In 2012, the Tear Film & Ocular Surface Society (TFOS) gathered 79 worldwide experts on contact lenses and the ocular surface to summarize and report on the state of understanding of contact lens discomfort (CLD).¹ The aim of this report was to provide an evidence-based approach to the definition, epidemiology, pathophysiology, management, and investigations into CLD.¹ The series of publications provided a snapshot of what was known at the time regarding CLD, which was defined as: “…a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreased wearing time and discontinuation of contact lens wear.”²

With this definition, the working group established several key points about CLD. First, while potentially obvious, it was recognized that CLD is fundamentally about the interaction between a contact lens and the ocular surface and, therefore, that discontinuation of lens wear should alleviate the condition in most cases.² This allowed the condition to be differentiated from other diseases that may contribute to contact lens discontinuation such as dry eye or meibomian gland dysfunction (MGD), establishing CLD as a distinct entity from previous interchangeably used terms such as “contact lens dry eye.” Second, the definition also delineated CLD from discomfort associated with neophyte lens wear and application, because identification and management of discomfort in these two situations are very different.² Third, the committee was also able to break down the pathophysiology of the condition into those that were lens-related and those that were environmentally related as well as how these two interact to create the patient condition and experience. Fourth and finally, the committee was also able to describe a purported natural history and sequence of events in the disease, in which those who experience CLD will struggle to achieve seamless contact lens wear, eventually leading to reduction in comfortable and total wear time before dropping out of lens wear temporarily and then completely.²

The epidemiology subcommittee highlighted the nonmodifiable and modifiable risk factors as well as the clarity, or lack thereof, of the risk profile for patients to develop CLD.³ Unfortunately, the lack of standardized tools or investigations to reliably measure comfort in contact lens wearers constrained the ability to sort through relevant risk factors for associations with CLD. Risk factors such as age and ethnicity show variable or no association with CLD, while there is some suggestion that females, those who have seasonal allergies, and those who are using certain medications may be more likely to have CLD.³

The subcommittee on therapeutic management of CLD also encountered similar issues to the definition and epidemiology groups in determining and evaluating the effects of different interventions; many of the studies within the literature are inconsistent or contradictory to others, or their clinical impact on the contact lens wear experience by patients who have CLD is marginal.⁴ There was recognition in the therapeutic report that each of the suggested interventions or management options would provide only an incremental improvement. However, it also noted that, in combination, they would be worthwhile to correctly “set the stage” for successful lens wear.

Therapeutic actions included suggestions to examine the impact of patients’ occupational or vocational environment, to look for the presence of coexisting disease such as allergy, and to reduce the use of certain medications known to have a drying effect such as isotretinoin or antihistamines.⁴ Management of abnormalities associated with medication toxicity (medicamentosa), the tear film, lid, conjunctiva and cornea, and lens fit are all obvious but important aspects to examine when determining the likelihood of lens wear success; all of these were recommended to be proactively managed.⁴

Switching to a daily disposable modality may provide a benefit in soft lenses, but changing from monthly to two-week replacement likely does not.⁵ Part of this benefit may be due to the elimination of a lens care solution, as this is a factor in CLD; some studies using the same lenses on a daily disposable versus reusable basis showed a preference for the former.⁴ However, replacement schedule had little to no impact for rigid lenses.⁶

Switching from different compositions of materials—particularly from hydrogels to silicone hydrogels—while done frequently in practice, is not supported by the research. However, there is more evidence that switching from rigid lenses to soft lenses may alleviate CLD if it is experienced due to rigid lens wear; the converse appears to confer no benefit.⁴

External wetting agents, in the form of rewetting eye drops, do appear to have some evidence to support their use in improving associated symptoms of dryness when these lenses are worn.⁴ Other interventions to improve the amount of tears on the surface, such as punctal plugs, also appear to have some evidence to support their use in improving contact lens wearing times.⁴

Investigation into the use of pharmacologics to aid in improving CLD have focused on the reduction of inflammation. Corticosteroids and nonsteroidal anti-inflammatory drugs have been proposed for use in this context to alleviate presumed contact lens-associated inflammation; however, the risk-to-benefit ratio for using these agents, associated side effects, and lack of clear evidence supporting improvement with their use have prevented widespread adoption of these agents in CLD.⁴ Cyclosporine, an immunomodulatory agent used for dry eye, also shows contradictory results in terms of improving contact lens wear and decreasing reliance on rewetting drops, making it unclear as to whether it has a role in CLD.⁴

The macrolide antibiotic azithromycin, which purportedly has anti-inflammatory effects (particularly on the lids)—and thus aids in the management of blepharitis—has had limited investigation for both duration and number of participants in reported studies for impacting CLD, but the results thus far are positive, suggesting that larger-scale studies would be warranted.⁷ The committee suggested that the field could investigate neuromodulatory agents to modify the signaling of ocular surface pain and discomfort, with agents such as the opioids and autologous serum as potential avenues for investigation.⁴

A 2020 PERSPECTIVE

Improving Ocular Surface Health to Overcome CLD From a theoretical point of view, the rationale for emphasizing ocular surface health in contact lens wear is sound; if the tear film and ocular surface are poor, then lenses on the surface of the eye would be uncomfortable no matter how engineered and compatible they are. At approximately this time, when the TFOS International Workshop on Meibomian Gland Dysfunction occurred, a paradigm shift occurred in the understanding of dry eye disease that recognized MGD as the leading cause of evaporative dry eye, the most prevalent form of dry eye disease. There is evidence to suggest that contact lens wear contributes to MGD,⁸ which in turn is associated with CLD.⁹

In either case, the management of MGD became a viable strategy for managing CLD. The premise was to treat MGD as an underlying condition and provide a robust lipid layer to maintain tear film stability during lens wear. Tear film stability is associated with greater contact lens wear success, with symptomatic lens wearers generally having a less stable pre-lens tear film compared to asymptomatic wearers.¹⁰

The treatment of MGD has also evolved significantly over the past decade. While warm compresses are still a mainstay of treatment, there has been a shift away from using hot water with towels, as was done traditionally, and toward using products with superior heat retention.¹¹ Vectored thermal pulsation¹² and a warming eye mask¹³ are two clinically accessible methods that have been shown to improve CLD. These results support the theory that managing meibomian gland health and supporting the lipid layer will likely continue as a primary strategy for addressing CLD.

Other aspects of eyelid health have also received significant attention for their contributing role to CLD. Microbial overburden on the eyelashes and margins has been associated with increased lens bioburden, which in turn is associated with discomfort.¹⁴ Additionally, Demodex folliculorum has also received renewed attention over the past decade as a possible culprit behind CLD.¹⁵ One study reported that approximately 93% of individuals who had contact lens intolerance had Demodex and that only 6% of those who had Demodex were discomfort-free.¹⁵

Over the past decade, the number of commercially available eyelid hygiene products has vastly increased. These products include pre-soaked cotton pads, gel cleansers, foaming cleansers,¹⁶ and even a hand-held rotary device.¹⁷ Unfortunately, not many studies have evaluated the effectiveness of these products in managing blepharitis, let alone CLD. Despite this, eyelid hygiene has been frequently recommended by clinicians to manage ocular surface disease, including MGD.¹⁸ Through the mechanism of reducing bioburden on the eyelids, two recent studies featuring microblepharoexfoliation¹⁷ and lid debridement¹⁹ demonstrated significant improvements in CLD after the procedure. Therefore, maintenance of ocular surface health, through regular eyelid hygiene and management of MGD, will likely continue to be the mainstay management option for CLD.

Tear Film Biomarkers for Eliciting Pathophysiology and Diagnosis Clinically, the diagnosis of CLD is still largely subjective and mainly revolves around querying symptoms. While subjective responses allow clinicians to learn about patients’ experiences and perspectives, they are not without limitations. Subjective responses can vary depending on patient mood or mental state.²⁰ As a result, there is a need for reliable objective metrics. Biomarkers are often used as objective metrics. For example, they could be used to determine risk and to diagnose, monitor, or even predict the prognosis of disease. The case for biomarkers is often presented in the context of diagnosing and managing diabetes (blood sugar levels) or hypertension (blood pressure), but biomarkers as a whole can have numerous applications.

For ocular surface pathologies, some examples of biomarkers available from the tear film may include inflammatory cytokines (e.g., interleukin-8 [IL-8])²¹ and proteases (e.g., matrix metalloproteinase-9 [MMP-9]).²² Biomarkers do not necessarily need to be small molecules within the tear film; they may also arise from physical properties of the tear film and ocular surface such as osmolarity, tear meniscus height, or lipid layer thickness. But, despite their potential to provide information, there have so far been significant limitations that must be addressed (e.g., large normal physiological range and large overlap between disease and normal values) that make reliable interpretation difficult.²³ Additionally, some biomarkers are difficult to access in a clinical setting, as they require special instruments or laboratory equipment.

While not yet widely clinically viable, alterations in biomarkers due to pathology can provide clues about the underlying pathology. While some suspect that inflammation may play a role in CLD, the clinical features of CLD do not reflect the classical signs of inflammation (redness, heat, swelling, pain, loss of function). Tear film biomarker studies found only a few inflammatory cytokines to be associated with lens wear and discomfort (leukotriene B4 [LTB4] and interleukin-17 [IL-17A]),^24,25 which could indicate that low-grade inflammation may accompany lens wear and CLD. This would support the modulation of inflammation having promise in managing CLD.²⁶

At the rate at which mass spectrometry and multiplexing technologies are advancing, researchers are getting better with the availability of more efficient and cost-effective tools to discover novel biomarkers and pathways. As we continue to elicit information on pathways involved from the biomarkers on the ocular surface, we may one day arrive at a point at which we could determine the precise etiology and pathophysiology of CLD in different patients and tailor treatments accordingly.

The Glycocalyx in CLD The corneal and conjunctival glycocalyx—a glycoprotein layer on the surface of epithelial cells—pins the tear film to the ocular surface and plays a role in stabilizing the tear film as it spreads across the ocular surface during a blink.²⁷ Despite its vital role on the ocular surface, the glycocalyx has been relatively understudied and has received very little attention with regard to CLD; this can possibly be attributed to the lack of ability to assess it clinically. Alteration or disruption to the glycocalyx, or the relative amounts of mucins, has been linked with ocular surface disease and may serve as a source of potentially useful biomarkers.²⁸ The glycocalyx could be visualized by using fluorescein wheat germ agglutinin (F-WGA) to highlight it.²⁹ In one study, contact lens wearers had a less pronounced glycocalyx across the cornea compared to non-lens wearers.²⁹ Additionally, symptomatic lens wearers have significantly reduced mucins on the superior palpebral lid wiper region compared to asymptomatic wearers.²⁹ These findings implicate a role of friction in CLD and emphasize the importance of mucins in supporting contact lens wear.

Minimizing Friction to Minimize CLD As the eyelid repeatedly blinks over the surface of the contact lens over the course of the day, mechanical friction between the lid wiper region of the superior eyelid and the contact lens surface can cause damage to the tissue, resulting in what has been termed “lid wiper epitheliopathy.” The etiology has been hypothesized to be the result of poor interfacial lubrication.³⁰ As a result, it was expected to appear in greater proportions in individuals who wear contact lenses and have CLD. However, a comprehensive review concluded that lid wiper epitheliopathy had almost no association with lens wear or symptoms.³¹ More research on the role of lid wiper epitheliopathy in contact lens wear would be valuable to help practitioners understand the relationship between interfacial interactions and symptoms of discomfort.

Because a higher coefficient of friction has been linked to discomfort,³² there has been innovative efforts to incorporate molecules for the sole function of increasing surface wettability and lubrication. This idea is illustrated in recent works involving grafting proteoglycan 4 (PRG4),³³ grafting a layer of hyaluronic acid,³⁴ and polymerizing a layer of dimethylacrylamide³⁵ on the surface of contact lenses.

BEYOND 2020

Since the completion of the TFOS International Workshop on CLD in 2013, significant strides have been made in improving contact lens materials, solutions, and understanding of CLD. Today, while contact lens solutions and materials are more advanced than they have ever been, CLD continues to plague many lens wearers and remains the primary reason for lens discontinuation.

Over the past decade, advances in different areas of clinical and basic sciences have continued to add to our understanding and ability to treat CLD. There was a focus on managing ocular surface disease and maintaining good eyelid hygiene, with the aim to strengthen and provide a robust tear film in the hopes of sustaining longer hours of comfortable lens wear. There was continued work in the area of tear film biomarkers to elicit the mechanism and pathophysiology underlying CLD as well as to aid in its diagnosis. There was work that revealed the glycocalyx in situ, opening up another avenue to explore CLD. Lastly, the idea of friction driving discomfort had inspired a number of innovative engineering solutions that may one day be used clinically to manage CLD. The advances in these areas have shown some promise in tackling CLD, and building upon them will bring us closer to overcoming CLD.

It is unfortunate that despite all of the strides that have been made, CLD still persists. However, we believe that there is still much to learn about this condition. This article has touched on only a few areas. As we step into the next decade, innovation and technological advancements will afford us many more opportunities to learn and study CLD, with the hope that one day, the mystery of CLD will be no more. CLS

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