Review article
Non-invasive objective and contemporary methods for measuring ocular surface inflammation in soft contact lens wearers – A review

https://doi.org/10.1016/j.clae.2017.05.008Get rights and content

Highlights

  • Epithelial metaplasia is a better conjunctival inflammatory biomarker for lens wear.

  • Tear cytokine levels are affected by the methods of collection and analysis.

  • Dendritic cell migration provides clue to the status of inflammation in vivo.

  • Individual susceptibility to lens induced ocular inflammation will be investigated.

Abstract

Contact lens wear is one of the primary risk factors for the development of ocular surface inflammatory events. The purpose of this review is to examine and summarize existing knowledge on the mechanisms of contact lens related ocular surface inflammation and the evidence for the effectiveness of current objective methods to measure ocular surface inflammation. Contact lens wear is postulated to trigger an inflammatory response on the ocular surface due to mechanical, chemical, hypoxic stress, or by the introduction of microbes and their toxins. Apart from the traditional signs of inflammation, such as swelling, oedema, redness and heat, on the ocular surface, other methods to measure ocular surface inflammation in sub-clinical levels include tear inflammatory mediator concentrations, conjunctival cell morphology, and corneal epithelial dendritic cell density and morphology. Tear inflammatory mediator concentrations are up- or down-regulated during contact lens wear, with or without the presence of associated inflammatory events. There is higher conjunctival cell metaplasia observed with contact lens wear, but changes in goblet cell density are inconclusive. Dendritic cell density is seen to increase soon after initiating soft contact lens wear. The long term effects of contact lens wear on dendritic cell migration in the cornea and conjunctiva, including the lid wiper area, require further investigation. Currently patient factors, such as age, smoking, systemic diseases and genetic profile are being studied. A better understanding of these mechanisms may facilitate the development of new management options and strategies to minimize ocular surface inflammation related to contact lens wear.

Introduction

The use of contact lenses is one of the primary risk factors associated with corneal and ocular surface inflammatory events [1], [2], [3], [4]. It has been reported that soft contact lens related corneal inflammatory and infiltrative events occur in 7–44% of wearers per year and are associated with significant morbidity and economic cost (>$175 million US dollars in 2010, USA) [1], [5], [6], [7]. Contact lens induced adverse events can be inflammatory and/or infectious in nature [2], [8]. Contact lens wear can induce hypoxic or mechanical stress on the ocular surface and may also act as a vehicle for microbial inoculation, leading to pathogenic events ranging from subtle epithelial injury and infiltration by pathogens, antigens and white blood cells to the most severe microbial keratitis (MK)[9].

It has been hypothesized that a contact lens on the eye induces an ocular surface inflammatory process. Efron has comprehensively shown how contact lens wear can lead to the five cardinal signs of inflammation (mild and severe) that are clinically seen on the ocular surface namely- rubor (redness), calor (heat), tumor (swelling), loss of function (Functio laesa) and dolor (pain), which is encompassed as discomfort [10], and this is consistent with the Merriam- Webster dictionary definition of inflammation. Even though the forms of inflammations are mild in successful contact lens wearers, cardinal signs, such as hyperaemia [11], increased ocular temperature when wearing contact lens [12], [13], symptoms [14], and corneal oedema in subjects who wear low oxygen transmissibility contact lenses [15], can be more readily observed than in non-contact lens wearers. These milder forms of inflammation can be managed by altering the contact lens material, fitting, decreasing wearing time and instillation of artificial tears [13], [15], [16], [17]. However, in severe cases, the contact lens induced inflammation can lead to adverse events that warrant discontinuation of lens wear [18].

A large proportion of soft contact lens wearers report ocular dryness and discomfort [19], [20]. It has been stated that this, so-called, ectopic corneal pain could be due to subclinical inflammation with the presence of normal tear secretion and corneal sensitivity [21], [22]. Contact lens wear has been shown to induce higher ocular temperature and conjunctival hyperemia, which supports the notion that soft contact lens wear induces ocular surface inflammation, along with other compromised ocular surface parameters, such as lower tear stability and higher ocular surface staining [13], [23], [24], [25].

This manuscript aimed to review the findings of these non-invasive contemporary techniques for detecting inflammatory responses at the cellular and molecular levels, including a) Ocular inflammatory response related to contact lens wear in humans; b) Recent objective methods used to evaluate the inflammatory responses on the ocular surface; and c) Potential factors that may be related to the risk of ocular inflammatory events in contact lens wearers.

Section snippets

Ocular surface inflammation in contact lens wear

The proposed mechanism driving this contact lens related inflammatory response can be described in two main steps: First, the ocular surface releases pro-inflammatory molecules and proteins [2], [26] in response to the presence of a contact lens. These proteins then modulate the ocular surface (i.e, migration of antigen presenting cells and changes in the morphology of conjunctival cells) and these changes further drive the inflammatory cascade, in a vicious cycle (Fig. 1) [27]. These

Evaluation of ocular surface inflammation at the cellular and molecular level

In this section, the methodology of sample collections and analyses of tear inflammatory mediators, conjunctival cell morphology, including goblet cell density and epithelial squamous metaplasia, and antigen presenting cells on the ocular surface and the effects of contact lens wear are discussed.

Factors affecting ocular surface inflammation

Contact lens wear related factors, such as duration of wear, lens power, replacement schedule and lens materials [1], [178]; and behaviors and non-modifiable patient factors, such as age and sex, must be taken into consideration when investigating contact lens related ocular surface inflammation. For example, the peak prevalence for contact lens induced corneal inflammatory events occurs in 15–44 years old [178], [179], [180], [181]. However, the effect of age and innate immune system in

Conclusion

Recent improvements in technology have significantly increased the ability to quantitatively and objectively assess the inflammatory status of the human ocular surface in vivo. This manuscript provided a review of contemporary techniques to measure the inflammatory responses on the ocular surface during contact lens wear, and highlighted the potential limitations of techniques and challenges comparing results across studies, suggesting that standardizing test methods and interpretations are

Conflict of interest

The authors have no proprietary or commercial interests in any concept or product discussed in this article.

This review did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

References (189)

  • J. Springer et al.

    Calcitonin gene-related peptide as inflammatory mediator

    Pulm. Pharmacol. Ther.

    (2003)
  • P.J. Pisella et al.

    Flow cytometric analysis of conjunctival epithelium in ocular rosacea and keratoconjunctivitis sicca

    Ophthalmology

    (2000)
  • L. Zhou et al.

    In-depth analysis of the human tear proteome

    J. Proteomics

    (2012)
  • T.F. Liu et al.

    Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes

    Cytokine

    (1998)
  • L.D. Hazlett et al.

    Extended wear contact lens usage induces Langerhans cell migration into cornea

    Exp. Eye. Res.

    (1999)
  • C.A. Dinarello

    Biologic basis for interleukin-1 in disease

    Blood

    (1996)
  • R.A. Black et al.

    Activation of interleukin-1 beta by a co-induced protease

    FEBS Lett.

    (1989)
  • F.L. van de Veerdonk et al.

    Inflammasome activation and IL-1beta and IL-18 processing during infection

    Trends Immunol.

    (2011)
  • S. Narayanan et al.

    The effect of interleukin-1 on cytokine gene expression by human corneal epithelial cells

    Exp. Eye Res.

    (2005)
  • W.P. Arend

    Interleukin-1 receptor antagonist

    Adv. Immunol.

    (1993)
  • L.P. Aristoteli et al.

    Isolation of conjunctival mucin and differential interaction with Pseudomonas aeruginosa strains of varied pathogenic potential

    Exp. Eye Res.

    (2003)
  • P. Argueso et al.

    Epithelial mucins of the ocular surface: structure, biosynthesis and function

    Exp. Eye Res.

    (2001)
  • A. Mann et al.

    Contact lens interactions with the tear film

    Exp. Eye Res.

    (2013)
  • A.K. Bhan et al.

    T-cell subsets and Langerhans cells in normal and diseased conjunctiva

    Am. J. Ophthalmol.

    (1982)
  • M. Tishler et al.

    Elevated tear interleukin-6 levels in patients with Sjogren syndrome

    Ophthalmology

    (1998)
  • P. Cho

    The cotton thread test on Chinese eyes: effect of age and gender

    J. Br Contact Lens Assoc.

    (1994)
  • H. Wagner et al.

    Risk factors for interruption to soft contact lens wear in children and young adults

    Optom. Vis. Sci.

    (2011)
  • D.M. Robertson

    The effects of silicone hydrogel lens wear on the corneal epithelium and risk for microbial keratitis

    Eye Contact Lens

    (2013)
  • D.F. Sweeney et al.

    Clinical characterization of corneal infiltrative events observed with soft contact lens wear

    Cornea

    (2003)
  • F. Stapleton et al.

    The epidemiology of contact lens related infiltrates

    Optom. Vis. Sci.

    (2007)
  • S.A. Collier et al.

    Estimated burden of keratitis – United States, 2010

    MMWR

    (2014)
  • A. Thakur et al.

    The proinflammatory cytokines and arachidonic acid metabolites in human overnight tears: homeostatic mechanisms

    J. Clin. Immunol.

    (1998)
  • D.F. Sweeney et al.

    Are inflammatory events a marker for an increased risk of microbial keratitis?

    Eye Contact Lens

    (2007)
  • N. Efron

    Contact lens wear is intrinsically inflammatory

    Clin. Exp. Optom.

    (2017)
  • G. Young et al.

    Soft contact lens-related dryness with and without clinical signs

    Optom. Vis. Sci.

    (2012)
  • D.K. Martin et al.

    The presence of a contact lens induces a very small increase in the anterior corneal surface temperature

    Acta. Ophthalmol. (Copenh.)

    (1986)
  • B. Golebiowski et al.

    Corneal nerve morphology, sensitivity, and tear neuropeptides in contact lens wear

    Optom. Vis. Sci.

    (2017)
  • P.B. Morgan et al.

    Central and peripheral oxygen transmissibility thresholds to avoid corneal swelling during open eye soft contact lens wear

    Biomed. Mater. Res. B. Appl. Biomater.

    (2010)
  • F. Stapleton et al.

    Impact of contact lens material, design, and fitting on discomfort

    Eye Contact Lens

    (2017)
  • M. Covey et al.

    Hypoxic effects on the anterior eye of high-Dk soft contact lens wearers are negligible

    Optom. Vis. Sci.

    (2001)
  • J. Santodomingo-Rubido et al.

    Adverse events and discontinuations during 18 months of silicone hydrogel contact lens wear

    Eye Contact Lens

    (2007)
  • K. Richdale et al.

    Frequency of and factors associated with contact lens dissatisfaction and discontinuation

    Cornea

    (2007)
  • K. Dumbleton et al.

    T.I.W.o.C.L.D. members of the, The TFOS international workshop on contact lens discomfort: report of the subcommittee on epidemiology

    Invest. Ophthalmol. Vis. Sci.

    (2013)
  • A. Muselier-Mathieu et al.

    Ocular surface assessment in soft contact lens wearers; the contribution of tear osmolarity among other tests

    Acta Ophthalmol.

    (2014)
  • C.W. McMonnies et al.

    Assessment of conjunctival hyperemia in contact lens wearers. Part II

    Am. J. Optom. Physiol. Opt.

    (1987)
  • C.W. McMonnies et al.

    Assessment of conjunctival hyperemia in contact lens wearers. Part I

    Am. J. Optom. Physiol. Opt.

    (1987)
  • J.J. Oppenheim et al.

    Properties of the novel proinflammatory supergene intercrine cytokine family

    Ann. Rev. immunol.

    (1991)
  • Y. Chen et al.

    Interferon-gamma-secreting NK cells promote induction of dry eye disease

    J. Leckoc. Biol.

    (2011)
  • The definition and

    classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop

    Ocul. Surf.

    (2007)
  • A. Poltorak et al.

    Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation

    Proc. Natl. Acad. Sci. U. S. A.

    (2000)
  • Cited by (30)

    • Tear proteomic analysis of young glasses, orthokeratology, and soft contact lens wearers

      2023, Journal of Proteomics
      Citation Excerpt :

      Although beneficial for slowing myopia progression, contact lens wear is the most common trigger of ocular surface inflammation and can result in discomfort, pain, and even scarring [6,7]. Studies showed that contact lens wear-related corneal inflammatory events occurred more often in teenagers and young adults aged 15 to 25 [8–11]. Moreover, ocular surface complications such as conjunctival injection and keratitis occur in up to 70% of asymptotic contact lens wearers [12].

    • Effects of contact lens wear on tear inflammatory biomarkers

      2022, Contact Lens and Anterior Eye
      Citation Excerpt :

      The direct contact of the lens surface with the eye can modify the normal ocular physiology, inducing immunological changes associated with a higher risk of infection [5]. Therefore, the use of these devices may itself activate subtler inflammatory mechanisms as a response to mechanical stress, hypoxia, or the presence of pathogens and their toxins [6]. Even though the forms of inflammations are mild in successful CL wearers in most cases, traditional signs such as swelling, edema, redness, and heat on the ocular surface can be more readily observed than in non-wearers [6].

    • Matrix metalloproteinases in keratoconus – Too much of a good thing?

      2019, Experimental Eye Research
      Citation Excerpt :

      A certain degree of MMP-driven ECM remodelling may be a necessary step for cornea healing, but an imbalance in this tightly regulated process may, in the long term, result in the progressive weakening of the cornea (Fig. 2). Eye rubbing and contact lens wearing have a clear link with ocular surface inflammation (Chao et al., 2017; Greiner et al., 1985). Although KC is generally considered a non-inflammatory eye condition (Krachmer et al., 1984), this is still under debate (Galvis et al., 2015; Ionescu et al., 2016; McMonnies, 2015).

    View all citing articles on Scopus
    View full text