Recurrent corneal erosion (RCE) syndrome is by definition a recurrent condition due to abnormal adhesion of the corneal epithelium to the underlying basal lamina.(1-6) Spontaneous breakdown or shearing of the corneal epithelium can lead to sudden onset of ocular pain, blurry vision, tearing, and photophobia—most commonly upon awakening.(1-6) Depending on the severity, duration and underlying etiology, RCE can be managed medically and/or by surgical intervention.(1-6)
Trauma is the most common cause of RCE.(1-8) Usually patients will have a remote history of a paper cut or fingernail to the eye, and later develop a spontaneous abrasion that occurs upon awakening.(1-12) According to some studies, 45-64% of RCE is due to prior history of ocular foreign body, injury with fingernails, tree branches, and paper cuts.(1-12)
Corneal dystrophies may also lead to RCE; these include epithelial basement membrane dystrophy (EMBD), Reis-Buckler dystrophy, lattice, macular and granular dystrophies, as well as Fuchs dystrophy.(1-13) These may account for 19-29% of cases of RCE.(1-13)
Prior corneal infections, meibomian gland dysfunction, ocular rosacea, band keratopathy, nocturnal lagophthalmos and dry eye syndrome have also been implicated in RCE etiology.(1-13) These etiologies, as well as diabetes, are considered lowest risk for development of RCE.(1-12)
Impairment of normal corneal healing is the hallmark of RCE.(1) Healing of a corneal epithelial defect occurs in 3 distinct phases:
- Epithelial cell migration
- Epithelial cell proliferation
- Epithelial cell differentiation(12,13)
Alterations in cell-cell and cell-matrix (fibronectin – integrin system) interactions, as well as modulation of extracellular matrix by newly expressed proteolytic enzymes play important roles.(12,13)
Eyes with RCE have a defective, loose adherence of the epithelium to the underlying stroma following initial injury.(12,13) This loose epithelium can be sheared off upon opening of the eyelids (e.g. upon awakening).(12,13)
In general, erosions occur secondary to inflammation from the inciting insult/trauma which disrupts the epithelial basement membrane and extracellular adhesions of the hemidesmosomes.(1-13) In affected patients, confocal microscopy demonstrates defects of the adhesion complex, deposits in basal epithelial cells, damaged sub-basal nerves, abnormal basement membrane and altered morphology of the anterior stroma.(1-13)
In addition, increase levels of toxic free fatty acids, interleukin-1 (IL-1) and matrix metalloproteinases (MMPs) in patients suffering from meibomian gland dysfunction, ocular rosacea and recurrent erosions is thought to result in faulty adhesion complexes and irregular basement membrane formation.(1-13)
Diagnosing recurrent corneal erosion
RCE is typically diagnosed with slit lamp examination and in concert with appropriate clinical history.(1-10) Usually patients will complain of mild to severe pain, especially upon awakening.(1-10) They may experience foreign body sensation, photophobia, blurred vision and tearing.(1-10)
There may be a spectrum of mild to severe corneal irregularities that ranges from epithelial microcysts to large areas of loose epithelium or frank epithelial defects.(1-13) Fluorescein staining may highlight these exam features—in particular non-staining lesions that protrude through the tear film may be identified—a commonly seen EBMD finding referred to as “negative staining”.(1-13) The lower half of the cornea is the most frequently effected location.(1-13) In patients with history of prior trauma, the erosion tends to occur at the site of trauma; in those with pre-existing corneal dystrophies, erosions may be symmetric, alternate in laterality, and rarely may be simultaneous.(1-13) Classification of RCE may be done by signs and symptoms. For example, microform erosions tend to be milder in symptoms and shorter in duration, but can occur with increased frequency.(1-13) Macroform erosions can persist for days, are larger, and are usually associated with history of trauma.(1-13)
Managing recurrent corneal erosion: medical, surgical, or both
RCE management may be medical, surgical, or a combination of the two. The primary treatment goal here is to allow for re-epithelialization and reestablishment of a strong basement membrane complex.
Medical management of RCE includes eye drops, pain relievers and sometimes oral medications.
Lubrication is first line treatment of RCE; use of preservative free artificial tears and ointment is very important. Beyond this, cyclosporine, lifitegrast and even serum tears may help provide a less inflamed ocular surface and promote healing.(1-5)
Autologous Serum tears
Tears produced from the patient’s peripheral blood have been shown to effectively treat RCE. These drops contain a mixture of growth factors and cytokines similar to natural tears and in some studies have demonstrated significant efficacy in preventing erosion recurrences.(1-8)
Punctal occlusion (plugs) may prove helpful in some cases where lubricating eye drops are insufficient.(1-8) Temporary occlusion with collagen plugs or permanent occlusion with silicone plugs may be considered.
Hypertonic saline in the form of eye drops or ointment may be used. These eyedrops are generally available over-the-counter (sodium chloride drops in 2, 5 and 10% concentrations). This may be effective in some cases as it can draw excess fluid out of the cornea, potentially permitting better adhesion of the epithelium.(1-8)
Cycloplegia (e.g. with cyclopentolate or atropine eye drops) may alleviate photophobia.(1-8)
Bandage Contact Lens (BCL)
Placement of a pressure patch or bandage contact lens may also permit uninterrupted healing of the ocular surface. If pursuing this treatment, it is important to monitor these patients carefully and prescribe a prophylactic antibiotic drop to decrease risk of a secondary infection. Fraunfelder et al. reported that 75% of patients with RCE treated for 3 months with an extended-wear BCL remained recurrence free at 1 year.(1-3,14)
Oral doxycycline may be effective in treatment of RCE as it is inhibitory against matrix metalloproteinase-9 (MMP-9) and can therefore promote corneal healing and reduce frequency of RCE.(10,13,15,16) Typical dosage here is 50mg twice daily.(10,13,15,16)
Topical steroids may be used as an adjunctive therapy to reduce ocular surface inflammation as well. Used together, topical steroids and oral doxycycline may provide a more effective means of preventing collagen and hemi-desmosome breakdown via inhibition of MMP-9 production.(10,13,15,16) In addition, this combination also downregulates the production of lipase (mechanism by which this is also effective for meibomian gland dysfunction).(10,13,15,16) This is important as increased lipase concentrations in the cornea create toxic fatty acids that compromise integrity and healing capabilities of the epithelium.(10,13,15,16) Therefore, in addition to traditional therapies such as warm compresses, lid hygiene and omega-3 supplementation, combined oral tetracyclines and topical steroids can be used for certain RCE patients—especially those with noted meibomian gland dysfunction.
When medical management fails, or RCE persists/progresses, more aggressive, surgical treatment may be required. Below outlines some surgical techniques that can be used alone or in combination.
Superficial keratectomy (SK), or epithelial debridement may be performed to remove loose corneal epithelium and allow regrowth of epithelium with better adhesion.(2,6,7- 9,11) Typically, a bandage contact lens is placed after performing SK; amniotic membrane may also be used to enhance and perhaps hasten the healing process.(2,6-9,11,14) Erosions may recur following SK, especially in cases of corneal dystrophy,and therefore other, more invasive modalities may be required for management. This includes stromal micropuncture, polishing of the ocular surface and phototherapeutic keratectomy (PTK).
Anterior Stromal Micropuncture (ASP)
Anterior stromal micropuncture is believed to incite a fibrocytic response, stimulating basement membrane production.(2,6-8,11,12,17) In addition, it is thought that epithelial adherence is enhanced by scar tissue induction between the epithelium and anterior stromal of the cornea: a study by Zauberman et al reported 62.5% efficacy for stromal micropuncture for RCE following only one treatment.(17) It is recommended that ASP be performed for erosions outside of the visual axis (best in the periphery!) due to potential scarring and subsequent visual disturbances.
Micropuncture may be performed alone or in conjunction with SK. This may be done simply at the slit lamp with the patient sitting upright, or with the patient supine under an operative microscope, depending on surgeon and patient preferences/comfort. Following administration of topical anesthetic, a 25-gauge needle attached to a 1-or-3cc syringe is used to create micropunctures approximately 0.5mm apart over the area of loose epithelium.(2,6-8,11,12,17) An alternative to manual micropuncture includes Nd:YAG laser micropuncture. This is performed using 0.4-0.5mJ pulses, applied anteriorly to the region of abnormal Bowman layer through an intact epithelium.(17,18) It is felt that laser application may enhance epithelial adhesion to basement membrane by inducing scar formation; success rates of up to 80% have been reported. (17,18)
Diamond Burr Polishing
Diamond burr polishing involves epithelial debridement (using a surgical sponge or blade) and polishing of Bowmans membrane.(1,2,4,6,9,11,12,19,20) A bandage contact lens is typically used for 4-5 days following this procedure to allow uninterrupted re-epithelialization. Post-procedure antibiotic and steroid are prescribed as well. There are some reports of higher and more long-term success rates with combined burr polishing and SK as it removes the epithelial basement membrane, allowing a smoother epithelium to regrow without dystrophy or trauma.(1,2,4,6,9,11,12,19,20) In addition, it encourages reactive fibrosis, which promotes scarring with a stronger epithelial adhesion to the underlying membranes.(1,2,4,6,9,11,12,19,20)
Alcohol delamination of the corneal epithelium involves application of topical anesthesia and 50-75µL of 20% alcohol to the ocular surface for 40-60 seconds.(1,2,4,6,21) The alcohol is then soaked up with a surgical sponge and the eye is copiously irrigated with sterile saline. The loosened epithelium can be removed in one sheet and sent for histopathologic analysis.(1,2,4,6,21) This technique does not involve disturbance of Bowmans layer and therefore has an extremely low incidence of corneal haze formation. (21) It is important to note that alcohol application to the ocular surface carries a risk of toxicity and should be performed under direct visualization through a microscope and should not be done at the slit lamp. Despite some studies highlighting success of this technique, traditional approaches such as SK, ASP +/- burr polishing are usually recommended as they are more likely to resolve severe/recalcitrant cases.(1,2,4,6,21)
Excimer laser phototherapeutic keratectomy (PTK)
Often considered a later step in treatment of RCE, PTK involves laser ablation of the cornea, removing loose epithelium and inducing a small amount of fibrosis in Bowmans membrane.(1,2,6,7,10,22-25) It has been shown that hemi-desmosomes and new basement membranes can grow back in as fast as 2 weeks following PTK.(1,2,6,7,12,22-25) The steps here typically involve epithelial debridement (manual or transepithelial using the laser itself), followed by low-energy (e.g. 10MHz with fluence of 180mJ/cm2) ablation of 5-6µm into the stroma (number of pulses may range from 15-200).(1,2,6,7,10,22-25) In a study conducted by O’Brart, 73% of patients suffering from RCE reported resolution following PTK.(22) In patients who are also candidates for refractive surgery, photorefractive keratectomy (PRK) can be considered; however, this should be approached with caution and extensive preoperative counseling/consent.(1,2,6,7,10,22-25) It is important to note that cornea haze may occur following PTK and/or PRK laser treatment (although it may resolve over time), and it also may induce astigmatism and refractive error (hyperopic shift being most common).(1,2,6,7,10,22-25) In some cases, mitomycin C may be applied to inhibit corneal scarring/haze.(1,2,6,7,10,22-25)
Complications of RCE and treatments
Albeit rare, complications of RCE and its treatment may be corneal haze and scarring (most commonly following burr polishing and PTK), infection (risk of infected epithelial defect following any sort of epithelial debridement and placement of BCL), and decreased vision. It is important to monitor these patients closely to avoid risk of infection and its sequelae.
With prompt and adequate diagnosis and treatment, RCE prognosis is excellent. Patients must be educated on the signs and symptoms of erosions so that they can seek out ophthalmic attention when necessary. Prophylactic treatment in patients with risk factors should also be considered in order to minimize long-term complications and decrease possible need for surgical intervention.
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