Lid Wiper Epitheliopathy

Etiology

The exact cause of LWE is unknown, but it is believed to be multifactorial in nature. One theory suggests that LWE is caused by friction between the eyelid and the cornea during blinking, which leads to microtrauma and inflammation of the lid wiper area. Another theory suggests that LWE is related to the increased exposure of the ocular surface due to incomplete blinking or poor eyelid closure, leading to desiccation of the cornea and conjunctiva.[1] 

Although boasting relatively high oxygen permeability (Dk/t), extended-wear contact lenses have also been associated with LWE because of their higher modulus and subsequent increase in the coefficient of friction.[2][3] 

Ultimately, LWE likely involves a combination of factors, including mechanical trauma, chemical irritation, inflammation, and environmental exposures. Mechanical trauma may be caused by contact lens wear, excessive blinking, or rubbing of the eyelids. Chemical irritation may result from topical medications, preservatives, or cosmetics. Inflammation may be further exacerbated by comorbid autoimmune diseases, infections, or allergic reactions. Exposure to irritants such as air pollution or cigarette smoke can also be associated with LWE.[4]

Epidemiology

Lid wiper epitheliopathy is a relatively new clinical entity, and epidemiological data on the condition is limited. While the prevalence of LWE is not well established in the literature, it is estimated to affect up to 88% of patients with dry eye disease.[5] 

No significant differences in prevalence rates based on sex have been reported for lid wiper epitheliopathy (LWE). However, studies have revealed that individuals of Asian descent have a nearly twofold higher prevalence rate of LWE compared to non-Asians. Furthermore, contact lens wearers are more likely to experience LWE compared to those who do not wear contact lenses. These findings highlight the importance of considering ethnicity and contact lens use as potential risk factors for the development of LWE.[2]

Currently, there is limited available data to establish definitive prevalence rates for lid wiper epitheliopathy (LWE) across different age ranges. Further research is needed to gather more comprehensive and reliable data to accurately classify prevalence rates in various age groups. The absence of sufficient data emphasizes the importance of ongoing research and studies to gain a better understanding of the age-related patterns and prevalence of LWE.

Pathophysiology

The lid-wiper region is composed of a thin layer of stratified squamous epithelium that overlies a dense layer of connective tissue. The lid wiper area is responsible for distributing the tear film evenly across the ocular surface. Damage to this area can lead to poor tear film quality and stability, resulting in a range of ocular symptoms, including foreign body sensation, burning, and redness.[6] LWE is characterized by inflammatory damage and changes in the conjunctival tissue covering the lid-wiper region, the part of the upper eyelid that comes into contact with the ocular surface during blinking.

The inflammatory response associated with LWE is believed to be mediated by cytokines and chemokines released by the damaged epithelium. Increased levels of inflammatory cytokines lead to a decrease in the number of goblet cells in the conjunctiva, further propagating ocular surface inflammation and damage. Additionally, the expression of keratinization-related proteins (filaggrin, TGase1, and cytokeratin 1/10) has been linked to conjunctival changes seen in LWE. This gives rise to the hypothesis that LWE results from anterior displacement of the mucocutaneous junction (Line of Marx) of the palpebral conjunctiva, disrupting the normal function of the lid wiper.[7]

Conjunctival changes noted in LWE include squamous metaplasia, hyperkeratosis, and epithelial thickening. The mechanical stress placed on this region during blinking is thought to cause damage to the epithelium, leading to the development of these changes.[8]

History and Physical

The diagnosis of LWE is based on a careful history and slit lamp examination. Patients typically present with symptoms of ocular discomfort, foreign body sensation, and contact lens intolerance. Patients can often localize the source of the foreign body sensation to the upper eyelid. Slit lamp examination of the lid wiper region may reveal signs of inflammation, such as lid marginal redness, swelling, and increased vascularization due to hypoxia, mechanical irritation, or other stressors.[9]

Using ophthalmic vital dyes is critical for properly assessing pathologic areas of devitalized cellular damage along the eyelid margins and goblet cells (lissamine green and rose bengal) and punctate epithelial erosions to the cornea (sodium fluorescein) epithelium. Although sodium fluorescein staining may highlight focal areas of epithelial defects along the cornea or bulbar conjunctiva, the most obvious way of highlighting LWE is with a lissamine green stain.[10] Patients may have localized injections of the superior bulbar conjunctiva, which may also include the superior eyelid margin.

Other supplemental diagnostic tests such as Schirmer, tear break-up time, tear osmolarity, and conjunctival impression cytology may also be supportive to diagnosis, particularly with associated dry eye and ocular surface disease.[11]

It is important to note that lid wiper epitheliopathy (LWE) often coexists with various comorbid ocular surface diseases. These conditions can include anterior blepharitis, posterior blepharitis (such as meibomian gland dysfunction and evaporative dry eye), chalazia, hordeola, aqueous deficiency dry eye, conjunctivochalasis, pinguecula, pterygia, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, cicatrizing conjunctivitis, marginal keratitis, punctate keratitis, ulcerative keratitis, among others.

In rare cases, lid margin disease may also encompass sebaceous cell carcinoma, basal cell carcinoma, and squamous cell carcinoma. The definitive diagnosis of these conditions typically requires a biopsy for confirmation. It is essential for healthcare professionals to consider these potential comorbidities and, when necessary, pursue appropriate diagnostic measures to ensure accurate identification and management of these associated ocular surface diseases.

Evaluation

During the evaluation of lid wiper epitheliopathy (LWE), it is important to perform a thorough examination using a slit lamp at low magnification. This examination should encompass the assessment of the eyelids, bulbar conjunctiva, and inferior palpebral conjunctiva to exclude other potential causes of foreign body sensation. To evaluate for corneal pathologies that may mimic LWE, the instillation of sodium fluorescein can be beneficial. This dye helps to visualize epithelial erosions, assess tear film stability, and identify keratitis.

To rule out conditions such as superior limbic keratoconjunctivitis (SLK), conjunctival foreign bodies, and giant papillary conjunctivitis (GPC), the patient should be instructed to look down and up while the superior and inferior eyelids are everted. This maneuver helps to assess the conjunctiva and rule out these specific etiologies. Subsequently, the application of lissamine green stain and/or rose bengal can be used to highlight lid wiper epitheliopathy. In patients with LWE, varying degrees of lissamine green or rose bengal staining will be observed, typically starting at the mucocutaneous junction, also known as the Line of Marx, on the upper lid.[10]

Treatment / Management

The primary objective in treating lid wiper epitheliopathy (LWE) is to minimize the mechanical stress exerted on the lid wiper region during blinking. Since LWE primarily stems from mechanical inflammation, reducing friction on the ocular surface becomes crucial. Treatment strategies focus on measures to achieve this goal.

Key treatment modalities include the application of warm compresses, lid scrubs, artificial tears, topical corticosteroids, and bandage contact lenses. These interventions help alleviate symptoms and promote healing by mitigating ocular surface friction. Additionally, addressing any associated ocular surface diseases, such as dry eye, meibomian gland dysfunction, and allergic conjunctivitis, is essential due to their frequent coexistence with LWE.

Furthermore, it is essential to co-manage any underlying systemic conditions that contribute to ocular surface diseases, such as Sjogren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus. A comprehensive approach encompassing the treatment of local ocular surface conditions and systemic factors is critical for achieving therapeutic success in LWE.

When conservative measures such as regular lid hygiene and palliative treatments do not reduce lid friction on the ocular surface, alternative treatment options can be considered. These approaches aim to alleviate symptoms and reduce inflammation associated with tear film abnormalities.

One approach involves punctal occlusion, which consists of blocking tear drainage channels to enhance tear retention on the ocular surface. This technique helps maintain a more stable tear film and reduces friction between the lid and the ocular surface. In addition, medications that target tear film inflammation can be employed. Topical steroids such as loteprednol, fluorometholone, prednisolone, and dexamethasone can be used to reduce inflammation within the tear film. Topical immunomodulators such as cyclosporine and lifitegrast can also be beneficial in managing tear film-related inflammation. Furthermore, oral antibiotics with antiinflammatory properties, such as doxycycline and azithromycin, can be utilized as adjunctive therapy. These medications help alleviate inflammation and modulate the ocular surface microenvironment, improving symptoms and managing lid wiper epitheliopathy.[12]

Procedure-based treatments can provide effective interventions specifically targeting lid margin pathology in cases of lid wiper epitheliopathy (LWE), particularly when there is evident lid margin staining (referred to as the "Line of Marx") on lissamine green or rose bengal staining.

Microblepharoexfoliation is a procedure that utilizes an electronic rotary sponge soaked in an antimicrobial foaming cleanser. This technique enables mechanical exfoliation of the lash follicle base and the lid margin itself, directly addressing the underlying pathology in the lid wiper region of LWE. This approach focuses on anterior blepharitis and LWE. Other procedure-based treatments, such as thermal pulsation and intense pulsed light, are more specifically designed for posterior blepharitis, particularly in cases of meibomian gland dysfunction. While these treatments may benefit some aspects of LWE, microblepharoexfoliation is better suited for directly addressing anterior blepharitis and LWE pathology.[13] 

It is important to note that all procedure outcomes are never curative. The time between treatments depends on various factors, including comorbid ocular surface disease and systemic conditions and patient compliance with home maintenance of warm compresses, lid scrubs, lubrication, and medications. Furthermore, discontinuation of contact lens use has not been shown to result in the resolution of clinical signs.[14]

Differential Diagnosis

• Superior limbic keratoconjunctivitis (SLK) is characterized by a hypersensitivity reaction to thiomersal or preservatives found in contact lens solutions and is often associated with thyroid eye disease. This condition typically manifests bilaterally but can exhibit asymmetry. Similar to lid wiper epitheliopathy (LWE), patients commonly experience pain, foreign body sensation, and intolerance to contact lens wear.

  Upon slit lamp examination, hypertrophy and inflammation of the superior bulbar conjunctiva are frequently observed, and these areas can be highlighted by lissamine green or rose bengal staining. Additionally, anterior segment findings may include punctate epithelial erosions and papillary hypertrophy of the superior tarsal conjunctiva.[15]

• Ocular foreign bodies on the cornea or conjunctiva are frequently encountered in clinical practice and can lead to significant symptoms. Patients often report pain, discomfort during blinking, bulbar conjunctiva redness, light sensitivity, and tearing. Corneal foreign bodies account for approximately 80% of cases, while tarsal or bulbar conjunctival foreign bodies make up around 13% of incidents.

  Prompt removal of the foreign body is crucial to prevent complications such as microbial keratitis and corneal scarring, potentially resulting in permanent vision loss. Following removal, the affected area should be treated with a combination of topical antibiotics and steroids to minimize the risk of infection and inflammation. Close monitoring of the patient's condition is necessary to ensure proper healing and address potential complications.[16]

• Floppy eyelid syndrome (FES) is a specific eyelid disorder primarily observed in men with a body mass index exceeding 30 kg/m². It is characterized by the spontaneous eversion or turning inside out of the eyelid during sleep, resulting from excessive eyelid laxity. Symptoms experienced by patients with FES resemble those of lid wiper epitheliopathy (LWE), including the sensation of a foreign object in the eye. On slit lamp examination, findings may include punctate epithelial erosions and chronic papillary conjunctivitis.

  One of the common complaints in individuals with FES is the presence of unilateral or bilateral discharge, which can be aqueous or mucoid. This discharge is often attributed to chronic exposure keratopathy, which occurs when the eyelid involuntarily everts during sleep, leading to prolonged ocular surface exposure.[17]

• Giant papillary conjunctivitis (GPC) is a specific form of conjunctivitis characterized by the formation of enlarged papillae on the superior tarsal conjunctiva. This condition typically occurs as a result of both allergic and traumatic responses to the wearing of contact lenses. Patients with GPC commonly present with symptoms such as ocular itching, decreased tolerance to contact lens wear, blurred vision, and excessive mucous production in the eyes. Complications associated with GPC can arise due to infrequent replacement of contact lenses, prolonged wearing of lenses, poor hygiene practices related to lens care, and a history of atopic conditions.

  The development of GPC is believed to result from mechanical trauma to the superior tarsal conjunctiva, coupled with an immunologic response by the conjunctiva to deposits on the anterior surface of the contact lens. These factors can trigger an inflammatory reaction leading to the formation of giant papillae. It is essential to recognize the association between GPC and contact lens wear and the potential underlying allergic and immunologic mechanisms involved.[18]

Staging

The severity of lid wiper epitheliopathy can be accurately graded through objective measurement (Korb et al grading protocol) and subjective photographic scales.[5][10] Determining the Korb LWE Severity Grade requires 3 steps:

While the Korb scale is objective, it requires accurate measurements in 2 dimensions and 3 steps to determine a final LWE Severity Grade. A subsequent method was developed by Lievens et al called the Photographic Lid Wiper Epitheliopathy (PLWE) scale. This method requires comparison to 4 standard photos with grade 0 through 3 lissamine green staining on the mucocutaneous junction of the superior tarsal conjunctiva.[10] One study revealed that due to its simplicity, 95% of clinicians preferred the PLWE scale over the Korb scale.[10]

Prognosis

The prognosis for Lid Wiper Epitheliopathy (LWE) is generally favorable, as many patients experience symptom resolution and improvement in clinical exam findings with the initiation of topical antiinflammatory medications and enhanced ocular surface lubrication. However, it is essential to note that discontinuing the use of contact lenses alone has not been demonstrated to resolve the clinical signs associated with LWE fully.[14]

Complications

Without proper treatment of LWE, patients are at risk of cicatrization of the superior tarsal conjunctiva and subsequent entropion with or without subsequent trichiasis.[19] Moreover, patients with epithelial breaks in the corneal surface are at risk of microbial keratitis and corneal scarring, resulting in permanent vision loss or irregular astigmatism.[20]