Lid Wiper Epitheliopathy
Lid wiper epitheliopathy (LWE)
Lid-wiper epitheliopathy (LWE) is defined as a disruption to the surface epithelium of the lid wiper, a portion of the marginal conjunctiva of the upper and lower lid that acts as a wiping surface to spread the tear film over the ocular surface. It is often observed as staining of the lid wiper area by vital dyes.
The etiology of LWE is likely multifactorial, with different causes proposed for those associated with contact lens wear and those associated with dry eye symptoms without contact lens wear. One of the leading hypotheses is increased friction between the lid wiper and ocular or anterior contact lens surface, leading to physical trauma and mechanical abrasion of the epithelial cells of the lid wiper.  Hyperosmotic insult from changes in tear osmolarity may play an important role in lower LWE as the lower lid wiper is less subject to friction-related damage due to a shorter excursion distance during blinks.  There may also be an inflammatory component as upregulation of inflammatory cells have been observed. 
Due to the association between LWE and dry eye symptoms, many risk factors of LWE overlap with those of dry eye, including but not limited to:
- Contact lens wear (both soft and rigid), especially in those with symptoms of dry eye 
- Presence of dry eye symptoms in non-contact lens wearers 
- Older age 
- Asian race 
- Low humidity and increased air flow environments 
- Activities that provoke front surface drying and/or incomplete/infrequent blinking, such as prolonged reading and/or computer use 
Tissue pathology and functional deficits underlying LWE remain to be elucidated further. Preliminary studies suggest cellular apoptosis and atypical keratinization of the lid wiper epithelium, as well as reduced fractal dimensions of the lid wiper microvascular network as possible tissue structure compromises indicated by the observed staining pattern.   These structural changes may be associated with further functional alterations of the lid wiper, such as changes in its sensitivity to touch.  
The lid wiper is observed as an epithelial elevation with a transitional stratified structure of squamous cells in the beginning followed by a conjunctival structure of cuboidal cells, some parakeratinized cells and goblet cells.   In a healthy eye, the tear film, glycocalyx of the cornea, and the conjunctival mucus (secreted mainly by the goblet cells) form a hydrated gel between the lid wiper and the ocular surface to provide lubrication and decrease friction during blinking. Increased friction in LWE may result from inadequate lubrication due to alterations in the normal tear film by contact lens or other underlying dry eye pathology. Possible alterations include: insufficient mucins, altered composition of mucin at the ocular surface, altered rate of evaporation, and altered lipid layer characteristics.     Although no cell morphology differences were observed, the number of goblet cells were reduced in some subjects who had LWE.  Increased friction may also occur in the setting of adequate lubrication due to increased eyelid pressure or abnormal blinking activity, especially during the complete blink following prolonged interblink intervals from incomplete blinks. 
Our knowledge of prevention of LWE is limited due to our limited understanding of the etiology. Current strategies focused on reducing friction and discomfort associated with contact lens may be beneficial to both prevention and treatment of contact lens-associated LWE. Such strategies might include reducing lens wearing time, increasing lens replacement frequency, changing lens material properties, changing lens dimensions (thickness, diameter, radius of curvature) or altering lens fit. Treatment of the underlying dry eye condition targeted at either the symptoms or etiology may also be useful in preventing LWE in those who have not yet developed the condition.
LWE is primarily diagnosed by observation of lid wiper staining by vital dyes, the defining feature of the condition. Because of its common association with dry eye symptoms and/or contact lens wear, a detailed history of dry eye-related symptoms and contact lens-associated discomfort should be collected to differentiate and/or rule out other similar conditions when establishing the diagnosis.
LWE is observed in normal or mildly symptomatic subjects but is more commonly associated with dry eye disease and with symptoms of dryness in both contact lens wearers and non-contact lens wearers. Therefore, a detailed history of contact lens wear and dry eye symptoms along with review of other risk factors associated with LWE would be most helpful in identifying those most at risk for LWE.
The area of the lid wiper is examined for staining with a slit lamp biomicroscope using 16× magnification, a cobalt blue filter, and a slit beam approximately 5 mm in width and 10 mm in height. With the upper eyelid everted, the lid wiper can be seen in white light as a long, thin pale band of tissue beneath the eye lashes extending laterally from inner to outer canthus. Disturbance to the superficial epithelium of the lid wiper is not visible in white light but can be observed with the aid of vital dyes.
Without staining, vascular injection (hyperemia) may be the only finding suggestive of lid-wiper epitheliopathy. These vascular changes, however, are usually subtle and difficult to observe, except when the condition is severe.
After staining with vital dyes, the most typical finding is a linear area of staining in the lid wiper between the crest of the sharp posterior (inner) lid border (i.e. the mucocutaneous junction, or line of Marx) and the subtarsal fold superiorly, from the medial upper punctum to the lateral canthus horizontally. 
Various approaches have been adopted for grading the severity of LWE. Subjective grading is based on the appearance of the lid wiper following instillation of various dyes, including characteristics such as:
- Linear area of staining (0 = <2 mm, 1 = 2-4 mm, 2 = 5-9 mm, 3 = ≥10 mm) 
- Staining pattern (0 = none, 1 = broken line, 2 = thin line, 3 = thick line/patch) 
- Severity of staining (0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe) 
There have also been attempts at automating grading of lid wiper staining using digital image capture of the stained lid wiper and subsequent image analysis, although they have yet to be widely adopted.  
The symptoms of LWE are those associated with dry eye, with or without contact lens wear, including but not limited to dryness, grittiness (scratchiness), soreness (irritation), and burning (watering).
Various staining approaches when examining the lid wiper have been used, including the use of fluorescein, lissamine green, rose Bengal, as well as combinations of these dyes.  There is no consensus on the best staining approach, although recent trends in the literature have been favoring a lissamine green only approach.
A few minutes after instillation of the dye, the upper eyelid is everted by grasping the eyelashes or external eyelid surface, but not any part of the lid margin posterior to the lashes, to prevent finger contact with the transitional or lid wiper epithelium and the possibility of iatrogenic staining.  A cobalt filter is used in the illumination system to enhance fluorescein staining. The horizontal length of the lid wiper, extending from the superior punctum to the lateral canthus, and the sagittal width of the lid wiper, extending from just proximal to the line of Marx to the subtarsal fold, can then be examined. The lid wiper is re-examined using white light and a slightly lower illumination level in order to reveal lissamine green staining.
Visualization of LWE with fluorescein can be enhanced by a Kodak Wratten 12 barrier yellow filter (transmitting above 495 nm) in the slit lamp observation system. The beam of the slit lamp is set to maximum width and 10 mm height, and the potentiometer is set to provide maximum illumination through a Wratten 47 or 47A cobalt blue exciter filter located in the illumination system. 
It is important to differentiate LWE from other physiological or pathological eyelid conditions that may take on a similar appearance. Staining of the normal line of Marx should be differentiated from staining of the lid wiper. Other conditions to consider include lid imbrication syndrome, blepharitis, papillary conjunctivitis, demodicosis, meibomian gland dysfunction. Iatrogenic lid wiper staining is also possible if care is not taken when manipulating lids during eversion.
Current therapies for LWE have been studied either by directly assessing their benefits on LWE or using LWE as a surrogate marker in the course of alleviating dry eye or contact lens discomfort.
Several options have demonstrated efficacy in treating LWE and its associated signs and symptoms in preliminary studies, including topical corticosteroids, oil-in-water emulsion lubricant eye drops, basic fibroblast growth factors and topical rebamipide.   Insertion of punctal plugs alleviated signs and symptoms of aqueous tear deficient dry eye, including LWE. Other treatments that have been proposed include strategies to improve blinking behavior, which may be beneficial in LWE associated with incomplete blinking behaviors, as well as improving contact lens wear comfort. 
The efficacy of these strategies remains to be validated further.
- Korb DR, Greiner JV, Herman JP, et al. Lid-wiper epitheliopathy and dry-eye symptoms in contact lens wearers. Eye & Contact Lens. 2002;28(4):211–216. https://journals.lww.com/claojournal/Abstract/2002/10000/Lid_Wiper_Epitheliopathy_and_Dry_Eye_Symptoms_in.11.aspx. Accessed Nov 22, 2020.
- Efron N, Brennan NA, Morgan PB, Wilson T. Lid wiper epitheliopathy. Progress in Retinal and Eye Research. 2016;53:140-174. http://www.sciencedirect.com/science/article/pii/S1350946216300131. Accessed Nov 26, 2020. doi: 10.1016/j.preteyeres.2016.04.004.
- Korb DR, Herman JP, Greiner JV, et al. Lid wiper epitheliopathy and dry eye symptoms. Eye and Contact Lens. 2005;31(1):2-8. Accessed Nov 28, 2020. doi: 10.1097/01.ICL.0000140910.03095.FA.
- McMonnies CW. An examination of the relationship between ocular surface tear osmolarity compartments and epitheliopathy. Ocular Surface. 2015;13(2):110-117. Accessed Nov 28, 2020. doi: 10.1016/j.jtos.2014.07.002.
- Golebiowski B, Chim K, So J, Jalbert I. Lid margins: Sensitivity, staining, meibomian gland dysfunction, and symptoms. Optometry and Vision Science. 2012;89(10):1443–1449. https://journals.lww.com/optvissci/Abstract/2012/10000/Lid_Margins__Sensitivity,_Staining,_Meibomian.5.aspx. Accessed Nov 28, 2020. doi: 10.1097/OPX.0b013e3182693cef.
- Morgan P, Petropoulos I, Read M, Malik R, Maldonado-Codina C. Confocal microscopy of the lid margin area of contact lens wearers. Contact Lens and Anterior Eye. 2013;36:e43.
- Alzahrani Y, Colorado L, Pritchard N, Efron N. Inflammatory cell upregulation of the lid wiper in contact lens dry eye. Optometry Vision Sci. 2016;93(8):917-924.
- Shiraishi A, Yamaguchi M, Ohashi Y. Prevalence of upper- and lower-lid-wiper epitheliopathy in contact lens wearers and non-wearers. Eye and Contact Lens. 2014;40(4):220-224. Accessed Nov 28, 2020. doi: 10.1097/ICL.0000000000000040.
- Pult H, Purslow C, Murphy PJ. The relationship between clinical signs and dry eye symptoms. Eye. 2011;25(4):502-510. Accessed Nov 28, 2020. doi: 10.1038/eye.2010.228.
- Li W, Yeh TN, Leung T, Yuen T, Lerma M, Lin MC. The relationship of lid wiper epitheliopathy to ocular surface signs and symptoms. Invest Ophthalmol Vis Sci. 2018;59(5):1878-1887. Accessed Nov 29, 2020. doi: 10.1167/iovs.17-23639.
- Jones L, Varikooty J, Keir N, Soong F, Patel P. The evaluation of lid wiper epitheliopathy in contact lens wearers in a controlled low humidity environmental exposure chamber. Invest Ophthalmol Vis Sci. 2013;54:5475.
- McMonnies CW. Psychological and other mechanisms for end-of-day soft lens symptoms. Optometry and Vision Science. 2013;90(6):e175-e181. Accessed Nov 28, 2020. doi: 10.1097/OPX.0b013e318292624b.
- Bandamwar KL, Papas EB, Garrett Q. Fluorescein staining and physiological state of corneal epithelial cells. Contact Lens and Anterior Eye. 2014;37(3):213-223. Accessed Nov 27, 2020. doi: 10.1016/j.clae.2013.11.003.
- Feenstra RPG, Tseng SCG. What is actually stained by rose bengal? Archives of Ophthalmology. 1992;110(7):984-993. Accessed Nov 27, 2020. doi: 10.1001/archopht.1992.01080190090035.
- Wang J, Jiang H, Mao X, Yan W. Quantitative analysis of microvascular network of the lid wiper area in contact lens wearers. Invest Ophthalmol Vis Sci. 2015;56(7):6068.
- Jalbert I, Madigan MC, Shao M, et al. Assessing the human lid margin epithelium using impression cytology. Acta Ophthalmologica. 2012;90(7):e547-e552. Accessed Nov 26, 2020. doi: 10.1111/j.1755-3768.2012.02482.x.
- Du Toit R, Vega JA, Fonn D, Simpson T. Diurnal variation of corneal sensitivity and thickness. Cornea. 2003;22(3):205-209. Accessed Nov 27, 2020. doi: 10.1097/00003226-200304000-00004.
- Millodot M. Diurnal variation of corneal sensitivity. British Journal of Ophthalmology. 1972;56(11):844-847. Accessed Nov 27, 2020. doi: 10.1136/bjo.56.11.844.
- Knop E, Knop N, Zhivov A, et al. The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: An in vivo confocal and histological study. Journal of Anatomy. 2011;218(4):449-461. Accessed Nov 27, 2020. doi: 10.1111/j.1469-7580.2011.01355.x.
- Parsons JH. I. the lids. II. the conjunctiva. In: The pathology of the eye. vol. I. histology. Hodder and Stoughton London; 1904.
- Ehlers N. On the lid margin, the meibomian glands and their secretion. Acta Ophthalmol. 1965;43:67-75. Accessed Nov 27, 2020.
- Knop N, Korb DR, Blackie CA, Knop E. The lid wiper contains goblet cells and goblet cell crypts for ocular surface lubrication during the blink. Cornea. 2012;31(6):668-679. Accessed Nov 27, 2020. doi: 10.1097/ICO.0b013e31823f8d8c.
- Berry M, Pult H, Purslow C, Murphy PJ. Mucins and ocular signs in symptomatic and asymptomatic contact lens wear. Optometry and Vision Science. 2008;85(10):E930-E938. Accessed Nov 28, 2020. doi: 10.1097/OPX.0b013e318188896b.
- Guillon M, Styles E, Guillon JP, Maïssa C. Preocular tear film characteristics of nonwearers and soft contact lens wearers. Optom Vis Sci. 1997;74(5):273-279. Accessed Nov 26, 2020. doi: 10.1097/00006324-199705000-00022.
- Young G, Efron N. Characteristics of the pre-lens tear film during hydrogel contact lens wear. Ophthalmic Physiol Opt. 1991;11(1):53-58. Accessed Nov 26, 2020.
- Guillon M, Maissa C. Contact lens wear affects tear film evaporation. Eye & Contact Lens. 2008;34(6):326–330. https://journals.lww.com/claojournal/Fulltext/2008/11000/Contact_Lens_Wear_Affects_Tear_Film_Evaporation.8.aspx. Accessed Nov 26, 2020. doi: 10.1097/ICL.0b013e31818c5d00.
- Korb DR. Tear film-contact lens interactions. Adv Exp Med Biol. 1994;350:403-410. Accessed Nov 26, 2020. doi: 10.1007/978-1-4615-2417-5_70.
- Yamamoto Y, Shiraishi A, Sakane Y, Ohta K, Yamaguchi M, Ohashi Y. Involvement of eyelid pressure in lid-wiper epitheliopathy. Curr Eye Res. 2015;19:1-8. Accessed Nov 28, 2020.
- McMonnies CW. Incomplete blinking: Exposure keratopathy, lid wiper epitheliopathy, dry eye, refractive surgery, and dry contact lenses. Contact Lens and Anterior Eye. 2007;30(1):37-51. Accessed Nov 28, 2020. doi: 10.1016/j.clae.2006.12.002.
- Lin MC, Yeh TN. Mechanical complications induced by silicone hydrogel contact lenses. Eye and Contact Lens. 2013;39(1):115-124. Accessed Nov 29, 2020. doi: 10.1097/ICL.0b013e31827c77fd.
- Guillon M, Maissa C. Assessment of upper and lower lid margin with lissamine green. Optom Vis Sci. 2008;84.
- Kunnen C, Jara, Percy Lazon De La, Holden BA, Papas EB. Automated assessment of lid margin lissamine green staining. Invest Ophthalmol Vis Sci. 2014;55(13):1976-1976. http://iovs.arvojournals.org/article.aspx?articleid=2267270. Accessed Nov 26, 2020.
- Varikooty J, Lay B, Keir N, et al. The relationship between clinical grading and objective image analysis of lid wiper epitheliopathy. Invest Ophthalmol Vis Sci. 2013;54(15):5460-5460. http://iovs.arvojournals.org/article.aspx?articleid=2150411. Accessed Nov 26, 2020.
- Itakura H, Kashima T, Itakura M, Akiyama H, Kishi S. Topical rebamipide improves lid wiper epitheliopathy. Clinical Ophthalmology (Auckland, NZ). 2013;7:2137.
- Korb DR, Herman JP, Finnemore VM, Exford JM, Blackie CA. An evaluation of the efficacy of fluorescein, rose bengal, lissamine green, and a new dye mixture for ocular surface staining. Eye & Contact Lens. 2008;34(1):61–64. https://journals.lww.com/claojournal/fulltext/2008/01000/An_Evaluation_of_the_Efficacy_of_Fluorescein,_Rose.15.aspx. Accessed Nov 26, 2020. doi: 10.1097/ICL.0b013e31811ead93.
- Yeniad B, Beginoglu M, Bilgin LK. Lid-wiper epitheliopathy in contact lens users and patients with dry eye. Eye and Contact Lens. 2010;36(3):140-143. Accessed Nov 26, 2020. doi: 10.1097/ICL.0b013e3181d94e82.
- Varikooty J, Srinivasan S, Subbaraman L, et al. Variations in observable lid wiper epitheliopathy (LWE) staining patterns in wearers of silicone hydrogel lenses. Contact Lens and Anterior Eye. 2015;38(6):471-476. Accessed Nov 26, 2020. doi: 10.1016/j.clae.2015.05.004.
- Itakura H, Kashima T, Itakura M, Akiyama H, Kishi S. Topical rebamipide improves lid wiper epitheliopathy. Clin Ophthalmol. 2013;7:2137-2141. Accessed Nov 29, 2020.
- El-Rayess HM, Greiner JV, Herman JP, Korb DR, Kleiner-Goudy SJ. Comparison of cortiosteroid and an oil-in-water emulsion in the treatment of lid wiper epitheliopathy (LWE). Invest Ophthalmol Vis Sci. 2009;50(13):546.
- Guthrie SE, Jones L, Blackie CA, Korb DR. A comparative study between an oil-in-water emulsion and nonlipid eye drops used for rewetting contact lenses. Eye and Contact Lens. 2015;41(6):373-377. Accessed Nov 29, 2020. doi: 10.1097/ICL.0000000000000138.
- Zhang C-, Mo J-. Preliminary observation of the clinical therapeutic effect of artificial tears combined with bFGF on lid-wiper epitheliopathy. International Journal of Ophthalmology. 2011;11(9):1654-1655. Accessed Nov 29, 2020. doi: 10.3969/j.issn.1672-5123.2011.09.057.
- Yokoi N, Niu M, Kato H, et al. Effect of punctal occlusion on aqueous tear deficient dry eye evaluated from tear film stability and blink-related friction. Invest Ophthalmol Vis Sci. 2015;56(7):4453.