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

450 CHAPTER 25 Diseases of the Conjunctiva

Figure 25-7 Hyperacute bacterial conjunctivitis with copious purulent discharge.

N. meningitidis. Other pathogens that can cause hyperacute conjunctivitis include S. aureus, Streptococcus species, H. influenzae, Moraxella (Branhamella) catarrhalis, E. coli, and P. aeruginosa.

Diagnosis

Hyperacute bacterial conjunctivitis is characterized by a sudden rapid onset of purulent conjunctivitis with abundant discharge, chemosis, and severe hyperemia (Figure 25-7). Complaints of ocular pain, tenderness of the globe, periorbital discomfort, and eyelid swelling are common.Typically, the purulent discharge is copious and quickly recurs when wiped or washed away. Laboratory assessment, including both conjunctival cultures and smears, is mandatory to confirm the diagnosis of hyperacute conjunctivitis before initiating medical treatment. Smears should be analyzed with Gram stain at the time of the initial visit. Cultures should be performed using blood, chocolate, and Thayer-Martin agar media.

N. gonorrhoeae hyperacute conjunctivitis, a disease primarily of the neonate and of sexually active adolescents or young adults, most likely results from direct contact with infected genitals or indirect contact by the hands. Nonsexually transmitted cases have also been reported. Ocular involvement does not occur often; only four cases of hyperacute conjunctivitis were reported among 800,000 cases of gonorrhea. The patient’s medical and sexual history must be reviewed, because associated systemic findings such as urethritis or vaginitis frequently occur and must be treated also. Potential sexual abuse should be considered when a child develops gonococcal conjunctivitis.

Gonococcal conjunctivitis usually is unilateral and progresses rapidly, often with periocular involvement.

Ocular pain with preauricular lymphadenopathy is common. The marked conjunctival inflammatory response includes chemosis and hyperemia with eyelid edema and a profuse, thick, yellow-green purulent exudate. If not treated promptly, the conjunctivitis can lead to preseptal cellulitis, bacterial keratitis, dacryoadenitis, and potential septicemia. Depending on the offending pathogen, hyperacute conjunctivitis also can lead to subsequent conjunctival membrane or symblepharon formation. If left untreated, N. gonorrhoeae can penetrate an intact cornea in 48 hours.

N. meningitidis hyperacute conjunctivitis usually occurs in children. It generally causes a milder conjunctivitis than that caused by N. gonorrhoeae, although the two are clinically similar. N. meningitidis hyperacute conjunctivitis can lead to devastating ocular and systemic complications if not treated promptly and effectively. Because of the potential danger, prophylaxis should be considered for close contacts. The disease often is bilateral and may occur in conjunction with meningococcemia, meningitis, and endogenous endophthalmitis. One report indicates that meningococcal conjunctivitis led to systemic meningococcal infection in 6 of 21 patients. In a study of 21 patients and a literature review of another 63 patients with primary meningococcal conjunctivitis, 9 were neonates, 55 were children, and 20 were adults, with a male-to-female ratio of 1.76:1.00. The most common ocular complication was corneal ulceration. Systemic disease developed in 17.8% of the patients and was significantly more frequent in patients receiving only topical therapy.

Management

Hyperacute bacterial conjunctivitis must be treated aggressively, because it carries potentially blinding consequences. Administration of topical and systemic antibiotics should begin immediately after specimens have been collected for laboratory analysis. Frequent irrigation of the conjunctiva with normal saline removes the purulent exudate, permitting better antibiotic access to the affected tissues. If gram-negative diplococci are identified on conjunctival smears, the patient should receive full doses of systemic antibiotics. Early diagnosis and aggressive systemic treatment can prevent the development of ocular, neurologic, or systemic complications. Concomitant C. trachomatis infection is common and must be treated. A study of 13 patients indicated that a single 1-g dose of intramuscular ceftriaxone is curative for gonococcal conjunctivitis. All patients’ cultures were negative 6 hours and 12 hours after treatment. However, the treatment can be repeated for 5 consecutive days if necessary.

Because of their broad potent bactericidal activity, the fluoroquinolone antibiotics are also an appropriate topical therapy for nongonococcal hyperacute conjunctivitis. Topical moxifloxacin or gatifloxacin should be administered initially in a dose of two drops every hour.

Adjunctive systemic therapy includes ampicillin, amoxicillin, Augmentin, or cefaclor, 250 mg four times daily, depending on the patient’s body weight and antibiotic sensitivities. Severe or disseminated infection requires hospitalization and treatment with intramuscular or intravenous antibiotics.

Chronic Bacterial Conjunctivitis

Etiology

Chronic bacterial conjunctivitis occurs infrequently, and its diagnosis and treatment may be difficult. S. aureus and M. lacunata are common causes. Other microorganisms that constitute normal flora may be implicated if overgrowth disrupts the normal balance among the organisms. Frequently, S. epidermidis is the etiologic agent in chronic blepharitis, which may alter the normal tear film composition. Proteus mirabilis, E. coli, Klebsiella pneumoniae, or S. marcescens may also cause chronic conjunctivitis. Environmental factors such as air pollution, allergies, and contact lens wear may influence the nature of the offending bacterial agent and the subsequent immunologic response. Lacrimal system problems are another common cause of chronic bacterial conjunctivitis.

Diagnosis

Chronic bacterial conjunctivitis may present with various nonspecific symptoms and signs that are difficult to evaluate. Complaints of intermittent irritation, foreign body sensation, burning, tearing, redness, and sticky eyelids are common. Clinically, the conjunctiva may exhibit a mild diffuse hyperemia, a thickened appearance, mucoid or mucopurulent discharge, and a papillary or follicular reaction. The differential diagnosis includes chronic conjunctivitis caused by chlamydia, HSV, acne rosacea, floppy eyelid syndrome, irritants, allergens, and factitious causes. Patients with chronic bacterial conjunctivitis must undergo a thorough evaluation of the eyelids, because of the high correlation of lid disease with chronic bacterial conjunctivitis. In the presence of chronic blepharitis or angular blepharoconjunctivitis, the eyelid margins often appear hyperemic and crusty with markedly reduced tear film quality and breakup time.The clinician also should carefully evaluate the lacrimal drainage system for signs of dacryocystitis or stagnant tear flow. Actinomyces israelii is a frequent cause of canaliculitis and chronic conjunctivitis. Other clinical findings include bacterial exotoxin hypersensitivity reactions, marginal corneal infiltrates, and phlyctenules. Conjunctival smears stained with Giemsa and Gram stains are extremely useful for evaluating the infectious versus inflammatory components of chronic bacterial conjunctivitis. Impression cytology may also be helpful in establishing a diagnosis. Because of the chronic nature of this condition, it is prudent to attempt to identify and target the specific causative agent. Cultures on blood and chocolate agar media with drug sensitivities may prove

helpful in isolating the offending organism and determining the appropriate anti-infective agent.

Management

The causative bacterial pathogen often inhabits the eyelid margins or the base of the eyelashes, even in asymptomatic patients. Successful treatment usually requires good eyelid hygiene by the patient, in conjunction with topical antibiotics. To eliminate any bacterial reservoir, concurrent blepharitis must be treated aggressively.Appropriate eyelid treatment consists of a routine of warm moist compresses applied for 10 to 15 minutes, massage of the eyelid margins, and, ideally, gentle eyelid scrubs two to four times daily. Compresses transfer heat to the eyelids, softening congealed meibomian gland secretions and freeing lid debris. Eyelid hygiene is crucial and must be performed by the patient on a regular ongoing basis. Lid scrubs may be accomplished with a warm washcloth, a cotton-tipped applicator, or a commercially available cleansing agent (see Chapter 3).

Because S. aureus often is associated with blepharitis, treatment may also require topical erythromycin or bacitracin ointment applied two or three times daily. If gram-negative bacteria are the offending organisms, baci- tracin-polymyxin B or an aminoglycoside ointment is the drug of choice. In cases of primary meibomianitis, adjunctive oral treatment consisting of tetracycline, 250 mg four times daily, doxycycline, or minocycline, 50 mg twice daily, for 10 to 21 days significantly improves the patient’s symptoms.The chronic bacterial conjunctivitis is treated with topical antibiotics that have broad antibacterial activity, such as trimethoprim-polymyxin B (Polytrim) or gentamicin solution applied four times daily. In recalcitrant cases, antibiotic treatment should be guided by culture and sensitivity results.

Antibiotic therapy should be limited to periods of disease exacerbation, with the eyelid hygiene providing the daily maintenance regimen. Occasionally, topical erythromycin, bacitracin, or bacitracin-polymyxin B ointment applied at bedtime for several weeks proves beneficial as part of the therapeutic protocol. This type of chronic therapy, however, always carries the risk of fostering overgrowth of resistant organisms.

If a significant inflammatory component or a response to bacterial exotoxin hypersensitivity in the form of marginal corneal infiltrates or phlyctenules is present, treatment may require concurrent topical steroid therapy. When chronic dacryocystitis is involved, treatment should include irrigation of the lacrimal system with trimetho- prim-polymyxin B or gentamicin. Adjunctive systemic antibiotic therapy may also be required (see Chapter 24).

Adenoviral Conjunctivitis

Etiology

Adenoviral infection is a common cause of acute follicular conjunctivitis. More than 45 immunologically distinct

452 CHAPTER 25 Diseases of the Conjunctiva

adenoviral serotypes have been identified, many of which are pathogenic for humans. Most adenoviral infections initially involve the upper respiratory tract or nasal mucosa (or both). Epidemic outbreaks of adenoviral conjunctivitis are recognized as the distinct clinical entities epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF). In clinical practice the exact viral serotype is rarely identified, and different viral serotypes have been implicated as the causative agent of both EKC and PCF. Viral transmission in epidemic outbreaks occurs through direct contact, via droplet transmission, in swimming pools, and, occasionally, through contact with contaminated ophthalmic instruments and solutions.

Diagnosis

Adenoviral conjunctivitis classically presents as an acute follicular conjunctivitis.The infection usually is unilateral at onset but often becomes bilateral after several days. The second eye frequently is less severely involved than the first. Symptoms of adenoviral conjunctivitis include moderate foreign body sensation, tearing, and a watery to mucoid discharge. Patients often experience eyelid crusting, particularly on awakening.

Initially, marked conjunctival injection develops, along with variable degrees of conjunctival chemosis. In addition to conjunctival injection, moderate to marked eyelid and periorbital edema may also occur (Figure 25-8). Occasionally, petechial subconjunctival hemorrhages form and are most easily observed on the bulbar conjunctiva (Figure 25-9).These hemorrhages may coalesce,resulting in diffuse subconjunctival hemorrhage. Ipsilateral preauricular or submandibular lymphadenopathy, with or without tenderness, is a common feature of adenoviral conjunctivitis (Figure 25-10). In severe cases pseudomembranes or true conjunctival membranes may form on the

Figure 25-9 Bulbar conjunctival injection and petechial hemorrhage.

lower or upper tarsal conjunctiva. These membranes result from the accumulation of mucus and inflammatory debris. Membranes and pseudomembranes can cause significant discomfort and foreign body sensation. Inadequately treated conjunctival membranes may lead to conjunctival scarring, symblepharon formation, and secondary cicatricial entropion.

When acute follicular conjunctivitis is accompanied by mild fever and pharyngitis, the clinical triad is recognized as PCF (Figure 25-11). An adenoviral infection seen most commonly in children, PCF is highly contagious and often is spread from contaminated swimming pools. Hence, PCF has been termed “swimming pool conjunctivitis.” Corneal involvement, however, distinguishes EKC from other forms of adenoviral conjunctivitis.The first manifestation of corneal disease in EKC is the appearance of

Figure 25-8 Epidemic keratoconjunctivitis affecting right eye first and then left eye. Note more intense involvement of right eye. Marked conjunctival injection and chemosis, subconjunctival hemorrhages, and eyelid edema are present. (Courtesy William Wallace, O.D.)

Figure 25-10 Palpation of preauricular node in patient with adenoviral conjunctivitis.

Figure 25-11 Follicular conjunctival changes in lower conjunctival fornix.

diffuse punctate epitheliopathy. A multifocal epithelial keratitis (discrete, coarse, epithelial erosions) ensues. Faint subepithelial opacities may begin to form under the epithelial lesions 10 to 14 days after the onset of infection (Figure 25-12). The punctate epithelial lesions resolve, but the subepithelial infiltrates may remain for an extended period, months or even years. When infiltrates or epithelial lesions occur on the visual axis, patients may experience decreased visual acuity. Besides loss of vision, the epithelial lesions and subepithelial opacities can cause bothersome glare, photophobia, and foreign body sensation. Extensive subepithelial infiltrates can cause permanent corneal scarring, resulting in reduction in visual acuity if scars occur on the visual axis or reduced acuity because of induced irregular astigmatism.

Most all cases of adenoviral conjunctivitis are diagnosed on the basis of a patient’s signs and symptoms. Microbiologic investigation often is not needed, but adenoviral isolation via tissue culture can be achieved with conjunctival samples. A rapid immunochromatography test (RPS Adeno Detector, Rapid Pathogen Screening, Inc.)

Figure 25-12 Multiple subepithelial corneal opacities in epidemic keratoconjunctivitis.

for visual qualitative detection of adenoviral antigens in human eye fluid that has good sensitivity for detection of adenovirus compared with cell culture is available. Other conditions that can have a similar clinical appearance include herpetic conjunctivitis, adult inclusion conjunctivitis, and hemorrhagic conjunctivitis. Severe membranous conjunctivitis can also occur in infections from group B streptococci or C. diphtheriae or, uncommonly, in Stevens-Johnson syndrome (SJS). The almost 50% occurrence of significant subepithelial infiltrates and their time course best differentiates EKC from these conditions. The conjunctivitis associated with EKC tends to be more severe than that caused by nonspecific adenoviral infection (Table 25-4). Patients can experience a considerable degree of discomfort and reduced visual function when infiltrates are extensive. Therefore they should receive assurance that symptoms may worsen before they begin to abate, typically about 5 days after the onset of symptoms.

Management

Adenoviral conjunctivitis is a self-limited infection. Most cases resolve spontaneously over approximately

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14 to 21 days. In patients who develop keratitis and subepithelial infiltrates, however, corneal infiltrates can last for many months. During the acute phase of adenoviral conjunctivitis, particularly in patients who are mildly or moderately symptomatic, supportive therapy, including cold compresses, decongestants, and lubricants, can help to relieve patients’ symptoms.

The use of antiviral agents in the management of adenoviral conjunctivitis has proved uniformly disappointing. Because of the relatively high degree of toxicity of antiviral agents and due to the generally self-limited course of the infection, currently available antiviral agents are not generally indicated.

Use of povidone iodine has been advocated by some for the treatment of adenoviral conjunctivitis. The only controlled study of this treatment option demonstrated no significant effect of 1.25% povidone iodine administered four times daily on either days to resolution or proportion of cases resolved at 1 and 2 weeks.

Topical nonsteroidal anti-inflammatory agents also do not appear to improve symptoms in adenoviral conjunctivitis. Topical ketorolac 0.5% used four times daily was shown to be no better than artificial tears at relieving the symptoms or signs of viral conjunctivitis and produced more stinging than artificial tears.

Topical antibiotics generally are not useful in managing adenoviral infections. Although secondary bacterial infection is possible, the risk of hypersensitivity and toxic reactions to topical antibiotics must be weighed against the potential benefit of preventing secondary bacterial infection.The exception is in patients who develop significant conjunctival membranes or pseudomembranes. After these membranes or pseudomembranes have been removed, patients should be treated with a broadspectrum antibiotic, because they may be at increased risk for secondary bacterial infection. In these patients consideration should also be given to the use of an antibiotic–steroid combination that may help prevent scarring.

The role of steroids in the management of EKC remains controversial. Subepithelial infiltrates associated with adenoviral infection represent a cell-mediated immune response, most likely to viral protein. Topical steroids enhance viral replication and increase viral shedding. Suppressing the immune response with steroids may interfere with clearing the viral antigen, which ultimately may prolong the course of the corneal disease. Although steroids are highly effective in reducing corneal infiltrates, some patients may develop a steroid dependence in which discontinuation of the steroid results in recurrence of the subepithelial infiltrates. These patients may require prolonged treatment with topical steroids for periods of months to even years and may be subject to the complications associated with chronic steroid use. The existence of an EKC-like variant of HSV keratoconjunctivitis should further discourage the routine use of topical steroids.The early epithelial phase of EKC can be

clinically indistinguishable from this form of diffuse herpetic keratitis, and treatment of herpetic keratitis with topical steroids leads to exacerbation of the herpetic infection. Steroids should be reserved for patients who are highly symptomatic or are visually impaired by subepithelial infiltrates. Clinicians should inform patients about the potential risks and benefits before instituting steroid treatment.As an alternative to topical steroids, the use of topical cyclosporin A in the management of adenoviral corneal subepithelial infiltrates has yet to be defined.

Educating patients about appropriate hygiene and adhering to standard infection control procedures in the office are extremely important aspects of management. Adenoviral infections are contagious, and infected individuals continue to shed virus in tears and from the nasopharynx for approximately 2 weeks. Patients should be educated with regard to transmission of the infection and should be instructed to adopt stringent, droplet, and contact infection control precautions. Direct hand-to-eye contact may result in the transmission of infection.

The practitioner’s office should follow proper recommended infection control procedures to prevent transmission of adenoviral conjunctivitis. Staff should carefully disinfect equipment, particularly tonometer tips, used in examining infected patients. Safe practice includes the use of barrier protection, such as gloves, while the practitioner examines patients with adenoviral conjunctivitis. Careful hand washing before and after patient examination is mandatory.

Herpes Simplex Conjunctivitis

Etiology

In the United States 70% of the population has immunologic evidence of prior HSV infection by the age of 15 to 20 years and 97% by the age of 60.The primary HSV infection is subclinical in 85% to 90% of cases. Of the two types of HSV, HSV-1 predominates, accounting for approximately 85% of adult cases and is responsible for infection above the waist. Type 1 and type 2 ocular infections are clinically indistinguishable, although type 2 infections tend to be more severe.

Herpetic conjunctivitis is usually a manifestation of primary HSV infection, which generally occurs in children between the ages of 6 months and 5 years. Most cases of herpetic ocular infection result from the nonvenereal form of the virus (HSV-1). Ocular infection with HSV-2 can occur in both newborns and adults. Infection may result from contact with the virus in the infected birth canal (herpetic neonatal conjunctivitis) or from autoinoculation after sexual contact with an infected partner.

Diagnosis

The acute onset of unilateral bulbar conjunctival injection and tearing in a young child should always bring to mind the possibility of primary herpetic infection. If the

Figure 25-13 Vesicular herpes simplex lesions of eyelid margin and periocular skin.

conjunctival injection is bilateral, the second eye will most commonly have become inflamed less than 1 week from the onset of infection in the first eye. Careful examination of the eyelids and periorbital skin may reveal the typical vesicular eruptions characteristic of herpes simplex dermatitis (Figure 25-13). These erythematous vesicular eruptions may appear similar to ulcerative staphylococcal blepharitis but tend to be unilateral and isolated (see Chapter 23). The dermatologic signs do not always occur, and acute follicular conjunctivitis may be the only manifestation of the primary infection. Conjunctival follicles are a prominent feature, and pseudomembrane formation is not uncommon. Many patients develop preauricular lymphadenopathy. Corneal involvement may manifest as diffuse punctate epitheliopathy, subepithelial infiltrates, or the appearance of a typical dendritic or geographic corneal ulcer (see Chapter 26). Rarely, dendritic or geographic bulbar conjunctival ulcerations occur.

Care must be taken to diagnose accurately any case of herpetic conjunctivitis. Herpetic conjunctivitis shares many of the clinical features of adenoviral conjunctivitis, and in the absence of recognizable corneal disease the two entities cannot easily be distinguished. Differentiation is particularly important if the practitioner contemplates using steroids as part of the management of adenoviral conjunctivitis, because the use of topical steroids exacerbates HSV infections.

Management

Herpetic conjunctivitis without corneal involvement usually is benign and self-limited. In patients with primary herpetic blepharoconjunctivitis, prophylactic treatment with antiviral agents to prevent corneal involvement is common practice. Trifluridine (Viroptic) usually is well tolerated and is effective against many strains of HSV. The typical dose is one drop every 2 hours for a maximum

of nine drops daily. One drop five times daily is sufficient when there is no corneal involvement. This dose is reduced to one drop every 4 hours when clinical improvement occurs.Treatment continues for 3 to 5 days after the infection has resolved clinically.

Steroids are specifically contraindicated in the treatment of HSV conjunctivitis, because they can increase virus replication and interfere with the host immune response to the infection.Topical antibiotics are also of limited value in treating HSV. The risk of bacterial superinfection is low, and the potential toxic and hypersensitivity reactions associated with topical antibiotic use may obscure the clinical course of the underlying viral infection.

Varicella-Zoster Conjunctivitis

Etiology

Herpes zoster results from reactivation of the dormant varicella virus, the same virus that generally is acquired during childhood and results in chickenpox. The incidence and severity of herpes zoster infections increase with age. An increased incidence of herpes zoster is also associated with immunocompromise. Peak incidence occurs between the ages of 50 and 75 years. In young patients with no history of malignancy or immunosuppression, herpes zoster infection may be the presenting sign of acquired immunodeficiency syndrome–related complex or frank acquired immunodeficiency syndrome. Ocular lesions occur in approximately 50% to 71% of the patients who develop active herpes zoster infection involving the first (ophthalmic) division of the trigeminal nerve, the most commonly affected division. Ocular involvement is much less common when the infection affects the second or third division of the trigeminal nerve.

Diagnosis

Patients with herpes zoster infection typically experience a prodrome of low-grade fever, headache, and pain or paresthesia along the affected dermatome. Subsequently, patients develop erythematous vesicular eruptions localized to the dermatome innervated by the affected nerve ganglia. The vesicular eruptions respect the midline, revealing the neurologic nature of the infection.The vesicles may affect the skin of the eyelids and extend onto the side and tip of the nose (Hutchinson’s sign), a result of spread along the nasociliary branch of the ophthalmic division of the trigeminal nerve (Figure 25-14). In the early stages vesicles may be subtle, such that careful examination of the skin and hairline are necessary to appreciate the lesions. After several days the eruptions begin to crust, at which point they usually become obvious.

In addition to eyelid swelling on the affected side, acute conjunctivitis is the most common ocular manifestation of herpes zoster infection. The conjunctivitis is

456 CHAPTER 25 Diseases of the Conjunctiva

Figure 25-14 Hutchinson’s sign in herpes zoster ophthalmicus. Note simultaneous involvement of the eye and the side and tip of the nose. (Courtesy William Wallace, O.D.)

predominantly follicular, although there may be a mixed papillary and follicular response. Regional lymphadenopathy on the affected side occasionally may develop. Because the conjunctivitis associated with zoster infection is largely indistinguishable from other types of viral conjunctivitis, recognition of the dermatologic features of the infection is the key to diagnosis. Herpes zoster infection can result in many other ocular manifestations, including keratitis (punctate, dendritic, or disciform), uveitis, and increased intraocular pressure. Cranial nerve palsies, optic neuritis, and retinitis also occur, though rarely.

Management

Conservative treatment of zoster-associated conjunctivitis, including cold compresses, lubricants, and decongestants, carries the lowest risk of treatment-related complications. Treatment of the acute conjunctivitis with topical broad-spectrum antibiotics may help to prevent secondary bacterial infection. Increased patient comfort by reduction of conjunctival inflammation may be affected by the use of topical steroids. Often, a combination antibiotic–steroid is used to accomplish both of these goals. In contrast to herpes simplex infection in which steroids are specifically contraindicated, topical steroids do not exacerbate herpes zoster infection. If steroids are used,the patient should be carefully monitored for intraocular pressure elevation.

The use of oral antiviral agents to treat the acute herpes zoster infection has been successful. Oral acyclovir, 800 mg five times daily for 7 days, effects a rapid resolution of the signs and symptoms of acute herpes zoster ophthalmicus, particularly if treatment is initiated within 72 hours of the initial skin eruption. Oral antiviral agents also reduce the duration and intensity of postherpetic neuralgia, which occurs in approximately 20% of patients. Although acyclovir has been effective and few complications are associated with its use, the limited bioavailability of acyclovir in oral form requires frequent dosing. Newer antiviral prodrugs include valacyclovir and famciclovir. Both of these agents provide an increase in bioavailability of the active drug, thus requiring less frequent dosing. In addition to the decreased dosing schedule, valacyclovir, 1,000 mg three times daily, and famciclovir, 500 mg three times daily, accelerate lesion healing, reduce the duration of viral shedding, and result in faster resolution of postherpetic neuralgia.

The increased bioavailability and decreased dose frequency, combined with the potential shorter duration of the associated postherpetic neuralgia, argue for careful consideration of these newer agents for the acute treatment of herpes zoster infections.

Inclusion Conjunctivitis

Etiology

Chlamydiae are obligate intracellular parasites that depend on the host cell to carry out metabolic biosynthesis.The genus includes two major species: C. trachomatis, which causes disease in humans, and Chlamydia psittaci, which infects primarily nonhumans. The many different serotypes cause a wide spectrum of disease states, including inclusion conjunctivitis, trachoma, lymphogranuloma venereum, and cervicitis or urethritis.

Chlamydial infection is the most common sexually transmitted disease in the United States, with an estimated 2.8 million new cases per year. In 2002 over 800,000 cases of chlamydial infection were reported to the CDC, with many more cases remaining unreported.

Approximately 75% of women and 50% of men have no urogenital symptoms. Chlamydial infections should be suspected in patients who develop nongonococcal urethritis, mucopurulent cervicitis, or pelvic inflammatory disease. Ocular infection commonly occurs by autoinoculation in the infected individual.

Diagnosis

Inclusion conjunctivitis presents in teenagers and sexually active adults as an acute or chronic follicular conjunctivitis often accompanied by a mucopurulent discharge. Upper respiratory symptoms and fever generally are lacking. The disease often occurs in patients who have acquired a new sexual partner in the last 1 to 2 months. After an incubation period of 5 to 12 days, there is acute onset of conjunctival injection, mixed follicular-papillary

Figure 25-15 Mixed follicular-papillary hypertrophy in adult inclusion conjunctivitis.

hypertrophy, and foreign body sensation (Figure 25-15). The disease usually is unilateral. A small, nontender, preauricular node on the affected side may develop during the initial stages of the infection. During the second week of the infection keratitis may develop, along with marginal or central infiltrates, superficial pannus, and even EKC-like opacities.The corneal involvement has a predilection for the superior cornea.

Patients often seek treatment during the acute phase of the disease, which practitioners may misdiagnose as a viral or bacterial conjunctivitis. Treatment with a variety of broad-spectrum topical antibiotics or topical steroids may initially help the patient’s symptoms, but because such treatment is inadequate to eradicate the systemic infection, the patient invariably returns with complaints of recurrent episodes of conjunctival injection and mucopurulent discharge. As in all cases of chronic conjunctivitis, conjunctival cultures and scrapings should be performed to establish a definitive diagnosis. Specimen culture has been the historical gold standard for laboratory diagnosis of Chlamydia infection. In addition, conjunctival scrapings with identification of inclusion bodies by Giemsa staining are considered diagnostic of chlamydial infections. Direct immunofluorescent and immunoenzyme antibody assay of conjunctival scrapings are rapid and easily performed diagnostic tests with fair sensitivity and good specificity. NAAT offer superior sensitivity for the detection of C. trachomatis infection but are more expensive and take longer to obtain results.

Management

Topical therapy of adult inclusion conjunctivitis by itself cannot effect a cure. Currently, the CDC recommends azithromycin 1 g orally in a single dose or doxycycline

100 mg orally twice a day for 7 days when not otherwise contraindicated. This single dose of azithromycin should be considered particularly for patients in whom compliance may be a problem.

Pregnant and lactating women and children younger than 8 years should avoid oral doxycycline therapy. In these patients erythromycin base, 500 mg four times daily for 7 days, or amoxicillin, 500 mg three times daily for 7 days, is an alternative to doxycycline. Once systemic therapy has been initiated, topical treatment with lubricants,vasoconstrictors,or a combination antibiotic–steroid may help to relieve the patient’s ocular symptoms.

All patients with suspected or confirmed chlamydial conjunctivitis should be tested for other sexually transmitted diseases and evaluation and consideration given to comanagement with a gynecologist or urologist. If left untreated, chlamydial vaginitis can result in severe pelvic inflammatory disease, ectopic pregnancy, and infertility. Sexual partners of infected individuals should also receive systemic antibiotics, even if no symptoms are present. In preadolescent children, sexual abuse must be considered in cases of confirmed chlamydial infection.

Trachoma

Etiology

Although C. trachomatis is the infectious agent of both trachoma and adult inclusion conjunctivitis, the clinical presentations and the epidemiologic characteristics of the two diseases are very different. Trachoma and its complications still represent a serious world health problem and today remain a major cause of preventable blindness. The incidence of trachoma is highest in unhealthy, dirty, crowded conditions typically associated with a low socioeconomic stratum. Trachoma affects approximately one-seventh of the world’s population. In the United States the disease is limited mostly to small pockets of Native American populations living in the Southwest. A global initiative to eliminate trachoma as a blinding disease, entitled GET 2020 (Global Elimination of Trachoma), was launched under the World Health Organization’s leadership in 1997.

Diagnosis

In its early stages trachoma presents as a chronic follicular conjunctivitis with a predilection for the superior tarsal and bulbar conjunctiva. Over time, the conjunctival reaction becomes papillary in nature and, with the inflammatory infiltration that occurs, the follicular character of the infection can become obscured. Patients experience symptoms of photophobia, tearing, and mucoid or mucopurulent discharge. Limbal edema and superior bulbar conjunctival hyperemia also may occur. Conjunctival follicles that form at the limbus are characteristic of severe trachoma. Primary corneal involvement often includes superior epithelial keratitis and superficial superior pannus formation. A wide variety of corneal infiltrates

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Figure 25-16 Conjunctival scarring with Arlt’s lines (arrows) in stage IV trachoma.

(superior, diffuse, limbal) may occur, and marginal ulcerations are common.

As the disease progresses conjunctival subepithelial scarring begins to replace the acute inflammatory signs. Fine, linear, horizontal subepithelial scars that form on the upper tarsal conjunctiva are known as Arlt’s lines (Figure 25-16). The scarring can result in entropion and trichiasis, which, in turn, can lead to corneal ulceration and scarring; these are the major blinding complications of trachoma. The involution of limbal follicles results in sharply demarcated limbal depressions known as Herbert’s pits, which are considered pathognomonic for trachoma. Patients with severe conjunctival scarring often develop secondary complications, including severe dry eye syndrome and punctal stenosis.

In areas endemic for this disease, the presence of two of the typical signs—upper tarsal follicles, pannus, or limbal follicles—is sufficient for the diagnosis of trachoma. In nonendemic populations trachoma must be differentiated from other causes of follicular conjunctivitis, such as Moraxella, adenoviral infection, HSV infection, molluscum, and chemical conjunctivitis. The practitioner should obtain a careful history, including travel to any area associated with endemic trachoma.The predilection of trachoma to affect the upper tarsal conjunctiva as well as the superior cornea has great diagnostic value. Laboratory studies may be useful in mild cases, either by isolating Chlamydia in tissue culture or by detecting chlamydial antibodies in serum or tears by means of immunofluorescent assay or with the use of NAAT.

Management

infection, and improved facial hygiene and environmental change, i.e., improved access to water and sanitation) forms the basis for treatment for elimination of blindness from trachoma.

Trachoma can be effectively treated with a 4- to 6-week course of topical tetracycline ointment. Additionally, oral tetracycline 250 mg four times a day or doxycycline 100 mg orally twice a day for 14 days is an effective option if not contraindicated. Alternatively, azithromycin in a single oral dose (20 mg/kg) was found to be equally effective in resolving active trachoma and offers the advantage of increased compliance. Reinfection rates are high, especially in endemic areas. In patients with severe conjunctival cicatrization, surgical intervention may be required to correct trichiasis and entropion and to prevent corneal scarring.

Molluscum Contagiosum

Etiology

Molluscum contagiosum is a dermatologic lesion caused by a poxvirus and is responsible for causing chronic or recurrent follicular conjunctivitis in patients who have lesions of the periorbital skin or eyelids.

Diagnosis

The eyelid lesion is smooth with a central area of umbilication (Figure 25-17). Detection of some lesions may be difficult, because the eyelashes can obscure them. Clinical manifestations of conjunctivitis include the chronic and intermittent occurrence of conjunctival hyperemia, tearing, and follicular hypertrophy of the lower tarsal conjunctiva. Symptoms frequently wax and wane, and patients often use multiple topical antibiotics and steroids without success. The treatment may allow

The World Health Organization recommended SAFE strategy (surgery of late-stage disease, antibiotics for acute

Figure 25-17 Molluscum contagiosum lesion (arrow) on lower eyelid of young child.

the condition to improve, but the untreated skin lesion continues to shed virus particles that cause a toxic reaction and chronic inflammation.

Management

The management of chronic follicular conjunctivitis associated with molluscum contagiosum is removal of the dermatologic lesion to prevent further spread of virus particles into the eye. This treatment is curative, and no further intervention is required. Multiple or recurrent molluscum lesions may be associated with systemic immunosuppression and may be a sentinel lesion in patients with human immunodeficiency virus infection.

Acute Hemorrhagic Conjunctivitis

Etiology

Both Enterovirus and Coxsackievirus are recognized as causing acute hemorrhagic conjunctivitis (AHC). During the last 25 years, several large epidemic outbreaks of AHC have occurred worldwide.

Diagnosis

A rapid onset of bulbar conjunctival injection,tearing,and pain characterizes AHC.The incubation period for AHC is often 1 day or less. This rapid onset contrasts with most cases of adenoviral conjunctivitis, which have a longer incubation period and duration.The conjunctiva develops moderate to severe hyperemia. Small petechial hemorrhages may subsequently form on the bulbar conjunctiva. The superior bulbar conjunctival petechial hemorrhages may increase and spread until there is diffuse and extensive subconjunctival hemorrhage. However, extensive subconjunctival hemorrhage is not a universal feature of the infection. Ocular examination or eyelid eversion may incite hemorrhaging. Most patients develop follicles in the lower tarsal conjunctiva and demonstrate regional lymphadenopathy. The cornea may demonstrate a fine punctate epithelial keratitis or subepithelial infiltrates. In addition to the acute conjunctivitis, several reports describe late neurologic complications, including asymmetric flaccid motor paralysis and cranial nerve palsies.

Management

AHC is self-limited over a period of 5 to 10 days. Because antiviral agents are ineffective, the preferred treatment consists of topical application of cool compresses and astringents. Patients require reassurance, because the appearance of diffuse subconjunctival hemorrhage in the presence of pain and tearing is quite stressful. Patient education should stress the severe communicability of this disorder, and appropriate precautions should be taken to limit the spread of the infection. Topical steroids have not demonstrated any significant effect and may actually prolong the infection.

Nonspecific Viral Conjunctivitis

Acute conjunctivitis is a common feature of many other viral illnesses.The clinical manifestations are nonspecific, and knowledge of the systemic manifestations of these diseases leads to the appropriate diagnosis. Most cases result in mild, acute, transient, bilateral, follicular conjunctivitis. Treatment of the conjunctivitis in each case is generally supportive, with cold compresses, decongestants, and lubricants used to ease the symptoms of acute conjunctivitis. Table 25-5 summarizes clinical features of the most common viral illnesses with which conjunctivitis is associated.

Nonviral Infectious Etiologies

Several other infectious agents can cause follicular conjunctivitis and should be included in the differential diagnosis of either acute or chronic follicular conjunctivitis.

Moraxella Conjunctivitis

M. lacunata has long been recognized as a cause of conjunctivitis. It may produce at least two types of conjunctival infections: acute angular blepharoconjunctivitis and chronic follicular conjunctivitis. Conjunctival hyperemia, pain, adherent eyelids on awakening, and follicular conjunctivitis characterize Moraxella conjunctivitis. Epidemic outbreaks can occur, and sharing eye makeup among school-aged girls has been identified as a risk factor for infection. Conjunctival scrapings demonstrate the characteristically large, square, diplobacillus organism.Traditional treatment of Moraxella conjunctivitis has included topical 0.25% zinc sulfate; however, topical 0.5% erythromycin or topical bacitracin ointment two to three times daily is more effective and less toxic.

Lyme Disease

Lyme disease, caused by the spirochete Borrelia burgdorferi, incites a variety of ocular manifestations, the most common being a conjunctivitis that occurs in up to 10% of patients with early disease. Although the characteristics of the conjunctivitis have not been clearly defined, several reports have described follicular conjunctivitis. Increased antibody titers to B. burgdorferi indicate the presence of Lyme disease. A history of tick bite or erythema chronicum migrans should alert the clinician to consider Lyme disease in the differential diagnosis in areas of the country where this disease is prevalent. Treatment of Lyme disease conjunctivitis should include topical tetracycline as an adjunct to oral doxycycline, 100 mg twice daily for 2 to 3 weeks,which is used to treat the systemic infection.

Parinaud’s Oculoglandular Syndrome

Parinaud’s oculoglandular syndrome constitutes a broad spectrum of conjunctival diseases caused by a variety of