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Abstract
Recurrent corneal erosion is a common condition affecting the epithelium membrane of the eye. It is often presented with a sharp pain in the morning during waking, photophobia, redness, and watering of the eye. These symptoms are resultant from relatively poor epithelial adhesion. Most patients with RCE have the etiology of the syndrome attributed to past mechanical trauma. There are several types of diagnostic available for the identification of the condition, with the slit-lamp technique being the most common. Finally, when it comes to management, lubrication is considered the first line of treatment.
Keywords used: Basement membrane, Cornea, Epithelium, RCE.
Introduction
Recurrent corneal erosion (RCE) is the end consequence of several disorders of the basement membrane and the epithelium of the cornea. Even though most individuals with unilateral RCE present the condition after a corneal injury that results in the sloughing of the corneal epithelium, concern must be given to the array of causes, particularly among those with bilateral RCE, who have no history of acute trauma. RCE has unknown pathophysiology. Nevertheless, its etiology is related to the presence of a poor attachment between the epithelium and its basement membrane or between the basement membrane and its underlying tissue.1 Etiology can be further categorized into primary and secondary disorders. Primary disorders are often symmetrical, bilateral, and can affect multiple regions of the cornea. They comprise genetic disorders and corneal dystrophies which affect the epithelium, anterior stroma, or basement membrane. 1 Of these, the map-dot fingerprint disorder is the most common.
On the other hand, secondary basement membrane disorders are acquired and often affect a single location in the cornea. 1 The most prevalent of these etiologies is mechanical trauma that is caused by the abrasion of plant material, a fingernail, and the edge of a piece of paper, among others, on the corneal epithelium. After the abrasion, there might be incomplete healing that results in the malformation of hemidesmosomes. Age-related changes also serve as predisposing factors to RCE. The epithelial tissue secretes the basement membrane throughout life; as a result, by 60 years of age, the thickness of the membrane will double.2 Moreover, aging can bring about regions of reduplication on the membrane. As reduplication or the thickening of the basement membrane occurs, the thickness of the epithelial membrane might supersede the length of the anchoring fibrils, thus facilitating the erosion of the epithelial layers.
Differential diagnoses
When making a diagnosis, a physician has to consider the predisposing conditions of the differential diagnosis. For RCE, these comprise corneal abrasion, neurotrophic keratitis, and herpes simplex keratitis.3
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Corneal abrasion: The presentation of recurrent epithelial defects due to corneal abrasion is usually rare; however, unlike RCE, the patient does not experience pain during waking. This is felt in any part of the day.
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Neurotropic keratitis: Although the signs and symptoms of neurotrophic keratitis are almost similar to that of RCE, the former is painless.
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Herpes simplex keratitis: Recurrent herpes simplex keratitis might elicit epithelial defect; nevertheless, a history of steady onset of pain, dendritic ulceration, and deep stromal infiltration are the main presentations that differentiate the condition from RCE.
Discussion
Epidemiology
RCE is the second most common cause of epithelial membrane dystrophy, in which 45-64% of the patients cases are due to prior physical injury.1 There is limited evidence showing the exact prevalence and incidence of RCE, as most cases often go misdiagnosed or undiagnosed. The rate of recurrence of the condition after mechanical trauma is 1 in 150.2 Moreover, it is more likely to affect more females than males. It often arises in adulthood, specifically among individuals aged 40 years and above; unless, it is resultant from Alports syndrome, or one of the corneal dystrophies, whereby it can be seen in children.1 It is also highly prevalent among patients diagnosed with ocular rosacea, dry eye syndrome, blepharitis, and blue eye syndrome.
Clinical Features
RCE can either be unilateral or bilateral. It is primarily characterized by recurrent incidences of sudden onset of pain, often at night or during waking in the morning. Nevertheless, it gradually subsides in the day and resumes again the next morning.1 This unpredictability might cause anxiety. Individual experiences vary in severity and duration. The cause of the pain manifestation in the morning remains unknown; however, it is purported that minimized tear secretion during sleep, and the rubbing of the epithelium against the tarsal conjunctiva during rapid eye movements are the most probable causes.2 Other presenting signs and symptoms include photophobia, ciliary and conjunctival congestion, redness, profuse lacrimation, and watering of the eyes.2 These symptoms are related to corneal de-epithelialization. Furthermore, the patient usually experiences a sensation of a foreign body being present in the eyes, and some report haloes or glares around lights (occurs when corneal edema develops) and inability to open eyelids. In the early stages, RCE might be asymptomatic.
Diagnosis
A diagnosis for RCE is established based on patient history and clinical examination; therefore, a detailed history, including prior episodes of corneal trauma, is required. Several diagnostic techniques can be utilized in assessing RCE; however, slit-lamp biomicroscopy is the best.4 A thorough slit-lamp examination should be done by using fluorescein staining and indirect illumination. The eye should be evaluated for signs of basement membrane dystrophy. Topical fluorescein operates on the principle that it can stain both the irregular and loose epithelium and define the non-stained lesions, which protrude across the tear film.1 Retroillumination technique highlight the loose and irregular epithelium and allow for the identification of cystic and map-like changes connected to dystrophy.
Other techniques that can be used to examine epithelial abnormalities include optical coherence tomography (OCT) using computerized videokeratography, which measures the size of the internal optical structures, cornea size, and identify hidden surface abnormalities and membrane dystrophies.4 In addition, the in vivo confocal microcopy method allows for the identification of epithelial basement membrane irregularities and microcysts that protrude into the corneal epithelium.4 In patients with mild RCE, diagnosis can be made based on history alone. On the other hand, in severe cases, both the patients history and diagnostic techniques should be used. The depth of corneal involvement affects the prognosis and hence, treatment options.
Management
Due to the chronic relapsing nature of this condition, patients are often frustrated by the frequent visits to the ophthalmologist. Regardless of its etiology, the primary pathogenic cause is the defective basement membrane and its poor adhesion to the underlying stroma. Therefore, management aims to repair and regenerate the epithelial basement membrane and relieve pain. There are several treatment options for RCE, with each having its distinct degree of efficacy. Therefore, patients must be evaluated on a case-by-case basis to facilitate the selection of the most suitable treatment regimen. However, there still lacks strong evidence concerning the efficacy of RCE therapies.5 Acute cases are managed by cycloplegia, patching, and topical antibiotic treatment.6 On the other hand, collagen shields or bandage soft contact lenses are used to alleviate pain in chronic situations.
Medical management
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Lubrication: It is regarded as the first line of treatment, and lubricants can be in the form of gels, drops, or ointments.1 Frequent application of preservative-free artificial tears coupled with a lubricating ointment at night prevents the epithelium from shearing against the eyelid during waking and the desiccation of the epithelium. Lubricants containing hypertonic sodium chloride are recommended as they have been illustrated to enhance epithelial adherence by reducing epithelial edema.7 Although this conservative treatment has proven to be helpful among most patients by relieving pain and promoting initial healing, it has been ineffective in decreasing the reoccurrence rate. Moreover, it has worsened the prognosis.
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Bandage soft contact lenses: It is recommended for RCE patients who are unresponsive to lubricants or have extensive erosions. It allows for the re-epithelization and healing by protecting the fragile regenerating epitheliums from the eyelids windshield-wiper effect.1 Once re-epithelialization is complete, the lens allows the stabilization of the epithelial layer, therefore, providing optimum conditions for the formations of hemidesmosomes. This suggests that the lenses should be worn for long durations to ensure that healing is complete. Furthermore, since epithelial detachment takes place during the night or immediately on waking, they should be worn continuously. Soft contact lenses and hydrogel lenses coupled with copious ocular lubricants worn for an extended basis have been illustrated to be an effective treatment modality. However, the continuous use of lenses long-term may result in vascularization, bacterial keratosis, and scarring. Therefore, they should be only used under close supervision and be worn for a period of no less than 6 weeks to several months.1 This allows the materialization of stable junctional complexes.
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MMP inhibitors: The corneal epithelium secretes an enzyme, metalloproteinase-9 (MMP), which is essential for wound healing. The expression of the protein is heightened in corneas with recurrent erosions; hence, this indicates that MMPs might play a role in the disintegration of anchoring molecules in the basement membrane during the regeneration and repair of the epithelium.1This is the principle behind the use of MMP inhibitors in the management of RCE. Topical steroids and oral doxycycline are the common MMP inhibitors used for RCE resistant cases. Combining these medications can result in rapid resolution and minimize the recurrence of RCE. In one randomized control trial, have been reported to topical steroids and oral doxycycline have been proven to reduce the activity of MMP, in which the latter did so by 70%.8 Furthermore, the other therapeutic benefits of these drugs might be their anti-inflammatory traits; doxycycline reduces the production and bioactivity of interleukin-1. 8 However, it is essential to note that although steroids are effective, extreme care should be taken when administering to thin corneal stroma to patients, as it might prevent collagen synthesis.
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Punctal occlusion: It is recommended for chronic dry eye cases that have shown resistance to lubrication alone. It is a one-time and straightforward intervention with the capability to facilitate more rapid epithelial healing and prevent reoccurrence through compounding the ocular surface residence time for both exogenous and natural tears.8 Initially, particularly among patients with mild to moderate tear film insufficiency, a dissolvable short-term punctual plug might be utilized. Nevertheless, in patients with severe dry eye, a long-term silicone punctal plug is recommended.
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Autologous serum: This serum contains several substances that are essential to the healing and regeneration of the epithelium. They include the transforming growth factors, Vitamin A, epidermal growth factor, fibronectin, and other cytokines.1 This composition is similar to that of tears; hence, it is a suitable substitute and complements the eye with essential nutrients that lack commercial preparations. It is regarded as safe and is not associated with any other secondary effects.
Surgical management
This is a treatment modality recommended for patients who show no response to medical management. Moreover, considering the relatively high success rate of conservative therapy, medication should not be administered for a long time when ineffective.1 Although there lack of clear guidelines indicative of surgical interventions, extensive erosions that occur more than once per month dictate surgical procedures. It is essential to note that the location of the RCE influences these interventions.
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Anterior stromal puncture: The therapeutic objective of this procedure is to improve the adhesion of the epithelium to the basement membrane. It achieves so by triggering reactive fibrosis and secretion of extracellular matrix proteins that facilitate the anchoring of the epithelium to its substrate.8 Although it has been associated with a reduced recurrence rate, it can result in scarring as the Bowmans membrane is pierced. As a result, it is recommended for patients with RCEs do not entail the central visual axis to avert physician-acquired vision loss and glare.
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Photo-therapeutic keratectomy (PTK): It manages erosion by ablating the outer layers of the cornea. The procedure is relatively simple. Following the application of topical anesthesia, the corneal epithelium is excised by subjecting it to the excimer laser, which facilitates the excision of the tissue with extreme care; hence, promoting minimal damage to the non-irradiated region. The laser then ablates the Bowmans membrane and the outer 6.0 ¼m thick anterior stromal layer.9 Given that the subsequent corneal surface is free from dystrophies or trauma, the epithelium membrane can re-grow and develop stronger adhesion with the underlying stroma. After that, new basement membranes and hemidesmosomes begin re-growing from as little as two weeks. Finally, cycloplegic and antibiotic drops are placed and the eye is padded. PTK has a relatively high degree of efficacy in treating RCE as it is associated with a 60 to 100% success rate.9 Post-operative pain is the main limitation of this procedure as the removal of the central corneal epithelium exposes the nervous plexus.
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Diamond burr superficial keratectomy: In this technique, loose sheets of the epithelial membrane are removed from the cornea by peeling with forceps and wiping with a cellulose sponge and iris spatula. In instances where the erosion has occurred within or close to the visual axis, the whole Bowmans layer is polished with a fine diamond burr by employing several circular motions to prevent irregular topography. Furthermore, a narrow 1-2mm ring of corneal epithelium is left intact to ensure its quick healing.1 The therapeutic results of the diamond burr technique are similar to that of the PTK.1 It is also a simple, cost-effective technique associated with fewer reoccurrences as compared to PTK.
Conclusion
RCE is among the most common optical epithelial membrane dystrophies. Most patients respond to simple conservative therapies; therefore, only a few require surgical interventions. As discussed, there lacks a definitive therapeutic approach to manage RCE; hence, the type of treatment provided is grounded on the degree of pathology.
References
Miller DD, Hasan SA, Simmons NL, Stewart MW. Recurrent corneal erosion: A comprehensive review. Clin Ophthalmol. 2019;13:325-335.
Diez-Feijóo E, Grau AE, Abusleme EI, Durán JA. Clinical presentation and causes of recurrent corneal erosion syndrome: Review of 100 patients. Cornea. 2014;33:6:571-5.
Verma, W. Recurrent corneal erosion differential diagnoses. Medscape. 2018.
Martin R. Cornea and anterior eye assessment with slit-lamp biomicroscopy, specular microscopy, confocal microscopy, and ultrasound biomicroscopy. Indian J Ophthalmol. 2018;66:2:195-201.
Watson SL, Lee MH, Barker NH. Interventions for recurrent corneal erosions. Cochrane Database Syst Rev. 2012:9:CD001861.
Lim CH, Turner A, Lim BX. Patching for corneal abrasion. Cochrane Database Syst Rev. 2016;7:7:CD004764.
Thakrar R., Houman D, Hemmati M. Treatment of recurrent corneal erosions. EyeNet Magazine. 2013.
Haitham AY, Shahien EA, Atya MA. Autologous serum eye drops versus systemic doxycycline and topical corticosteroids in the treatment of recurrent corneal erosion. Journal of the Egyptian Ophthalmology Practice. 2013:106:206-209.
Chan E, Jhanji V, Constantinou M, Amiel H, Snibson GR, Vajpayee RB. A randomized controlled trial of alcohol delamination and phototherapeutic keratectomy for the treatment of recurrent corneal erosion syndrome. Br J Ophthalmol. 2014;98:2:166-71.
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