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

510 CHAPTER 26 Diseases of the Cornea

Figure 26-34 Corneal eschar in patient who sustained a thermal burn from a curling iron. (Courtesy of Pat Caroline.)

Determination of the degree of tissue involvement is particularly important in evaluating the severity of alkali burns. Corneal haze and limbal or conjunctival ischemia indicate more severe involvement and a poorer visual and ocular prognosis. Areas of limbal or conjunctival ischemia or necrosis, which appear white and devoid of blood vessels, indicate damage to the limbal stem cells responsible for epithelial cell regeneration. Severe alkali burns cause destruction of superficial ocular tissue and consequent corneal scarring, symblepharon, entropion, and keratitis sicca (Figure 26-35). Corneal penetration of an alkaline substance produces uveitis,cataract,and secondary glaucoma.

Management

The long-term prognosis of a patient with a chemical burn depends on immediate irrigation.When a history of recent chemical injury is reported, copious ocular irrigation must be immediately instituted in an effort to neutralize the offending agent and to wash away any accompanying particulate debris. If a patient telephones with this complaint, the patient, a friend, or a family member must be instructed to perform irrigation before and during transport. Phosphate-buffered solutions and Diphoterine, a non–phosphate-buffered solution, restores the normal ocular pH more quickly than saline or tap water and is recommended for initial irrigation. Sterile saline,

Table 26-2

Classification of Ocular Burns

eyewash solution, or on-site irrigation with clean water can also be used for initial irrigation if a buffered solution is unavailable. A phosphate buffer should not be used after the initial first aid because this has been shown to increase corneal calcification. Immediate ocular irrigation is also recommended for thermal burns. Irrigation cools the corneal surface and removes inflammatory substances. The patient should be instructed to present for in-office care after thorough irrigation. A patient with a severe alkali burn to the eyes and face should be transported immediately to an emergency medical facility after ocular irrigation, unless life-threatening issues take precedence.

If the patient presents as an office ocular emergency reporting a recent chemical burn injury, ocular irrigation should be instituted immediately, even before implementing other aspects of patient check-in and ocular examination. Instilling a drop of topical anesthetic into each eye will enhance patient cooperation during irrigation. The globe must be thoroughly irrigated using a buffered solution (see Figure 3-22). The solution stream should be directed toward the fornices. A 20to 30-minute irrigation is needed, and litmus paper may be used to determine the effectiveness of irrigation in neutralizing the agent (end point, 7.3–7.7). If patient cooperation is poor for ocular irrigation, use of an eyelid speculum may be helpful (Figure 26-36). For both chemical and thermal burns, all particulate debris must be removed using appropriate techniques, and necrotic epithelium should be removed with a sterile cotton-tipped applicator (see Figure 26-15).

The main treatment objectives of both thermal and chemical burns are to promote epithelialization, reduce inflammation,and minimize ulceration and scarring. If the cornea shows no signs of opacification or conjunctival blanching after irrigation, lesions can be treated medically. Severe acid and thermal burns involving more than superficial tissue injury and grades II, III, and IV alkali burns should be managed by a corneal specialist. Antibiotic prophylaxis using broad-spectrum agents, such as 0.5% moxifloxacin drops three times daily and 0.3% tobramycin or ciprofloxacin ointment in the conjunctival sac at bedtime, protect the tissue from secondary infection. Concurrent use of a low-potency topical steroid such as 0.12% prednisolone or 0.1% fluorometholone

alcohol drops four times daily helps to reduce the inflammatory response. However, the use of steroids beyond the first 7 days may increase the risk of corneal ulceration. More extensive burns may require pupillary dilation and cycloplegia with a long-acting agent such as 5% homatropine. If tolerated, a therapeutic soft contact lens can be used to promote epithelial healing and adhesion. After removal of corneal eschar, a mild thermal burn is treated similarly to a corneal abrasion.

Figure 26-36 Spring-type Barraquer eyelid speculum is shown in place. (Reprinted with permission from Casser L, Fingeret M, Woodcome HT. Speculum insertion. In: Atlas of primary eyecare procedures, ed. 2. Norwalk, CT:Appleton & Lange, 1997: 98–99.)

The patient is followed daily until the corneal injury resolves. Unless an anterior uveitis is present, the cycloplegic, steroid, and antibiotic can be discontinued once the epithelium has healed. If healing of the mild alkali burn does not proceed as expected, it is possible that ischemia is present, necessitating reevaluation of the treatment.

More severe burns typically require extensive medical and surgical treatment. Ascorbate and citrate have been shown to reduce the risk of corneal ulceration and perforation.The use of topical sodium citrate 10% and topical sodium ascorbate 10% every 2 hours and oral vitamin C (500 mg) every 6 hours has been recommended for grades II, III, and IV burns. Oral tetracyclines have also been shown to reduce collagenase activity, decreasing corneal ulceration after chemical burns. Doxycycline 100 mg twice daily is recommended for grades II, III, and IV chemical burns. Surgical options include conjunctival transplantation, amniotic membrane transplantation, limbal stem cell transplantation, and lamellar keratoplasty.

Because of nerve damage and epithelial irregularity, dry eye is common after burn injuries; preservative-free lubricants are crucial in the long-term treatment. Patient education about the use of protective eyewear in circumstances when accidents may occur is very important and may help to prevent future injury.

Photokeratitis

Etiology

The most common type of radiation burn sustained by the cornea is due to excessive exposure to ultraviolet (UV) light. The UV radiation spectrum ranges from 100 to 400 nm.

512 CHAPTER 26 Diseases of the Cornea

UVC (100 to 290 nm) is mainly filtered by the ozone layer but can be found in artificial situations such as arc welding lamps. UVB (290 to 320 nm) causes sunburn and is responsible for most of the harmful effects of UV radiation. UVA (320 to 400 nm) produces tanning and the photosensitivity reaction.The cornea absorbs UV radiation up to 295 nm, primarily in the epithelium and Bowman’s membrane.

The most common sources of excessive UV light exposure include direct sunlight, reflection of sunlight off snow when protective sunwear is not worn (“snow blindness”), and exposure to an electric welding arc without using appropriate filters. Corneal damage from UV exposure has also been reported in glassblowers. Photokeratitis can occur in tanning booths if protective goggles are defective or even briefly removed. This is more likely to occur with defective lamps or lamps that emit lower UVB radiation levels.

Diagnosis

The patient with photokeratitis typically reports a recent history of excessive UV light exposure.When the cause is related to excessive sunlight or sunlamp exposure, the patient generally exhibits the dermatologic manifestations of sunburn on the face or other skin areas, including erythema and blistering if severe. Ocular symptoms include pain, photophobia, tearing, and blepharospasm. The onset of symptoms usually occurs within 24 hours after excessive UV light exposure.

External examination reveals erythema and swelling of the affected skin areas. Slit-lamp examination reveals diffuse conjunctival injection and punctate epithelial erosions of the cornea with corresponding NaFl staining. If the epithelial lesions are extensive and if lacrimation is profuse, corneal edema also may be noted.

Management

As with any superficial keratitis,the corneal lesions related to excessive UV radiation generally resolve within 8 to 24 hours. Supportive therapy for mild cases may include topical lubricating agents only, including drops during the day and ointment at bedtime. As with a sunburn, cold compresses applied to the eyes three to four times daily may also provide some symptomatic relief.

Broad-spectrum antibiotic drops, such as 0.3% tobramycin, 0.3% ciprofloxacin, or the newer generation fluoroquinolones, moxifloxacin or gatifloxacin, may be instilled four times daily to prevent secondary infection as the epithelium heals. A broad-spectrum ophthalmic ointment, such as 0.3% ciprofloxacin, may be instilled into the conjunctival sac at bedtime for prophylaxis. In more pronounced cases, pupillary dilation and cycloplegia with a long-acting agent such as 5% homatropine may help to relieve pain from associated ciliary spasm.

Anecdotal evidence suggests that some burning pain associated with UV radiation keratitis may last for days to weeks, even after complete resolution of the keratitis.

Patients should be advised of the value of protective eyewear to prevent UV radiation keratoconjunctivitis, including appropriate filters for occupational or industrial use and appropriate sunwear for outdoor use that offers UV light-blocking capability.

Dellen

Etiology

Dellen are small areas of corneal thinning typically located at the limbus.They are caused by localized drying of the cornea usually due to poor spreading of the tear film. The tear film disruption is often due to a local surface elevation of the conjunctiva in the adjacent perilimbal area. Pterygium, pinguecula, conjunctival chemosis, subconjunctival hemorrhage, scarring from ocular surgery, filtering blebs, nerve palsies, scleritis, and episcleritis commonly result in dellen,but any mass that prevents close apposition of the eyelids to the cornea can be responsible for their formation. The use of systemic medications with anticholinergic side effects, such as antihistamines, may precipitate or exacerbate the clinical signs or symptoms.

Diagnosis

Patients with dellen usually present with a foreign body sensation or slight discomfort. They often have a history of irritated eyes, which have recently become worse. They commonly report redness of their eyes and focal conjunctival injection is usually noted. Slit-lamp examination reveals a small, oval, saucer-like excavation usually less than 2.0 mm in size located on the corneal side of the limbus (Figure 26-37).The oval-shaped dellen has its long axis parallel to the limbus and occurs more frequently on the temporal margin. Although the lesion has clearly defined borders, its base appears hazy and dry. The wall of the excavation is steeper on the corneal side and more sloping on the limbal side. The epithelium is typically intact, and the stroma in not inflamed. NaFl pools in the excavation. Actual staining is variable in the early stages but likely develops in advanced cases.

Early in the development of a dellen, the stroma is intact but thinned due to loss of fluid. Stromal degeneration can occur, and true scarring with or without vascularization develops if the dellen is allowed to persist. The formation of a descemetocele in a long-standing dellen that required a corneoscleral patch graft has been reported.

Management

Treatment for dellen is directed toward rehydrating the cornea and, if possible, removing the cause. Nonpreserved artificial tears administered every 2 hours and lubricating ointment instilled into the conjunctival sac at bedtime usually allow resolution within 48 hours. If the dellen is diagnosed early in its development and treated aggressively, it can resolve within 24 hours. Very severe dellen may require prophylactic topical antibiotics such

as polymyxin B-bacitracin or erythromycin ointment. If the dellen has formed secondary to an inflammation such as scleritis or episcleritis, appropriate therapy should be initiated. Patients should be asked to return for evaluation in 1 to 7 days depending on the severity of the lesion.

used in formulating them. After routine use of topical anesthetic, mydriatic, or cycloplegic agents, it is common to observe a fairly prominent toxic keratitis characterized by punctate epithelial erosions in the inferior one-third to one-half of the cornea. Prolonged use of topical anesthetics can result in permanent scarring and visual loss.

Toxic Keratitis

Etiology

A wide range of substances that are toxic to the cornea may produce epithelial insult known as toxic keratitis. This terminology is generally reserved for mild superficial corneal irritation after contact with a harmful substance. Solutions foreign to the eye that commonly cause toxic keratitis include shampoos, lotions, and chlorinated pool water. Toxic corneal reactions have been reported from tonometer tips contaminated with 70% isopropyl alcohol or hydrogen peroxide that was not fully removed after disinfection of the probe. Irreversible corneal scarring has resulted from inadvertent ocular contamination with chlorhexidine gluconate, a skin cleanser used preoperatively. The mistaken use of nonophthalmic products for eyedrops may result in various forms of corneal trauma.

The term medicamentosa refers to toxic keratitis related to the use of topical ophthalmic agents. A number of topical ophthalmic preparations are known to cause toxic keratitis, including antivirals, antibiotics, antifungals, anesthetics, antiglaucoma medications, and contact lens solutions. Aminoglycoside antibiotics are reported to cause the most frequent ocular reactions followed by glaucoma medications.The causative agents may be the active ingredients of these preparations or the preservatives

Diagnosis

The patient with toxic keratitis or medicamentosa generally reports recent exposure to the offending substance or the use of an ophthalmic preparation on a shortor long-term basis. In the case of mild toxic keratitis, the patient may have few or no symptoms. More involved cases may produce very definite symptoms of redness, irritation, burning, tearing, and ocular discomfort upon instillation.

Clinical signs are also of variable severity. Mild medicamentosa may manifest as scattered punctate epithelial erosions in the inferior third of the cornea in a patient who is being treated with topical medications. More pronounced toxic keratitis may present as diffuse punctate epithelial erosions and punctate epithelial keratopathy in the exposed interpalpebral corneal area or over the entire cornea (Figure 26-38). Conjunctival involvement may range from none, to mild inferior bulbar injection, to prominent diffuse injection, chemosis, and follicles. Accompanying dermatitis of the lids suggests an allergic hypersensitivity reaction rather than a toxic keratitis.

Patients abusing topical anesthetics such as tetracaine and proparacaine will likely conceal the use of the anesthetic and will repeatedly deny anesthetic use even after extensive treatment, such as a penetrating keratoplasty. Patients typically have a history of a corneal injury that

514 CHAPTER 26 Diseases of the Cornea

Figure 26-38 Diffuse punctate epithelial erosions in a patient with toxic keratitis. (Courtesy of Pat Caroline.)

prompted anesthetic use such as a corneal abrasion, RCE, or corneal surgery. The anesthetic is often obtained from a physician or is stolen. These patients are commonly health care employees or have friends or family members who are health care workers with access to the anesthetic.

Punctate keratopathy is seen in the early stages of toxic keratitis secondary to anesthetic abuse. In later stages eyelid edema, hyperemia, a large epithelial defect (up to 95% of the cornea), and dense ring-shaped stromal infiltrates are present (Figure 6-6). The appearance of the stromal ring-shaped infiltrates is similar to that of an Acanthamoeba infection. Corneal cultures are generally negative, and unless the anesthetic use is discontinued, the corneal appearance will continue to progress despite the use of antibiotic, antifungal, and corticosteroid medications.

Management

Discontinuation or avoidance of the offending agent usually brings resolution of the toxic keratitis within a few days. The risk-to-benefit ratio of treating toxic keratitis should be assessed, because ceasing topical ophthalmic medications may exacerbate the original condition. In general, mild medicamentosa can be tolerated without treatment, both from the patient and examiner standpoints, until the condition prompting initial treatment is resolved and the medication is discontinued. If toxic keratitis results in intolerance of a certain contact lens solution or a needed therapeutic agent, alternative therapy should be chosen. Preservative-free medications should be prescribed if available.

In the case of mild transient toxic keratitis, patient comfort may be enhanced with the use of topical nonpreserved lubricating agents while the condition resolves. In the case of more pronounced toxic keratitis, particularly with conjunctival injection, topical decongestant agents

may be used, such as 0.1% naphazoline drops instilled four times daily, until resolution occurs.

More severe forms of toxic keratitis may require prophylactic antibiotic therapy to protect the inflamed cornea. The use of topical aminoglycosides should be avoided, however, as they tend to exacerbate the condition.The use of a mild steroid,such as 0.12% prednisolone drops four times a day, aids the resolution of more advanced cases. Any allergic component involving the eyelids or conjunctiva should be treated appropriately.

If topical anesthetic abuse is suspected, discontinuation is critical. A broad-spectrum topical antibiotic such as 0.5% moxifloxacin three times daily is used to protect the disrupted corneal epithelium from secondary infection as the tissue heals. Topical NSAIDs, such as 0.1% diclofenac sodium solution or 0.5% ketorolac solution, and a therapeutic soft contact lens help to reduce pain. Cycloplegic and topical steroids are indicated if an anterior chamber reaction is present.Toxic keratitis can heal without permanent vision loss within days after discontinuing the use of the anesthetic but may result in permanent scarring, vascularization, and visual loss. Surgical treatment, such as a penetrating keratoplasty, may be necessary.

The role of a topical anesthetic is as a surgical and diagnostic agent. In addition to informing the patient, education of eye care employees as well as other medical personnel regarding the devastating effects of long-term anesthetic use is essential. Psychiatric counseling may also be helpful with some.

BACTERIAL AND BACTERIAL-RELATED KERATITIS

Superficial Punctate Keratitis

Etiology

The term superficial punctate keratitis (SPK) is commonly used to describe superficial punctate corneal epithelial disruptions of multiple etiologies. It is important to recognize that SPK often consists of two forms: punctate epithelial erosions and punctate epithelial keratopathy. Punctate epithelial erosions refer to fine focal corneal epithelial lesions, usually slightly depressed, that may be difficult to view with the slit lamp but stain prominently with NaFl, rose bengal, and lissamine green (Figure 26-39). They are found in many primary and secondary corneal conditions.Punctate epithelial keratopathy describes accumulations of epithelial cells that are surrounded by a focal inflammatory cell infiltrate,as often accompanies staphylococcal blepharokeratoconjunctivitis.These lesions appear as larger grayish white opacities more easily identified with the slit lamp than punctate epithelial erosions.Although punctate epithelial keratopathy lesions stain well with rose bengal and lissamine green, they stain poorly with NaFl.

Figure 26-39 Mild diffuse inferior punctate epithelial erosions stained prominently with NaFl. (Courtesy of Pat Caroline.)

SPK with a bacterial origin usually is associated with blepharitis, the most common cause of which is infection of the lid margins and glands with Staphylococcus. Additionally, conjunctivitis from organisms such as

Streptococcus, Moraxella, and Haemophilus may also cause SPK.

Diagnosis

Patients with SPK typically report ocular foreign body sensation, photophobia, redness, and tearing. Patients with an associated blepharitis or blepharoconjunctivitis may also complain of debris on the lids and redness of their lid margins as well as previous episodes, characterized by exacerbations and remissions. If there is a concurrent conjunctivitis, the patient may note an ocular discharge and difficulty opening the lids in the morning.

Examination typically reveals diffuse SPK erosions and also may disclose punctate epithelial keratopathy that is visible as small grayish opacities in the epithelium. The location and pattern of this keratitis can be helpful in determining the etiology (Box 26-1) and in distinguishing the condition from bacterial-related causes. SPK from blepharitis usually is more severe in the inferior one-third of the cornea where it contacts the staphylococcal exotoxins from infection of the lower lid. In cases of SPK caused by bacterial conjunctivitis, the entire cornea may be involved.

Associated ocular and periocular findings also help determine the cause. In blepharitis the lid margins usually are thickened, red, and scaly; lashes may be missing (madarosis). With bacterial conjunctivitis, there is infection of the conjunctiva and a mucopurulent discharge.

Management

Treatment of SPK is directed toward the underlying cause. Bacterial conjunctivitis should be treated with topical antibiotics (see Chapter 25), and staphylococcal blepharitis should be treated with lid hygiene and antibiotics (see Chapter 23).Additional supportive treatment

Box 26-1 SPK Staining Patterns in a Variety

of Disease Conditions

Diffuse

Bacterial conjunctivitis

Viral conjunctivitis

Medicamentosa

Allergic conjunctivitis

Superior

Superior limbic keratoconjunctivitis

Vernal keratoconjunctivitis Inclusion keratoconjunctivitis Trachoma

Inferior

Staphylococcal blepharitis Ectropion

Entropion

Lagophthalmos Exposure keratopathy

Interpalpebral

Keratoconjunctivitis sicca Exposure keratopathy

UV keratopathy

Sectoral

Trichiasis

Trauma

Pinguecula

Pterygium

Linear

Mechanical abrasion

Trichiasis

Entropion

Foreign body

to reduce symptomatology caused by SPK may include the use of artificial tears four to six times daily.

Interstitial Keratitis

Etiology

IK, also known as nonulcerative keratitis, syphilitic keratitis, and immune stromal keratitis, is a nonulcerative inflammation of the corneal stroma generally with stromal vascularization. The condition is characterized by stromal inflammation without primary epithelial or endothelial involvement. Although corneal thinning is not a feature of the active stage of inflammation, it is a potential sequela.

IK is a manifestation of both infectious and noninfectious disease (Box 26-2). Occasionally, the ocular findings may be the initial sign of an underlying undiagnosed disease.

Box 26-2 Causes of Interstitial Keratitis

Bacterial infection

Syphilis (congenital and acquired) Tuberculosis

Leprosy

Lyme disease

Brucellosis

Chlamydia

Viral infection

Herpes simplex

Herpes zoster

Epstein-Barr

Mumps

Rubeola

Parasitic infection

Leishmaniasis

Onchocerciasis

Trypanosomiasis

Acanthamoeba

Microsporidiosis

Systemic disease

Cogan’s syndrome

Sarcoidosis

Lymphoma

Other

Gold toxicity

Arsenic toxicity

Contact lens related

Table 26-3

Clinical Characteristics of Interstitial Keratitis

Historically, syphilis has been described as the most common cause of IK. However, with the advent of antibiotics, the completion of the genome sequence of Treponema pallidum, and improved serodiagnosis, congenital and acquired syphilis has become less common with fewer than 500 new cases of syphilitic IK occurring each year in the United States. Thus the eye care practitioner is more likely to see postsyphilitic sequelae of corneal scarring and ghost vessels rather than active keratitis. Herpetic eye disease has become the leading cause of IK in North America.

Diagnosis

The diagnosis of IK begins with the distinction between active and residual corneal disease. At the time of active corneal inflammation, the most common symptoms include pain, tearing, photophobia, decreased vision, and blepharospasm. The bilateral or unilateral inflammation may be caused by active infection or an immune response to disease.

Slit-lamp examination of active IK often reveals perilimbal injection, stromal infiltration, edema, neovascularization, and potentially an immune ring. The exact appearance of the cornea depends on the specific etiology and stage of the disease (Table 26-3).The epithelium, with or without edema, is generally intact but can erode over superficial infiltrates.The stromal inflammation may be sectoral, diffuse, central, paracentral, or peripheral. An anterior uveitis with fine endothelial keratic precipitates may accompany active corneal disease. Without treatment the inflammation generally resolves in weeks to months. Upon resolution, scarring typically is present and may be accompanied by stromal thinning. Reduplication of Descemet’s membrane and endothelial decompensation with stromal edema may remain as

Figure 26-40 Inactive interstitial keratitis in a patient with congenital syphilis.The presentation was bilateral. (Courtesy of Dr.Tammy Than.)

features of inactive IK (Figure 26-40).The corneal vascularization from the active stage remains as ghost vessels in the stroma once blood flow has subsided. On occasion, lipid exudation occurs in association with the neovascularization that may resolve slowly or remain indefinitely.

Management

A comprehensive review of systems, physical examination, ocular examination, and laboratory testing with a multidisciplinary approach to determine the etiology of IK is essential. Treatment should be aimed at addressing any underlying systemic disease and may involve the use of systemic steroids or immunosuppressive drug therapy depending on the cause.

Although active IK eventually resolves spontaneously, corneal scarring with decreased vision may result. To shorten the course of the corneal disease and to prevent unnecessary vision loss and the potential need for a penetrating keratoplasty, treatment should include 1% prednisolone acetate or an equivalent, one drop every 1 to 6 hours depending on the degree of inflammation. Additionally, a topical cycloplegic agent, such as 5% homatropine, can be used two to three times per day for a concomitant anterior uveitis. The steroid should be slowly tapered once improvement is noted, but long-term low-dose steroid therapy may be necessary to avoid recrudescence. Follow-up examinations should be scheduled every 3 to 7 days initially and then every 2 to 4 weeks as inflammation subsides. Close monitoring of IOP is mandatory because of steroid use.

Phlyctenular Keratoconjunctivitis

Etiology

A phlyctenule is a focal nodule composed of leukocytes, generally the result of a delayed hypersensitivity reaction to microbes or their toxins. For this antigenic response to occur, the patient must have a history of previous exposure and sensitization to the causative organism

or allergen. Reintroduction of the allergen causes development of the phlyctenule approximately 48 hours later.

In the United States the most common cause of phlyctenular keratoconjunctivitis, also known as phlyctenulosis, is Staphylococcus aureus. S. aureus is a prevalent microbe, and its cell wall antigens have been proven to cause phlyctenulosis in rabbits.

Tuberculosis has reemerged in the United States among recent immigrants and patients with acquired immune deficiency syndrome. It has been suggested that hypersensitivity to tuberculoprotein has a role in the development of phlyctenules. Considering the ease of air travel and the fact that approximately one-third of the world’s population has been infected with tuberculosis, the possibility of tuberculosis exists in every patient with phlyctenulosis. Many patients who exhibit phlyctenulosis also have a high rate of positive skin and radiology tests for tuberculosis. It is not uncommon for patients with phlyctenulosis to relate a history of recent exposure to, or family members with, known tuberculosis.

Rarely, phlyctenulosis has been associated with pneumococci, Koch-Weeks, Candida albicans, Chlamydia, viruses, roundworm nematodes, rosacea dermatitis, and meibomianitis. Malnutrition, vitamin deficiency, and poor public health conditions increase the incidence of phlyctenulosis.

Diagnosis

The most common symptoms of phlyctenulosis include bilateral tearing, irritation or pain, mild to severe photophobia, and itching. Symptoms are usually more severe if there is corneal involvement and may include blepharospasm. The patient may report previous similar episodes.

Slit-lamp examination reveals single or multiple phlyctenules that appear as pinkish white nodules on the cornea or conjunctiva, ranging in size from just visible to several millimeters in diameter.They typically appear first at the limbus and can easily be mistaken for catarrhal ulcers. Unlike catarrhal ulcers, phlyctenules are adjacent to the limbus, and the long axis of a phlyctenule is perpendicular to the limbus rather than parallel to it.

Along with the phlyctenule, examination often reveals conjunctival hyperemia, a scanty watery discharge, and diffuse corneal staining. If the phlyctenule is caused by Staphylococcus, an associated blepharitis is common. Phlyctenules typically last from 10 to 14 days and occur primarily in children, with girls more frequently affected than boys.

Conjunctival phlyctenules appear on the limbus or bulbar conjunctiva. Lesions are usually close to the limbus near the free lid margin but can present anywhere on the bulbar conjunctiva. They rarely affect the palpebral conjunctiva. They often are surrounded by hyperemia. Corneal phlyctenules typically start at the limbus and are accompanied by a leash of conjunctival vessels (Figure 26-41). Initially, the overlying epithelium is intact

but often erodes, leading to an epithelial defect that stains with NaFl. These phlyctenules can progress toward the center of the cornea as the more peripheral margin heals and the central area remains active.

The vessels associated with the phlyctenule also migrate toward the center of the cornea and produce focal neovascularization. Triangular corneal scars with their base at the limbus often form as phlyctenules heal. These scars can be vascularized. Scarring in the central cornea can decrease visual acuity if the phlyctenulosis is long-standing. Corneal perforation in phlyctenulosis is rare but has been reported.

Management

A thorough history and examination is important to determine the cause of phlyctenulosis. Inspect the lid margins for signs of staphylococcal blepharitis and question the patient regarding recent infections or tuberculosis exposure. If there is reason to suspect tuberculosis or if no other cause can be found, a tuberculin skin test may be indicated. If diarrhea or gastrointestinal distress is present, consider a stool examination for nematodes.

Although phlyctenules can resolve spontaneously, they usually ulcerate and scar before resolution. To prevent scarring, treatment should include 1% prednisolone acetate, one drop every 2 to 4 hours for 3 to 4 days. Also, instill prophylactic antibiotic ointment or drops, such as bacitracin, erythromycin, or polymyxin B/trimethoprim, into the conjunctival sac four times a day and continue as

long as the steroid is used. Alternatively, a steroid– antibiotic combination product, such as tobramycin– dexamethasone or tobramycin–loteprednol, may be used to improve patient compliance. The steroid should be tapered rapidly once improvement is noted. Typically, total antibiotic–steroid therapy continues for 10 to 14 days. If Staphylococcus blepharitis is suspected, recommend warm compresses and lid scrubs two to three times a day followed by an application of antibiotic ointment, such as bacitracin, to the lid margins. Because many cases of staphylococcal blepharitis are chronic, lid scrubs with baby shampoo or commercial preparations may be necessary each day indefinitely. Artificial tears can be used up to four times a day for comfort.

A course of oral tetracycline or erythromycin may be a reasonable treatment alternative for patients with chronic or recurrent phlyctenular keratoconjunctivitis. Some clinicians recommend 250 mg tetracycline three times daily for 3 weeks followed by 250 mg once daily for 2 months. In children under 8 years of age, erythromycin 25 mg/kg in four divided doses may be used. Additionally, a recent study reported topical cyclosporine 2% as a safe and effective therapy for children with severe phlyctenular keratoconjunctivitis not responding to oral medications.

Patients with phlyctenulosis should be reevaluated in 3 to 4 days. Significant improvement in signs and symptoms should occur within 48 hours. If the tuberculin skin test is positive, chest x-rays and a medical consultation are indicated.

Corneal Infiltrative Events

Etiology

A corneal infiltrative event (CIE) is a broad term used to describe corneal inflammation associated with infiltrates. These infiltrates are usually the result of an antigen-anti- body reaction or hypoxia.Typically, cultures are negative, with Gram and Giemsa stains of corneal scrapings from these areas exhibiting neutrophils but no bacteria. The patient’s antibody response results in corneal infiltration by polymorphonuclear leukocytes and other cells resulting from antigen interaction. CIEs can be associated with soft contact lens wear, in which case they are further classified (see Contact Lens–Related Corneal Complications, below). Alternatively, CIEs can stem from long-standing staphylococcal blepharoconjunctivitis and acute conjunctivitis caused by β-hemolytic Streptococcus, Haemophilus aegyptius, and Moraxella lacunata and have been reported in association with chronic dacryocystitis.

Diagnosis

Patients with CIE complain of pain, tearing, foreign body sensation, and photophobia.When asked, they often report a history of soft contact lens wear or staphylococcal lid disease. CIE is common in adults but is quite rare in children.

Examination reveals single or multiple intraepithelial infiltrates separated from the limbus by a clear (lucid) interval (Figure 26-42). This lucid area is about 2 mm wide and can be bridged by vessels. The infiltrates are usually between 0.5 mm and 2 mm in size and are most commonly found at the 2, 4, 8, and 10 o’clock positions where the lid margins cross the cornea. Early in the process the infiltrate is elevated due to accumulation of cells and debris.The infiltrate can become ulcerated and exhibit positive staining centrally, ranging from punctate to a full-thickness epithelial break. Edema can develop

Table 26-4

CIE Compared With Bacterial Keratitis

Figure 26-42 Multiple small intraepithelial corneal infiltrates.

around the infiltrates. Although this edema usually is limited to the epithelium, it also can be found in the anterior stroma. The anterior chamber is typically quiet. As the eye becomes more involved, the infiltrates can become more extensive. The spread of lesions is more common in patients with blepharitis and is usually concentric with the limbus. It is possible for individual infiltrates to coalesce and form a ring-like infiltrate around the entire cornea.

Management

It is important to differentiate between true infection of the corneal tissue and CIE (Table 26-4).The examiner must look for signs of bacterial corneal ulcers such as discharge or anterior chamber reaction and evaluate the patient’s history for risk factors known to be associated with bacterial keratitis.These risk factors include extended wear of contact lenses, contaminated ophthalmic solutions, poor personal hygiene, diabetes mellitus, recent