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Simple Summary: Based on our previous studies on the levels of selected matrix metalloproteinases (MMPs) in patients with recurrent corneal erosions (RCE), we made a detailed assessment of their possible contribution to the development of corneal epithelial basement membrane dystrophy. The existing literature describing the structure, nomenclature, activation, and substrate specificity of metalloproteinases, as well as factors affecting their activity, are summarized. A separate section focuses on the effect of metalloproteinases on the corneal healing process, which is a preview of the final considerations on the effect of metalloproteinases on the development of recurrent corneal erosions and corneal epithelial basement membrane dystrophy. Our previous experimental studies revealed elevated metalloproteinase concentrations in the corneal epithelium of patients with recurrent corneal erosions concomitant with epithelial basement membrane dystrophy. These MMP concentrations are correlated with histopathology and confocal microscopy findings typical of this group of patients. Based on the consistency of the obtained results, the authors suggest a contribution of matrix metalloproteinases to the development of corneal epithelial basement membrane dystrophy. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes which are members of the zinc endopeptidase family. They have the ability to degrade extracellular matrix elements, allowing for the release of binding molecules and cell migration. Although metalloproteinases regulate numerous physiological processes within the cornea, overexpression of metalloproteinase genes and an imbalance between the levels of metalloproteinases and their inhibitors can contribute to the inhibition of repair processes, the development of inflammation and excessive cellular proliferation. The involvement of MMPs in the pathogenesis of dystrophic corneal diseases needs clarification. Our analyses focus on the involvement of individual metalloproteinases in the pathogenesis of recurrent corneal erosions and highlight their impact on the development of corneal epithelial basement membrane dystrophy (EBMD). We hypothesize that abnormalities observed in patients with EBMD may result from the accumulation and activation of metalloproteinases in the basal layers of the corneal epithelium, leading to basement membrane degradation. A barrier formed from degradation materials inhibits the normal migration of epithelial cells to the superficial layers, which contributes to the development of the aforementioned lesions. This hypothesis seems to be lent support by the elevated concentrations of metalloproteinases in the corneal epithelium of these patients found in our previous studies on the relationships between MMPs and recurrent corneal erosions. [ABSTRACT FROM AUTHOR]

Purpose: To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. Overview: RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. Summary: Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the long-term efficacy of phototherapeutic keratectomy (PTK) in treating epithelial basement membrane dystrophy (EBMD). Methods: Preoperative and postoperative records were reviewed for 58 eyes of 51 patients with <3 months follow-up (range 3-170 months) treated for EBMD with PTK after failure of conservative medical treatment at Byers Eye Institute of Stanford University. Symptoms, clinical findings, and corrected distance visual acuity (CDVA) were assessed. The primary outcome measure was symptomatic recurrence as measured by erosions or visual complaints <3 months after successful PTK. Results: For eyes with visual disturbances (n=30), preoperative CDVA was ∼20/32 (0.24 Log-MAR, SD 0.21) and postoperative CDVA was ∼20/25 (0.07 LogMAR, SD 0.12; P<0.0001). Twenty-six eyes (86.7%) responded to treatment, with symptomatic recurrence in 6 eyes (23.1%) at an average of 37.7 months (SD 42.8). For eyes with painful erosions (n=29), preoperative CDVA was ∼20/25 (0.12, SD 0.19) and postoperative CDVA was ∼20/20 (0.05. SD 0.16; P=0.0785). Twenty-three eyes (79.3%) responded to treatment, with symptomatic recurrence in 3 eyes (13.0%) at an average of 9.7 months (SD 1.5). The probability of being recurrence free after a successful treatment for visual disturbances and erosions at 5 years postoperatively was estimated at 83.0% (95% confidence interval 68.7%-97.0%) and 88.0% (95% confidence interval 65.3%-96.6%), respectively. Conclusion: The majority of visual disturbances and painful erosions associated with EBMD respond to PTK. For those with a treatment response, symptomatic relief is maintained over long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Epithelial basement membrane dystrophy (EBMD) is by far the most common corneal dystrophy. In this study, we used a newly developed method of immunofluorescence staining and imaging to study the entire corneal nerve architecture of a donor with unilateral EBMD. Method: Two fresh eyes from a 56-year-old male donor were obtained; the right eye of the donor was diagnosed with EBMD and the left was normal. After slit lamp examination, the corneas were immunostained with anti-β-tubulin III antibody. Images were recorded by a fluorescent microscope equipped with a Photometrics digital camera using MetaVue imaging software. Results: The left cornea appeared normal as observed by slit lamp and stereomicroscope, but the right eye had numerous irregular geographic patches in the basement membrane. Immunofluorescence showed no difference in the stromal nerve distribution between the 2 eyes, but there were areas without innervations in the EBMD cornea. Subbasal nerve fibers also showed tortuous courses and fewer divisions. There was a significant decrease in the density of subbasal nerve fibers and the number of terminals in the right eye. Conclusion: We show for the first time detailed nerve architecture in an EBMD cornea. Our results suggest that EBMD-induced abnormalities of basement membrane altered epithelial nerve architecture and decreased nerve density, contributing to the pathology of the disease. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy by in vivo laser corneal confocal microscopy. Methods: Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM). The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy. Results: Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic) highly reflective materials were observed in the "map" area, mainly in the basal epithelial cell layer. In "fingerprint" lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient. Conclusion: HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities. [ABSTRACT FROM AUTHOR]

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