Figure 6-1: Pneumococcal corneal ulcer with hypopyon.

Table 6-2: Treatment of bacterial, fungal, and amebic keratitis.¹

Table 6-3: Drug concentrations and dosages for treatment of bacterial or fungal keratitis.

Pseudomonas Corneal Ulcer

Pseudomonas corneal ulcer begins as a gray or yellow infiltrate at the site of a break in the corneal epithelium (Figure 6-2). Severe pain usually accompanies it. The lesion tends to spread rapidly in all directions because of the proteolytic enzymes produced by the organisms. Although superficial at first, the ulcer may affect the entire cornea. There is often a large hypopyon that tends to increase in size as the ulcer progresses. The infiltrate and exudate may have a bluish-green color. This is due to a pigment produced by the organism and is pathognomonic of P aeruginosa infection.

Pseudomonas is a common cause of bacterial corneal ulcers. Cases of Pseudomonas corneal ulcer may follow minor corneal abrasion or the use of soft contact lenses-especially extended wear lenses. Corneal ulcers caused by this organism can vary from quite benign to devastating. The organism has been shown to adhere to the surface of soft contact lenses. Some cases have been reported following the use of contaminated fluorescein solution or eye drops. It is mandatory that the clinician use sterile medications and sterile technique when caring for patients with corneal injuries.

Scrapings from the ulcer may contain long, thin gram-negative rods that are often few in number. Drugs recommended for use in treatment are listed in Tables 6-2 and 6-3.

Moraxella liquefaciens Corneal Ulcer

M liquefaciens (diplobacillus of Petit) causes an indolent oval ulcer that usually affects the inferior cornea and progresses into the deep stroma over a period of days. There is usually no hypopyon or only a small one, and the surrounding cornea is usually clear. M liquefaciens ulcer almost always occurs in a patient with alcoholism, diabetes, or other immunosuppressing disease. Scrapings may contain large, square-ended gram-negative diplobacilli. Drugs recommended for use in treatment are listed in Tables 6-2 and 6-3. Treatment can be difficult and prolonged.

Group A Streptococcus Corneal Ulcer

Central corneal ulcers caused by beta-hemolytic streptococci have no identifying features. The surrounding corneal stroma is often infiltrated and edematous, and there is usually a moderately large hypopyon. Scrapings often contain gram-positive cocci in chains. Drugs recommended for use in treatment are listed in Tables 6-2 and 6-3.

Staphylococcus aureus, Staphylococcus epidermidis, & -Hemolytic Streptococcus Corneal Ulcers

Central corneal ulcers caused by these organisms are now being seen more often than formerly, many of them in corneas compromised by topical cortico-steroids. The ulcers are often indolent but may be associated with hypopyon and some surrounding corneal infiltration. They are often superficial, and the ulcer bed feels firm when scraped. Scrapings may contain gram-positive cocci-singly, in pairs, or in chains. Infectious crystalline keratopathy (in which the cornea has a crystalline appearance) has been described in patients receiving long-term therapy with topical steroids; the disease is often caused by - hemolytic streptococci. Tables 6-2 and 6-3 show recommended drug regimens.

Mycobacterium fortuitum-chelonei & Nocardia Corneal Ulcers

Ulcers due to M fortuitum-chelonei and Nocardia are rare. They often follow trauma and are often associated with contact with soil. The ulcers are indolent, and the bed of the ulcer often has radiating lines that make it look like a cracked windshield. Hypopyon may or may not be present. Scrapings may contain acid-fast slender rods (M fortuitum-chelonei) or gram-positive filamentous, often branching organisms (Nocardia). See Tables 6-2 and 6-3 for recommended drug regimens.

2. FUNGAL KERATITIS

Fungal corneal ulcers, once seen most commonly in agricultural workers, have become more common in the urban population since the introduction of the corticosteroid drugs for use in ophthalmology. Before the corticosteroid era, fungal corneal ulcers occurred only if an overwhelming inoculum of organisms was introduced into the corneal stroma-an event that can still take place in an agricultural setting. The uncompromised cornea seems to be able to handle the small inocula to which urban residents are ordinarily subjected.

Fungal ulcers are indolent and have a gray infiltrate, often a hypopyon, marked inflammation of the globe, superficial ulceration, and satellite lesions (usually infiltrates at sites distant from the main area of ulceration) (Figure 6-3). The principal lesion-and often the satellite lesions as well-is an endothelial plaque with irregular edges underlying the principal corneal lesions, associated with a severe anterior chamber reaction and a corneal abscess.

Most fungal ulcers are caused by opportunists such as Candida, Fusarium, Aspergillus, Penicillium, Cephalosporium, and others. There are no identifying features that help to differentiate one type of fungal ulcer from another.

Scrapings from fungal corneal ulcers, except those caused by Candida, contain hyphal elements; scrapings from Candida ulcers usually contain pseudohyphae or yeast forms that show characteristic budding. Tables 6-2 and 6-3 list the drugs recommended for the treatment of fungal ulcers.

3. VIRAL KERATITIS

Herpes Simplex Keratitis

Herpes simplex keratitis occurs in two forms: primary and recurrent. It is the most common cause of corneal ulceration and the most common corneal cause of blindness in the USA. The epithelial form is the ocular counterpart of labial herpes, with which it shares immunologic and pathologic features as well as having a similar time course. The only difference is that the clinical course of the keratitis may be prolonged because of the avascularity of the corneal stroma, which retards the migration of lymphocytes and macrophages to the lesion. herpes simplex virus (HSV) ocular infection in the immunocompetent host is usually self-limited, but in the immunologically compromised host, including patients treated with topical corticosteroids, its course can be chronic and damaging. Stromal and endothelial disease has previously been thought to be a purely immunologic response to virus particles or virally induced cellular changes. However, there is increasing evidence that active viral infection can occur within stromal and possibly endothelial cells as well as in other tissues within the anterior segment such as the iris and trabecular endothelium. This highlights the need to assess the relative role of viral replication and host immune responses prior to and during therapy for herpetic disease. Topical corticosteroids may control damaging inflammatory responses but at the expense of facilitation of viral replication. Thus, whenever topical corticosteroids are to be used, antivirals are likely to be necessary. Any patient undergoing topical corticosteroid therapy for herpetic eye disease must be under the supervision of an ophthalmologist.

Serologic studies suggest that almost all adults have been exposed to the virus, though many do not recollect any episodes of clinical disease. Following primary infection, the virus establishes latency in the trigeminal ganglion. The factors influencing the development of recurrent disease, including its site, have yet to be unraveled. There is increasing evidence that the severity of disease is at least partly determined by the strain of virus involved. Most HSV infections of the cornea are still caused by HSV type 1 (the cause of labial herpes), but in both infants and adults a few cases caused by HSV type 2 (the cause of genital herpes) have been reported. The corneal lesions caused by the two types are indistinguishable.

Scrapings of the epithelial lesions of HSV keratitis and fluid from skin lesions contain multinucleated giant cells. The virus can be cultivated on the chorioallantoic membrane of embryonated hens' eggs and in many tissue cell lines-eg, HeLa cells, on which it produces characteristic plaques. In the majority of cases, however, diagnosis can be made clinically on the basis of characteristic dendritic or geographic ulcers and greatly reduced or absent corneal sensation.

A. Clinical Findings:

Primary ocular herpes simplex is infrequently seen but is manifested as a vesicular blepharoconjunctivitis, occasionally with corneal involvement, and usually occurs in young children. It is generally self-limited, without causing significant ocular damage. Topical antiviral therapy may be used as prophylaxis against corneal involvement and as therapy for corneal disease.

Attacks of the common recurrent type of herpetic keratitis (Figure 6-4) are triggered by fever, overexposure to ultraviolet light, trauma, psychic stress, the onset of menstruation, or some other local or systemic source of immunosuppression. Unilaterality is the rule, but bilateral lesions develop in 4-6% of cases and are seen most often in atopic patients.

1. Symptoms- The first symptoms are usually irritation, photophobia, and tearing. When the central cornea is affected, there is also some reduction in vision. Since corneal anesthesia usually occurs early in the course of the infection, the symptoms may be minimal and the patient may not seek medical advice. There is often a history of fever blisters or other herpetic infection, but corneal ulceration can occasionally be the only sign of a recurrent herpetic infection.

2. Lesions- The most characteristic lesion is the dendritic ulcer. It occurs in the corneal epithelium, has a typical branching, linear pattern with feathery edges, and has terminal bulbs at its ends (Figure 6-5). Fluorescein staining makes the dendrite easy to identify, but unfortunately herpetic keratitis can also simulate many corneal infections and must be considered in the differential diagnosis of many corneal lesions.

Geographic ulceration is a form of chronic dendritic disease in which the delicate dendritic lesion takes a broader form. The edges of the ulcer lose their feathery quality. Corneal sensation, as with dendritic disease, is diminished. The clinician should always test for this sign.

Other corneal epithelial lesions that may be caused by HSV are a blotchy epithelial keratitis, stellate epithelial keratitis, and filamentary keratitis. All of these are usually transitory, however, and often become typical dendrites within a day or two.

Subepithelial opacities can be caused by HSV infection. A ghost-like image, corresponding in shape to the original epithelial defect but slightly larger, can be seen in the area immediately underlying the epithelial lesion. The "ghost" remains superficial but is often enhanced by the use of antiviral drugs, especially idoxuridine. As a rule, these subepithelial lesions do not persist for more than a year.

Disciform keratitis is the most common form of stromal disease in HSV infection. The stroma is edematous in a central, disk-shaped area, without significant infiltration and usually without vascularization. The edema may be sufficient to produce folds in Descemet's membrane. Keratic precipitates may lie directly under the disciform lesion but may also involve the entire endothelium because of the frequently associated anterior uveitis. The pathogenesis of disciform keratitis is generally regarded as an immunologic reaction to viral antigens in the stroma or endothelium, but active viral disease cannot be ruled out. Like most herpetic lesions in immunocompetent individuals, disciform keratitis is normally self-limited, lasting weeks to months. Edema is the most prominent sign, and healing can occur with minimal scarring and vascularization. A similar clinical appearance is seen with primary endothelial keratitis (endothelitis), which can be associated with anterior uveitis together with raised intraocular pressure and a focal inflammation of the iris. This is thought to be due to viral replication within the various anterior chamber structures.

Stromal HSV keratitis in the form of focal areas of infiltration and edema, often accompanied by vascularization, is likely to be predominantly due to viral replication. Corneal thinning and perforation may develop rapidly, particularly if topical corticosteroids are being used. If there is stromal disease in the presence of epithelial ulceration, it may be difficult to differentiate bacterial or fungal superinfection from herpetic disease. The features of the epithelial disease need to be carefully scrutinized for herpetic characteristics, but a bacterial or fungal component may be present and the patient must be managed accordingly. Stromal necrosis also may be caused by an acute immune reaction, again complicating the diagnosis with regard to active viral disease. Hypopyon may be seen with necrosis as well as secondary bacterial or fungal infection.

Peripheral lesions of the cornea can also be caused by HSV. They are usually linear and show a loss of epithelium before the underlying corneal stroma becomes infiltrated. (This is in contrast to the marginal ulcer associated with bacterial hypersensitivity-eg, to S aureus in staphylococcal blepharitis, in which the infiltration precedes the loss of the overlying epithelium.) Testing for corneal sensation is unreliable in peripheral herpetic disease. The patient is apt to be far less photophobic than patients with nonherpetic corneal infiltrates and ulceration usually are.

B. Treatment:

The treatment of HSV keratitis should be directed at eliminating viral replication within the cornea, while minimizing the damaging effects of the inflammatory response.

1. Debridement- An effective way to treat dendritic keratitis is epithelial debridement, since the virus is located in the epithelium and debridement will also reduce the viral antigenic load to the corneal stroma. Healthy epithelium adheres tightly to the cornea, but infected epithelium is easy to remove. Debridement is accomplished with a tightly wound cotton-tipped applicator. Topical iodine or ether has no value and can cause chemical keratitis. A cycloplegic such as atropine 1% or homatropine 5% is then instilled into the conjunctival sac, and a pressure dressing is applied. The patient should be examined daily and the dressing changed until the corneal defect has healed-usually within 72 hours. Adjunctive therapy with a topical antiviral accelerates epithelial healing. Topical drug therapy without epithelial debridement for epithelial keratitis offers the advantage of not requiring patching but involves a hazard of drug toxicity.

2. Drug therapy- The topical antiviral agents used in herpetic keratitis are idoxuridine, trifluridine, vidarabine, and acyclovir. (Topical acyclovir for ophthalmic use is not available in the USA.) Trifluridine and acyclovir are much more effective in stromal disease than the others. Idoxuridine and trifluridine are frequently associated with toxic reactions. Oral acyclovir may be useful in the treatment of severe herpetic eye disease, particularly in atopic individuals who are susceptible to aggressive ocular and dermal (eczema herpeticum) herpetic disease.

Viral replication in the immunocompetent patient, particularly when confined to the corneal epithelium, usually is self-limited and scarring is minimal. It is then unnecessary and potentially highly damaging to use topical corticosteroids. Regrettably, the clinician sometimes immunosuppresses the patient by using corticosteroids to reduce local inflammation. This is based on the misconception that reducing inflammation reduces the disease. Even when the inflammatory response is thought to be purely immunologically driven, such as in disciform keratitis, topical cortico-steroids are often best avoided if the episode is likely to be self-limited. Once topical corticosteroids have been used, this usually commits the patient to requiring the drug to control further episodes of keratitis, with the potential for uncontrolled viral replication and the other steroid-related side effects such as bacterial and fungal superinfection, glaucoma, and cataract. Topical corticosteroids may also accelerate corneal melting, thus increasing the risk of corneal perforation. If it becomes necessary to use topical corticosteroids because of the severity of the inflammatory response, it is absolutely essential that appropriate antiviral therapy be used to control viral replication.

3. Surgical treatment- Penetrating keratoplasty may be indicated for visual rehabilitation in patients with severe corneal scarring, but it should not be undertaken until the herpetic disease has been inactive for many months. Postoperatively, recurrent herpetic infection may occur as a result of the surgical trauma and the topical corticosteroids necessary to prevent corneal graft rejection. It may also be difficult to distinguish corneal graft rejection from recurrent stromal disease. Systemic antiviral agents should be used for several months after keratoplasty to cover the use of topical steroids.

Corneal perforation due to progressive herpetic stromal disease or superinfection with bacteria or fungi may necessitate emergency penetrating keratoplasty. Cyanoacrylate tissue adhesives can be used effectively to seal small perforations, and lamellar "patch" grafts have been successful in selected cases. Lamellar keratoplasty has the advantage over penetrating keratoplasty of reduced potential for corneal graft rejection. A therapeutic soft contact lens or tar-sorrhaphy may be required to heal epithelial defects associated with herpes simplex keratitis.

4. Control of trigger mechanisms that reactivate HSV infection- Recurrent HSV infections of the eye are common, occurring in about one-third of cases within 2 years after the first attack. A trigger mechanism can often be discovered by careful questioning of the patient. Once identified, the trigger can often be avoided. Aspirin can be used to avoid fever, excessive exposure to the sun or ultraviolet light can be avoided, situations that might cause psychic stress can be minimized, and aspirin can be taken just prior to the onset of menstruation.

Varicella-Zoster Viral Keratitis

Varicella-zoster virus (VZV) infection occurs in two forms: primary (varicella) and recurrent (herpes zoster). Ocular manifestations are uncommon in varicella but common in ophthalmic zoster. In varicella (chickenpox), the usual eye lesions are pocks on the lids and lid margins. Rarely, keratitis occurs (typically a peripheral stromal lesion with vascularization), and still more rarely epithelial keratitis with or without pseudodendrites. Disciform keratitis, with uveitis of varying duration, has been reported.

In contrast to the rare and benign corneal lesions of varicella, the relatively frequent ophthalmic herpes zoster is often accompanied by keratouveitis that varies in severity according to the immune status of the patient. Thus, although children with zoster keratouveitis usually have benign disease, the aged have severe and sometimes blinding disease. Corneal complications in ophthalmic zoster often occur if there is a skin eruption in areas supplied by the branches of the nasociliary nerve.

Unlike recurrent HSV keratitis that usually affects only the epithelium, VZV keratitis affects the stroma and anterior uvea at onset. The epithelial lesions are blotchy and amorphous except for an occasional linear pseudodendrite that only vaguely resembles the true dendrites of HSV keratitis. Stromal opacities consist of edema and mild cellular infiltration and initially are subepithelial. Deep stromal disease can follow with necrosis and vascularization (Figure 6-6). A disciform keratitis sometimes develops and resembles HSV disciform keratitis. Loss of corneal sensation is always a prominent feature and often persists for months after the corneal lesion appears to have healed. The associated uveitis tends to persist for weeks or months, but with time it eventually heals. Scleritis (sclerokeratitis) can be a serious feature of VZV ocular disease.

Intravenous and oral acyclovir have been used successfully for the treatment of herpes zoster ophthalmicus, particularly in immunocompromised patients. The oral dosage is 800 mg five times daily for 10-14 days. Therapy needs to be started within 72 hours after appearance of the rash. The role of topical antivirals is less certain. Topical corticosteroids may be necessary to treat severe keratitis, uveitis, and secondary glaucoma. The use of systemic corticosteroids is controversial. They may be indicated in reducing the incidence and severity of postherpetic neuralgia, but the risk of steroid complications is significant. Unfortunately, systemic acyclovir has little influence on the development of postherpetic neuralgia. However, the condition is self-limited, and reassurance can be helpful as a supplement to analgesics.

4. ACANTHAMOEBA KERATITIS

Acanthamoeba is a free-living protozoan that thrives in polluted water containing bacteria and organic material. Corneal infection with Acanthamoeba is an increasingly recognized complication of soft contact lens wear, particularly when homemade saline solutions are used. It may also occur in non-contact lens wearers after exposure to contaminated water or soil.

The initial symptoms are pain out of proportion to the clinical findings, redness, and photophobia. The characteristic clinical signs are indolent corneal ulceration, a stromal ring, and perineural infiltrates. The earlier forms of the disease with changes confined to the corneal epithelium are being more frequently recognized. Acanthamoeba keratitis is commonly misdiagnosed initially as herpetic keratitis.

The diagnosis is confirmed by scrapings and by culturing on specially prepared media. Corneal biopsy may be required. Histopathologic sections reveal the presence of amebic forms (trophozoites or cysts). Contact lens cases and solutions should be cultured. Often the amebic forms can be identified in the contact lens case fluid.

The differential diagnosis includes fungal keratitis, herpetic keratitis, mycobacterial keratitis, and Nocardia infection of the cornea.

In the early stages of the disease, epithelial debridement may be beneficial. Medical treatment is usually started with intensive topical propamidine isethionate (1% solution) and either polyhexamethylene biguanide (0.01-0.02% solution) or fortified neomycin eyedrops (Tables 6-2 and 6-3). Acanthamoeba spp may have variable drug sensitivities and may acquire drug resistance. Treatment is also hampered by the organisms' ability to encyst within the corneal stroma, necessitating prolonged treatment. Topical corticosteroids may be required to control the associated inflammatory reaction in the cornea.

Keratoplasty may be necessary in advanced disease to arrest progression of the infection or after resolution and scarring to restore vision. Once the organism has reached the sclera, medical and surgical treatment are usually fruitless.

PERIPHERAL CORNEAL ULCERS

1. MARGINAL INFILTRATES & ULCERS

The majority of marginal corneal ulcers are benign but extremely painful. They are secondary to acute or chronic bacterial conjunctivitis, particularly staphylococcal blepharoconjunctivitis and less often Koch-Weeks (Haemophilus aegyptius) conjunctivitis. They are not an infectious process, however, and scrapings do not contain the causal bacteria. They are the result of sensitization to bacterial products, antibody from the limbal vessels reacting with antigen that has diffused through the corneal epithelium.

Marginal infiltrates and ulcers (Figure 6-7) start as oval or linear infiltrates, separated from the limbus by a lucid interval, and only later may ulcerate and vascularize. They are self-limited, usually lasting from 7 to 10 days, but those associated with staphylococcal blepharoconjunctivitis usually recur. Treatment for blepharitis (shampoo scrubs, antimicrobials) usually will clear the problem; topical corticosteroids may be needed for severe cases. Topical corticosteroid preparations shorten their course and relieve symptoms, which are often severe, but treatment of the underlying blepharoconjunctivitis is essential if recurrences are to be prevented. Before starting corticosteroid therapy, great care must be taken to distinguish this entity, formerly known as "catarrhal corneal ulceration," from marginal herpetic keratitis. Since marginal herpetic keratitis is usually almost symptomless because of corneal anesthesia, differentiating it from the painful, hypersensitivity-type marginal ulcer is not difficult.

2. MOOREN'S ULCER(Figure 6-8)

The cause of Mooren's ulcer is still unknown, but an autoimmune origin is suspected. It is a marginal ulcer, unilateral in 60-80% of cases and characterized by painful, progressive excavation of the limbus and peripheral cornea that often leads to loss of the eye. It occurs most commonly in old age but does not seem to be related to any of the systemic diseases that most often afflict the aged. It is unresponsive to both antibiotics and corticosteroids. Surgical excision of the limbal conjunctiva in an effort to remove sensitizing substances has recently been advocated. Lamellar tectonic keratoplasty has been used with success in selected cases. Systemic immunosuppressive therapy may be helpful in advanced disease.

3. PHLYCTENULAR KERATOCONJUNCTIVITIS

This hypersensitivity disease (due to delayed hypersensitivity to bacterial products, eg, the human tubercle bacillus) was formerly a major cause of visual loss in the USA, particularly among the Eskimos and Native Americans. Phlyctenules are localized accumulations of lymphocytes, monocytes, macrophages, and finally neutrophils. They appear first at the limbus, but in recurrent attacks they may involve the bulbar conjunctiva and cornea. Corneal phlyctenules, usually bilateral, cicatrize and vascularize, but conjunctival phlyctenules leave no trace.

Most cases of phlyctenular keratoconjunctivitis in the USA today are caused by delayed hypersensitivity to S aureus. The antigen is released locally from staphylococci that proliferate on the lid margin in staphylococcal blepharitis. Rare phlyctenules have occurred in San Joaquin Valley fever, a result of hypersensitivity to a primary infection with Coccidioides immitis. In this disease they are not visually important, however.

In the tuberculous type, the attack may be triggered by an acute bacterial conjunctivitis but is associated typically with a transient increase in the activity of a childhood tuberculosis. Untreated phlyctenules run a course to healing in 10-14 days, but topical therapy with corticosteroid preparations dramatically shortens the course to a day or two and often decreases scarring and vascularization. The corticosteroid response in the staphylococcal type is less dramatic, however, and treatment consists essentially of eliminating the causal bacterial infection.

4. MARGINAL KERATITIS IN AUTOIMMUNE DISEASE(Figure 6-9)

The corneal periphery receives its nourishment from the aqueous humor, the limbal capillaries, and the tear film. It is contiguous with the subconjunctival lymphoid tissue and the lymphatic arcades at the limbus. The perilimbal conjunctiva appears to play an important role in the pathogenesis of corneal lesions that arise both from local ocular disease and from systemic disorders, particularly those of autoimmune origin. There is a striking similarity between the limbal capillary network and the renal glomerular capillary network. On the endothelial basement membranes of the capillaries of both networks, immune complexes are deposited and immunologic disease results. Thus, the peripheral cornea often participates in such autoimmune diseases as rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosus, scleroderma, midline lethal and Wegener's granulomatosis, ulcerative colitis, Crohn's disease, and relapsing polychondritis. The corneal changes are secondary to scleral inflammation, with or without scleral vascular closure (see Chapter 7). The clinical signs include vascularization, infiltration and opacification, and peripheral guttering that may progress to perforation. Treatment is directed toward control of the associated systemic disease; topical therapy usually is ineffective, and systemic use of potent immunosuppressive drugs often is required. Corneal perforation may require keratoplasty.

5. CORNEAL ULCER DUE TO VITAMIN A DEFICIENCY

The typical corneal ulcer associated with avitaminosis A is centrally located and bilateral, gray and indolent, with a definite lack of corneal luster in the surrounding area (Figure 6-10). The cornea becomes soft and necrotic (hence the term, "keratomalacia"), and perforation is common. The epithelium of the conjunctiva is keratinized, as evidenced by the presence of a Bitot spot. This is a foamy, wedge-shaped area in the conjunctiva, usually on the temporal side, with the base of the wedge at the limbus and the apex extending toward the lateral canthus. Within the triangle the conjunctiva is furrowed concentrically with the limbus, and dry flaky material can be seen falling from the area into the inferior cul-de-sac. A stained conjunctival scraping from a Bitot spot will show many saprophytic xerosis bacilli (Corynebacterium xerosis; small curved rods) and keratinized epithelial cells.

Avitaminosis A corneal ulceration results from dietary lack of vitamin A or impaired absorption from the gastrointestinal tract and impaired utilization by the body. It may develop in an infant who has a feeding problem; in an adult who is on a restricted or generally inadequate diet; or in any person with a biliary obstruction since bile in the gastrointestinal tract is necessary for the absorption of vitamin A. Lack of vitamin A causes a generalized keratinization of the epithelium throughout the body. The conjunctival and corneal changes together are known as xerophthalmia. Since the epithelium of the air passages is affected, many patients, if not treated, will die of pneumonia. Avitaminosis A also causes a generalized retardation of osseous growth. This is extremely important in infants; for example, if the skull bones do not grow and the brain continues to grow, increased intracranial pressure and papilledema can result.

Mild vitamin A deficiency should be treatment in adults with a dose of 30,000 units/d for 1 week. Advanced cases will require much higher doses initially (20,000 units/kg/d). Sulfonamide or antibiotic ointment can be used locally in the eye to prevent secondary bacterial infection. The average daily requirement of vitamin A is 1500-5000 IU for children, according to age, and 5000 IU for adults.

6. NEUROTROPHIC KERATITIS

If the trigeminal nerve, which supplies the cornea, is interrupted by trauma, surgery, tumor, inflammation, or in any other way, the cornea loses its sensitivity and one of its best defenses against degeneration, ulceration, and infection-ie, a healthy blink reflex. In the early stages of a typical neurotrophic ulcer, fluorescein solution will produce punctate staining of the superficial epithelium. As this process progresses, patchy areas of denudation appear. Occasionally the epithelium may be absent from a large area of the cornea.

In the absence of corneal sensation, even a severe keratitis may produce little discomfort. Patients must be warned to look out for redness of the eye, reduced vision, or increased conjunctival discharge and to seek ophthalmic care as soon as any of these develop.

Keeping the cornea moist with artificial tears and lubricant ointments may help to protect it. Once a keratitis develops, it must be treated promptly. The most effective management is to keep the eye closed either by careful horizontal taping of the eyelids, by tarsorrhaphy, or by means of ptosis induced with botulinum toxin A. Swim goggles may be useful at night. Secondary corneal infection must be treated appropriately.

7. EXPOSURE KERATITIS

Exposure keratitis may develop in any situation in which the cornea is not properly moistened and covered by the eyelids. Examples include exophthalmos from any cause, ectropion, the floppy lid syndrome, the absence of part of an eyelid as a result of trauma, and inability to close the lids properly, as in Bell's palsy. The two factors at work are the drying of the cornea and its exposure to minor trauma. The uncovered cornea is particularly subject to drying during sleeping hours. If an ulcer develops it usually follows minor trauma and occurs in the inferior third of the cornea.

This type of keratitis will be sterile unless it is secondarily infected, and the therapeutic objective is to provide protection and moisture for the entire corneal surface. The treatment method depends upon the underlying condition: a plastic procedure on the eyelids, correction of exophthalmos, or use of the options mentioned above in the discussion of neurotrophic keratitis.

EPITHELIAL KERATITIS

CHLAMYDIAL KERATITIS

All five principal types of chlamydial conjunctivitis (trachoma, inclusion conjunctivitis, primary ocular lymphogranuloma venereum, parakeet or psittacosis conjunctivitis, and feline pneumonitis conjunctivitis) are accompanied by corneal lesions. Only in trachoma and lymphogranuloma venereum, however, have they been blinding or visually damaging. The corneal lesions of trachoma have been the most studied and are of great diagnostic importance. In order of appearance they consist of (1) epithelial microerosions affecting the upper third of the cornea; (2) micropannus; (3) subepithelial round opacities, commonly called trachoma pustules; (4) limbal follicles and their cicatricial remains, known as Herbert's peripheral pits; (5) gross pannus; and (6) extensive, diffuse, subepithelial cicatrization. Mild cases of trachoma may show only epithelial keratitis and micropannus and may heal without impairing vision.

The rare cases of lymphogranuloma venereum have shown fewer characteristic changes but are known to have caused blindness by diffuse corneal scarring and total pannus. The remaining types of chlamydial infection cause only micropannus, epithelial keratitis, and, rarely, subepithelial opacities which are not visually significant.

Chlamydial keratoconjunctivitis responds to systemic sulfonamides (except for the rare C psittaci infections, which are sulfonamide-resistant), tetracyclines, or erythromycin.

DRUG-INDUCED EPITHELIAL KERATITIS

Epithelial keratitis is not uncommonly seen in patients using antiviral medications (idoxuridine and trifluridine) and several of the broad-spectrum and medium-spectrum antibiotics such as neomycin, gentamicin, and tobramycin. It is usually a superficial keratitis affecting predominantly the lower half of the cornea and interpalpebral fissure and may cause permanent scarring. The preservatives in eyedrops, particularly benzalkonium chloride, are a potent cause of toxic keratitis.

KERATOCONJUNCTIVITIS SICCA (SJÖGREN's SYNDROME)

Epithelial filaments in the lower quadrants of the cornea are the cardinal signs of this autoimmune disease in which secretion of the lacrimal and accessory lacrimal glands is diminished or eliminated. There is also a blotchy epithelial keratitis that affects mainly the lower quadrants. Severe cases show mucous pseudofilaments that stick to the corneal epithelium.

This keratitis of Sjögren's syndrome must be distinguished from the keratitis sicca of such cicatrizing diseases as trachoma and ocular pemphigoid, in which the goblet cells of the conjunctiva have been destroyed. Such cases sometimes still produce tears, but without mucus the corneal epithelium sheds the tears and continues to be dry.

Treatment of keratoconjunctivitis sicca calls for the frequent use of tear substitutes and lubricating ointments, of which there are many commercial preparations. When goblet cells have been destroyed, as in the cicatricial conjunctivitides, mucus substitutes must be used in addition to artificial tears. Topical vitamin A may help to reverse the epithelial keratinization. Moisture chambers or swim goggles may be required. Lacrimal punctal plugs and punctal occlusion are important in the management of advanced cases.

ADENOVIRUS KERATITIS

Keratitis usually accompanies all types of adenoviral conjunctivitis, reaching its peak 5-7 days after onset of the conjunctivitis. It is a fine epithelial keratitis best seen with the slit lamp after instillation of fluorescein. The minute lesions may group together to make up larger ones.

The epithelial keratitis is often followed by subepithelial opacities. In epidemic keratoconjunctivitis (EKC), which is due to adenovirus types 8 and 19, the subepithelial lesions are round and grossly visible. They appear 8-15 days after onset of the conjunctivitis and may persist for months or even (rarely) for several years. Similar lesions occur very exceptionally in other adenoviral infections, eg, those caused by types 3, 4, and 7, but tend to be transitory and mild, lasting a few weeks at most.

Although the corneal opacities of adenoviral keratoconjunctivitis tend to fade temporarily with the use of topical corticosteroids, and although the patient is often made temporarily more comfortable thereby, corticosteroid therapy may prolong the corneal disease and is therefore not recommended. No medication is needed.

OTHER VIRAL KERATITIDES

A fine epithelial keratitis may be seen in other viral infections such as measles (in which the central cornea is affected predominantly), rubella, mumps, infectious mononucleosis, acute hemorrhagic conjunctivitis, Newcastle disease conjunctivitis, and verruca of the lid margin. A superior epithelial keratitis and pannus often accompany molluscum contagiosum nodules on the lid margin.

DEGENERATIVE CORNEAL CONDITIONS

KERATOCONUS

Keratoconus is an uncommon degenerative bilateral disease that may be inherited as an autosomal recessive or autosomal dominant trait. Unilateral cases of unknown cause occur rarely. Symptoms appear in the second decade of life. The disease affects all races. Keratoconus has been associated with a number of diseases, including Down's syndrome, atopic dermatitis, retinitis pigmentosa, aniridia, vernal catarrh, Marfan's syndrome, Apert's syndrome, and Ehlers-Danlos syndrome. Pathologically, there are disruptive changes in Bowman's layer with keratocyte degeneration and ruptures in Descemet's membrane.

Blurred vision is the only symptom. Many patients present with rapidly increasing myopic astigmatism. Signs include cone-shaped cornea (Figure 6-11); linear narrow folds centrally in Descemet's membrane (Vogt's lines), which are pathognomonic; an iron ring around the base of the cone (Fleischer's ring); and, in extreme cases, indentation of the lower lid by the cornea when the patient looks down (Munson's sign). There is an irregular or scissor reflex on retinoscopy and a distorted corneal reflection with Placido's disk or the keratoscope-all of which often being more obvious in the early stages than the other corneal signs. Color-coded topography units provide more accurate information on the degree of corneal distortion (Figure 2-26). Generally, the fundi cannot be clearly seen because of corneal astigmatism.

Acute hydrops of the cornea may occur, manifested by sudden diminution of vision associated with central corneal edema. This arises as a consequence of rupture of Descemet's membrane and may be triggered by the patient rubbing the eye. The condition may be mistaken for extreme thinning with impending perforation. Acute hydrops usually clears gradually without treatment but often leaves apical scarring.

Rigid contact lenses will markedly improve vision in the early stages by correcting irregular astigmatism. Keratoconus is one of the most common indications for penetrating keratoplasty. Surgery is indicated when a contact lens can no longer be effectively worn or when peripheral thinning will affect the surgery.

Keratoconus is often slowly progressive between the ages of 20 and 60, although an arrest in progression of the keratoconus may occur at any time. If a corneal transplant is done before extreme corneal thinning occurs, the prognosis is excellent; about 80-95% obtain good best-corrected sight.

CORNEAL DEGENERATION

The corneal degenerations are a rare group of slowly progressive, bilateral, degenerative disorders that usually appear in the second or third decades of life. Some are hereditary. Other cases follow ocular inflammatory disease, and some are of unknown cause.

Marginal Degeneration of the Cornea

A. Terrien's Disease:

This is a rare bilateral symmetric degeneration characterized by marginal thinning of the upper nasal quadrants of the cornea. Males are more commonly affected than females, and the condition occurs more frequently in the third and fourth decades. There are no symptoms except for mild irritation during occasional inflammatory episodes, and the condition is slowly progressive. The clinical picture consists of marginal thinning and peripheral vascularization with lipid deposition. Perforation is a known complication, especially from trauma. Tectonic (structural) keratoplasty may be required. Histopathologic studies of affected corneas have revealed vascularized connective tissue with fibrillary degeneration and fatty infiltration of collagen fibers.

Because the course of progression is slow and the central cornea is spared, the prognosis is good.

B. Band (Calcific) Keratopathy:

(Figure 6-12.) This disorder is characterized by the deposition of calcium salts in the anterior layers of the cornea. The keratopathy is usually limited to the interpalpebral area and appears as a band. The calcium deposits are noted in the basement membrane, Bowman's layer, and anterior stromal lamellas. A clear margin separates the calcific band from the limbus, and clear holes may be seen in the band, giving the Swiss cheese appearance. Symptoms include irritation, injection, and blurring of vision.

Calcific band keratopathy has been described in a number of inflammatory, metabolic, and degenerative conditions. It is characteristically associated with juvenile rheumatoid arthritis. It has been described in long-standing inflammatory conditions of the eye, glaucoma, and chronic cyclitis. Band keratopathy may also be associated with hyperparathyroidism, vitamin D intoxication, sarcoidosis, and leprosy. Treatment consists of removal of the corneal epithelium by curettage under topical anesthesia followed by irrigation of the cornea with a sterile 0.01-molar solution of ethylenediaminetetraacetic acid (EDTA) or application of EDTA with a cotton applicator. The excimer laser has shown particular value in the treatment of band keratoplasty, or the band can be removed surgically.

Climatic Droplet Keratopathy (Labrador Keratopathy, Spheroid Degeneration of the Cornea) (  Figure 6-13)

Climatic droplet keratopathy affects mainly men who work out of doors. The corneal degeneration is thought to be caused by exposure to ultraviolet light and is characterized in the early stages by fine subepithelial yellow droplets in the peripheral cornea. As the disease advances, the droplets become central, with subsequent corneal clouding causing blurred vision. Treatment in advanced cases is by corneal transplantation.

Salzmann's Nodular Degeneration

This disorder is always preceded by corneal inflammation, particularly phlyctenular keratoconjunctivitis or trachoma. Symptoms include redness, irritation, and blurring of vision. There is degeneration of the superficial cornea that involves the stroma, Bowman's layer, and epithelium with superficial whitish-gray elevated nodules sometimes occurring in chains.

Corneal transplantation is rarely required; superficial lamellar keratectomy or phototherapeutic (laser) keratectomy can result in visual improvement.

Rigid contact lenses will significantly improve visual acuity in most cases.

ARCUS SENILIS (Corneal Annulus, Anterior Embryotoxon)

Arcus senilis is an extremely common, bilateral, benign peripheral corneal degeneration that may occur at any age but is far more common in elderly people as part of the aging process. Arcus senilis in people under age 50 is often associated with hyper- cholesterolemia; blood lipid studies should be done.

Pathologically, lipid droplets involve the entire corneal thickness but are more concentrated in the superficial and deep layers, being relatively sparse in the corneal stroma.

There are no symptoms. Clinically, arcus senilis appears as a hazy gray ring about 2 mm in width and with a clear space between it and the limbus (Figure 6-14). No treatment is necessary, and there are no complications.

HEREDITARY CORNEAL DYSTROPHIES

This is a group of rare hereditary disorders of the cornea of unknown cause characterized by bilateral abnormal deposition of substances and associated with alteration in the normal corneal architecture that may or may not interfere with vision. These corneal dystrophies usually manifest themselves during the first or second decade but sometimes later. They may be stationary or slowly progressive throughout life. Corneal transplantation, when indicated, improves vision in most patients with hereditary corneal dystrophy.

Anatomically, corneal dystrophies may be classified as epithelial, stromal, and posterior limiting membrane dystrophies.

Epithelial Corneal Dystrophies

A. Meesman's Dystrophy:

This slowly progressive disorder is characterized by microcystic areas in the epithelium. The onset is in early childhood (first 1-2 years of life). The main symptom is slight irritation, and vision is slightly affected. The inheritance is autosomal dominant

B. Anterior Membrane Dystrophies (Cogan's, Map-Dot-Fingerprint):

Map or fingerprint patterns are seen at the level of the epithelial basement membrane. Debris, cysts, and dots also may be noted. Recurrent erosion is common. Vision usually is not significantly affected. In Cogan's dystrophy, intraepithelial opacities are seen in the pupillary area

C. Others:

Reis-Bücklers dystrophy is a dominantly inherited dystrophy affecting primarily Bowman's layer. The disease begins within the first decade of life with symptoms of recurrent erosion. Opacification of Bowman's layer gradually occurs and the epithelium is irregular. No vascularization is usually noted. Vision may be markedly reduced.

Vortex dystrophy, or cornea verticillata, is characterized by pigmented lines occurring in Bowman's layer or the underlying stroma and spreading over the entire corneal surface. Visual acuity is not markedly affected. Such a pattern of radiating pigmented lines may also be seen in patients treated with chlorpromazine, chloroquine, indomethacin, or amiodarone as well as in Fabry's disease.

Stromal Corneal Dystrophies

There are three primary types of stromal corneal dystrophies:

A. Granular Dystrophy:

This usually asymp-tomatic, slowly progressive corneal dystrophy most often begins in early childhood. The lesions consist of central, fine, whitish "granular" lesions in the stroma of the cornea. The epithelium and Bowman's layer may be affected late in the disease. Visual acuity is slightly reduced. Histologically, the cornea shows uniform deposition of hyaline material. Corneal transplant is not needed except in very severe and late cases. The inheritance is autosomal dominant

B. Macular Dystrophy:

This type of stromal corneal dystrophy is manifested by a dense gray central opacity that starts in Bowman's layer. The opacity tends to spread toward the periphery and later involves the deeper stromal layers. Recurrent corneal erosion may occur, and vision is severely impaired. Histologic examination shows deposition of acid mucopolysaccharide in the stroma and degeneration of Bowman's layer. Penetrating keratoplasty is often required.

The inheritance is autosomal recessive.

C. Lattice Dystrophy:

Lattice dystrophy starts as fine, branching linear opacities in Bowman's layer in the central area and spreads to the periphery. The deep stroma may become involved, but the process does not reach Descemet's membrane. Recurrent erosion may occur. Histologic examination reveals amyloid deposits in the collagen fibers. Penetrating keratoplasty is common, as is recurrence of the dystrophy in the graft. The hereditary pattern for lattice dystrophy is autosomal dominant.

Posterior Corneal Dystrophies

A. Fuchs' Dystrophy:

This disorder begins in the third or fourth decade and is slowly progressive throughout life. Women are more commonly affected than men. There are central wart-like deposits on Descemet's membrane, thickening of Descemet's membrane, and defects of size and shape of the endothelial cells. Decompensation of the endothelium occurs and leads to edema of the corneal stroma and epithelium, causing blurring of vision. Corneal haze is slowly progressive. Histologic examination of the cornea reveals the wart-like excrescences over Descemet's membrane that are secreted by the endothelial cells. Thinning and pigmentation of the endothelium and thickening of Descemet's membrane are characteristics. Penetrating keratoplasty, often combined with extracapsular lens extraction and a posterior lens implant, is often needed. Cataract surgery alone can trigger endothelial decompensation in advanced disease

B. Posterior Polymorphous Dystrophy:

This is a common disorder with onset in early childhood. Polymorphous plaques of calcium crystals are observed in the deep stromal layers. Vesicular lesions may be seen in the endothelium. Edema occurs in the deep stroma. The condition is asymptomatic in most cases, but in severe cases epithelial and total stromal edema may occur. The inheritance is autosomal dominant.

MISCELLANEOUS CORNEAL DISORDERS

THYGESON'S SUPERFICIAL PUNCTATE KERATITIS

Superficial punctate keratitis is an uncommon chronic and recurrent bilateral disorder more common in females. It is characterized by discrete and elevated oval epithelial opacities that show punctate staining with fluorescein, mainly in the pupillary area. The opacities are not visible grossly but can be easily seen with the slit lamp or loupe. Subepithelial opacities underlying the epithelial lesions (ghosts) are often observed as the epithelial disease resolves.

No causative organism has been identified, but a virus is suspected. A varicella-zoster virus has been isolated from the corneal scrapings of one case.

Mild irritation, slight blurring of vision, and photophobia are the only symptoms. The conjunctiva is not involved.

Epithelial keratitis secondary to staphylococcal blepharoconjunctivitis is differentiated from superficial punctate keratitis by its involvement of the lower third of the cornea and lack of subepithelial opacities. Epithelial keratitis in trachoma is ruled out by its location in the upper third of the cornea and the presence of pannus. Many other forms of keratitis involving the superficial cornea are unilateral or are eliminated by their histories.

Short-term instillation of corticosteroid drops will often cause disappearance of the opacities and subjective improvement, but recurrences are the rule. The ultimate prognosis is good since there is no scarring or vascularization of the cornea. Untreated, the disease runs a protracted course of 1-3 years. Long-term treatment with topical corticosteroids may prolong the course of the disease for many years and lead to steroid-induced cataract and glaucoma. Therapeutic soft contact lenses have been used to control symptoms in especially bothersome cases. Cyclosporine topical drops, 1% or 2%, have been effective as a substitute for steroids.

RECURRENT CORNEAL EROSION

This is a fairly common and serious mechanical corneal disorder that presents some classic signs and symptoms but may be easily missed if the physician does not look for it specifically. The patient is usually awakened during the early morning hours by a pain in the affected eye. The pain is continuous, and the eye becomes red, irritated, and photophobic. When the patient attempts to open the eyes in the morning, the lid pulls off the loose epithelium, resulting in pain and redness.

Three types of recurrent corneal erosions can be recognized:

1. Acquired recurrent erosion (traumatic): The patient usually gives a history of previous corneal injury. It is unilateral, occurs with equal frequency in males and females, and the family history is negative. The recurrent erosion occurs most frequently in the center below the pupil no matter where the site of the previous corneal injury was.

2. Recurrent erosion associated with corneal disease: After corneal ulceration heals, the epithelium may break down in a recurrent fashion (as in HSV "metaherpetic" ulcer).

3. Recurrent erosion associated with corneal dystrophies: Recurrent erosions of the cornea may be observed in patients with Cogan's microcystic corneal dystrophy, lattice dystrophy, fingerprint dystrophy, and Reis-Bücklers corneal dystrophy.

Recurrent corneal erosion is due to a defect in the basement membrane of the corneal epithelium. The hemidesmosomes of the basal layer of the corneal epithelium fail to adhere to the basement membrane, and the corneal epithelium remains loose over the basement membrane with very slight subepithelial edema. The loose epithelial layers are vulnerable to separation and erosion.

Instillation of a local anesthetic relieves the symptoms immediately, and fluorescein staining will show the eroded area. This is typically a small area in the lower central cornea.

Treatment consists of a pressure bandage on the eye to promote healing. Mechanical denuding of the loose corneal epithelium may be necessary. The other eye should be kept closed most of the time to minimize movement of the lid over the affected eye. Bed rest is desirable for 24 hours. The cornea usually heals in 2-3 days. To prevent recurrence and to promote continued healing, it is important for these patients to use a bland ointment (eg, boric acid or other ocular lubricant) at bedtime for several months. In more severe cases, artificial tears are instilled during the day. The use of hypertonic ointment (glucose 40%) or 5% saline drops (Adsorbonac 5%) is often of value. Therapeutic soft contact lenses and needle micropuncture of Bowman's layer as well as excimer laser shallow keratectomy have been useful in cases that do not respond to more conservative management.

INTERSTITIAL KERATITIS DUE TO CONGENITAL SYPHILIS

This self-limited inflammatory disease of the cornea is a late manifestation of congenital syphilis. There has been a sharp decrease in the incidence of the disease in recent years-almost to the point of extinction in some parts of the USA. It occasionally starts unilaterally but almost always becomes bilateral weeks to months later. It affects all races and is more common in females than males. Symptoms appear between the ages of 5 and 20. Pathologic findings include edema, lymphocytic infiltration, and vascularization of the corneal stroma.

Interstitial keratitis may be immune in nature since Treponema pallidum is not found in the cornea during the acute phase. It has been postulated that these organisms enter the cornea at birth and that later in life there is a violent hypersensitivity to intracorneal viral antigen.

Clinical Findings

A. Symptoms and Signs:

Other signs of congenital syphilis may be present, such as saddle nose and Hutchinson's triad (interstitial keratitis, deafness, and notched upper central incisors). The patient complains of pain, photophobia, and blurring of vision. Physical signs include conjunctival injection, corneal edema, vascularization of the deeper corneal layers, and miosis. There is an associated severe anterior granulomatous uveitis and blepharospasm due to photophobia. The grayish-pink appearance of the cornea (due to edema and vascularization) that occurs in the acute phase is sometimes referred to as a "salmon patch."

B. Laboratory Findings:

Serologic tests for syphilis are positive.

Complications & Sequelae

Corneal scarring and vascularization occur if the process has been particularly severe and prolonged. Secondary glaucoma may result from the uveitis.

Treatment

There are no specific measures. Treatment is aimed at preventing the development of posterior synechiae, which will occur if the pupil is not dilated.

Both eyes should be dilated with frequent instillation of 2% atropine solution. Corticosteroid drops often relieve the symptoms dramatically but must be continued for long periods to prevent recurrence of symptoms. Dark glasses and a darkened room may be necessary if photophobia is severe. Treatment should be given for systemic syphilis, even though this usually has little effect on the ocular condition.

Corneal scarring may necessitate corneal transplant, and glaucoma, if present, may be difficult to control.

Course & Prognosis

The corneal disease process itself is not affected by treatment, which is aimed at prevention of complications. The inflammatory phase lasts 3 or 4 weeks. The corneas then gradually clear, leaving ghost vessels and scars in the corneal stroma.

INTERSTITIAL KERATITIS DUE TO OTHER CAUSES

Although congenital syphilis is no longer a common cause of interstitial keratitis, the disease still occurs as a complication of other granulomatous diseases, eg, tuberculosis and leprosy. Certain viruses (eg, cytomegalovirus, measles virus, mumps virus) as well as the spirochete of Lyme disease have been described as causing a type of interstitial keratitis. Treatment is usually symptomatic, but it is important to establish the cause.

Cogan's syndrome is a rare disorder generally believed to be a vascular hypersensitivity reaction of unknown origin. It is a disease of young adults and is characterized by nonsyphilitic interstitial keratitis and a vestibuloauditory difficulty. Corticosteroids are reputed to be of value, but some degree of visual impairment and complete nerve deafness usually supervene.

CORNEAL PIGMENTATION

Pigmentation of the cornea may occur with or without ocular or systemic disease. There are several distinct varieties.

Krukenberg's Spindle

In this disorder, brown uveal pigment is deposited bilaterally upon the central endothelial surface in a vertical spindle-shaped fashion. It occurs in a small percentage of people over age 20, usually in myopic women. It can be seen grossly but is best observed with the slitlamp. The visual acuity is only slightly affected, and the progression is extremely slow. Pigmentary glaucoma must be ruled out by yearly intraocular pressure measurements.

Blood Staining

This disorder occurs occasionally as a complication of traumatic hyphema with secondary glaucoma and is due to hemosiderin in the corneal stroma. The cornea is golden brown, and vision is decreased. In most cases the cornea gradually clears in 1-2 years.

Kayser-Fleischer Ring

This is a pigmented ring whose color varies widely from ruby red to bright green, blue, yellow, or brown. The ring is 1-3 mm is diameter and located just inside the limbus posteriorly. In exceptional cases there is a second ring. The pigment is composed of fine granules immediately below the endothelium. It involves Descemet's membrane, rarely the stroma. Electron microscopic studies suggest that the pigment is a copper compound. The intensity of the pigmentation can be reduced markedly by the use of chelating agents.

These rings, which were long considered to be pathognomonic of hepatolenticular degeneration (Wilson's disease), have recently been described in three nonwilsonian patients with chronic hepatobiliary disease and in one patient with chronic cholestatic jaundice. Recognition of the Kayser-Fleischer rings, however, remains important, since such notice calls attention to the possibility that the patient has Wilson's disease. Specific medical treatment with the copper chelating agent penicillamine may dramatically improve a disease that would otherwise inevitably be fatal.

Iron Lines (Hudson-StŠhli Line, Fleischer's Ring, Stocker's Line, Ferry's Line)

Localized deposits of iron within the corneal epithelium may occur in sufficient quantity to become visible clinically. The Hudson-StŠhli line is a horizontal line at the junction of the middle and lower thirds of the cornea, corresponding to the line of lid closure, in otherwise normal elderly patients. Fleischer's ring surrounds the base of the cone in keratoconus. Stocker's line is a vertical line associated with pterygia, and Ferry's line develops adjacent to limbal filtering blebs. Similar iron deposits are seen at the site of corneal scars.

CONTACT LENSES

Glass contact lenses were first described in 1888 by Adolf Fick and were then used for the treatment of keratoconus by Eugene Kalt. Poor results were achieved until 1945, when Kevin Tuohy of Los Angeles produced a plastic precorneal lens with a diameter of 11 mm. Since that time, advances in contact lens technology have produced several different varieties of lenses, which are broadly divided into two types: rigid and soft lenses. The basic requirement for success of contact lenses is to overcome the effect on oxygen supply to the cornea from wearing an occlusive lens. The optical features of contact lenses are discussed in Chapter 21.

Rigid (Hard) Lenses:

A. Standard Hard Lenses:

These direct descendants of Tuohy's lens are made of polymethylmethacrylate (PMMA, Perspex), are impervious to oxygen, and thus rely on pumping of tears into the space between the lens and the cornea during blinking to provide oxygen to the cornea. They are smaller than the corneal diameter. Always for daily wear, these lenses are easy to care for, are relatively inexpensive, and correct vision efficiently, particularly if there is significant astigmatism. Unfortunately, many persons cannot tolerate them. Corneal edema due to corneal hypoxia and spectacle blur (poor vision with spectacle correction after a period of contact lens wear) are common complaints

B. Gas-Permeable Hard Lenses:

These are rigid lenses made from cellulose acetate butyrate, silicone acrylate, or silicone combined with polymethylmethacrylate. They have the advantage of high oxygen permeability, thus improving corneal metabolism, and greater comfort, while retaining the optical properties of rigid lenses. They are generally used on a daily wear basis but can be used on an extended-wear (24-hour) basis in exceptional circumstances. In keratoconus, the gas-permeable lens has become the lens of first choice.

Soft Lenses

A. Cosmetic Soft Lenses:

Hydrogel lenses, based on hydroxymethyl methacrylate (HEMA), are considerably more comfortable than rigid lenses but are flexible and thus conform to the surface of the cornea. Regular astigmatism can be partially corrected by incorporating cylinder into the soft lens; irregular astigmatism is poorly corrected. The oxygen permeability and water content values vary among different types of hydrogel lens. They are more difficult to care for and more expensive than rigid lenses. Complications are also more common and include ulcerative keratitis, (particularly if the lenses are worn overnight), immune corneal reactions to deposits on the lenses, giant papillary conjunctivitis, reactions to lens care solutions (especially those containing the preservative thimerosal), corneal edema, and corneal vascularization.

Cosmetic soft contact lenses are usually worn on a daily wear basis. For aphakic correction, it is occasionally necessary to resort to extended wear because of the patient's inability to insert and remove the lenses themselves. Extended wear increases the risks associated with use of contact lenses.

B. Disposable Soft Lenses:

These lenses are designed to be discarded daily or sometimes after extended wear for 1 week. They eliminate the need for contact lens solutions and theoretically reduce the risk of ulcerative keratitis by minimizing bacterial adherence to the lens surface. They do appear to be safe if worn on a daily wear basis, but overnight wear, even for one night, is associated with a significant risk of ulcerative keratitis.

C. Therapeutic Soft Lenses:

The use of therapeutic soft contact lenses has become an indispensable part of the ophthalmologist's management of external eye disease. The lenses form a soft barrier between the outside and the cornea, providing protection against trichiasis and exposure. Lenses with high water content can act as a "stent" for epithelial healing, such as in the treatment of recurrent erosions. Patients with pain due to epithelial disease, such as in bullous keratopathy, particularly benefit from therapeutic soft contact lenses. Lenses with low water content can be used to seal small corneal perforations or wound leaks. In all cases of therapeutic contact lens wear, infection can occur. Antimicrobial coverage may be indicated if epithelial defects exist.

Contact Lens Care

It is essential that all contact lens wearers be made aware of the risks associated with contact lens wear-particularly those patients choosing the high-risk varieties such as extended-wear lenses for cosmetic optical correction purely on the grounds of convenience. All wearers must be under the regular care of a contact lens practitioner. Many of the chronic complications of contact lens wear are asymptomatic in their early and easily treated stages. Any contact lens should be removed immediately if the eye becomes uncomfortable or inflamed, and ophthalmic attention must be sought immediately if symptoms do not rapidly resolve.

Contact lenses require regular cleaning and disinfecting, and in the case of soft and gas-permeable lenses removal of protein deposits is required. Disinfection regimens include heat, chemical soaking, and hydrogen peroxide systems. All are effective if used according to the manufacturer's instructions, though heat systems may be preferable for combating resistant organisms such as Acanthamoeba. Soft and gas-permeable lenses are much less durable than hard lenses; contact lenses vary in tolerance to disinfection.

There is a significant trend among soft lens wearers toward the use of nonpreserved contact lens care systems because of the development of preservative- related hypersensitivity reactions. It is important that such individuals be aware of the ability of organisms such as Pseudomonas and Acanthamoeba to survive in nonpreserved saline solutions, such as may be found in their contact lens storage cases. The use of nonpreserved contact lens solutions requires much greater vigilance in the regular disinfection of lenses and lens storage cases.

CORNEAL TRANSPLANTATION

Corneal transplantation (keratoplasty) is indicated for a number of serious corneal conditions, eg, scarring, edema, thinning, and distortion. The term penetrating keratoplasty denotes full-thickness corneal replacement; lamellar keratoplasty denotes a par- tial-thickness procedure.

Younger donors are preferred for penetrating keratoplasties; there is a direct relationship between age and the health and number of the endothelial cells. Because of the rapid endothelial cell death rate, the eyes should be enucleated soon after death and refrigerated immediately. Whole eyes should be used within 48 hours, preferably within 24 hours. Modern storage media allow for longer storage. Corneoscleral caps stored in nutrient media may be used up to 6 days after donor death, and preservation in tissue culture media allows storage for as long as 6 weeks.

For lamellar keratoplasty, corneas can be frozen, dehydrated, or refrigerated for several weeks; the endothelial cells are not important in this partial-thickness procedure.

Technique

The recipient eye is prepared by a partial-thickness cutting of a circle of diseased cornea with a suction trephine (cookie cutter action) and full-thickness removal with scissors or partial-thickness removal with dissection.

The donor eye is prepared in two ways. For penetrating keratoplasty, the corneoscleral cap is placed endothelium up on a suction Teflon block; the trephine (Figure 6-15) is pressed down into the cornea, and a full-thickness button is punched out. In lamellar keratoplasty, a partial-thickness trephine incision is made in the cornea of a whole globe and the lamellar button is dissected free. Certain refinements in technique, such as free hand grafts, may be necessary.

Refined sutures (Figure 6-16) and instruments and sophisticated operating microscopes and illuminating systems have significantly improved the prognosis in all patients requiring corneal transplants. There is no significant value to blood type matching in corneal transplant surgery.

Corneal graft rejection continues to be a major management problem (see Chapter 16), as does the difficulty in controlling postgraft astigmatism.

REFRACTIVE CORNEAL SURGERY

The inconvenience of spectacles to many wearers and the complications associated with contact lenses have resulted in a search for surgical solutions to the problem of refractive error.

Radial Keratotomy

In the late 1940s, Sato of Japan created anterior and posterior corneal incisions to alter the curvature of the cornea. Results were poor, and endothelial decompensation with corneal edema occurred frequently. In 1972, Fyodorov of the USSR began to use anterior corneal cuts only. Currently, the operation consists of radial incisions involving 90% of the corneal thickness and extending from a clear optical zone (usually the central 3 mm or more of the cornea) toward but not reaching the limbus. The amount of correction achieved is modified by the size of the optical zone and the number and depth of the incisions. Various formulas and computer programs are used to determine the value of these parameters in each case.

There is general agreement that radial keratotomy does reduce the degree of myopia and is most effective for myopia in the lower range (-2 to -4 diopters). There is a significant degree of unpredictability in the final result, with under- or overcorrection or even progressive hyperopia. Glare and fluctuations of vision during the day are commonly reported side effects. Delayed healing of corneal incisions, with corneal infections occurring up to 2 years after the procedure, have been reported. Endophthalmitis, traumatic cataract, and endothelial cell loss are rare but have been reported.

Keratomileusis

In 1961, Barraquer of Colombia reported on the technique of myopic keratomileusis for the correction of high degrees of myopia. The procedure has been performed in other countries but by relatively few surgeons. A deep lamellar corneal autograft is cut; the tissue is frozen and then reshaped with a cryolathe to obtain a flatter curvature after thawing; and the autograft is then sutured back into position. Expensive cryolathe and microkeratome equipment is required. The procedure has also been used for hyperopia. Automated lamellar keratoplasty (ALK) is a new form of this procedure.

Complications of keratomileusis include improper depth of the lamellar bed, delayed epithelialization over the resutured tissue, interface epithelial growth and opacity, and irregular astigmatism.

Procedures to Correct Astigmatism

Various patterns of keratotomy have been described to correct corneal astigmatism. Irregular astigmatism continues to be a serious problem following most corneal operations, including radial keratotomy and penetrating keratoplasty, and after cataract surgery. Troutman and others have described relaxing incisions, compression sutures, and wedge resections for postkeratoplasty astigmatism, utilizing a surgical keratometer. Various techniques for cataract incision, such as scleral tunnel incisions and clear corneal incisions as well as altering incision location, have been reported as useful in preventing postoperative astigmatism after cataract surgery.

Alloplastic Corneal Implants

Disks of many different materials have been inserted into corneal stromal pockets, initially to control corneal edema but more recently to correct refractive errors. In most cases, the corneal tissue anterior to the implant undergoes necrosis. Hydrogel and polysulfone lenses have been more successful than other types of lenses tried so far. Use of alloplastic corneal implants would remove the need to rely on autologous or homologous material in refractive surgery. A plastic ring meant to be implanted intrastromally is under investigation and shows promise as a refractive surgery procedure.

Clear Lens Removal & Phakic Lens Implants

A few surgeons around the world have advocated the removal of clear lenses in high degrees of myopia, suggesting that the risk of doing so is minimal owing to the safety of extracapsular lens extraction. The procedure is controversial because of a significant risk of retinal detachment in high myopes. Phakic lens implants are under investigation for treatment of high refractive errors.

Lasers

A further approach to refractive corneal surgery involves the use of lasers (see Chapter 24). The excimer laser has received the most publicity, but other machines such as the solid-state neodymium:YAG laser and "minilasers" have been shown to be effective also. Laser photorefractive keratectomy (PRK) produces precisely controlled flattening of the anterior cornea to reduce myopia. The procedure also is done for astigmatism and hyperopia. Anterior stromal haze, irregular astigmatism, and regression have been observed after PRK. In the United States, theFood and Drug Administration (FDA) has given approval for PRK to two laser companies; the procedure has been done in many other countries for years.

Laser in situ keratomileusis (LASIK) is a procedure that utilizes a motorized microkeratome to cut a shallow lamellar corneal disk which is folded back to allow excimer laser photoablation to the stromal bed. The flap is then folded back into position. The patient is more comfortable immediately after surgery than with PRK, and best vision is restored earlier. Irregular astigmatism and interface problems are among the complications of this procedure.

Controversy exists over the choice between surface ablation (PRK) and LASIK. In general, PRK is used for lower (-6.00 D or less) and LASIK for higher levels of myopia. Improved methods of surface ablation or other techniques may eliminate the need for LASIK in the future. Generally, LASIK is not approved by the FDA.

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List of Figures

	Figure 6-1: Pneumococcal corneal ulcer with hypopyon.
	Figure 6-2: Pseudomonsa ulcer related to 24-hour contact lens wear.
	Figure 6-3: Corneal ulcer caused by Candida albicans.
	Figure 6-4: Corneal scar caused by recurrent herpes simplex keratitis.
	Figure 6-5: Dendritic figures seen in herpes simplex keratitis.
	Figure 6-6: Herpes zoster keratitis.
	Figure 6-7: Marginal ulcer of temporal cornea, right eye. (Courtesy of P Thygeson.)
	Figure 6-8: Advanced Mooren's ulcer.
	Figure 6-9: Marginal keratitis. (Courtesy of M Hogan.)
	Figure 6-10: Keratomalacia with ulceration associated with xerophthalmia (dietary) in an infant. (Photo by Diane Beeston.)
	Figure 6-11: Keratoconus.
	Figure 6-12: Calcific band keratopathy. (Courtesy of M Hogan.)
	Figure 6-13: Two photos showing climatic droplet (Labrador) keratodystrophy. Inset at left shows slitlamp view. (Photo at left courtesy of A Ahmad.)
	Figure 6-14: Arcus senilis. (Photo by Diane Beeston.)
	Figure 6-15: A popular vacuum corneal punch and trephine. (Barron-Katena.)
	Figure 6-16: Penetrating keratoplasty with 10-0 nylon running suture, 3 months after operation.

List of Tables

	Table 6-1: Principal types of epithelial keratitis (in order of frequency of occurence).
	Table 6-2: Treatment of bacterial, fungal, and amebic keratitis.1
	Table 6-3: Drug concentrations and dosages for treatment of bacterial or fungal keratitis.

10.1036/1535-8860.ch6

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