatic and asymptomatic contact lens wearers. Optom Vis Sci. 1999;76:700-704.
11. Coles C, Brennan NA, Connor HR, McIlroy RG. Do Silicone-Hydrogels Really Solve End-of-Day Comfort Problems? Program presented at American Academy of Optometry meeting, Dec. 8, 2006.
12. Mishima S, Gasset A, Klyce SD, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5:264-276.
13. Nichols JJ, King-Smith PE. Thickness of the preand post-contact lens tear film measured in vivo by interferometry. Invest Ophthalmol Vis Sci. 2003;44:68-77.
14. Korb DR, Baron DF, Herman JP, et al. Tear film lipid layer thickness as a function of blinking. Cornea. 1994;13:354-359.
15. Efron N, Morgan PB. Hydrogel contact lens dehydration and oxygen transmissibility. CLAO J. 1999;25:148-151.
16. McConville P, Pope JM, Huff JW. Limitations of in vitro contact lens dehydration/rehydration data in predicting on-eye dehydration. CLAO J. 1997;23:117-121.
17. Luo L, Li DQ, Corrales RM, Pflugfelder SC. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye Contact Lens. 2005;31:186-193.

Contact Lens Spectrum, Issue: May 2007