The tear film is an extremely complex structure, containing more than 660 individual proteins, mucins and lipids. Although we often refer to three layers in the tear film – the mucin, aqueous, and lipid layers – these layers are not as discrete as once thought. Many tear film components move through more than one layer, keeping the layers interconnected and interdependent. In a healthy eye, these components work in harmony to help protect and lubricate the cornea and provide a smooth refracting surface; the tear film is essential for both excellent vision and ocular comfort.
Scientific understanding of the tear film has been evolving rapidly in recent years, thanks to better diagnostic and assessment tools, as well as a renewed focus on the causes of meibomian gland dysfunction (MGD) and dry eye. While we still do not fully understand the natural functions of each of the hundreds of unique tear film components, we are confident they all have a purpose.
Like oils anywhere, lipids in the tear film provide an important lubricating function. But very importantly for the eye, the various polar and non-polar lipids form the outermost layer of the tear film, where they are key in helping prevent evaporation of the aqueous layer.1 We know that in eyes with reduced or abnormal lipid production from MGD, tear break-up time increases as the aqueous evaporates much more rapidly.2 By hindering aqueous layer evaporation, lipids help to minimise feelings of dryness and discomfort for the contact lens wearer.3
Contact lenses and lipids
The presence of a contact lens dramatically alters the tear film in a number of ways. It isolates the mucin layer behind the lens, thins the pre-lens tear film and disrupts the lipid layer.3 The less robust pre-lens tear film layer then breaks up and evaporates more readily than normal. Ideally, contact lenses should interact with and support tear film lipids and other components so they can mitigate these negative effects of lens wear.
Yet, despite all the known benefits of lipids in the tear film, contact lens practitioners have historically thought of lipids as undesirable. Lipids can be a source of clinically visible deposits on contact lenses, where they aggregate into ‘jelly bumps’ and can cause discomfort and blur vision.4
Some contact lens materials have been shown to repel lipids and other tear film components. Another option is to take inspiration from the tear film, and look at active integration of lipids and other tear film components into the lens material.
The senofilcon A material (used in Acuvue Oasys) has been recognised as one that attracts lipids, but it is also highly regarded as a comfortable lens material, which seems counterintuitive, given the commonly held belief that more lipids equate to more lens deposits, which are associated with discomfort.
A few years ago, researchers looked at the deposition of lipids on senofilcon A lenses that had been worn for 14 days and cleaned and stored daily using a polyquad multipurpose disinfecting solution. Wearers were classified as either symptomatic (noticeably declining comfort throughout the day, with wear time reduced to <eight hours) or asymptomatic (wear time >10 hours with minimal change in comfort). Interestingly, lenses retrieved from the asymptomatic group had significantly more lipids than those worn by symptomatic group (p=0.001).5 This finding ran contrary to the conventional wisdom that increased lipids are associated with problems in contact lens wear.
As scientists, we began to suspect that outstanding lens performance could be achieved because of lipids, rather than despite of them. It seemed that, more than just noting the presence of a specific tear film component, it might be more important to know where that component is, what form it is in, and how well it is distributed. A naturally occurring tear film component that is integrated into the lens in its natural form (without being degraded) and that is broadly distributed throughout the lens could, in fact, have positive attributes.
Integrated vs deposited lipids
It is important to make a distinction between deposits and integrated tear film components.
Deposits are distinctly separate from the material with which they are associated. Think of salt crystals on a rock or on the rim of a glass. In this aggregated form, the salt can be clearly distinguished from the rock or glass. It has a different texture and colour from the underlying surface. But when it is dissolved in water, salt loses its ‘separateness’ and becomes fully integrated into the water. Saltwater does not look or feel different than water without salt, but the salt does alter the buoyancy, pH and antimicrobial properties of the water.
Lipids are not salts, of course, but the saltwater analogy is helpful in visualising how a tear film component can be integrated into a lens, rather than just being deposited on its surface.
Correlating lipids, dehydration and comfort
The monthly contact lens, Acuvue Vita with HydraMax Technology (senofilcon C) was developed with the philosophy of maximising and maintaining lens hydration in mind, given the need to deliver reliable, superior comfort over a 30-day wear period. This focus on lens hydration, and the potential role of lipids in that process stemmed from the work of the Tear Film and Ocular Surface Society (TFOS).6
The TFOS working group on the effect of contact lens material, design and care systems on wearing comfort evaluated the literature for a multitude of factors that could correlate to lens wearing comfort. They concluded that a change in bulk hydration showed a relationship with comfort for most materials, and reinforced the need for the development of improved methods to investigate lens dehydration.
Understanding the role of lipids in helping to limit dehydration of the tear film led the research and development team for the Acuvue Vita lens to hypothesize that (a) lipids – in their natural state – should be present throughout the lens, versus being deposited on the surface, (b) higher amounts of integrated natural lipid should result in decreased levels of evaporation lens’ surface of, and (c) lipid uptake should relate to lens wearing comfort. It also prompted refinement of a method to better measure evaporation of water through and from the lens' surface (pervaporation rate).
Correlating lipids, dehydration and comfort
To begin to tackle these hypotheses, Heynen and colleagues used fluorescent cholesterol esters and confocal microscopy to confirm that over the course of 30 days of exposure in vitro, lipids tended to distribute homogeneously for all silicone hydrogel lenses tested (senofilcon C/Acuvue Vita, samfilcon A/Ultra, comfilcon A/Biofinity, lotrafilcon B/Air Optix Aqua), though the dynamics over the month varied slightly by material (figure 1).7
Figure 1: Cross section of lipid density and distribution levels in lenses. Tear film lipids are shown as yellow spheres. For illustration purposes only
Next, as part of a clinical study, lenses worn for 30 days were collected and analysed for cholesterol and cholesterol esters via liquid chromatography-mass spectrometry, a well established method for analysing lipid uptake. This testing confirmed differences in amounts of lipids integrated across the four materials listed above, with the senofilcon C material having the highest levels of lipid uptake.
The average total amount of lipid taken up from the study subjects’ tear film was 20.4 ±2.31μg per lens in the senofilcon C group, more than twice the lipid uptake from the samfilcon A (9.8 ±1.48μg) or comfilcon A (9.0 ±0.85μg) lenses. The surface-coated lotrafilcon B lenses contained only 0.5 ±0.05μg of lipids, on average.8
Importantly, these lipids must remain in their natural state, where they can function normally, rather than denaturing and aggregating into clinical deposits. Another ex vivo scientific study provides evidence that these well-distributed lipids are performing as intended while in the lens.
The rate of evaporation through senofilcon C lenses that had been worn for 30 days of daily wear was 33% less than that of other monthly lenses tested.9,10
Finally, total lipid uptake and correlation to subjective comfort was evaluated in a clinical study. The four monthly replacement contact lenses materials mentioned (senofilcon A/Acuvue Vita, samfilcon A /Ultra, comfilcon A/Biofinity, and lotrafilcon B/Air Optix Aqua) were worn by subjects in a masked, randomised, parallel, 30-day clinical trial during which 533 subjects (approximately 130 per lens group) wore the lenses on a daily-wear basis, cleaning and storage with a multipurpose solution (Opti-Free PureMoist).
Subjective comfort data (overall comfort, lens awareness, and dryness) was collected from each patient using a five-point Likert scale. After 30 days, the worn lenses were collected and analysed for cholesterol and cholesterol esters via liquid chromatography-mass spectrometry, as reported above.
The comfort measures from the clinical trial were plotted against the ex vivo lipid uptake measures. There was a strong correlation (r2=0.85 to 0.99) between lipid uptake of the four lens materials and subjective comfort attributes (figure 2a to c). The lenses with the highest lipid quantity were most likely to be rated excellent or very good for overall comfort and not feeling dry and had the lowest rates of lens awareness.11
Figure 2: Linear regression plots demonstrate a positive correlation between ex vivo lipid integration after 30 days of wear and clinical measures of performance, including overall comfort (a), not being aware of lens (b), and not feeling dryness throughout the day (c). Error bars represent 95 % confidence interval values obtained for ex vivo lipid integration after 30 days of wear. Open and closed symbols represent % Top 2 Box (% T2B) and % Bottom 2 Box (% B2B) datasets, respectively
Reflecting on the beneficial properties of lipids discussed at the beginning of this article, the findings of comfort being linked to lipid uptake should not be surprising. Nature gave our eyes their beneficial lipids.
Acuvue Vita embraces these natural components from the tear film and integrates them into the contact lens to help improve performance.
Tear inspired hypothesis
Lipids that are integrated into the lens in their natural form (without being degraded) and broadly distributed throughout the lens could have positive attributes.
What we need to know:
- Are lipids found in the lens, and how are they distributed?
- Is the lipid uptake profile different than other lens technologies?
- Does lipid uptake impact lens evaporation levels?
- How does lipid integration impact lens performance?
Zohra Fadli is Senior Manager in Research and Development, Charles Scales is Principal Scientist in Research and Development and Cristina Schnider is Director, Global Professional Affairs at Johnson & Johnson Vision Care, in the USA.
References
1 Green-Church KB, Butovich I, Willcox M, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Tear Film Lipids and Lipid–Protein Interactions in Health and Disease. Invest Ophthalmol Vis Sci 2011;52(4):1979-93.
2 Foulks GN. The correlation between the tear film lipid layer and dry eye disease. Surv Ophthalmol 2007;52(4):369-74.
3 Craig JP, Willcox MDP, Agueso P, et al. The TFOS International Workshop on Contact Lens Discomfort: Report of the contact lens interactions with the tear film subcommittee. Invest Ophthalmol Vis Sci. 2013;54:TFOS123-TFOS156.
4 Gromacki SJ. Soft contact lens deposition. Contact Lens Spectrum, April 2006.
5 Subbaraman L, Babaei Omali N, Heynen M, et al. Could lipid deposition on contact lenses be beneficial? Contact Lens & Anterior Eye 2015; 38 (Suppl 1): e-10. (can be accessed at www.contactlensjournal.com/article/S1367-0484(14)00249-5/pdf)
6 Jones L, Brennan NA, Gonzalez-Meijome J, et al. The TFOS international workshop on contact lens discomfort: Report of the contact lens materials, design, and care subcommittee. Invest Ophthalmol Vis Sci 2013;54:TFOS37-TFOS70.
7 Heynen M, Qiao H, Subbaraman L, et al. Location of non-polar lipids in monthly replacement silicone hydrogel contact lens materials. Optom Vis Sci 2016;93:E-abstract 165116.
8 Subbaraman L, Omali N, Lada M, Canavan K, et al. An in-vitro uptake model to predict ex-vivo lipid deposition on worn silicone hydrogel contact lenses. Optom Vis Sci 2016;93: E-abstract 160111.
9 Riederer D, Scales C, Santa Maria B, Ferran M, Fadli Z. New methods for measuring water transport through hydrogel contact lenses. Invest Ophthalmol Vis Sci 2017;58:ARVO E-Abstract 3071
10 Riederer D, Scales C, Santa Maria B, Fadli Z. Permeation and pervaporation of water through contact lens materials. Optom Vis Sci 2016;93:E-abstract 160110.
11 Canavan K, Ebare K, lada M, Fadli Z. Contact lens lipid uptake and correlation to comfort. Optom Vis Sci 2016;93:E-abstract 165118.