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The Tear Film and Contact Lens Wear

2 CPD in Australia | TBA in New Zealand | 5 October 2017

By Dr. Emma Gillies

The tear film is a remarkable fluid, much more than just ‘water’ it is a delicate, yet complex structure comprised of many different compounds – proteins, mucins, lipids, inflammatory markers, ions, salts to name but a few. The correct structure, and indeed layering of these components, is critical to maintain the health of the ocular surface. Even a slight change in tear film stability can lead to significant discomfort.

An understanding of the composition, function and structure of the tear film is fundamental to successful contact lens wear, as even the most sophisticated contact lens material and effective contact lens solution will potentially fail on an eye with a poor-quality tear film and unhealthy ocular surface.

The tear film fulfils several critical roles outlined in table one.1,2,3

The tear film volume is known to be around 7µl.15 In the open eye situation, this volume is distributed between the fornices, the upper and lower tear menisci and the pre-ocular tear film that bathes the cornea and bulbar conjunctiva, with the exact distribution varying with the inter-individual differences in the size and shape of these areas. Recent tomographic, interferometric, and reflectance spectral techniques indicate central corneal tear film thickness values of around three to five microns.16,17

Our understanding of the ‘structure’ of the tear film has evolved over time. Historically, it was considered to be a fairly basic discrete tri-laminar structure, comprising an inner mucin layer, middle aqueous layer and an outer lipid layer; with the first concepts being proposed in the 1940s18 and modified slightly in the 1970s.19

Over the past 10 years, research in this area has found the tear film to be a much more complicated interdigitating network, the interactions of which are critical to maintain the integrity and functions of the cornea and ocular surface (See Figure 1). Let’s consider each of the three main components in turn, starting with the innermost.

Mucin

The ocular mucins contribute to the critical role of maintaining the homeostasis of the ocular surface. They make the superficial epithelial cells of the conjunctiva and cornea wettable, provide lubrication and form a physical protective barrier against pathogens. Mucins adhere to particulate contaminants to aid their removal and provide mucosal immunity against pathogens. A reduction in mucus make individuals more susceptible to infection or disease.20

Mucins are produced by bulbar and palpebral conjunctival goblet cells and surface epithelial cells of the cornea. Goblet cells are abundant throughout the conjunctival epithelium of the tarsus, fornix, and specialised areas such as the plica semilunaris.21

Membrane-bound Mucins

Membrane-bound mucins are attached to the superficial epithelial cells of the cornea and form the dense glycocalyx. These mucins are in direct contact with the hydrophobic corneal epithelial cells – they are long, high molecular weight amphiphilic molecules that are bound to the cornea on one end and have a hydrophilic tail on the other. Their dis-adhesive nature play a critical role in protecting the ocular surface, allowing the lids to glide over corneal epithelial cells during blinking.22 The hydrophilic tail molecule binds water and these mucins are thought to maintain the hydration of the ocular surface.21 Examples include MUC1, MUC4 & MUC16.22

Secretory mucins are further sub-divided into:

Gel forming are the largest mucins, they have the capability to trap allergens and debris to facilitate their clearance from the mucosal surface.21 Gel forming mucins can form a highly hydrated gel with the aqueous component of the tear film, and may therefore be responsible for the lubrication of the ocular surface and reduce shear stress during blinking or rubbing (eg: MUC2 & MUC 5AC).22

Soluble mucins are the smallest mucin subtype and are dissolved in the aqueous component of the tear film (e.g. MUC7). The role of MUC7 is not fully understood. Proposed functions include prevention of pathogen binding, contributing to the hydration of the ocular surface and lubrication during the blink.23

Aqueous

The aqueous provides oxygen and nutrients to the avascular cornea and flushes away epithelial debris, toxins and foreign bodies. It is the thickest layer of the tear film, accounting for approximately 98 per cent of the total tear film thickness. It is produced by the lacrimal glands via hormonal, sympathetic and parasympathetic stimuli.24,25,26

The aqueous phase of the tear film is rich in beneficial proteins with important antibacterial and protective properties, and is crucial to the health of the ocular surface. More than 450 proteins have been identified in tears, along with peptides and free amino acids.27 As expected, given the current mixed phase model of the tear structure, both mucins and lipids are present in the aqueous, along with glucose, urea and other elements such as inflammatory markers, antioxidants and healing growth factors.

Of the 450 identified proteins in the tear film, just four proteins together represent 80–90 per cent of the total amount, with Lysozyme being the most abundant (see Table 2).

Lipid

The lipid layer serves to prevent the evaporation of the aqueous phase, aid in the lubrication of the ocular surface and help maintain tear film stability. It is produced mainly by the meibomian glands which are found in the tarsal plates of the upper and lower eyelids.33 There are approximately 20 to 30 meibomian glands on the lower lid and 30 to 40 on the upper lid.34 Lipid secretions containing dozens of oils and waxes are constantly synthesised and secreted, pushing meibum slowly toward the marginal orifice.33 In a normal eye the lipid layer is between 50-100nm thick; any thinner and tear stability may be reduced.35

Over 100 subtypes of lipid have been categorised in tears,36 and these fall into two main groups:

1) Polar or amphiphilic lipids which are found innermost in the tear film structure, and

2) Non-polar lipids, found outermost, closest to the air.

Each layer has unique characteristics and provides differing, yet crucial functions.

The inner polar lipid layer is thought to stabilise the lipid layer by acting as an interphase between the outer non-polar hydrophobic layer and the aqueous layer. Due to the amphiphilic nature of the polar lipids, they orient themselves perpendicular to the tear film so that their hydrophobic tail is immersed in the non-polar layer and their hydrophilic head is in contact with the aqueous phase of the tears.37

The outer non-polar phase is thought to be the thicker lipid phase and its role is primarily to retard water evaporation.38

This precise arrangement of the two types of lipid is thought to form an ‘envelope’ over the aqueous to help lubrication and prevent evaporation.

The Impact of a Contact Lens

Most soft contact lenses are between 70-100 μm thick; 15–30 times thicker than the tear film. When a contact lens is introduced, the tear film is split into a post-lens (1–3μm) and thicker pre-lens (2–3μm) film.39 We are suddenly asking this highly complex, specialised fluid to continue to function as normal, while supporting a foreign object that is at least 15 times thicker than the original film itself. It is extraordinary that we are able to wear, lubricate and maintain clear vision through contact lenses at all!

The presence of the contact lens creates new interfaces within the tear film and this division or split impacts both the biophysical and biochemical properties of the tear film. When a contact lens is placed on the eye, it disrupts the lipid layer of the tear film,40 increasing evaporation41 and reducing tear film thickness.42 The non-invasive tear break up time (NITBUT) typically reduces from 15-30 seconds to five to six seconds over soft contact lenses.42,43 The evidence to date specifically suggests that decreased tear film stability and increased tear evaporation are associated with contact lens discomfort. Decrease in break up time is also thought to contribute toward the increased end of day discomfort reported by many wearers.42 Add challenging environments, and eye fatigue may start to manifest itself.44

Contact Lenses and Deposits

As soon as a contact lens is placed onto the ocular surface, the lens material and tear film begin to interact. The absorption of tear film components changes the quality of the lens surface. The uptake of components from the tear film and release of solution components from the lens following overnight soaking changes the composition of the tear film. It is impossible to prevent this interaction.13

The traditional view is that deposition of tear film components on a contact lens is deleterious, causing immunological responses, increasing adherence of bacteria and altering surface properties.

However, Professor Lyndon Jones questioned this way of thinking about the tear film at the 2015 British Contact Lens Association conference in Liverpool, UK, proposing, “Maybe we were wrong about deposits. Tear film components are there for a reason. We should be looking for materials, and solutions that selectively deposit the components we want and resist those we don’t”.45

A New Way of Thinking

Manufacturers have historically tried to develop materials that interact as little as possible with the tear film, resisting its deposition in an attempt to resist build up on the lenses. However, with modern lens materials being replaced in four weeks or less, deposit resistance has become less important. Perhaps a more sensible approach is to develop materials that positively interact with the tear film, encouraging the deposition of certain components and minimising that of others.13

Optimal biocompatibility will be achieved with materials that maintain these tear film elements in their natural state, permitting them to undertake their inherent biological functions. Incorporating elements into the contact lens materials that are able to mimic the functions of key tear film components may also assist the tear film stability, and materials that integrate beneficial tear film components. Such contact lens materials may indeed improve tear film stability in challenging conditions and environments.

With this in mind, let’s examine the interaction between the tear film and three different contact lens materials; Etafilcon A (Acuvue Moist), Senofilcon A (Acuvue Oasys brand lenses) and Senofilcon C (Acuvue Vita).

Etafilcon A and Lysozyme

Etafilcon A is classified as an FDA Group IV material – high water content, ionic. Of all the Group IV materials, Etafilcon A attracts much more positively charged  protein than the others. There are two reasons for this: the methacrylate in the material confers a greater negative charge, and the pore size of the material is large enough to allow the much smaller and positively charged lysozyme to be absorbed inside the lens matrix rather than just adsorbed onto the surface. But, when does an attraction become a deposit!

Protein deposition on contact lenses is influenced by a number of factors including: water content, material charge (ionic or non-ionic) and pore size, polymer type, and density of the lens matrix. It is also influenced by surface modifications and the type of care regimen used. Once lysozyme becomes bound to the contact lens surface, it undergoes conformational changes that result in protein denaturation.46,47 This results in loss of enzymatic function and an antigenic reaction as the body no longer recognises the molecule. The typical response is contact lens associated papillary conjunctivitis.

With etafilcon A, lysozyme retains most of its activity and is primarily located within the bulk of the lens rather than on the surface.13 Thus lysozyme can also move freely through the lens matrix, diffuse to the lens surface and then interact with any bacteria or any adhered lens contaminants on the surface of the material.13 Lysozyme does not increase bacterial adhesion to lenses and does not decrease surface wettability and it appears that lysozyme only negatively impacts the comfort of the contact lens once it denatures.13 Other proteins, such as lactoferrin, are synergistic with lysozyme and have the potential to reduce gram negative and gram positive bacteria which are involved in the pathogenesis of contact lens related microbial keratitis and inflammation.13

An in vitro study examined the amounts of lysozyme absorbed into various lens types over 28 days of incubation,48 (see Table 3).

It can be seen that there are significant differences in the total amount of lysozyme uptake between material types. Less uptake of the charged protein with the non-ionic SiHy lenses is not unexpected, but when the two hydrogels are compared, there is a significant difference between ionic etafilcon A (1435μg) and non-ionic, group II omafilcon A (41μg). The percentage of lysozyme that remains in its active state is of great importance – in this form the protein continues to work as intended, it is not denatured. For etafilcon A, 90 per cent of the absorbed protein remains active.48

Role of Internal Wetting Agents

Poly Vinylpyrrolidone (PVP) is an amphiphilic homopolymer which, like membrane bound mucins, has both water loving and lipid loving functional groups distributed throughout.49 It is also a humectant with the ability to hold more than double its weight in water. This feature contributes to the maintenance of the hydration of the lens material. The role of PVP in Acuvu lenses is to mimic the role of the membrane bound mucins (that are covered when a contact lens is placed on the ocular surface) on the surface of the contact lens, increasing the pre-lens tear film stability, improving comfort and visual stability (see Figure 3).

Koh and co-workers evaluated the impact of an internal wetting agent on sequential higher order aberrations (HOA) in symptomatic CL wearers wearing 1-Day Acuvue (no internal wetting agent) and 1-Day Acuvue Moist (with internal wetting agent PVP). They found a significant decrease in HOA with 1-Day Acuvue Moist, demonstrating increased tear film stability. Subjective comfort scores were also significantly higher with this lens.50

Senofilcon A

PVP is an ideal wetting agent for silicone hydrogel materials as it is able to interact with both the lipophilic lens components (silicone) and the hydrophilic components to form a homogenous material that maintains hydration and lubricity. Acuvue Oasys was designed to increase tear film stability, particularly in challenging ocular environments. The material has an exceptionally low CoF through the combination of a hydrated silicon polymer and the incorporation of high molecular weight PVP, distributed homogenously throughout the lens matrix. The mucomimetic properties of Senofilcon A have produced a material that has never been beaten on comfort in 15 clinical studies posted on www.clinicaltrials.gov.51 Brennan and Coles found that the surface property of the contact lens (measured by CoF) is the principal determinant of comfort.52 No significant relationship was found between reported comfort scores and the other material properties (modulus, dk/t or water content).

The mucomimetic properties of the Senofilcon A material have been further advanced in Acuvue Oasys 1 day. While the base polymer is the same as the reusable material, the material properties have been modified by increasing the density of the cross linkers within the lens matrix. This has the effect of creating a more dis-adhesive surface, mimicking the function of the natural membrane bound mucins of the cornea/tear interface at the anterior lens/anterior tear film interface.53 The role of these mucins is to reduce friction between the ocular surface and the eyelid during the blink. Replicating this property on the surface of the contact lens reduces the effort required during blinking, reducing the symptoms of tiredness. In a clinical study, eight out of 10 patients rarely or never experienced the symptoms of tired eyes.54

Senofilcon C

The lipids of the tear film are vital in preventing water evaporation from the aqueous layer. Lipids only become problematic in contact lens wear when they degrade to form heterogeneous aggregates, or deposits.

Senofilcon C has been formulated so that the ratio of hydrated to lipohilic silicons is balanced, allowing a higher volume of PVP to be homogenously integrated through the lens matrix. This allows the key tear film components, particularly lipids, to spread homogenously across the surface and throughout the lens, without heterogeneous precipitation or deposition.55

The Senofilcon C material is able to support a stable tear film, maintaining hydration (the primary cause of drop out in monthly replacement wearers is loss of hydration resulting in compensating behaviours) and comfort over a 30 day wearing regime.56

Summary

The tear film is highly specialised and has a number of crucial roles in maintaining the comfort, vision and health of the eye. The complex mixture of lipids, components in the aqueous, and mucins all combine to create this extraordinary fluid. Contact lens tear interactions cannot be prevented, so rather than repel and block the natural tear film components, perhaps the better approach is to work with this interaction and aim to integrate and mimic key helpful components in the contact lens itself. The result of which can lead to contact lenses that; 

  • maintain low levels of inflammatory response
  • integrate lipid to aid end of day comfort
  • mimic the disadhesive properties of the mucin layer to reduce symptoms of tiredness
  • maintain low levels of CoF
  • maintain a stable tear film and vision for the wearer.

Remember, there is nothing bad about the different components of the tear film, the key to contact lens success is to work with these components, not against them.

 

 
 

Dr. Emma L Gillies, PhD BSc(Hons) MCOptom, gained her optometry degree and PhD from Glasgow Caledonian University. She has taught contact lens studies to undergraduate and post graduate students at Glasgow and Sydney universities, and worked in private practice for 13 years in both the UK and Australia. Dr. Gillies is the professional affairs manager for Johnson and Johnson Australia and New Zealand.

This CPD article was supplied by Johnson & Johnson


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' Perhaps a more sensible approach is to develop materials that positively interact with the tear film '