Corneal epithelial damage

Topical ocular appUcation of cocaine can result in serious corneal epithelial damage therefore clinical uses of this drug are limited. Although it is no longer used for such routine ophthalmic procedures as tonometry, the drug is useful in the diagnosis of Horner s syndrome (see Chapter 22). However, when administering hydroxyamphetamine, 48 hours must elapse before the subsequent test because cocaine inhibits the uptake of hydroxyamphetamine into the presynaptic vesticles. In addition, due to its ability to loosen the corneal epithelium, it can be helpful in the debridement of herpetic corneal ulcers. 

Corneal epithelial damage has been attributed to a perfluorocarbon (14). 

Corneal epithelial damage was evaluated by a slitlamp biomicroscope with a cobalt filter (SL-2, Kowa), according to the criteria shown in Table 2, by fluorecein staining of the cornea before, and in the 1st, 3rd, 6th and 12th month of application. 

Table 4. Corneal epithelial damage after topical application of ofloxacin...

As another extracellular component in the cornea, the Bowman s layer is an acellular and amorphous band between the corneal epithelium and stroma. The layer is about 8-12 [im thick and consists of randomly arranged collagen fibers (types I and III) and proteoglycans. The physiological function of Bowman s layer is not yet completely understood, since not all animal species exhibit this membrane in the corneal structures, but an important role in the maintenance of the corneal epithelial structure is expected or probable, since a damaged Bowman s membrane usually results in scarring during wound repair [16],... 

Both systemic and topical ocular steroid therapy can retard corneal healing. Persistent punctate staining of the cornea can indicate epithelial damage by the corticosteroid if the original disease has been eliminated. Effects on collagen synthesis and fibroblast activity have been proposed as a possible mechanism. 

Figure 12-9 Corneal acute inflammation./wset Corneal epithelial cells that have been activated by proinflammatory molecules. Activated cytokines disperse though the stroma and in the limbal vessels. Proteases (represented by the large scissors ) can damage the basement membrane, leading to growth factor and angiogenic factor release. (From McDermott AM, Perez V, Huang AJ, et al. Pathways of corneal and ocular surface inflammation a perspective from the Cullen Symposium, Ocul Surf 2005 0ct 3(4 Suppl) S131-138.)...

Cytotoxicity Issues. In-vivo hemolysis has been observed with parenteral administration of all of the parent CDs. In-vitro studies with human erythrocytes have demonstrated that the damaging effect of the CDs is in the order p-CD > ot-CD > y-CD. This cellular destruction has also been observed in studies with human skin fibroblasts and intestinal cells, P388 murine leukaemic cells, E. coli bacterial cells, and immortalized human corneal epithelial cells.f " Mechanistic studies suggest that CDs extract either cholesterol (p-CD and y-CD) or phospholipids (a-CD) from the cell membrane causing small pores which allow leakage and eventually lead to cell lysis. 

Diclofenac can cause reduced comeal sensitivity, starting from 15 minutes after instillation and measurable after 1 hour (3). This corneal hypesthesia can be useful in reducing pain and discomfort in ocular inflammation and after surgery. In chronic treatment, however, the effect of diclofenac on corneal nerves can cause either increased healing time of the corneal epithelium or a neurotrophic epitheliopathy in patients with conditions that predispose to epithelial damage, such as dry eyes. In contrast, flurbiprofen, indometacin, and ketorolac tro-methamine did not cause corneal hypesthesia. 

Following damage, corneal epithelial cells can regenerate. A thick protective layer of glycoprotein from mucous secretions protects the epithelium from mechanical trauma. Endothelial cells, however, do not have the same potential to regenerate (e.g., mitosis). 

Taylor SD, Sanders ME, Tullos NA, et al. The cholesterol-dependent cytolysin pneumolysin from Streptococcus pneumoniae binds to lipid raft microdomains in human corneal epithelial cells. PloS One. 2013 8(4) e61300. Alving CR, Habig WH, Urban KA, Hardegree MC. Cholesterol-dependent tetanolysin damage to liposomes. 

Vapor contact with the conjxmctiva may be the victim s first symptom. Severe conjxmctival irritation and blepharospasm may lead to loosening of corneal epithelial cells and swelling and edema of the cornea. Mucosal damage starts in the nose and descends down the respiratory mucosa in a dose-dependent fashion. Immediate pain, lacrimation, and irritation accompany the damage. DA vapor causes vomiting that develops within 1-2 min after exposure to DA. 

Topical anesthesia not only provides adequate surface anesthesia before debridement, it also has the beneficial effect of loosening the corneal epithelium. If both tetracaine and proparacaine are on hand, tetracaine is the preferred agent due to its greater effect on the corneal epithelium. Debridement may be accomplished with either a moistened cotton-tipped applicator or an Algerbrush. Both techniques effectively remove loose and damaged epithelial tissue. Debridement should be followed by irrigation and management of the corneal defect as an abrasion (see Chapter 26). 

Verticillate epithelial keratopathy due to amiodarone, in which there is whorl-shaped pigmentation of the cornea, has been proposed to be worsened by soft contact lenses (SEDA-15, 171). Two patients with hard contact lenses and amiodarone-associated keratopathy both complained of increased sensitivity to sunlight and were fitted with ultraviolet light-blocking lenses instead, as a precaution against further corneal damage however, the authors did not think that the contact lenses had contributed to the damage (102). 

Porcine corneal models have been used to develop in vitro/ex vivo models able to detect recovery of ocular injury. In preliminary studies porcine corneas cultured for at least 120 h showed regeneration of the damaged stratified epithelium by treatment with 3 % SLS and Ethanol [84], The model was further optimized and developed towards an ocular irritancy assay based on porcine corneas with reversibility as an endpoint, called the Porcine Corneal Ocular Reversibility Assay (PorCORA) [85]. The assay uses an air-interface porcine corneal culture system, and is maintained in culture for 21 days, similar to the in vivo observation period, to determine reversibility of corneal injury as measured by sodium fluorescein and to detect potential compromised epithelial barrier function. 

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