CORNEAL ABRASION and RECURRENT CORNEAL EROSION

Signs and Symptoms

Corneal abrasion is one of the most common urgent clinical entities in practice.1-11 Patients present with some or all of the following: acute pain, photophobia, pain upon blinking and upon eye movement, lacrimation, blepharospasm, foreign body sensation, blurry vision and a history of contact lens wear or ocular trauma.2-11 Biomicroscopy of the injured area often reveals diffuse corneal edema and epithelial disruption. In severe cases, when edema is excessive, folds in Descemet’s membrane may be visible. Cobalt blue light inspection with the instillation of sodium fluorescein dye will illuminate the damaged segment in bright green.4 In more severe cases, the trauma that caused the corneal damage may have the potential to create an anterior chamber reaction.4,11

Pathophysiology

The cornea has distinct layers; epithelium, Bowman’s membrane, stroma, Dua’s layer, Descemet’s membrane and endothelium.12-14 The corneal epithelium is actually composed of three tissues: the stratified surface epithelium, whose microvilli increase surface area and permit adherence of the tear film by interacting with its mucous layer; the wing cell layer (containing the corneal nerves); and the mitotically active basement membrane. Bowman’s membrane is a structure that prevents penetrating injuries. The stroma is composed of 250 well organized lamellar sheets of collagen. It helps create the cornea’s optical power and contributes to its transparency. Dua’s layer, sometimes referred to as pre-Descemet’s layer (PDL), is a histologically confirmed row of acellular keratocytes composed of five to eight lamellae of predominantly type-1 collagen bundles arranged in transverse, longitudinal and oblique directions.13,14 Identification of this layer of the cornea has explained the corneal biomechanics of posterior corneal pathologies such as acute hydrops seen in keratoconus, descemetocele and pre-Descemet’s membrane dystrophies.13 It is connected to beams of collagen emerging from the anterior surface of its periphery, which continue as the beams of the trabecular meshwork (TM).14 The new data provides an insight into the origins of the collagen core of the TM and may impact future research into the TM and glaucoma.13,14 Descemet’s membrane and the endothelium constitute the innermost layers of the cornea, and are necessary to maintain the health, metabolism and hydration of the entire tissue.12

There are two categories of corneal abrasion: superficial (not involving Bowman’s membrane) and deep (penetrating Bowman’s membrane, but not rupturing Descemet’s membrane). Abrasions may result from foreign bodies, contact lenses, chemicals, fingernails, hair brushes, tree branches, dust and numerous other etiologies.1-13

The cornea has remarkable resilience as a result of complex healing properties.15-18 The epithelium adjacent to any insult expands in size to fill in the defect, usually within 24 to 48 hours.12,15-17 Damaged cells release protein kinase C delta, stimulating CAP37, an innate immune system molecule that modulates corneal epithelial cell migration, adhesion, and proliferation.15-17 This explains the rapid healing of superficial injuries and relatively rare rates of infection. Lesions that are purely epithelial often heal quickly and completely without intervention and without subsequent scarring. Lesions that extend below Bowman’s membrane produce scar formation.12,15-17 The creation of post injury corneal opacity is mediated by the complex actions of many cytokines, growth factors and chemokines.17 These substances are produced by epithelial cells, stromal cells, bone marrow-derived cells, lacrimal tissues and nerves.17 Stromal opacity after corneal injury is specifically related to the presence of myofibroblasts with decreased corneal crystallins, along with the disorganized extracellular matrix produced by these cells and their chemokines.17 Regeneration of a fully functional epithelial basement membrane also appears to play a critical role in the maintenance of corneal epithelial and stromal transparency after corneal injuries.17,18

The corneal epithelial basement membrane is positioned between basal epithelial cells and the stroma.18 This highly specialized extracellular matrix functions to anchor epithelial cells to the stroma and provide scaffolding during embryonic development.18 Basement membranes are composed of a diverse assemblage of extracellular molecules composed of four primary components: collagens, laminins, heparan sulfate proteoglycans and nidogens.18 The basement membrane zone (BMZ) is located in the uppermost region of the stroma. When collagen VII, a constituent of the region, is destabilized by the process of injury, the BMZ undergoes pathological changes that affect the function of the epidermal junction, creating an environment conducive to recurrent erosion.18

Management

Treatment for corneal abrasion begins with the patient’s history. The time, place and activity surrounding the injury should be recorded. Visual acuity should be recorded before any procedures or drops are given, if possible. If the blepharospasm is sufficiently intense to preclude an acuity measurement, one drop of topical anesthetic can be administered with the VA measured immediately thereafter (pinhole, if necessary). If the possibility exists for an open globe, an unopened bottle of anesthetic should be used.

The eye exam should proceed in a logical fashion from external adenexa to funduscopic examination. The eyelids should be everted and fornicies scrutinized to rule out the presence of foreign material. Fluorescein dye (without anesthetic) should be instilled to identify the corneal defects. The Seidel test is used to rule out full thickness injuries. The abrasion should be documented for size, shape, location and depth. It should be cleaned and scrutinized for foreign matter. The anterior chamber should be observed for any evidence of inflammation. A dilated examination should be completed to rule out any posterior effects from the trauma, if indicated.

Ophthalmic treatment is initiated by using adequate cycloplegia if the patient is sufficiently symptomatic. Topical fluoroquinolone antibiotics QID or another suitable broad spectrum agent can be used to protect against infection.3,11,19,20 Cold compresses, artificial tears and over-the-counter analgesics can be used to relieve acute pain. In cases where pain is severe, topical nonsteroidal anti-inflammatory medications or a thin, low-water-content bandage contact lens can be prescribed.2-7,10,19 A pressure patch, while not commonly used, is not contraindicated and is still considered useful for larger abrasions unless the injury is contact lens-related.19 Patients should be re-evaluated every 24 to 48 hours until the abrasion is re-epithelialized.2–8

Riboflavin-ultraviolet A (UVA) treatment is a procedure that induces collagen crosslinking to stiffen the corneal stroma.23-25 Like the use of vitamin C drops (which must be compounded), the procedure induces a reduction in stromal swelling while increasing resistance to microbial and enzymatic degradation. While studies have centered on corneal ectatic diseases, the procedure demonstrates promise for corneal injuries of all types that demonstrate delayed healing times.23-25 Standard protocol for this procedure requires the eyes have a minimum corneal thickness of 400µm after epithelial debridement.25 This prerequisite has been stipulated to protect the corneal endothelium and intraocular tissues from the deleterious effect of ultraviolet-A (UVA) radiation.25 Studies with contact lens-assisted corneal crosslinking has shown promise for patients with thin corneas.24

Reports have recognized tetracyclines and their derivatives for their ability to protect the cornea, inhibiting matrix metalloproteinases (MMP) independent of antimicrobial properties.26-28 These compounds—primarily through restriction of gene expression of neutrophil collagenase, epithelial gelatinase suppression of alpha1-antitrypsin degradation and scavenging of reactive oxygen species—are able to limit production of the inflammatory mediator MMP.27,28 Oral tetracyclines can be used along with other topical therapeutic agents to inhibit collagenolytic degradation of the cornea.26-28 Topical steroids can also be employed following early-stage repair of superficial ocular injuries to increase the efficiency of corneal wound healing by suppressing inflammatory enzymes.27,28

Using 50mg to 100mg of doxycycline BID PO for four to 12 weeks in addition to the other topical medications has demonstrated efficacy in patients with recurrent corneal erosion syndrome who have failed other forms of treatment.26-28 This noninvasive treatment modality is also effective with ocular lubricant management.26-28 However, these studies admit the need for randomized controlled trials using standardized methods to establish the benefits of many of these newer treatments.

Patients with a history of corneal abrasions are prone to recurrent corneal erosions secondary to altered formation of the hemidesmosomes of the epithelial basal cell layer.9-26 When the hemidesmosomal anchoring fibers are not established properly, a peeling off of the epithelium can result. This most frequently occurs upon awakening (morning syndrome).9-22,28-30 Patients who suffer from corneal dystrophies (epithelial basement membrane dystrophy, Meesmann’s corneal dystrophy, Reis–Bucklers dystrophy, honeycomb dystrophy and granular and lattice dystrophies) are also more susceptible to recurrent corneal erosions.9,31,32 In cases such as these, palliative treatment should include hyperosmotic solutions and lubricants. When recurrent erosion does occur, patching and bandage lenses may be employed.2,4,5,10,31,33

When these modalities fail to promote adequate corneal healing, manual debridement or superficial PTK may assist.26,34 Oral tetracycline, topical steroids and collagen crosslinking can also be employed following debridement.23-30 Anterior stromal puncture is yet an-other option.30 The procedure involves repeated puncturing of the Bowman’s layer, penetrating into the anterior one-third of the corneal stroma with either a Nd:YAG laser or a short (5/8in) 25-gauge bent needle on a tuberculin syringe.30,35 Both options serve to produce purposeful scarring, which strengthens the adherence of the overlying superficial epithelium to the Bowman’s layer.30,35 While the complications of the needle-based procedure include pain, potential for infection, reduced acuity secondary to excessive scarring and accidental penetration, a new laser-based practice has been evaluated in small studies to reduce the frequency of attacks while only producing mild post procedural discomfort.35

Tarsorrhaphy is used primarily for recalcitrant epithelial defects.36 Here the eyelids are temporarily sutured together, providing a complete form of patching and complete immobilization of the eyelid, which yields more efficient healing.36 Often, the sutures are left tied but not knotted and then taped to the forehead so they can be tightened and loosened for the purpose of opening the lids to instill medications. Partial tarsorrhaphy can be accomplished when complete closure is not required. While a tarsorrhaphy is simple, safe and effective, it can be somewhat unsightly and create cosmetic concern for the patient. This is typically only done in extreme cases such as neurotrophic keratitis.

Amniotic membrane transplantation (AMT) is a surgical modality used to create a temporary “tissue” patch for non-healing corneal lesions secondary to limbal stem cell deficiency.37,38 While traditional AMT is surgical in nature, newer options such as AmbioDry (IOP Ophthalmics) only require a bandage lens over the transplant. The membrane can serve as a reconstructive graft for both cornea and conjunctiva.37,38 AMT is primarily used to treat conditions where the normal corneal reparative process is either faulty or cannot gain momentum.35,37,38 AMT can be sutured onto a viable corneal limbus, attached via fibrin glue or applied via the novel approach of Prokera (Bio-Tissue).38 Prokera sup-ports a bioactive amniotic membrane within a rigid ring with an inner open-ing of 15.5mm to 17.9mm and an outer diameter of 21.6mm. This large diameter biological bandage has been used in a variety of non-healing corneal disorders with great success.38

A dendritic polymer known as a dendrimer seems to have applications as a nano-adhesive to improve corneal wound repair.39-42 The agent is composed entirely of the biocompatible products glycerol and succinic acid.39 The adhesive has advantages over sutures in the repair of corneal lacerations, securing unstable LASIK flaps and RK incisions, and closing leaky cataract surgical incisions.39-42 Other applications for potential usage of the adhesive includes ocular emergencies involving perforation of tissues due to trauma or infections. It may also be applied to strengthen or build up weak tissues that have been compromised by the destructive processes associated with inflammation.39-42

Clinical Pearls

To promote healing, prevent recurrent erosion and reduce corneal edema, a hypertonic solution or ointment may be prescribed. The minimum period of recommended application for this type of therapy is one month; however, unusual cases may require permanent use.

In cases where excess epithelium impairs regrowth, a cotton-tipped applicator saturated with anesthetic may be used to debride the loose tissue.

When significant inflammation is present, topical steroids may be required. They must be used judiciously as they can retard corneal healing, raise IOP and increase risk for infection.

Worsening subepithelial infiltration, increased pain and injection in the setting of an epithelial break may be a sign of secondary bacterial infection, especially in patients who are imunocompromised.

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