Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

530 CHAPTER 26 Diseases of the Cornea

Figure 26-48 Disciform corneal scar secondary to HSK disciform (stromal) keratitis. (Courtesy of Pat Caroline.)

Generally, necrotizing IK should be treated in the same manner as disciform keratitis, but necrotizing keratitis is much less responsive to steroids.As with disciform keratitis, the steroid must be tapered very slowly, often over a period of months or years. Conjunctival flaps may be necessary as may temporary or permanent tarsorrhaphy, and penetrating keratoplasty.

The use of oral antivirals for the treatment of herpetic eye disease has been the subject of many studies. The HEDS group evaluated the use of oral acyclovir when used with topical steroids and trifluridine in patients with stromal keratitis without concomitant epithelial keratitis. Oral acyclovir did not alter the duration or success rates in treating stromal keratitis. In addition, oral acyclovir did not prevent the development of stromal keratitis in patients with epithelial disease. However, the HEDS group reported that 400 mg of oral acyclovir twice daily decreased the recurrence rate of any type of ocular HSV disease to 19% compared with 32% in the placebo group. As would be expected from a medication that prevents duplication of but does not eradicate the virus, this effect continues only as long as the drug is being used. After discontinuing the acyclovir treatment, there was no significant difference between the acyclovir group and the placebo group in the rate of recurrences. Patients who have had recurrences of stromal disease and patients at risk from vision loss from epithelial disease should be considered candidates for long-term oral acyclovir prophylaxis. Although not formally tested in controlled studies, it would be expected that other oral antivirals, such as famciclovir or valacyclovir, would have similar effects on HSK recurrences.

Accumulating evidence suggests the use of oral antivirals for acute as well as prophylactic therapy of HSK. A recent study that compared oral valacyclovir with topical acyclovir found a more rapid reduction in symptoms and faster resolution in those treated with oral valacyclovir. Efforts to improve the treatment of HSK include

the development of additional antiviral medications and an HSV vaccine.

Herpes Zoster Ophthalmicus

Etiology

Varicella-zoster virus is a member of the Herpesviridae family. The viral contagion is transmitted via aerosolized water droplets or close physical contact with infected lesions. The primary infection results in varicella or chickenpox. The varicella infection can have potentially devastating ocular sequelae; the most common is anterior uveitis followed by SPK. After the primary infection, latent infection occurs in multiple ganglia throughout the body. Herpes zoster is the resultant reactivation of the latent varicella-zoster virus and most often occurs in elderly and immunocompromised patients. Factors such as physical and emotional trauma, immunosuppressive medications, irradiation, cancer, tuberculosis, malaria, and syphilis are known to reactivate the virus.

Herpes zoster is found worldwide and affects both sexes equally. It is more common in individuals over the age of 40 and rarely occurs in children. Approximately 95% of all adults in the United States have blood antibodies to herpes zoster, and about 20% experience a reactivation of the virus.

When reactivation occurs, the virus passes along the sensory nerve and erupts on the tissue innervated by that nerve (dermatome).The thoracic ganglion ranks first and the trigeminal ganglion second in order of frequency of zoster involvement. The ophthalmic division of the trigeminal ganglion is involved 20 times more frequently than the maxillary and mandibular branches and is known as herpes zoster ophthalmicus (HZO).

The nasociliary branch of the trigeminal nerve supplies the conjunctiva, cornea, iris, ciliary body, anterior choroid, and the skin of the upper lid and the tip of the nose. Herpes zoster involvement of the terminal branch of the nasociliary is indicated by cutaneous vesicles on the tip of the nose and is often referred to as Hutchinson’s sign.Their presence of this sign increases the chances of serious ocular involvement.

Diagnosis

Patients with HZO typically report a history of influenzalike illness with headache, malaise, fever, and chills for 2 to 3 days before the appearance of a forehead rash. At the same time they may notice pain, tingling, burning, itching,erythema,and edema of the skin over the affected nerve. Some patients also have ocular symptoms of pain, tearing, and foreign body sensation. A few days later, patients develop flushing of the skin and an eruption of vesicles along the distribution of the nerve. Untreated, these vesicles become pustular and hemorrhagic in 3 to 4 days, developing crusts in 7 to 10 days. Severe pain is common both while the vesicles are present because of inflammation of the neurons and after the vesicles are

healed because of scarring in and around the nerves. Permanent scarring of the skin also is quite common unless aggressive therapeutic measures are taken with systemic antiviral therapy before the vesicles erupt. Involvement of the ophthalmic branch of the trigeminal nerve usually causes lymphadenopathy.

Ocular involvement can develop as soon as several days, to as long as years, after vesicle formation. Ocular involvement may include lid edema, follicular conjunctivitis, corneal changes, anterior uveitis, glaucoma, episcleritis, scleritis, Horner’s syndrome, extraocular muscle palsy, chorioretinitis, optic neuritis, and scarring of the lids and lacrimal canalicular system. It is possible, but rare, to have ocular complications, such as uveitis and disciform keratitis, without any skin lesions.

Corneal changes can occur within the first week of the disease or months later and can result in significant vision loss. Corneal involvement may result from direct viral infection, antigen-antibody reactions, delayed cellmediated hypersensitivity reactions, and neurotropic damage. Patients with corneal involvement report varying symptoms, including decreased vision, pain, and photophobia. The corneal changes include SPK and pseudodendritic keratitis and occur in a significant number of patients with HZO. Punctate epithelial keratitis is the earliest corneal finding and is coarse in appearance, with blotchy swollen epithelial cells.The lesions are numerous and located peripherally in the cornea. They probably contain live virus and may either resolve or progress to dendrite formation.

The dendritic corneal lesions of HZO are more superficial,smaller,and have blunter ends than do the dendrites caused by herpes simplex, which often have terminal bulbs (Table 26-6).They usually occur 4 to 6 days after the skin vesicles erupt and stain moderately well with rose bengal and NaFl (Figure 26-49). In addition to dendritic keratitis, mucous plaque keratitis may also occur almost anytime in the course of the disease but typically occurs

Table 26-6

Differential Diagnosis of Herpes Simplex and Herpes Zoster

Figure 26-49 Dendritic corneal lesion (arrows) resulting from herpes zoster ophthalmicus, shown stained with rose bengal and NaFl.

532 CHAPTER 26 Diseases of the Cornea

A

B

Figure 26-50 Mucous plaque keratitis associated with herpes zoster. (A) Initial presentation. (B) Note migratory nature of lesions 3 weeks later. (Courtesy Marc A. Michelson, MD.)

3 to 4 months after the initial infection. These plaques appear as elevated, sharply demarcated, opaque, gray-white lesions that are variable in size and shape.They stain well with rose bengal but poorly with NaFl. A poor tear film and neurotropic corneal changes are common in these cases.Viral cultures are negative, and the lesions appear to be mucous deposits on abnormal epithelial cells, which can migrate or disappear with time (Figure 26-50).

Anterior stromal infiltrates can develop under the dendritic HZO lesions and appear as hazy, granular, nummular, subepithelial opacities. They have been observed in close proximity to enlarged corneal nerves, which possibly represents a perineuritis from viral destruction of the sensory nerves. These lesions are responsive to topical steroids, indicating they are most likely caused by a local immune reaction to the epithelial dendrites.

The lesions can be self-limiting or chronic and rarely result in scarring or vision loss.

Deep corneal edema with folds in Descemet’s membrane, in the presence of an intact epithelium, can develop from 3 to 4 months after acute HZO. This disciform keratitis may involve the full thickness of the cornea and may be surrounded by a ring-like cellular infiltrate called a Wessley ring. It is considered to be an immune response to viral antigens and responds quickly to topical steroids, especially when initiated early. Unfortunately, it is common to have recurrences when steroids are tapered or discontinued and can lead to corneal scarring or, more seriously, corneal melt. There is often an associated anterior uveitis with keratic precipitates as well as diffuse corneal edema, endothelial cell loss, and increased IOP secondary to trabeculitis.

A significant number of patients with HZO develop impaired sensation of the cornea, bulbar conjunctiva, and eyelid margins secondary to trigeminal ganglionitis and damage to the sensory nerves innervating the skin and other tissues. The resulting corneal anesthesia produces a decreased blink rate and loss of the normal nasolacrimal reflex with a secondary reduction in aqueous tear production. A neurotropic keratitis can occur as early as 10 days and up to several years after the HZO infection. The characteristic neurotropic ulcer occurs in the inferior cornea or interpalpebral area, similar to exposure keratitis. The ulcers are ovoid in shape and have an opaque appearance with underlying stromal edema. These ulcers are slow to heal, are susceptible to secondary bacterial infections, and may result in scarring with neovascularization and potentially corneal penetration.

Management

Systemic antiviral therapy promotes resolution of HZO skin lesions and reduces the incidence and severity of dendriform keratopathy, anterior uveitis, and stromal keratitis by decreasing the rate of virus replication. All patients with acute HZO should receive antiviral therapy with the goal of minimizing ocular complications. Acyclovir, valacyclovir, and famciclovir are FDA approved for management of herpes zoster. Acyclovir usually is administered orally in dosages of 800 mg five times per day for 7 days. Valacyclovir has better bioavailability when taken orally and can be used with a recommended dosage of 1 g three times a day for 7 days. Famciclovir, which has bioavailability similar to valacyclovir, has an increased half-life and also has the advantage of less frequent administration than acyclovir: 500 mg three times a day for 7 days.

For antivirals to have the maximum effect, treatment should be started within 72 hours of the vesicular eruptions. Effectiveness of antiviral therapy started beyond 72 hours has not been established, but reports suggest a benefit. Because HZO is often more chronic in patients who are immunocompromised, they should be treated more aggressively and potentially for a longer duration

than patients with a healthy immune system. The use of intravenous antivirals may be required.

The early corneal changes of SPK and pseudodendrites usually are self-limiting, lasting weeks to months, and require no treatment. Artificial tears and cool compresses may be helpful for symptomatic relief.

Use of topical steroids usually is not necessary if there is only mild inflammation and good vision. Prednisolone acetate 1% can be used four times a day for corneal changes caused by inflammation such as stromal infiltrates and disciform keratitis. Some authors suggest using prophylactic antibiotics along with the steroid. If there is any possibility that herpes simplex is present, a topical ophthalmic antiviral agent should be used concurrently with the steroid. To avoid recurrences of inflammation, steroids must be tapered very slowly. A cycloplegic agent such as homatropine 5% used two to three times a day can decrease pain and help prevent or control anterior uveitis and synechiae.

Mucous plaque keratitis can be treated with 10% acetylcysteine but also resolves without treatment. Keeping the eye moist with artificial tears may be helpful. Exposure keratitis and neurotropic keratitis are best treated with artificial tears, lid taping at bedtime, and, if necessary, tarsorrhaphy. Therapeutic contact lenses should not be used because of the risk of developing infectious ulcers in an eye with decreased sensitivity.

Corneal scarring that affects vision is best treated with penetrating keratoplasty. Penetrating keratoplasty generally is considered to have a poor outcome after HZO because of recurrent or chronic inflammation, vascularization, glaucoma, and poor tear film quality. The chances of success seem to improve, however, if the corneal surface is protected after surgery by lubricants, therapeutic lenses, or tarsorrhaphy or if there has been a long interval since the previous occurrence.

Because chronic pain is a common occurrence with herpes zoster, management should also include consultation with a dermatologist, family practitioner, or pain specialist as needed.

Thygeson’s Superficial Punctate Keratitis

Etiology

TSPK is a chronic epithelial keratitis of unknown etiology, suggested to be due to chronic subclinical viral infection in the deep layers of the basal epithelium. Support for this theory includes the protracted course of this condition, its tendency to recur, the lack of effect by antibiotics on its clinical course, and lack of bacterial isolation from eyes affected by the condition. The clinical presentation of corneal mononuclear cell infiltrates, the rapid resolution of these infiltrates with topical steroids, and their rapid reappearance if topical steroids are stopped too quickly support the possibility that the primary presentation is a typical immunologic response.

Additionally, TSPK has been associated with histocompatability antigen HLA-DR3, suggesting that immune mechanisms play a role.

Diagnosis

When Thygeson described this condition in 1961, he noted that the disease was chronic, bilateral, and had a long duration with exacerbations and remissions. Also noted was the typical punctate epithelial keratitis that showed no response to antibiotics or epithelial debridement, a rapid response to very low doses of steroids, and eventual healing without scars. These features, with few variations, are still characteristic of the disease today. Although the disease is bilateral in most patients, there are reports of unilateral cases and cases with marked asymmetry between the two eyes.

The duration of the disease is quite long, lasting weeks to years. Authors have reported an average duration of 2.5 to 3.5 years. It has been suggested that the use of topical ophthalmic steroids may increase the duration of the disease. Most authors have reported no gender or age predilection; however, there may be a mild female predominance. The age at onset ranges from 2.5 years to 70 years, with a mean in the late twenties.

Patients with TSPK usually report an insidious onset of symptoms such as foreign body sensation or pain, tearing, photophobia, slightly decreased vision, burning, and itching.These symptoms are primarily the result of epithelial disruption, with decreased vision occurring due to infiltrates on the visual axis and irregularity of the corneal surface. However,there have been reported cases without symptoms.

Examination of these patients reveals multiple, graywhite,coarse,granular,intraepithelial lesions (Figure 26-51). Subepithelial opacities, which may be caused by edema, also may be seen. The intraepithelial lesions are of variable size and may number between 12 and 20. They are more numerous in the pupillary zone and appear as stellate, round, or oval areas composed of smaller punctate opacities.

The lesions are often slightly raised and stain variably with NaFl and rose bengal. They come and go and change locations quickly. The eye usually is white with little, if any, accompanying conjunctival reaction. Corneal sensitivity may be reduced or normal.

The differential diagnoses of TSPK include viral, toxic, bacterial, chlamydial, exposure, and dry eye causes of punctate epithelial keratopathy. Most of these conditions resolve in shorter time periods and are found to have a more obvious conjunctival involvement. Considering the lack of laboratory confirmatory tests, the diagnosis of TSPK remains solely clinical.

Management

Mild cases of TSPK can be treated with artificial tears four to eight times a day and lubricating ointment at bedtime

for symptomatic relief. It is important to counsel the patient regarding the chronic nature of the disease.

Moderate to severe cases may require topical steroids for relief of symptoms.A mild steroid such as 0.12% prednisolone, 0.1% fluorometholone, or 0.2% loteprednol should be used four times a day for 1 week and then tapered slowly on the basis of resolution of symptoms and clinical examination. Some patients may require the tapering over the course of months, with some requiring weekly or biweekly use of steroids to control symptoms. The use of steroids has been found to control exacerbations in about 50% of cases.

Therapeutic soft contact lenses may also be used to increase comfort, but they can be responsible for inducing exacerbations.The lenses need to be worn every day, and patients should be monitored closely for contact lens–induced problems.

Patients experiencing exacerbations of TSPK may be followed weekly while undergoing therapy. Patients in remission may be followed every 3 to 12 months.

FUNGAL KERATITIS

Etiology

Although corneal infection can be caused by more than 100 fungal species, classified in 56 genera, the primary

pathogens come from two main groups: filamentous and yeast organisms. Worldwide, septate filamentous organisms most commonly cause corneal ulcers and include

Fusarium, Aspergillus, Curvularia, and Penicillium species. Candida species, another common corneal pathogen, is from the yeast group.

The most common fungal isolates vary by geographic location. In the southern United States the septate filamentous organisms, Fusarium species, are the most common cause of fungal corneal ulcers because they thrive in hot and humid environments. Aspergillus or Candida is the most likely cause of fungal keratitis in northern regions. Several recent studies reported Candida as the most common cause of fungal keratitis in the northeastern United States.

The incidence of fungal keratitis also varies by geographic location.The relative prevalence of filamentous fungal keratitis increases toward the tropical latitudes. Overall,the incidence of fungal keratitis has increased over the last 20 years.This may be due to widespread topical steroid or antibiotic use, contact lens use, or improvements in diagnosis.

Patients who develop fungal keratitis frequently have a history of previous corneal trauma with vegetation such as sticks, branches, and soil. Agriculture workers and gardeners are specifically predisposed. However, in metropolitan areas where agricultural

employment is low, predominant risk factors include chronic ocular surface disease, systemic disease (particularly diseases associated with immunosuppression), contact lens wear, and steroid use. Additionally, there have been several recent case reports of fungal keratitis after LASIK and photorefractive keratectomy. Fungal keratitis can occur at any age, but several studies suggest the age range between 31 and 42 years as most likely to be affected; males are affected more frequently than females.

Diagnosis

Patients with fungal keratitis present with the same basic symptoms as those with bacterial corneal ulcers. These symptoms include photophobia, decreased visual acuity, redness, swelling of the lids, discharge, and reports of a “white spot’’ on the eye. Pain may be less than that expected from the clinical picture.

Although there is no pathognomonic clinical picture of fungal ulcers, there are characteristics that aid in the correct diagnosis. Characteristic clinical features of filamentous keratitis include serrated margins, dirty white with a dry rough texture, and satellite lesions. Filamentous fungal ulcers appear as unifocal or multifocal infiltrates with fine feathery edges and relatively mild stromal inflammation. Corneal yeast infections appear as unifocal or multifocal dense infiltrates. The ulcer can be elevated above the corneal surface and can exhibit branching lines that radiate from the ulcer margin into the stroma. Satellite infiltrates often develop subsequent to,

and in the same location as,these distinct branching lines. The formation of a dense, white, endothelial plaque and a white ring of polymorphonuclear cells in the mid-periph- ery of the cornea are fairly common, and corneal vascularization may be present (Figure 26-52). In general, the eye tends to react severely even if the ulcer is superficial,including folds in Descemet’s layer, ciliary flush, and an anterior chamber reaction possibly with a hypopyon. Although bacterial corneal ulcers are associated with a hypopyon and fibrin in the anterior chamber more frequently than fungal ulcers, no significant differences have been observed between the frequencies of immune rings, keratic precipitates,perineural infiltrates,endothelial plaque,and cells or flare in the anterior chamber. It is generally held that microbiologic investigations should be performed because a definitive diagnosis between fungal and bacterial keratitis cannot be made by clinical appearance alone.

Gram and Giemsa stains assist in the diagnosis of fungal infection by staining the fungal hyphae. Laboratory evaluation of suspected fungal ulcers should be performed in the same way as for suspected bacterial ulcers. Clinicians can comfortably use an Amies transport medium device to culture fungal corneal ulcers as an alternative to in-office direct plating.

Although most fungi grow in Sabouraud’s without cycloheximide medium within 48 hours, others can take as long as 2 to 3 weeks. Thioglycolate broth and blood agar are other useful media for culturing fungi. Additional procedures such as the use of calcofluor white stain and potassium hydroxide wet mount may improve the detection of fungal pathogens. Because rapid diagnosis of

536 CHAPTER 26 Diseases of the Cornea

fungal keratitis can often improve the visual outcome, research is being conducted on polymerase chain reaction as a method for early and correct diagnosis. Confocal microscopy is also being investigated for use in fungal keratitis diagnosis and follow-up.

If not done routinely, clinical laboratory diagnostic evaluations should be considered any time fungal keratitis is suspected. More routine methods of laboratory evaluation yield no positive results.

Management

Treatment of fungal keratitis is a prolonged process, with therapy typically lasting about 6 weeks. Because of this long-term treatment and the known toxicity of antifungal drugs, treatment generally is not started unless there is microbiologic (culture or smear) support for a fungal infection. Because of the difficulty in treatment and the prolonged course, a patient suspected of a fungal keratitis should be referred to a corneal specialist.

If the smear shows a septate hyphal fragment suggestive of filamentous fungi, natamycin 5% is the drug of choice. Natamycin 5% is the only antifungal agent commercially available for ophthalmic use in the United States and is effective against Fusarium and Aspergillus. If natamycin is not available or there is no positive response to treatment, amphotericin B 0.15% plus flucytosine is the next treatment of choice.

If the smear shows the oval buds or pseudohyphae of yeast, treatment is initiated with amphotericin B 0.15% with or without flucytosine. If the ulcer fails to respond to this treatment, the most common alternative is fluconazole 1% applied topically in conjunction with 200 mg taken orally.

Several topical antifungal agents have been shown to have synergistic activity. Amphotericin B and subconjunctival rifampin are more effective than amphotericin B alone. As mentioned earlier, amphotericin B and flucytosine have synergistic effects. Because antifungal agents penetrate the cornea very poorly, daily mechanical debridement of the corneal epithelium is necessary when treating any fungal keratitis.

Most antifungal agents reach fungistatic, not fungicidal, concentrations in the cornea. Because of this, topical steroids, which allow the fungi to replicate more freely, are generally contraindicated in the treatment of fungal ulcers.

Because fungal ulcers resolve very slowly and antifungal agents are toxic to the cornea, it can be difficult to determine whether the antifungal agent is clinically effective. Lack of progression of the ulcer is generally considered to be the first sign of efficacy. Improvement is suggested when the patient has decreased pain, the infiltrate is smaller, satellite lesions are disappearing, and the feathery margins of the ulcer become more rounded. Therapy is continued for at least 6 weeks and is modified, if needed, primarily based on the culture results.

Other antifungal agents are available and may need to be considered if the current treatment is ineffective.

Topical treatment is often unsuccessful in fungal keratitis with approximately 20% to 25% of cases requiring surgery. The gold standard surgical intervention is penetrating keratoplasty; however, a recent report stated that lamellar corneal surgery was effective in eradicating fungal infection in 92.7% of 55 surgeries. In patients with advanced and nonresponsive fungal keratitis, the use of amniotic patch grafts and cyanoacrylate glue application with the concurrent use of antifungals may help resolve inflammation and promote healing.

ACANTHAMOEBA KERATITIS

Etiology

Acanthamoeba is a free-living, opportunistic, nonparasitic protozoan found in soil, fresh water, salt water, tap water, distilled water, bottled mineral water, chlorinated swimming pools, sewage, and saliva. There have only been a relatively few reported cases of infection despite the abundance of potential exposure opportunities. It has been reported that more than 80% of immunocompetent individuals contain serum antibodies against Acanthamoeba antigens, suggesting common exposure. Pathogenic and nonpathogenic isolates occur with 24 named species of Acanthamoeba identified. Isolates from keratitis patients reveals that pathogenicity may be limited to certain genotypes. The exact mechanism of corneal infection by this organism is uncertain but seems to involve many factors, including epithelial trauma, a large inoculum of organism, and compromised host defense mechanisms.

Acanthamoeba have adapted to withstand the variety of environmental conditions they experience by switching their phenotype. In harsh environmental conditions, Acanthamoeba transforms into its resistant cyst form.The cyst form is resistant to various antimicrobial agents, presenting a significant problem in treatment. In favorable conditions the cysts transform into their vegetative infective trophozoite forms, resulting in a reinfection of the tissue.

Acanthamoeba ocular infection was first described in 1973. Acanthamoeba keratitis can occur in both healthy and immunocompromised individuals and is initiated by contact with contaminated water. Most Acanthamoeba keratitis cases described in the mid-1980s involved dailywear soft contact lens wearers who were using saline made from distilled water and salt tablets. Cases have also been described in extended-wear soft contact lens wearers and rigid contact lens wearers. In a survey of corneal specialists, it was found that 85% of the reported cases were in contact lens patients using primarily daily-wear or extended-wear soft lenses.

Acanthamoeba keratitis can occur in patients other than contact lens wearers.This condition may result after corneal contamination or injury from water or vegetative matter.

Acanthamoeba keratitis has been reported after penetrating keratoplasty in a patient with no identifiable risk factors for this condition. Fungal, viral, chlamydial, and bacterial infections, including crystalline keratopathy caused by the viridans group of streptococci, have been reported concurrent with Acanthamoeba keratitis. It is theorized that these organisms, along with damaged host cells, may potentiate Acanthamoeba infection by serving as an initial source of nutrition for the protozoan.

Diagnosis

The patient with Acanthamoeba keratitis typically presents with symptoms of redness, irritation, severe pain due to radial neuritis, photophobia, and reduced visual acuity. History of corneal contamination with water, saliva, or vegetative matter may be elicited with careful questioning. The duration of symptoms may vary from days to weeks, with waxing and waning of signs and symptoms common. Not infrequently, the condition has been present for weeks or months, and treatment with multiple agents for viral or bacterial keratitis had been attempted without result.

Clinical signs of Acanthamoeba keratitis include lid edema, conjunctival injection, and usually a fluctuating anterior chamber reaction. Early in the disease course an edematous necrotic dendritiform keratitis, central or paracentral infiltration, or elevated epithelial lines may be evident. Late in the course a prominent complete or partial stromal ring-shaped infiltrate with recurrent epithelial breakdown is highly suggestive of this

condition (Figure 26-53). Subepithelial infiltrates, similar to those seen in viral or chlamydial corneal infections, have been noted late in the disease away from the site of original infection and with minimal to no accompanying inflammatory signs. It has been theorized that an immunologic mechanism may be responsible for these late-onset steroid-responsive infiltrates.

Acanthamoeba keratitis should be suspected in at-risk patients who exhibit a deteriorating corneal condition unresponsive to multiple therapy regimens. Early diagnosis is important for a successful outcome. Definitive diagnostic information is obtained through laboratory analysis. Epithelial material can be scraped and placed in a tube containing saline and then agitated, centrifuged, and examined by wet-field microscopy for cysts. Keratoplasty biopsy has been used to identify encysted organisms as well as trophozoites, the stage when the amoebas emerge from dormant cysts to become actively feeding cells. Specular microscopy has been used as a noninvasive“photographic biopsy’’to identify Acanthamoeba cysts within the corneal stroma. Alternative microbiologic techniques have been evaluated to diagnose Acanthamoeba keratitis. More recently, routine microbiologic techniques have been used to identify Acanthamoeba keratitis.The cysts may be identified using Gram and Giemsa stains, and Acanthamoeba may be isolated from a corneal scraping plated onto a nonnutrient agar enriched with E. coli and incubated at 32°C for 4 weeks sealed in a plastic box. Amoebae are usually visible by light microscopy after 1 week.

Management

Acanthamoeba keratitis poses an extremely challenging clinical management problem with the potential for treatment failure. The condition should be treated by a provider experienced in its management. The free-living trophozoite stage of infection is responsive to treatment, while the cysts are highly resistant. Aggressive medical therapy is initiated using multiple antibacterial, antifungal, and antiamoebic agents. If diagnosed early, there is the potential for complete recovery of vision.

Prevention of Acanthamoeba keratitis is its best treatment. Contact lens–wearing patients must be educated carefully as to the proper use and care of their lenses. Homemade saline is no longer an approved or accepted contact lens solution. It is advisable not to wear contact lenses while swimming or in hot tubs, although swimming goggles may provide some protection from water exposure. Prescription swimming goggles may be preferable for correction of high refractive errors in this setting. Rigid contact lens wearers should be advised not to contaminate their lenses with saliva.Water contamination of contact lenses, including the case, should be avoided. It also is important that eye care providers remain alert to the possibility of this diagnosis so that the signs and symptoms of Acanthamoeba keratitis might be recognized as early in the disease course as possible, which may enhance the success of medical treatment.

Table 26-7 summarizes the commonly used treatments. For a more detailed discussion of treatment and management options, the reader is referred to several reviews in the current literature.

Penetrating keratoplasty may be needed after pharmacotherapy if a visually debilitating corneal scar remains. The use of keratoplasty as a therapy for Acanthamoeba keratitis that is not responding to medical therapy is a subject of debate. It is preferable to perform the surgery when active inflammation is not present, and recurrence appears to be common if it is

Table 26-7

performed too soon; however, the success rate is higher before the organism has disseminated throughout the cornea and caused excessive tissue damage.The success of currently available medical treatment suggests that surgical intervention in the presence of active Acanthamoeba keratitis is contraindicated until a medical cure has been achieved.

CONTACT LENS–RELATED CORNEAL COMPLICATIONS

There are approximately 33 million contact lens wearers in the United States, and each year approximately 6% of those experience some form of contact lens–related problem. Contact lens wear results in significant alterations in corneal function, including changes in corneal epithelium and endothelium function, tear composition, oxygen levels, and carbon dioxide levels.These changes can result in a wide variety of ocular disorders and exacerbate preexisting conditions.Table 26-8 outlines the variety of potential contact lens–related complications including corneal neovascularization (Figure 26-54), giant papillary conjunctivitis (Figure 26-55) and corneal SPK secondary to toxic/sensitivity response to contact lens solution (Figure 26-56). These conditions can be benign in nature, but many have serious, even sight-threatening, complications and are associated with all modalities of contact lens wear.

Infiltrative Events

Infiltration of the cornea is a common adverse event strongly associated with contact lens wear. The Cornea and Contact Lens Research Unit (Australia) devised a classification system for corneal infiltrates associated with contact lens wear identifying six distinct etiologies. The classification system was designed to aid in diagnosis, management, and treatment of corneal infiltrates and to assist in investigation into the etiology of each. The six categories are microbial keratitis, contact lens–induced

Corneal neovascularization (Figure 26-54)

Microcysts

Corneal abrasion (for detailed discussion see Corneal Abrasion) (see Figure 26-14)

Giant papillary conjunctivitis (Figure 26-55)

Hypersensitivity to CL care solutions (Figure 26-56)

Bacterial conjunctivitis

Infiltrative events: includes six subcategories: microbial keratitis, CL-induced peripheral ulcer, CL-induced red eye, infiltrative keratitis, asymptomatic infiltrative keratitis, and asymptomatic infiltration

Extension of limbal blood vessels into clear corneal tissue

Mild to moderate injection, collection of tiny, clear, epithelial cysts

Watering, redness, epithelial defect

Cobblestone-appearing papillae under upper lid, mucous discharge

Chemosis and injection of conjunctiva, SPK

Injection, chemosis, tearing, mucopurulent discharge

Severe injection, chemosis, possible ulceration of corneal epithelium and stroma, mucopurulent discharge, stromal infiltrate

None initially, though may lead to blurred vision in late stages

Burning, foreign body sensation, tearing, photophobia, and possible decreased vision

Acute pain, photophobia, blurred vision

Itching, blurred vision, reduced CL wear time

Ocular irritation soon after CL insertion

Blurred vision, photophobia, foreign body sensation

Pain, photophobia, blurred vision

Severe pain, photophobia, blurred vision, foreign body sensation

peripheral ulcer, contact lens–induced acute red eye, infiltrative keratitis, asymptomatic infiltrative keratitis, and asymptomatic infiltrates.The details of each category are outlined in Table 26-9.

It is critical to distinguish between the different etiologies of infiltrative events associated with contact lens wear. The classification system separates the different categories into clear clinical differences based on signs and symptoms. As a result the seriousness of the condition can be judged, and appropriate treatment and management options can be made. For instance, microbial keratitis (Figure 26-54 to Figure 26-57) is the most serious of the infiltrative events because of its potential to be sight threatening and requires aggressive treatment and management. This potentially severe entity can be contrasted to relatively benign asymptomatic infiltrates (Figure 26-58), which require contact lens discontinuation until resolution and subsequent refitting of the contact lenses.

It is also important to differentiate a red eye associated with contact lens wear from other potential causes. The definitive diagnosis can pose a clinical challenge with respect to excluding other conditions that cause an acute red eye with corneal infiltration. EKC, chlamydial keratoconjunctivitis, marginal infiltrative keratitis,

Acanthamoeba keratitis, and bacterial keratitis are among the most prominent differential diagnoses.To rule out other possible diagnoses, other signs and symptoms need to be assessed thoroughly such as the presence or absence of conjunctival follicles, lymphadenopathy, mucopurulent or purulent discharge, and bilateral involvement. Anecdotal experience suggests that prominent perilimbal injection and chemosis are important features of the infiltrative red eye reaction.

One critical distinction to make is whether a focal corneal infiltrate is infected with bacteria or is a sterile immunologic response. Many clinicians advocate routine scraping for smears and cultures of corneal infiltrates associated with soft contact lens wear to determine definitively whether active bacterial keratitis is present. Investigators have found that sterile infiltrates usually are smaller (less than 1 mm), multiple or arcuate, and lack significant pain, epithelial staining, or anterior chamber reaction. Conversely, infected ulcers are associated with increased pain, a larger size (over 2 mm), more extensive epithelial staining, a discharge, and a more prominent anterior chamber reaction. When in doubt it is best to assume that a lesion is infected and initiate appropriate laboratory analysis and aggressive therapeutic intervention.