Special Article Spontaneous Blinking from a Tribological Viewpoint HEIKO PULT, MSC, PHD, 1,2,3 SAMUELE G.P. TOSATTI, PHD, 4 NICHOLAS D. SPENCER, MA, PHD, 5 JEAN-MICHEL ASFOUR, DIPL-PHYS, 6 MICHAEL EBENHOCH, DR-ING, 7 AND PAUL J. MURPHY, BSC, MBA, PHD8

ABSTRACT The mechanical forces between the lid wiper and the ocular surface, and between a contact lens and the lid wiper, are reported to be related to dry eye symptoms. Furthermore, the mechanical forces between these sliding partners are assumed to be related to the ocular signs of lidwiper epitheliopathy (LWE) and lid-parallel conjunctival folds (LIPCOF). Recent literature provides some evidence that a contact lens with a low coefficient of friction (CoF) improves wearing comfort by reducing the mechanical forces between the contact lens surface and the lid wiper. This review discusses the mechanical forces during spontaneous blinks from a tribological perspective, at both low and high sliding velocities, in a healthy subject. It concludes that the coefficient of friction of the ocular surfaces appears to be strongly comparable to that of hydrophilic polymer brushes at low sliding velocity, and that, with increased sliding velocity, there is no wear at the sliding partners’ surfaces thanks to the presence of a fluid film between the two sliding partners. In contrast, in the case of dry eye, the failure to maintain a full fluid film lubrication regime at high blinking speeds may lead to increased shear rates, resulting in deformation and wear of the sliding pairs. These shear rates are most likely related to tear film viscosity. Accepted for publication December 2014. From 1Dr. Heiko Pult, Optometry & Vision Research, Weinheim, Germany, 2 Cardiff University, School of Optometry & Vision Sciences, Cardiff, UK, 3 Ophthalmic Research Group, Life and Health Sciences, Aston University, Birmingham, UK, 4SuSoS AG, Duebendorf, Switzerland, 5Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, Zurich, Switzerland, 6Dioptic GmbH, Weinheim, Germany, 7ZF Friedrichshafen AG, Friedrichshafen, Germany, and 8University of Waterloo, School of Optometry & Vision Science, Waterloo, Canada. Financial support: None. The authors have no commercial or proprietary interest in any concept or product discussed in this article. Single-copy reprint requests to Dr. Heiko Pult (address below). Corresponding author: Dr. Heiko Pult, MSc, PhD, Steingasse 15, 69469 Weinheim, Germany. Tel: 0049 (0) 6201 477804. E-mail address: [email protected] heiko-pult.de © 2015 Elsevier Inc. All rights reserved. The Ocular Surface ISSN: 15420124. Pult H, Tosatti SGP, Spencer ND, Asfour JM, Ebenhoch M, Murphy PJ. Spontaneous blinking from a tribological viewpoint. 2015;13(3): 236-249.

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KEY WORDS blinking, coefficient of friction, contact lens, lid wiper, tear film, tribology, viscosity

I. INTRODUCTION hen two surfaces are in contact and move relative to each other, friction is observed. This phenomenon is studied by tribologists and has a critical impact on everyone’s daily life. Without friction, it would not be possible to drive a car on the road or ignite a lighter. On the other hand, a friction value that is too high will not allow a snowboarder to slide downhill, or it will make it impossible to slide a heavy cardboard box from one corner of a room to another. In addition to the two sliding surfaces, one other component often participates in the tribological system: lubricant. For example, synthetic oil is used to lubricate the pistons inside an engine, and shaving foam and water facilitate a razor sliding over the skin, reducing wear and friction, and minimizing skin irritation, respectively. (Wear is a term used to describe the removal and deformation of material on a surface, as a result of mechanical action by the opposite surface.) In the eye, during a spontaneous complete blink, the upper and lower eyelids move with respect to the ocular globe and the corneal surface, while being lubricated by the tear film. The speed of eyelid movement during a blink varies between patients, with an average speed reported to be between 17 and 28 cm.s1, and a maximum blink speed of around 40 cm.s1.1,2 A spontaneous blink does not result in a significant demonstration of Bell’s movement, but the downward movement of the upper lid will still cause the eyeball to move backward (posteriorly) by around 0.9 mm.2,3 At the same time, and based on a hydrodynamic model of the human eyelid wiper model, the upper lid slightly lifts off the cornea by 1.1 mm (h, Figures 1 and 2) in the closing phase.4,5 This ensures that the force the eyelid applies to the ocular surface during the closing phase of the blink is significantly higher than that during the opening phase of the blink4 and allows the tears to flow from under the upper eyelid during the blink, assisting in tear drainage. The lower lid, as well as moving vertically upward, moves both inward (nasal direction, 4.50.9 mm)6 and tilts slightly inward.2,7 At the same time as the upper lid moves

W

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al

OUTLINE I. Introduction II. Tribological Models III. Tribological Model of the Eye A. Healthy Subjects B. Dry Eye Patients IV. Parameters Influencing the Tribology of the Eye A. Tear Film Viscosity B. Lid Pressure and Modulus C. Lid-Wiper Geometry D. Blink Speed E. Surface Roughness and Texture F. Lubricant Thickness G. Contact Lenses V. Conclusions

downward, it also constricts horizontally (3.11.0 mm).6 In contrast to the lower lid, the upper lid does not tilt inward, but follows the corneal shape, with the lid margin remaining perpendicular to the tangent of the cornea.7 This was observed from a side view from the fully opened lid position to just before lids closed.7 As a result of these movements, the upper lid, when closed, slightly overlaps the lower eyelid, producing an ”over-blink.”6,7 The action of blinking is important for the eye and for good visual performance, since the action of blinking serves to produce a smooth optical surface by re-forming the tear film, which undergoes a destabilization process during the interblink interval. It also acts to remove unwanted debris or foreign bodies that become trapped in the tear film, helping them to be removed through tear drainage.8,9 However, even though blinking is vital for maintaining optical performance, ocular surface health, and tear film drainage, in the presence of an insufficient tear film, the mechanical forces involved in blinking can damage the lid wiper and/or the ocular surface.10-12 (The lid wiper is that portion of the central, posterior eyelid in apposition to the ocular surface). Contact lenses are optical devices made from biocompatible polymers that rest on the corneal and ocular surface, and which are lubricated by the tear film. The lenses have limited movement on the surface, which is important for optical stability, but interact with the movement of the eyelids during blinking. It is important, therefore, that among the physical and chemical properties that contact lenses should possess, there should be a low coefficient of friction between the upper lid and the contact lens surface. This may have a particular influence on contact lens wearing comfort.13-15 Consequently, new soft contact lens materials have been developed to reduce friction between the contact lens surface and the lid-wiper. Such “comfort-enhancing” contact lenses show a reduced coefficient of friction when measured under eye-simulating conditions in vitro.16 We hypothesize that, with increased sliding velocity, there is no wear at the sliding partners’ surfaces, thanks to the presence of a fluid film between the two sliding partners.

Due to the ocular surfaces being strongly comparable to those of hydrophilic polymer brushes, no wear between sliding partners in low sliding velocity can be assumed. This may be different in dry eye, due to insufficient brush-to-brush lubrication and altered tear film viscosity. Dry eye symptoms at high sliding velocity, both in the presence or absence of contact lenses, may be more likely related to the tear film than the surfaces. In contrast, in the case of low sliding velocity, dry eye symptoms in both groups may be more likely related to the surfaces of the sliding partners. In this paper, we discuss friction between the upper eyelid and the cornea or contact lens surfaces during spontaneous, complete blinks, according to the most widespread tribological theories. II. TRIBOLOGICAL MODELS In classical tribology, the relationship between coefficient of friction, load, relative speed, and lubricious fluid properties e in particular viscosity e has been described in the wellknown Stribeck curve17 (Figure 3). In this model, three different regimes have been identified: boundary lubrication, dominated by the close contact of the solid surfaces; the mixed regime, where occasional contact between the solid surfaces occurs; and the hydrodynamic regime, where a full lubricant film is present between the two surfaces moving relative to each other. In boundary friction, the material surface quality mainly influences friction, where as in hydrodynamic friction, where both surfaces are fully separated, friction depends on the viscosity of the fluids between the surfaces. Using this model and applying it to the non-contact lens blink cycle, the hydrodynamic regime is reported to be dominant, and, as such, the cycle has low friction.18 Furthermore, one can observe that at the beginning, end, and return points of the blinking cycle, boundary lubrication may be expected to be predominant, due to the low lid velocities and the constant load that should squeeze the tear film apart. So, according to the theory behind the Stribeck curve, under this condition an increase in the coefficient of friction is to be expected. However, this is not the case for the eye, or for other biological systems that are known to be highly lubricious under a wide variety of conditions.19,20 Also, according to the Stribeck curve, the coefficient of friction is expected to significantly decrease when transitioning from boundary friction to hydrodynamic friction. Such behavior, to the best of the authors’ knowledge, has been widely described for various hard-hard tribopairs, but not for contact lenses or for the ocular surface.17 Indeed, when comparing different lubricious systems found in nature, e.g., the propulsion of snails, food transport through the digestive system, the articulation movement or, as in this case, eyelid blinking, a common component can be identified, i.e., the presence of so-called surface brushes that consist of hydrophilic, surface-tethered, sugar-containing biomolecules.20,21 Molecules that are placed in a “good solvent” tend to disperse in order to maximize their entropy. However, upon being tethered to a surface, the molecules are

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Figure 1. Schematic model of lid e cornea interaction with lid velocity (v), lid pressure against the cornea (p), and tear film thickness (h).4,5

Figure 3. Schematic of a Stribeck curve showing lubricant thickness variation. Linear scale: 1¼ boundary lubrication, 2¼ mixed lubrication, 3¼ hydrodynamic, or full fluid film lubrication. The grey, dashed line shows the increase in lubricant thickness between the sliding partners; the black, dashed line represents brush-to-brush friction.

constrained and are no longer able to disperse. To compensate for this “crowding,” and to avoid the high entropy cost of having the molecules entangled with each other, there is an incentive to form a surface-brush structure.21-23 For example, if one imagined that the space occupied by a molecule in solution is represented by a sphere, the bigger the molecule (i.e., higher molecular weight), the bigger the sphere and, thus, its diameter (generally described for macromolecules as the “radius of gyration”[Rg]). When two such spheres adsorb onto a surface, they are able to sit on the surface like two, well-spaced “mushrooms” (Figure 4) with no overlap of the spheres unless the distance between

them is smaller than Rg. However, once a critical surface density is reached, in order to fit more molecules into the same space, it is necessary that the shape of the sphere, i.e., the molecules, changes. Since entanglement will be too energetically costly, the molecule will stretch out in order to compensate for the crowding at the surface, and thus a brush is formed (Figure 4). For a given system, e.g., mucin on the corneal surface, the brush regime depends mainly on both the surface density and the molecular weight of the adsorbed biomolecules.21-23 The brush regime is dependent on both the structural properties of the tethered (bio-) molecules, as well as on

Figure 2. Schematic model of lid-contact lens-cornea interaction with lid velocity (v1, v2), lid pressure against the cornea (p), and tear film thickness (h1,2).4,5

Figure 4. Schematic of end-grafted polymer chains in the presence of a good solvent. When s>2Rg, the chain conformation resembles that of the free molecules in solution, with radius of gyration Rg. This is designated as the “mushroom” conformation. If s14 mg/mL), which contributes to full fluid film lubrication.34 Mucins enable brush-to-brush friction due to their high hydration and by generating repulsive steric and electrostatic forces.34 Additionally, mucins can adhere to contact lens surfaces to reduce the coefficient of friction of worn contact lenses.34,36 Lubricin is a protein that has been reported to play a critical role in articulating joints.37-39 Schmidt et al40 determined that lubricin is also produced by ocular surface epithelia and acts as a boundary lubricant at the human cornea-eyelid biointerface. For the purposes of this paper, lubricin is assumed to be associated with the glycocalyx. When considering the “tribology of blinks,” the classic form of the Stribeck curve cannot be applied, because of the presence e in a healthy tear film e of the glycocalyx and the gel-forming mucin brush-like structure on the ocular surface33,41 and lid wiper.32 The expected high coefficient of friction in the low-speed regime, caused by the solid contacts, does not occur because of the presence of the brush (Figure 3). In addition to the hydrophilic polymer brushes formed by the mucins, the tribological model of the eye may be influenced by physical parameters, such as lid pressure, blink speed, surface roughness and texture, as well as by material parameters, such as elastic modulus (of tissue or contact lenses), and by tear film composition, which ultimately has an influence on the tear film viscosity and lubricant thickness. The tear film viscosity is also influenced by the temperature.42,43 It is important to determine if, and how, these parameters influence the model, either in the high-speed regime, where the dominating parameter is given by the tear film properties, or in the low speed regime, where the dominating parameter is the hydrophilic surface brush. A. Healthy Subjects The shear stress (and the coefficient of friction) between the cornea and the eyelid is affected by the amount of normal force exerted by the lid, the shear distribution within the tear film/mucin system, and the extent to which the sliding partners make contact with each other (e.g., through in an incomplete mucin layer). In healthy subjects, it is assumed that any complete blink quickly transitions from brush lubrication to full fluid film lubrication at increasing blink speed.1,18,44 A recent mathematical model of contact lens wear demonstrated that very shortly after the beginning of a blink, full fluid film lubrication between a contact lens and the upper lid wiper occurs.5 With this quick transition to the full fluid film regime, there is no wear between the sliding partners, with or without contact lenses. Even at blink speeds of 100 mm.s1 and 200 mm.s1, the shear stress produced are only 0.8 kPa and w1.3 kPa, respectively.5 During contact lens wear in a healthy subject, the coefficient of friction of the contact lens surface does not

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al correlate with wear at the lid wiper in the hydrodynamic regime. Since the upper lid movement mainly occurs in the full fluid film regime, it can be assumed that any friction between the partners (cornea-lid wiper; contact lens-lid wiper) mainly depends on the properties of the tear film, such as its viscosity. The latter is a critical parameter in the determination of the shear rate at high blink speeds, as shown by Dunn et al.5 From this, one can conclude that in healthy subjects, once in full fluid film lubrication, the ocular surface and the lid wiper can tolerate high shear rates without any adverse event related to clinical signs or causing symptoms.2 B. Dry Eye Patients While in healthy patients a blink occurs mainly in the full fluid film regime, with brushes reducing friction to a minimum at low speeds, this is expected to be different in a dry eye patient. In dry eye, the tear film insufficiency is thought to cause friction during blinks.45-48 For example, in a dry eye patient, the mucin layer and glycocalyx brushes are expected to be10,33,49 collapsed, damaged, less densely packed, less hydrated, thinner or absent.10,31,47 This will result in a higher coefficient of friction at low sliding velocities. Further, the increased viscosity of the abnormal tear film will also result in significantly increased hydrodynamic pressure at high velocity. Thus, the theoretical curve (Figure 5) drawn from this hypothesis approaches the classical Stribeck curve. Several variables may contribute to increased friction during blinks in dry eye patients. Such variables may include the brushes of the sliding partners, tear film viscosity, lid pressure, sliding partner modulus, lid-wiper geometry, blink speed, surface roughness and texture, and lubricant thickness. IV. PARAMETERS INFLUENCING THE TRIBOLOGY OF THE EYE A. Tear Film Viscosity For a liquid with Newtonian properties, as slidingpartner movement speed increases, assuming the presence of a homogenous lubricant film that it is sufficiently thick, the film will separate the partners. In this case, the

Figure 5. Schematic sketch showing friction in healthy (green curve) and dry eyes (red curve).

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coefficient of friction becomes dependent on the lubricant viscosity. Further increase in speed results in an increase in the coefficient of friction, due to the viscosity of the lubricating fluid itself.17 In contrast, the tear film has non-Newtonian properties and is to be considered as a shear thinning liquid.50-52 Based on the tear film’s non-Newtonian properties,50 the viscosity of the tear film is highest at low shear rates (10 mPa.s1), which occur during the opened eye resting state, promoting the stability of the tear film over the ocular surface. During eyelid movement in blinking, tear film viscosity is reduced (1 mPa.s1) to avoid damaging the ocular surface while blinking.52-56 Due to the non-Newtonian properties of the healthy tear film, hydrodynamic drag from increasing blink velocity will be very low. This arrangement is altered in dry eye patients, when tear film viscosity is significantly higher.50 Dry eye patients show different tear film compositions10,36,49,56 and tear film viscosities in comparison to healthy subjects, with viscosity reported to be approximately three times higher in dry eye patients.50 Furthermore, slightly increased temperature variation of the unstable tear film in dry eye patients were reported.43 Consequently, the film itself may exhibit a higher viscosity at the cooler temperature of the ocular surface.42 As a result, viscous fluid friction will also increase, probably to a higher level than that tolerated by the ocular surface and lid wiper. It is hypothesized that this is a mechanism for producing lidwiper epitheliopathy (LWE) and lid-parallel conjunctival folds (LIPCOF).1,57 LWE is a clinically observable alteration of the epithelium of the lid wiper. LWE appears to be the most sensitive conjunctival tissue of the ocular surface.31 Only a small portion of the marginal conjunctiva of the upper lid acts as a wiping surface to spread the tear film over the ocular surface or over the surface of a contact lens.47 This is because the palpebral surface of the upper lid arches away from the ocular surface, and so creates a space (Kessing’s space).58 This contacting surface at the lid margin has been termed the “lid wiper.”47 LWE is assumed to be related to increased friction in blinks,10,47,59,60 which might follow from an insufficient tear film.10,46 LWE is significantly related to LIPCOF (Figure 6) and both are increased in contact lens wearers compared to non-lens wearers.61This may support the mechanical hypothesis, since the coefficient of friction of the eyelid against the contact lens materials e used in this study e is likely higher than that against the cornea.13,16,62 LIPCOF are small bulbar conjunctival folds along the lower lid margin and are observed as extending perpendicularly from the temporal and nasal limbus.45,46,63 Bulbar conjunctival folds were first described by Middlemore in 1835 without any classification.64 To our knowledge, Hughes later named these prominent folds conjunctivochalasis (CCH).65 The term CCH has changed over time. Meller and Tseng described CCH as being used in the 1980s to describe “moderate CCH” and in the 1990s for “mild

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al altered42,55,56; the hydrodynamic pressure and the shear stress will significantly increase, potentially deforming the elastic sliding surfaces, (Figure 7).73,74 Increased hydrodynamic pressure will result in increased deformation. These levels of shear stress in dry eye patients may exceed known figures in terms of corneal sensitivity and lid margin sensitivity (Figure 8) and may contribute to the symptoms of discomfort in dry eye.75 Even though shear stress of the tribological model is mainly in the direction of motion, some component of this force can be assumed to contribute to mechanical stimulation of the sliding partners, especially the lid wiper and cornea. These areas are the most sensitive tissues of the ocular surface,31 and sensitivity thresholds lie significantly below shear-stress forces at increased blink speed, when combined with a viscous tear film. Figure 6. Lid-parallel conjunctival folds along the temporal lower lid margin.

CCH.” CCH is manifested by the easy displacement of conjunctiva from the episclera and the formation of pleated folds, especially visible just over the rim of the lower lid.64,66 However, LIPCOF, as described in this report, represent a much milder stage, with fold thickness of around 0.08 mm67 and less looseness than that commonly described in CCH.57,68 Based on the assumption that gel-forming mucins form networks of tangled, linear polymers that are responsible for the non-Newtonian thixotropic, or viscoelastic, properties of mucin gels,69,70 it is generally thought that mucins are the main components contributing to the viscosity of the tear film,55 with tear proteins and lipids also being involved.52,54-56 Furthermore, the viscosity of a lubricant can dramatically impact the transition to full fluid film lubrication.71 While a higher viscosity supports a transit to hydrodynamic friction at lower speeds, in full fluid film lubrication, a higher viscosity has the negative effect of creating high fluid shear forces, resulting in an increased shear stress or coefficient of friction.72 Therefore, the nonNewtonian behavior of the tear film promotes a lowerspeed transition and maintains lower friction in the full fluid film regime. Based on the variation in composition of the tear film in dry eye patients, this property may be

B. Lid Pressure and Modulus Increased pressure is associated with increased friction between sliding partners.10,46-48,76-79 According to Jones et al,4 the pressure and shear stress under the eyelid act at a small band along the lid wiper (across a length of approximately 0.1 mm), while Shaw et al80 concluded that a band of the eyelid margin, significantly larger than Marx’s line,81-83 has primary contact with the ocular surface. Shaw et al proposed that a mean pressure of 8.03.4 mmHg was the most reliable estimate of static upper eyelid pressure.80 Also, assuming a loss of tissue tension in older people,84 lid pressure, and therefore LWE, should be less in older patients. However, to our knowledge, such an effect is not reported in literature; rather the prevalence of dry eye is known to be higher in an older population.49 The modulus of the partner surfaces appears to be important in full fluid film lubrication at high loads.73 The pressure in the film does not affect the viscosity of the lubricant significantly, but it changes the shape of the solid bodies, especially in partners with low elastic modulus.73,74 This deformation of the contacting partners will lead to displacement of the partner materials (Figure 7). This deformation may be more obvious in the eye when there is increased tear film viscosity, lid pressure, blink speed, or partner modulus. For example, in the blink model of Dunn et al, the width of the lid wiper at the beginning of a blink (at low speed) was shown to be larger than at maximum speed.5 This was based on a defined modulus

Figure 7. Sketch of deformation and displacement of conjunctiva (A-B) and cornea (C-D) in high blink speed (dashed lines show original shape). Deformation and displacement is greater for the conjunctiva.

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Figure 8. Schematic graph showing shear rates at different sliding velocities for a dry eye (red) and a healthy tear (blue) films, compared to pressure references in terms of touch sensitivity of the cornea, lid margins, lid wiper and bulbar conjunctiva (the shear rates [red and blue]) are mainly in the direction of motion and only a component of this force contributes to the mechanical stimulation of the sliding partners).

(1.25 MPa) and lid wiper radius (0.5 mm). In lower modulus partners and with a larger lid wiper radius, a higher boundary friction and delayed transition to full fluid film lubrication, if it occurs at all, can therefore be assumed. It can also be concluded that, while lid pressure may not significantly affect friction in blinks, it is more likely that the partner modulus will. C. Lid-Wiper Geometry In a dry eye patient with a poor mucin layer and glycocalyx brushes, a rapid transition to the full fluid film lubrication regime may be important in order to avoid wear during blinks. This may depend on lid-wiper geometry. The proper position and profile of the sliding partners is essential in the transition from boundary to hydrodynamic friction and has been intensively investigated in engineering (Figures 9 and 10).85-89 The relative position of the sliding partners is key in developing the

Figure 9. Stable sliding motion is shown on the left. The fluid pressure between the block and the substrate is larger than the external pressure and balances the load of the block. Unstable sliding motion is shown on the right. The fluid pressure between partners is below the external pressure and the two partners will be sucked together leading to boundary friction and a large friction force.72

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appropriate hydrodynamic pressure that can separate both partners during sliding (Figure 9). In addition, this separation is assisted by building up a proper lubricant wedge between the sliding partners. Building up of such a wedge strongly depends on the partner profile (Figure 10).85-89 Based on the hydrodynamic model of Jones et al,4 the lid wiper slightly lifts away from the cornea during a blink, as confirmed by Dunn et al.5 Both calculations were based on a defined geometry of the lid wiper. Furthermore, a lifting off of the lid wiper from the contact lens during a blink, of at least 1 mm, was described. This was accompanied by a variation in the lid-wiper geometry, being flatter when closer to the contact lens, at the beginning of a blink. This was based on the assumption that the contact lens modulus is lower than that of the lid wiper.5,90 To our knowledge, the exact width of the stained area of the lid wiper in LWE is not known, but from our clinical experience, it can be suggested to be at least half of a lid margin thickness in grades 2, being around 1 mm (based on a lid margin thickness of 1.7 to 2.0 mm).91,92

Figure 10. Two different geometries of blocks. The right block will likely transit more rapidly to hydrodynamic friction than the left block (dashed arrows highlight building up of a lubricant wedge).72

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al Interestingly, increasing width of LWE is positively related to symptoms.45,47,48 However, a larger contact area would result in lower normal force and lower coefficient of friction.72 It was also shown by Jones et al4 and Dunn et al5 that the lid-wiper contour changes during blinks, and it may be assumed that such changes, and the anatomical contour of the lid wiper, play an important role in this tribological system. This failure of rapid transition from brush-to-brush friction to full fluid film lubrication may be based on inappropriate positioning and profile of the lid wiper. D. Blink Speed Blink speed has not been well evaluated in terms of dry eye. However, in tribology, sliding speed is a vital parameter in the Stribeck curve. Blink speed is important for separation of the lid wiper from the contacting partner to produce full fluid film lubrication.5 Increasing speed results in a transition from boundary to full fluid film lubrication, and it is possible that the blink speed is different between symptomatics and asymptomatics. Such further investigation may be of interest in understanding the relationship between blink speed and friction in blinks. Interestingly, in a pilot study by Pult et al, LIPCOF are positively correlated to blink speed of the upper lid and negatively correlated to lower lid closure speed; a higher upper lid closing speed in spontaneous, complete blinks was observed in patients with higher LIPCOF scores, while a lower closing blink speed of the lower lid was associated with a higher LIPCOF score.1 This may be for many reasons; however, one hypothesis was that increased blink speed of the upper lid, combined with a more viscous tear film, results in increased shear stress and hydrodynamic pressure impacting the conjunctiva, producing conjunctival folds (Figure 8).1 Lower lid blink speed may be related in increased LIPCOF due to increased initial boundary friction and break-loose forces reducing subsequent lower lid blink speed. Increased boundary friction may be related to collapsed brushes between the bulbar conjunctiva and the lower lid wiper. This may be supported by evidence, since LIPCOF were reported to be correlated with mucin loss. Berry et al10 analyzed mucins from the ocular surface in the area where temporal LIPCOF were observed (at the temporal, corneal limbus), and they concluded that decreased mucin production is associated with the severity of lower lid LWE and LIPCOF. E. Surface Roughness and Texture In general, the minimum lubricant thickness needed in full fluid film lubrication depends on the surface roughness, given that the film thickness needs to exceed the roughness on both sliding surfaces. Considering surface roughness to be solely dependent on microvilli size (300 nm), the minimum tear film thickness for hydrodynamic friction may be in the range of only 0.6 mm. However, the actual appropriate surface roughness of healthy corneal epithelium, conjunctiva, and lid wiper has not been reported in the literature, to our knowledge.

A surface roughness of the ocular surface and the lid wiper above 0.70 mm is unlikely. In addition, the effect of the membrane-associated mucins (glycocalyx), which lower the surface roughness of the cornea and the lid wiper,32 resulting in low brush-to-brush friction even at low velocity, needs to be considered. Consequently, the surface roughness of the ocular surface and the lid wiper may not be a determining factor in surface wear in spontaneous blinks. Nevertheless, further research is needed to determine the impact of surface roughness of the ocular surface and the lid wiper in symptomatics with collapsed brushes. Besides surface roughness, the texture of the partner surfaces may affect friction between partners. Such microtextures are used in engineering to improve sliding between partners separated by a lubricant.93 During hydrodynamic lubricated sliding, the textured surfaces exhibit friction values that are as much as 80% lower than an untextured surfaces.93 The cornea, as well as the tarsal conjunctiva, is covered by microvilli and microplicae,94-98 which produce just such a micro-textured surface. In addition, the surface is covered by the glycocalyx,41 which is altered in dry eye patients.49,69,98-100 This glycocalyx extends anteriorly from the microvilli and microplicae by approximately 300 nm and can extend laterally between the microvilli.96 Microvilli may be shorter at the conjunctiva than at the cornea, as reported in an experiment with Guinea pigs.96 The second partner of this tribological system is the lid wiper. The lid wiper shows a conjunctival structure32 and possibly similar mechanical sensitivity thresholds as the cornea.31 The epithelial thickening of the lid wiper is composed of a stratified cuboidal and partly columnar epithelium with goblet cells.101 The goblet cells and goblet cell crypts in the lid wiper may provide the condition for a sufficient overlying mucineaqueous gel at the surface of the lid wiper, providing proper lubrication between the lid wiper and the ocular surface in blinks and eye movements.32 Based on the reported changes of the tear film, and of microvilli and microplicae in dry eye patients and contact lens wearers,99 a change in this natural micro-texture and glycocalyx may impact the tribological system of spontaneous complete blinks. Collapsed brushes may result in increased friction in low velocity, which may hinder the transition to hydrodynamic friction. F. Lubricant Thickness Insufficient lubricant thickness may hinder full separation of the sliding partners. Lubricant thickness needs to be higher than the surface roughness of contacting partners to obtain full fluid film lubrication. Although relative thickness is controversial, tear film thickness is thought to be different between dry eye patients and healthy patients.102,103 The normal thickness of the tear film is close to 3 mm,104 while tear film thickness of dry eye patients may be similar or close to 2 mm.83,84 Tear film thickness will also significantly increase during the closing phase of a blink due to a decreasing lid-aperture size.105 The hydrodynamic tear film thickness ranges from 0.1 to 2 mm,

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al depending on surface roughness.18,106 Mixed-regime lubrication may then occur in a very thin tear film only when combined with increased surface roughness and collapsed brushes. Such a situation may occur for dry eye patients who commonly suffer from an insufficient mucin layer, since LWE and LIPCOF are reported to be significantly correlated to mucin quantity and quality in contact lens wearers.10,33,41,69,107 After a blink, the central tear film gradually thins, while the tear film reservoir in the tear menisci increases.108 Furthermore, tear film stability is decreased in dry eye patients and even though a dry eye patient might blink before tear film break-up, the tear film of the dry eye patient might be very thin before the start of the next blink cycle107 and probably too thin to sufficiently separate the contacting partners of the lid and cornea. This may be a factor in the closing phase of a blink. Indeed LWE was reported to significantly increase after exposure of contact lens wearers to a controlled low humidity over a period of 3 hours.59 LIPCOF scores significantly decreased after a 6-week treatment of dry eyes with liposomal eye sprays.109 Both observations indicate that when tear film thinning is too rapid, due to evaporation, this will increase LWE and LIPCOF. High friction and wear between cornea and conjunctiva and the lid wiper may also follow if a thin tear film is combined with a deficient mucin layer, hindering a rapid transition to hydrodynamic friction. G. Contact Lenses The coefficient of friction of the first-generation soft, silicone-hydrogel contact lenses was substantially higher than that of the cornea.62,110 Subsequently, new materials were developed with a lower coefficient of friction, which are reported to correlate with improved contact lens wearing comfort.13,111 These low-coefficient-of-friction lenses either have high water content surfaces (water-gradient material, Delafilcon A), or incorporated wetting agents such as poly(vinylpyrrolidone) (PVP) or poly(vinyl alcohol) (PVA).5,112,113 In vitro measurement of the coefficient of friction of soft contact lenses depends on many variables.16,114-118 The in vitro coefficient of friction during lubrication is potentially influenced by sliding speed (velocity), normal force, and solution viscosity. A comparison between measurements can only be drawn when evaluated in the same experiment,16 and it is not yet clear how these in vitro measurements can be transferred to what happens in vivo. To ensure brush-to-brush friction measurements of the contact lens material, the sliding speed in the experiments needs to be very low (0.1mm/s),16 since at a sliding speed of even 0.3 mm/s, the surface properties of the partners (contact lens-lid wiper) become less dominant in terms of friction and wear.5 It is therefore questionable if contact lens surfaces have a primary effect on the lid wiper at high velocity, since even low-coefficient-of-friction lenses present a hydrophilic surface brush30 that mimics the brush-to-brush friction in healthy non-contact lens wearers. 244

However, for high-coefficient-of-friction lenses, the contact lens surface will affect the coefficient of friction most at the very beginning of the blink cycle. The coefficient of friction will be even higher in contact lens wearers with coexisting dry eye (Figure 11). In such a scenario, lid-wiper mucins will be negatively impacted and there will be a poorly formed brush on both the contact lens and the lid wiper, increasing friction at low blink speed. Additionally, one can expect a similar effect of increasing (high-viscosity-induced) viscous drag at high blink speed, as already discussed in dry eye patients. When combined, this could produce possible co-existing effects from the in vivo coefficient of friction of contact lenses at low velocity and the higher hydrodynamic pressure in high sliding velocity. Interestingly, this situation may be modifiable, since mucins can adhere to contact lens surfaces, positively impacting the coefficient of friction,34,36,119 and the quality and quantity of mucins can be different in the same patient when refitted with another lens material.36 Since the pre-lens tear film thickness is reported to be 3 mm120 in non-dry eye contact lens wearers, and since this figure is comparable to the tear film thickness of noncontact lens wearers, the same mechanism as already described in the non-contact lens wearer may be assumed for the non-dry eye contact lens wearer. Furthermore, the surface roughness (Ra) of soft contact lenses ranges from 2.76 nm to 12.99 nm,121 which is also comparable to that of the ocular surface.

Figure 11. Coefficient of friction in contact lens wearers in low- and high-friction-coefficient contact lenses, and with healthy and collapsed brushes of the lid wiper, in relation to sliding velocity. A (red line): Highest coefficient of friction at low velocity in a dry eye patient (collapsed brush on the lid wiper) wearing high-coefficient-of-friction lenses (insufficient brush at contact lens surface). High shear forces observed at higher velocity due to increased tear film viscosity. B (yellow dashed line): Increased coefficient of friction at low velocity in normal tear film (sufficient brush of the lid wiper) and high-coefficientof-friction lenses (insufficient brush at contact lens surface). Low shear forces at higher velocity due to low viscosity and non-Newtonian properties of the tear film. C (orange dashed line): Increased coefficient of friction at low velocity in a dry eye patient (collapsed brush on the lid wiper) wearing low-coefficient-of-friction lenses (sufficient brush at contact lens surface). High shear forces at increased velocity due to increased tear film viscosity. D (green line): Lowest coefficient of friction at low velocity in normal tear film (sufficient brush on the lid wiper) and low-coefficient-of-friction lenses (sufficient brush at contact-lens surface). Low shear forces at higher velocity due to low viscosity and nonNewtonian properties of the tear film.

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SPONTANEOUS BLINKING FROM A TRIBOLOGICAL VIEWPOINT / Pult, et al In dry-eye patients, the lack of natural brushes and the further tear film thinning because of the presence of the contact lens is expected to lead to a general increase of friction and wear. In order to counteract this negative effect, a lens carrying a densely packed polymeric brush capable of resisting higher contact pressures is needed. Currently, this can be achieved by using water-soluble surface-brushes commonly defined in the field as wetting agents.5,112 The use of such hydrophilic materials would explain why several studies report wettability of soft contact lenses to be related to contact lens discomfort.111,122,123 In those soft contact lenses with a silicone hydrogel core material (water content w33%) covered by a thin surfacegel layer (water content >80%), the lid pressure appears to be key. At low lid pressure, Dunn et al found the analyzed coefficient of friction to be below m¼0.02; however; at high lid pressure, the gel layer collapsed, resulting in stick-slip friction with a break-loose or static coefficient of friction above m¼0.5.5 Nevertheless, new silicone-hydrogel contact lenses show coefficients of friction close to that of the human cornea.115 Therefore, the lubrication regime should not be much different between contact lens wearers of low-coefficient-of-friction lenses and non-contact lens wearers. Modulus, hydrodynamic forces, and lid pressure may be linked together in contact lens wear. The contact pressure acting on the eyelid, and thus the resulting shear stress, is expected to be higher when this is “pressed” (with equal force) against a contact lens that has a higher modulus than the cornea. The new generation of silicone hydrogel contact lenses appears to show an improved level of comfort compared to the first generation of silicone hydrogel lenses.13,112,123 This could be related to the lower modulus of these materials in comparison to older hydrogel systems. However, it is difficult to make a direct connection, since there are no studies in which only modulus has been varied as a single parameter. As discussed above, increased tear film viscosity results in significantly higher shear stress at high sliding velocity. It is suggested that tear film viscosity is related to tear proteins and lipids,52,54,55 and tear film composition can be altered significantly by wearing contact lenses.56 Tear film proteins and the lipid layer in contact lens wearers can be very different from those of non-contact lens wearers.56 Berry et al reported a mucin fragmentation change between lens types that likely impacts the viscosity of the tear film.36 Interestingly, this study reported that the adaptation to a different lens material, in terms of mucin fragmentation, did not occur in symptomatic contact lens wearers, resulting in discomfort. Corresponding to this effect, soft contact lens wearers also show higher degrees of LWE and LIPCOF than non-contact lens wearers,61 and contact lens wearers are more likely to be symptomatic if they have increased LWE and LIPCOF scores.46 The coefficient of friction of the contact lens surface appears to be correlated with the wear between sliding partners at low velocity only, and these low velocities may occur only

at the beginning and end of a blink cycle, and at the reversal point. Other sliding scenarios between lid wiper and ocular surface or contact lens need to be taken into account when considering wear between sliding partners, such as eye movements, including vergences and saccades, but these have not been considered in this review. There are remarkable differences in the in vitro coefficients of friction of soft contact lenses,16 and it is reported that those contact lenses with lower coefficients of friction result in greater wearing comfort.13,111,113 In a pilot in vivo confocal microscopy study, Morgan et al reported that inflammatory signs of the lid wiper in contact lens wearers were higher late in the afternoon compared to morning observations.60 This was more pronounced in high-coefficient-of-friction lenses, compared to lowcoefficient-of-friction lenses. Interestingly, friction between the cornea and the soft contact lens back-surface still corresponds to brush-to-brush friction.5 The coefficient of friction of the back surface of a contact lens may have an additional effect on wearing comfort and may be an under-estimated factor. Even though corneal and conjunctival sensitivity of contact lens wearers adapts to contact lens wear, symptomatic contact-lens wearers appears not to adapt to supra-threshold stimuli.124 Assuming that viscous shear forces in full fluid film lubrication of 1.10 kPa (at 10 cm.s1 blink speed) in a healthy subject are tolerated, any soft contact lens surface properties at or below this shear force should not lead to any differences in wearing comfort. However, many coefficients of friction of soft contact lens materials are much higher, while the coefficients of friction of the new “comfort-enhancing” lenses are much lower (Figure 12). This effect between the contact lens back surface and the cornea and conjunctiva may also be related to wearing comfort.18 Indeed, refitting experienced contact lens wearers with low-coefficient-of-friction lenses led to significantly improved LIPCOF and LWE after 3 months in one pilot study.125 In summary, in healthy eyes the friction between the sliding partners e the cornea and lid wiper or contact lenses and lid wiper e is independent of the surface of the partners when moving at high velocity, since full fluid film lubrication is operating. Contact lenses with higher intrinsic lubricity may not induce wear on the lid wiper in high sliding velocity either, because of the presence of full fluid film lubrication. In contrast, at low velocity, well-formed brushes are vital to reduce the coefficient of friction, particularly at the beginning and end of blinks, as well as at the reversal points, and perhaps during other low-velocity eye movements. In dry-eye patients, the collapsed brushes appear to be the dominant factor in determining friction between the sliding partners. An additional component of shear stress in blinks may be a delayed transition to full fluid film lubrication and viscous forces that are too high at high sliding velocities. Failure of a proper transition may be due to the partner moduli, the geometry of the lid wiper, blink speed, collapsed brushes, improper surface roughness or tear film viscosity, low film thickness, or evaporation.

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Figure 12. Coefficient of friction in relation to sliding velocity. Empty circles represent different soft contact lens materials, based on Roba et al,16 and the white box represents the cornea,115 all measured in the boundary regime. Black boxes represent full fluid film lubrication based on Dunn et al5 and the grey box is an interpolation of their curve at a blink speed of 200 mm/s. The black circles demonstrate assumed viscous fluid shear in dry eye patients with increased viscosity (extrapolated data; based on the data of Dunn et al5 and 3 times higher viscosity of the dry eye tear film50).

The markedly increased viscosity of the tear film in dry eye patients50 will result in much higher viscous fluid shear stress between contacting partners than in healthy patients. This may also explain why the stained area of the lid wiper in LWE is much larger than the assumed touching zone. Composition of the tear film appears to be vital and can also affect the non-Newtonian properties of the tear film.108,126 The effect of the increased viscous shear on the ocular surface and lids may be compounded by the increased blink rate in dry eye patients.127,128 The coefficient of friction of the back surface of the contact lens may play a dominant role, since the friction that occurs during small movements and low velocities happens in the brush-to-brush regime.5 However, in contrast to symptomatic contact lens wearers, asymptomatic wearers 1) may adapt to this wear, or 2), and more likely, wellformed brushes at the cornea and limbal region may reduce mechanical forces between the ocular surface and the back surface of contact lenses to a minimum. V. CONCLUSIONS In healthy patients, the friction between cornea and lid or contact lens surface and lid is in the full fluid film regime at high sliding velocity and in the brush-to-brush regime at low sliding velocity. The coefficient of friction of the partners (cornea or contact lens and the lid wiper) may play a vital role in contact lens wearing comfort if there are insufficient or collapsed brushes at the beginning and end of spontaneous blinks and at the reversal points. Friction between the contact lens back surface and cornea mainly depends on the coefficient of friction of the contact lens being brush-to-brush. In a dry eye tear film, shear stress between the lid and the ocular 246

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Spontaneous Blinking from a Tribological Viewpoint.

The mechanical forces between the lid wiper and the ocular surface, and between a contact lens and the lid wiper, are reported to be related to dry ey...
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