The cornea functions both as a protective barrier and as a “window” through which light rays pass to the retina. Its transparency is due to its uniform structure, avascularity, and deturgescence (see Chapter 1). Deturgescence, or the state of relative dehydration of the corneal tissue, is maintained by the bicarbonate “pump” provided by the endothelium and the barrier function of the epithelium and endothelium. The endothelium is more important than the epithelium in the mechanism of dehydration, and damage to the endothelium is far more serious than damage to the epithelium. Destruction of the endothelial cells causes edema of the cornea and loss of transparency, which is more likely to persist because of the limited potential for recovery of endothelial function. Damage to the epithelium usually causes only transient, localized edema of the corneal stroma that clears with the rapid regeneration of epithelial cells. Evaporation of water from the precorneal tear film produces hypertonicity of the film. Together with direct evaporation, this draws water from the superficial corneal stroma in order to maintain the state of dehydration.
Penetration of the intact cornea by drugs is biphasic. Fat-soluble substances can pass through intact epithelium, and water-soluble substances can pass through intact stroma. Therefore, to pass through the cornea, drugs must be soluble in both lipids and water.
Corneal Resistance to Infection
The epithelium is an efficient barrier to the entrance of microorganisms into the cornea. If the epithelium is defective, the avascular stroma and Bowman's layer become susceptible to infection with a variety of organisms, including bacteria, Acanthamoeba, and fungi. Streptococcus pneumoniae (the pneumococcus) is a true bacterial corneal pathogen; other pathogens require a heavy inoculum, compromised barrier function, or a relative immune deficiency to produce infection.
Moraxella liquefaciens, which occurs mainly in alcoholics (as a result of pyridoxine depletion), is a classic example of the bacterial opportunist, and in recent years a number of new corneal opportunists have been identified. Among them are Serratia marcescens, Mycobacterium fortuitum-chelonei complex, viridans streptococci, Staphylococcus epidermidis, and various coliform and proteus organisms, along with viruses, Acanthamoeba, and fungi.
Local or systemic corticosteroids modify the host immune reaction in several ways and may allow opportunistic organisms to invade and flourish.
Since the cornea has many pain fibers, most superficial or deep corneal lesions cause pain and photophobia. The pain of epithelial disease is worsened by movement of the lids (particularly the upper lid) over the cornea and usually persists until healing occurs. Since the cornea serves as the “window” of the eye and refracts light rays, corneal lesions usually blur vision, especially if centrally located.
Photophobia in corneal disease is the result of painful contraction of an inflamed iris. Dilation of iris vessels is a reflex phenomenon caused by irritation of the corneal nerve endings. Photophobia, severe in most corneal disease, is minimal in herpetic keratitis because of the hypesthesia associated with the disease, which can be a valuable diagnostic sign.
Although tearing and photophobia commonly accompany corneal disease, there is usually no discharge except in purulent bacterial ulcers.
Investigation of Corneal Disease
Obtaining a thorough history is important. A history of trauma can often be elicited, foreign bodies and abrasions being the two most common corneal lesions, and eliciting any history of corneal disease in the patient or the family can be critical. The keratitis of herpes simplex infection is often recurrent, but since recurrent erosion is extremely painful and herpetic keratitis is not, these disorders can be differentiated by their symptoms. The patient's use of topical medications should be investigated, since corticosteroids may have been used and may have predisposed to bacterial, fungal, or viral disease, especially herpes simplex keratitis. Immuno-suppression also occurs with systemic diseases, such as diabetes, AIDS, and malignant disease, as well as with specific immunosuppressive therapy. All medications and preservatives can cause contact dermatitis or corneal toxicity; the importance of toxicity as a cause of corneal and conjunctival disease should not be underestimated.
The keys to examination of the cornea are adequate illumination and magnification. The slitlamp is essential in proper examination of the cornea; in its absence, a loupe and bright illumination can be used for gross inspection. Examining the light reflection, while moving the light carefully over the entire cornea, will identify rough areas indicative of epithelial defects. Fluorescein staining can highlight superficial epithelial lesions that might otherwise not be apparent. Examination, particularly after trauma, is often facilitated by instillation of a local anesthetic, but sterile drops must be used. Confocal microscopy assists diagnosis, particularly in suspected Acanthamoeba or fungal infection.
To select the proper therapy for corneal infections, especially due to bacteria, fungi, or Acanthamoeba laboratory aid is essential. Since a delay in identifying the correct organism may severely compromise the ultimate visual result, it should be achieved as soon as possible. Examination of corneal scrapings, stained with Gram's and Giemsa's stains, may allow identification of the organism, particularly bacteria, while the patient waits. Polymerase chain reaction (PCR) may provide rapid identification of herpes viruses, Acanthamoeba, and fungi. Cultures for bacteria are usually obtained in all cases at first presentation. Cultures for fungi, Acanthamoeba, or viruses may be undertaken if the clinical features are typical or there is lack of response to treatment for bacterial infection. Appropriate therapy is instituted as soon as the necessary specimens have been obtained. It is important that therapy is not withheld if an organism cannot be identified on microscopic examination of corneal scrapings, although it may have to be empirical based upon the clinical features.
Morphologic Diagnosis of Corneal Lesions
The corneal epithelium is involved ...