26 MICROSPORIDIAL INFECTION

a chronic, bilateral keratoconjunctivitis in immunocompromised patients, particularly patients with acquired immunodeficiency syndrome (AIDS) and a significantly reduced CD4+ T lymphocyte count. There are also recent reports of unilateral and bilateral microsporidial keratoconjunctivitis in well patients, mostly with a history of topical steroid use. Much less commonly, ocular microsporidiosis presents as a unilateral stromal ulcerative keratitis in immunocompetent individuals. There is one reported case of microsporidial sclerouveitis.

Four genera and five species have been the reported agents in ocular microsporidiosis: Encephalitozoon hellem, E. cuniculi and Septata intestinalis are the causes of keratoconjunctivitis, and Vittaforma (Nosema) corneae and Trachipleistophora hominis are the causes of ulcerative keratitis. The source and method of transmission remain unclear. Some cases have been associated with exposure to household pets or contaminated water. Ocular inoculation may occur by horizontal transmission from nasopharyngeal, gastrointestinal or urinary tract colonization in immunocompromised individuals or from trauma or contact lenses.

COURSE/PROGNOSIS

Keratoconjunctivitis

If untreated, chronic infection of the conjunctival and corneal epithelium persists. In the absence of retinal complications associated with AIDS and with effective treatment, the visual prognosis is excellent.

●Other techniques: fluorescent microscopy using speciesspecific antisera; periodic acid-Schiff, Grocott-methenamine silver and modified trichrome stains may be positive.

●Culture of conjunctival or corneal scrapings negative for bacteria, viruses and fungi and viral PCR negative.

Ulcerative keratitis

Clinical signs and symptoms

●Foreign body sensation.

●Photophobia.

●Decreased vision.

●Slowly progressive, often central, corneal ulcer with variable clinical appearance; from disciform stromal infiltrate which may mimic herpes simplex stromal keratitis, to suppurative ulceration with epithelial breakdown, to severe corneal thinning and perforation.

●Anterior chamber reaction and conjunctival injection.

●Refractory to topical antibiotic and anti-inflammatory therapy.

Laboratory findings

●Immune status: normal.

●Gram’s stain of corneal biopsy: spores may be seen within stromal keratocytes.

●Electron microscopy of corneal biopsy or penetrating keratoplasty recipient button required to make the diagnosis and characterize the species involved in all reported cases.

DIAGNOSIS

Keratoconjunctivitis

Clinical signs and symptoms

●Intense foreign body sensation.

●Marked photophobia.

●Blepharospasm.

●Nonspecific or papillary conjunctival hyperemia.

●Diffuse, coarse, punctate, intraepithelial corneal opacities with focal epithelial surface erosions. Occasionally mild anterior stromal infiltrates. May mimic adenoviral keratoconjunctivitis.

●No intraocular inflammation.

TREATMENT

Keratoconjunctivitis

Local

●Topical fumagillin 70 μg/mL can be prepared from fumagillin bicyclohexylammonium salt (Fumadil B). Sixty milli-

grams is dissolved in 20 mL of sterile Dacriose. The solution is passed through a 0.22-μm filter into three opaque, sterile dropper bottles (10 mL). Keep refrigerated. Remains stable for 1 to 3 weeks. Use hourly while awake as initial therapy, decreasing to three or four times daily for maintenance treatment.

Laboratory findings

●Immune status: significant decrease in CD4+ T lymphocytes and human immunodeficiency virus (HIV) seropositivity in many cases.

●Gram’s stain smear of conjunctival or corneal scrapings: numerous gram-positive, ovoid spores in the cytoplasm of epithelial cells.

●Electron microscopy of centrifuged conjunctival or corneal scrapings: characteristic wide ovoid, 2–5 μm spores and species-specific features.

●In vivo confocal microscopy: may be useful for rapid, noninvasive identification of corneal intraepithelial spores.

Systemic

●Albendazole, an orally administered broad-spectrum antihelminthic agent, has been reported to be useful in combination with topical fumagillin in treating ocular microsporidial infection, particularly in the presence of multiorgan microsporidiosis. There is one report of successful treatment with debridement and oral itraconazole.

Ulcerative keratitis

●There are no reported cases of microsporidial ulcerative keratitis cured with topical fumagillin. Penetrating corneal transplantation appears to be the only treatment that has proven successful.

COMPLICATIONS

Microsporidial keratoconjunctivitis may persist as chronic infection, but remains confined to epithelial cell layers. Ulcerative keratitis, however, tends to progress and may lead to corneal perforation. Recurrence of keratitis following penetrating keratoplasty has not been reported.

COMMENTS

Topical antibiotics, anti-inflammatories, propamidine and metronidazole have all proved to be ineffective in the treatment of microsporidial keratoconjunctivitis.

REFERENCES

Cali A, Meisler D, Lowder CY, et al: Corneal microsporidiosis: characterization and identification. J Protozool 38:S215–S217, 1991.

Chan CML, Theng JTS, Li L, et al: Microsporidial keratoconjunctivitis in healthy individuals. Ophthalmol 110:1420–1425, 2003.

Font RL, Samaha AN, Keener MJ, et al: Corneal microsporidiosis: report of case, including electron microscopic observations. Ophthalmol 107:1769–1775, 2000.

Font RL, Su GW, Matoba AY: Microsporidial stromal keratitis. Arch Ophthalmol 121:1045–1047, 2003.

Gritz DC, Holsclow DS, Neger RE, et al: Ocular and sinus microsporidial infection cured with systemic albendazole. Am J Ophthalmol 124:241– 243, 1997.

Lewis NL, Francis IC, Hawkins GS, et al: Bilateral microsporidial keratoconjunctivitis in an immunocompetent non-contact lens wearer. Cornea 22:374–376, 2003.

Lowder CY, McMahon JT, Meisler DM, et al: Microsporidial keratoconjunctivitis caused by Septata intestinalis in a patient with acquired immunodeficiency syndrome. Am J Ophthalmol 121:715–717, 1996.

Rauz S, Tuft S, Dart JK, et al: Ultrastructural examination of two cases of stromal microsporidial keratitis. J Med Microbiol 53:775–781, 2004.

Rosberger DF, Serdarevic ON, Erlandson RA, et al: Successful treatment of microsporidial keratoconjunctivitis with topical fumagillin. Cornea 12:261–265, 1993.

Sridhar MS, Sharma S: Microsporidial keratoconjunctivitis in a HIV-sero- negative patient treated with debridement and oral itraconazole. Am J Ophthalmol 136:745–746, 2003.

disease that is usually self-limited and the lesions can be asymptomatic or inflamed, depending on the location and stage of the lesion. The average incubation period is 2 to 3 months but may range between 1 week to 6 months.

Molluscum contagiosum has a bimodal incidence in otherwise healthy individuals. Children and adolescents are often infected by direct contact, whereas young adults may acquire the virus through sexual contact. When the mode of transmission is sexual, lesions usually are also present on the inner thighs and lower abdomen. Overall, the greatest incidence is between the ages of 15 and 35 years of age. Most of the lesions are 2 to 3 mm long and have a central umbilication with a caseous material. Usually, there are fewer than 10 lesions and often only two or three lesions around the lids.

The incidence, size and number of lesions can be much greater in immunocompromised individuals; there may be more than 20 lesions on an upper and a lower eyelid and they can range in size from 1 to 6 mm. These atypical lesions may coalesce; atypical presentation may be a sign of an immunocompromised host, such as a patient with acquired immune deficiency syndrome, who has undergone chemotherapy, who receives corticosteroids, who has atopic dermatitis, who has undergone splenectomy and who has Wiskott–Aldrich syndrome.

COURSE/PROGNOSIS

The virus can be spread through direct contact or fomites. It is contagious in moist, close-contact conditions such as in swimming pools and saunas and during wrestling or sex. No exclusion from school, work or swimming pools is necessary. Direct hand-to-eye contact and infected cosmetics can be modes of transmission. There is no evidence of acquired immunity. The virus replicates in the epithelial cells; cellular destruction occurs, causing the central umbilication. The virus particles go from lid lesions to tear film, thus affecting all ocular surfaces and often causing a toxic keratoconjunctivitis. The lesions may resolve spontaneously in 2 to 12 months, but there may be recurrences for as long as 8 years. Surgical treatment is usually required, but immunocompromised individuals may still have recurrences in 6 to 8 weeks.

27 MOLLUSCUM CONTAGIOSUM

078.0

Alan B. Leahey, MD

Allentown, Pennsylvania

Frank G. Baloh, MD

Allentown, Pennsylvania

ETIOLOGY/INCIDENCE

Molluscum contagiosum is a large, enveloped, double-stranded DNA virus of the Poxviridae family that can produce small, pearly pink and white umbilicated lesions on the skin and, less commonly, on mucous membranes. The periocular skin, eyelid and ocular surface can be infected, as can be the face, abdomen and groin. This poxvirus replicates in the cytoplasm of epidermal cells inducing cell lysis. It is a mildly contagious skin

DIAGNOSIS

Clinical signs and symptoms

The lesions of molluscum contagiosum can affect the eye and the lid by infecting the periocular skin surface and the lid margin, causing a toxic follicular keratoconjunctivitis. The limbus, bulbar conjunctiva and cornea can also be involved. The typical umbilicated lesions can occur on any of these ocular surfaces and cause further inflammation, such as conjunctival scarring, punctate epithelial keratopathy, pannus, pseudodendrite, subepithelial infiltrates, corneal ulceration, corneal perforation and punctal occlusion. The follicular conjunctivitis can cause pseudotrachoma with superior epithelial keratitis and corneal scars; thus, if left untreated when the ocular surface is involved, significant visual loss can result.

The umbilicated, dome-shaped, pearly pink and white papules are 2 to 3 mm and usually smooth and elevated. Cheesy-type material is present in the central craters. Usually, several lesions are seen in the periocular area.

Laboratory findings

The craters in acanthotic epidermis are filled with epithelial cells with large eosinophilic intracytoplasmic inclusion bodies (molluscum or Henderson–Patterson bodies) as viewed with light microscopy when virus particles are deep in the epidermis. As virus particles migrate to the granular layer of the epidermis, the inclusion bodies become basophilic.

Immunocompromised individuals have a dense mononuclear infiltrate at the base of the lesions.

Differential diagnosis

●Warts.

●Verrucae vulgaris.

●Papillomas.

●Milia.

●Sebaceous cysts.

●Herpes simplex virus.

●Lichen planus.

●Keratoacanthoma.

●Sebaceous cell carcinoma.

●Chlamydial infection.

TREATMENT

Local

●Spontaneous resolution.

●Excision.

●Curettage.

●Chemical cauterization (trichloroacetic acid, phenol, iodine, triretinoin).

●Cryotherapy.

●Liquid nitrogen.

●Cidofovir cream 3% (nucleotide analog of deoxycytidine) in patients positive for human immunodeficiency virus (HIV).

●Cantharidin 0.9% (blistering agent).

●Imiquimod cream 5% (immune response modifier).

Systemic

●Intravenous cidofovir in patients positive for HIV.

Many of these lesions will resolve in 2 to 12 months, but many require a surgical or medical option described above. Curettage of the central lesion will speed resolution by bleeding into the central cavity. Often, a combination of treatments such as excision or curettage and double freeze-thaw cryotherapy is required to remove lid lesions that cause ocular complications. Immunocompromised individuals are more difficult to treat because there may be recurrence in 6 to 8 weeks.

venereal disease in adult transmission. Prevalence of molluscum contagiosum in HIV patients may be as high as 5–18%. These individuals should also undergo a dilated retinal examination to rule out another opportunistic infection that could affect the eye, such as cytomegalovirus.

SUMMARY

Molluscum contagiosum of the periocular skin and lid margin is best diagnosed on the basis of clinical appearance and confirmed through excisional biopsy. Numerous local surgical therapies have been described, but excision or curettage combined with cryotherapy seems to be the most effective in nonimmunocompromised individuals. In immunocompromised individuals, recurrence rates are much higher regardless of the treatment. Atypical molluscum lesions require that the HIV status of the infected individual be determined.

REFERENCES

Charles NC, Friedberg DN: Epibulbar molluscum contagiosum in acquired immune deficiency syndrome: case report and review of the literature. Ophthalmology 99:1123–1126, 1992.

Charteris DG, Bonshek RE, Tullo AB: Ophthalmic molluscum contagiosum: clinical and immunopathological features. Br J Ophthalmol 79:476–481, 1995.

Goodman DS, Teplitz ED, Wishner A, et al: Prevalence of cutaneous disease in patients with acquired immunodeficiency sysndrome (AIDS) or AIDS-related complex. J Am Acad Dermatol 17(2 Pt 1):210–220, 1987.

Hoeprich PD, Jordan MC, Ronald AR, eds: Infectious diseases: a treatise of infectious processes. 5th edn. Philadelphia, JB Lippincott, 1994.

Krachmer JH, Mannis MJ, Holland EJ: Cornea: fundamentals of cornea and external disease. St Louis, Mosby, 1997.

Lucius RW, Santander S: Opportunistic infections of the anterior segment in the HIV population. Ophthalmol Clin North Am 10:85–96, 1997.

Meadows KP, Tyring SK, Pavin AT, et al: Resolution of recalcitrant molluscum contagiosum virus in lesions in human immunodeficiency virus-infected patients with cidofovir. Arch Dermatol 133:1039–1041, 1997.

Robinson MR, Udell IJ, Garber PF, et al: Molluscum contagiosum of the eyelids in patients with acquired immune deficiency syndrome. Ophthalmology 99:1745–1747, 1992.

Seitz B: Chronische einseitige Keratokonjunktivitis bei Molluscum contagiosum der Oberlidkante. Klin Monatsbl Augenheilkd 204:142–143, 1992.

Theos AU, Cummins R, Silverberg NB, Paller AS: Effectiveness of imiquimod cream 5% for treating childhood contagiosum in a double-blind, randomized pilot trial. Cutis 74(2):134–138, 141–142, 2004.

COMPLICATIONS

Loss of vision secondary to corneal vascularization, corneal perforation and scarring from a toxic keratoconjunctivitis or primary corneal lesions must be prevented. The overzealous treatment of lid lesions could lead to entropion or ectropion with resultant exposure keratitis.

COMMENTS

Atypical numerous, confluent molluscum contagiosum lesions may be an indicator of systemic immunocompromise and HIV status should be determined because of the association of a

28 MORAXELLA 372.02

Audina M. Berrocal, MD

Miami, Florida

Jaime R. Gaitan, MD

Miami, Florida

ETIOLOGY/INCIDENCE

Moraxella organisms are aerobic, oxidase positive, gram-nega- tive diplococci or coccobacilli morphologically indistinguish-

COMMENTS

Mucormycosis is a vision and life threatening condition. The only hope for preserving life and vision is early recognition and aggressive medical and surgical treatment.

REFERENCES

Fairley C, Sullivan TJ, Bartley P, et al: Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient. Ophthalmology 107:555– 558, 2000.

Ferry AP, Abedi S: Diagnosis and management of rhino-orbitocerebral mucormycosis (phycomycosis): a report of 16 personally observed cases. Ophthalmology 90:1096–1104, 1983.

Newman RM, Kline LB: Evolution of fundus changes in mucormycosis. J Neuro-ophthalmol 17:51–52, 1997.

Peterson KL, Wang M, Canalis RF, Abemayor E: Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope 107:855–862, 1997.

Radner AB, Witt MD, Edwards JE, Jr: Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case report and review. Clin Infect Dis 20:163–166, 1995.

Seiff SR, Choo PH, Carter SR: Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthalmic Plast Reconstr Surg 15:28– 31, 1999.

Strasser MD, Kennedy RJ, Adam RD: Rhinocerebral mucormycosis: therapy with amphotericin B lipid complex. Arch Int Med 156:337–339, 1996.

Thomas PA: Current perspectives on ophthalmic mycoses. Clin Microbiol Rev 16:730–797, 2003.

Yohai RA, Bullock JD, Aziz AA, Markert RJ: Survival factors in rhino- orbital-cerebral mucormycosis. Surv Ophthalmol 39:3–22, 1994.

COURSE/PROGNOSIS

Children usually recover from mumps in about 10 to 12 days. About 1 child in every 10 who gets mumps develops symptoms of meningitis and symptoms of encephalitis are seen much less often. About 1 out of every 4 teenage or adult men who contract mumps develops orchitis. In rare cases of mumps, temporary or permanent hearing loss develops in one or both ears. Abdominal pain associated with pancreatitis or inflammation of the ovaries is observed infrequently. Ocular disease generally does not present until 10 days to three weeks after the onset of the acute illness. Ocular disease may be prolonged, however, lasting weeks or months.

DIAGNOSIS

Clinical signs and symptoms

Mumps presents with fever of up to 103ºF (39.4ºC), headache and loss of appetite. Swelling of the cheeks and jaw become quickly apparent. Other symptoms may include hearing loss, abdominal pain, or scrotal pain and swelling in males. Nervous system involvement may result in complaints of stiff neck, severe headache, nausea and vomiting, drowsiness, and convulsions.

Ocular symptoms may present from 10 days to 3 weeks after the onset of the acute systemic mumps infection. These ocular complications, in approximate decreasing order of frequency, can include dacryoadenitis, optic neuritis, conjunctivitis, scleritis, keratitis, uveitis, retinitis, oculomotor palsies, opsoclonus, and transient elevation of intraocular pressure.

30 MUMPS 072.9

Ian H. Kaden, MD

Randolph, New Jersey

Roger F. Meyer, MD

Ann Arbor, Michigan

ETIOLOGY/INCIDENCE

Mumps is an acute contagious disease caused by the mumps virus. It is usually spread by aerosolized saliva, secondary to

Laboratory findings

The diagnosis of mumps should be suspected from the history and physical examination during the acute phase and can be confirmed by acute and convalescent serologic studies. The mumps virus has been shown to be present in the saliva as long as 7 days before and 9 days after the appearance of parotid swelling.

Differential diagnosis

Early symptoms of fever and headache in mumps may be confused with other viral illness, including the common cold. The subsequent development of parotid swelling makes the diagnosis of mumps infection, more likely. Abdominal pain associated with cases of orchitis and pancreatitis has been confused with acute appendicitis. Ocular complications seen in cases of

Ocular

The first indications of Newcastle disease infection usually appear in the eye with the sudden onset of:

●Burning;

●Foreign body sensation;

●Pain;

●Chemosis;

●Lacrimation; and

●Photophobia.

The infection progresses to an acute follicular conjunctivitis, with the following:

●Serous or mucopurulent discharge;

●Subconjunctival hemorrhages, exudates, or both.

The eyelids usually are affected, becoming edematous and developing follicles; the cornea can occasionally become involved, with:

●Fine keratic precipitates;

●Round subepithelial opacities.

Duke-Elder S, ed: System of ophthalmology. St Louis, CV Mosby, 1965: VIII:369–372; 1976:XV:110.

Hanson RP: Paramyxovirus infections. In: Hubbert WT, McCulloch WF, Schnurrenberger PR, eds: Diseases transmitted from animals to man. 16th edn. Springfield, Charles C Thomas, 1975:851–858.

Lamer L: Sur un cas de conjonctivite de la maladie de Newcastle. Can J Ophthalmol 4:390–393, 1969.

Montgomery RD, Maslin WR, Boyle CR: Effects of Newcastle disease vaccines and Newcastle disease/infectious bronchitis combination vaccines on the head-associated lymphoid tissues of the chicken. Avian Dis 41:399–406, 1997.

Schemera B, Toro H, Herbst W, et al: Conjunctivitis and disorders of general health status in humans caused by infection with Newcastle disease virus. DTW 94:383–384, 1987.

Zehetbauer G, Kunz C, Thaler A: Cases of pseudo fowl plague (Newcastle disease) in man in lower Austria. Wien Klin Wochenschr 83:878–880, 1971.

Other ocular symptoms include:

●Decreased visual acuity;

●Decreased accommodation.

TREATMENT

Ocular

There is no specific treatment for Newcastle disease; it is a benign, self-limited condition that normally runs its course in 7 to 10 days. Therapy should be directed toward preventing complications such as secondary bacterial infection and toward relieving symptoms. The use of topical ocular broad-spectrum antibiotics, such as neosporin (neomycin, polymyxin B, and bacitracin) may be of some value, although this has not been definitively demonstrated. The application of hot compresses gives some symptomatic relief.

Systemic

Bedrest may be indicated in more severe cases; the patient should be instructed to avoid eyestrain or any activity that might increase the severity of the ocular symptoms.

PRECAUTIONS

Although Newcastle disease usually runs its course in 7 to 10 days, in rare instances some blurring of vision or difficulty of accommodation may persist longer.

There is some concern that the Newcastle disease virus may develop into a more severe human pathogen. The virus, a parainfluenza type, has demonstrated its genetic plasticity by assuming four pathologic forms.

Recent efforts to develop effective poultry vaccines have resulted in unexpected adverse effects of some vaccines on immune system functions, further suggesting the possibility of viral mutation and subversion of the host’s immune response.

REFERENCES

Charan S, Mahajan VM, Rai A, Balaya S: Ocular pathogenesis of Newcastle disease virus in rabbits and monkeys. J Comp Pathol 94:159–163, 1984.

32 NOCARDIOSIS 039

John D. Bullock, MD, MPH, MSc

Dayton, Ohio

Ronald E. Warwar, MD

Dayton, Ohio

ETIOLOGY/INCIDENCE

Nocardiosis is typically caused by Nocardia asteroides, which is named for the star-like appearance of the colonies on agar plate. Once thought to be a fungus, it is classified in the bacterial family Nocardiaceae, which includes the aerobic Actinomycetes. The organism reproduces through fragmentation of its hyphae into bacillary and coccoid elements. It is distinguished by a propensity for filamentary growth with true branching. It is a ubiquitous natural soil saprophyte often found in decaying organic matter. N. asteroides is a facultative, intracellular parasite that can persist and grow within macrophages. The basis of nocardial pathogenicity is its cell wall composed of complex lipids, peptides and polysaccharides, making it resistant to macrophage phagolysosomal fusion.

Nocardiosis typically affects debilitated, immunosuppressed patients, but 20% to 50% of patients may be otherwise healthy.

Systemic nocardiosis

●Typically respiratory tract entry.

Ocular nocardiosis

●Exogenous.

●Extraocular or intraocular infection most often associated with trauma, also associated with previous ocular surgery (including refractive surgery/LASIK), contact lens use and corticosteroid use.

●Endogenous.

●Via hematogenous spread to the eye.

●Mean patient age is 46 years; male-to-female ratio of 4:1.

●Bilateral in 30%.

●Occurs in 3% of systemic cases.

DIAGNOSIS

Clinical signs and symptoms

Systemic nocardiosis

●Bronchitis or pneumonia.

●Often presents with cough and low-grade fever.

●Malaise, weight loss and night sweats possible.

●On chest radiograph, typically shows rapidly developing lobar or segmental infiltrate.

●Sites of dissemination: central nervous system (25% to 40%), skin and subcutaneous tissues, kidney, liver and lymph nodes.

●Mycetoma (maduromycosis or Madura foot).

●Chronic, deep subcutaneous tissue and bone infection; usually involves lower extremities.

Ocular nocardiosis

●Keratitis.

●Symptoms of pain, photophobia, blepharospasm and lid swelling.

Ocular nocardiosis

●Keratitis/scleritis.

●Topical: sulfacetamide 15% to 30% or amikacin 2.5% to 5% with or without topical trimethoprim 16 mg/mL-sulfa- methoxazole 80 mg/mL every 15 to 30 minutes until clinical improvement.

●Systemic: oral trimethoprim 1.6 g-sulfamethoxazole 320 mg b.i.d. or intravenous amikacin 15 mg/kg/day.

●Consider subconjunctival injection: trimethoprimsulfamethoxazole.

●Endophthalmitis.

●Vitrectomy and/or intravitreal amikacin with or without cefazolin.

REFERENCES

Brooks JG, Mills RAD, Coster DJ: Nocardial scleritis. Am J Ophthalmol 114:371–372, 1992.

Bullock JD: Endogenous ocular nocardiosis: a clinical and experimental study. Trans Am Ophthalmol Soc 81:451–531, 1983.

●Deep corneal infiltration and vascularization may be seen with prolonged infection.

●Chorioretinitis, subretinal abscess, scleritis, endophthalmitis, dacryocystitis, periorbital and orbital cellulites.

●Poor prognosis with frequent loss of vision.

Mortality rates

●Otherwise healthy patients: 15%.

●Nonimmunosuppressed patients with underlying disease: 20%.

●Patients receiving immunosuppressive agents: 80% to 100%.

Laboratory findings

●Blood culture, sputum culture, or culture of material directly aspirated.

●Gram’s stain.

●Gram-positive filamentous structures with an intermittent or a beaded staining pattern; weakly acid-fast.

●Grocott–Gomori methenamine-silver nitrate and periodic acid-Schiff stains.

●Culture.

●Slow growing; may take 2 to 4 weeks to appear, but its isolation is significant as it rarely represents a contaminant.

●Will grow on virtually any medium without antibiotics; yield may be increased by the use of selective media such as Thayer–Martin agar with antibiotics or paraffin agar.

●Antibiotic susceptibility tests are often unreliable.

●Histopathologic features of nocardial endophthalmitis: suppurative and necrotizing inflammatory response in the choroid and retina.

titis with topical trimethoprim-sulfamethoxazole. Am J Ophthalmol 99:601–602, 1985.

Ferry AP, Font R, Weinberg RS, et al: Nocardial endophthalmitis: report of two cases studied histopathologically. Br J Ophthalmol 72:55–61, 1988.

Gregor RJ, Chong CA, Augsburger JJ, et al: Endogenous Nocardia asteroides subretinal abscess diagnosed by transvitreal fine-needle aspiration biopsy. Retina 9:118–121, 1989.

Katten HM, Pflugfelder SC: Nocardia scleritis. Am J Ophthalmol 110:446– 447, 1990.

King LP, Furlong WB, Gilbert WS, Levy C: Nocardia asteroides infection following scleral buckling. Ophthalmic Surg 22:150–152, 1991.

Sridhar MS, Gopinathan U, Garg P, et al: Ocular Nocardia infections with special emphasis on the cornea. Surv Ophthalmol 45:361–378, 2001.

Zimmerman PL, Mamalis N, Alder JB, et al: Chronic Nocardia asteroides endophthalmitis after extracapsular cataract extraction. Arch Ophthalmol 111:837–840, 1993.

33 OCULAR CANDIDIASIS 112.89

Srilakshmi Maguluri, MD

Nashville, TN

Franco M. Recchia, MD

Nashville, TN

Sean P. Donahue, MD, PhD

Nashville, TN

Denis M. O’Day, MD, FACS

Nashville, TN

directly from the eye should be attempted to confirm the presence of the organism.

Isolate recovery and identification

Most Candida species are readily isolated on blood agar and Sabourauds dextrose agar. A pasty, white colony appears 24 to 48 hours after inoculation. A number of rapid species identification diagnostic kits are available, as well as polymerase chain reaction (PCR) for organism identification from tissue and fluid samples. Candida species are easily visualized on smear with Gram stain as well as with special fungal stains such as Gomori methenamine silver stain and KOH.

Isolate recovery from cornea

In the case of a keratitis or corneal ulceration, corneal scrapings should be obtained for culture and smear. If the site of the suspected infection is deeper in the corneal stroma, corneal biopsy or elevation of a LASIK flap may be necessary to obtain an adequate specimen.

hours in 500 mL of 5% dextrose in water. In treating early cases of Candida chorioretinitis, in which the lesions are confined to the retina and choroid, a minimal cumulative dose of 200 to 500 mg may be adequate to control the infection. If there is significant vitreous involvement, i.e. endophthalmitis, therapy should be continued until the total cumulative dose of amphotericin B is between 1000 and 1500 mg. Due to potential life-threatening complications with amphotericin B treatment, ophthalmologists should manage antifungal therapy with the aid of an internist who is skilled in infectious diseases.

Fluconazole and voriconazole are emerging as better systemic agents than amphotericin B in terms of coverage and toxicity profiles. In vitro investigation of voriconazole treatment for Candida endophthalmitis shows 100% susceptibility of Candida species. These newer agents can be a good alternative to amphotericin B for treatment of refractory cases, or those with significant systemic toxicity to amphotericin B. Further prospective studies are needed to corroborate their efficacy and lack of toxicity in the management of candidal endophthalmitis.

Periocular infections

Periocular infections caused by Candida species can be diagnosed by culturing conjunctival and eyelid scrapings and any reflux material obtained after irrigation of the lacrimal sac.

Specimen recovery from posterior segment

Vitreous biopsy is performed in the case of chorioretinits, vitritis, or endophthalmitis. In addition, a complete diagnostic microbiologic workup should be performed if a fungal etiology is suspected and not already documented. Serial blood cultures are necessary as part of the complete workup if the patient does not already have culture-positive candidemia.

Local delivery of intravitreal therapy for endophthalmitis

Intravitreal injections of amphotericin B have been used in patients with chorioretinitis without vitritis and mild vitritis. Both 5- and 10-microgram doses of intravitreal amphotericin B have been shown to have no retinal toxicity. Su et al report the use of 5 to 10 microgram per 0.1 cc of fluconazole intravitreally to successfully treat candidal endophthalmitis in 8 patients. However, further large scale prospective randomized clinical trials need to corroborate the efficacy and document lack of retinal toxicity before these newer agents become standard intravitreal treatment.

TREATMENT

Topical medical treatment for anterior segment involvement

Most infections respond rapidly to a loading dose of 0.15% amphotericin B every 5 minutes for 1 hour and then hourly for the first 48 hours. Topical natamycin 5% suspension is less effective. The penetration of both drugs into deeper stroma is poor. Removal of corneal epithelium dramatically enhances the penetration and efficacy of these agents. Triazoles are also useful as topical agents. Fluconazole can be applied topically as a 0.2% solution in a balanced salt solution with adequate corneal and aqueous levels attainable. A new triazole, voriconazole, also shows promise when administered as a 1% solution topically.

Clotrimazole, an older imidazole, applied as a cream 8 to 12 times per day has also been successfully used. Subconjunctival injections are unnecessary and are of unproven efficacy. In those rare situations where systemic therapy is indicated fluconazole or voriconazole are likely to be the most efficacious.

Medical management of posterior segment involvement

Systemic

Systemic treatment is indicated for suspected candidal chorioretinitis or endophthalmitis. Intravenously administered amphotericin B can be used in this context. Efforts should be made to reach a dosage of 0.7 to 1.0 mg/kg/day as quickly as possible. Treatment may be also given on alternate days to increase drug tolerance. The drug is infused slowly over 4 to 6

Surgical treatment for anterior and posterior segment

In the absence of descemetocele formation, perforation or visually significant scarring, penetrating keratoplasty is rarely required for candidal corneal infections.

Therapeutic vitrectomy combined with intravitreal amphotericin B is indicated for eyes with prominent vitreous involvement. Vitrectomy removes inflammatory debris and fungal elements as well as scaffolding for vitreoretinal traction bands and epiretinal membranes that contribute later to the development of macular pucker and retinal detachment. It also allows intravitreal delivery of amphotericin B. Because of the frequent association of endogenous candidal endophthalmitis with systemic candidiasis, intravitreal amphotericin B should be an adjunct to intravenous therapy rather than a substitute.

Sub macular surgery and membrane removal may be beneficial in the setting of choroidal neovascular membrane without underlying fibrosis.

COMMENTS

The use of systemic steroids, topical corticosteroids, or both, in the management of patients with keratitis or endophthalmitis caused by Candida species, is controversial. Corticosteroids can inhibit the severe inflammatory host response that is sometimes highly destructive to the eye. Some clinicians believe that it is possible and desirable to halt such destruction without simultaneously depressing the host immune response. The use of steroid therapy adjunctively in a patient with fungal keratitis is complex and may be unwise.

ETIOLOGY/INCIDENCE

Ocular histoplasmosis is prevalent in North America, especially within the Mississippi and Ohio River valleys in which exposure to Histoplasma capsulatum, a bimorphic fungus with spores in the soil, is endemic. It has been estimated that ocular findings are present in approximately 2 million individuals, among whom 100,000 are at risk of losing vision in 1 or both eyes due to choroidal neovascularization (CNV). CNV associated with the ocular histoplasmosis syndrome is a visionthreatening complication that primarily affects working-age adults.

The etiology of ocular histoplasmosis is believed to begin with systemic infection with H. capsulatum via the respiratory tract, resulting in a mild upper respiratory-type infection. Although no serologic confirmation of H. capsulatum infection in patients with ocular histoplasmosis has been reported, it is generally believed that asymptomatic focal infection of the choroid occurs at the time of the initial benign systemic infection. This focal infection may resolve as an atrophic scar that disrupts Bruch’s membrane. However, the infection may affect the retinal pigment epithelium and choriocapillaris and can result in serous and hemorrhagic retinal detachments associated with CNV. The initiator for CNV development is unknown and likely multi-factorial as genetic predisposition, immune system function, and initial inoculum of the fungus each may play a role.

DIAGNOSIS

Clinical signs and symptoms

The diagnosis of ocular histoplasmosis can be made on a clinical basis when findings of the classic triad of peripapillary chorioretinal scarring, punched-out ‘inactive’ chorioretinal scars, and hemorrhagic or neurosensory macular lesions or disciform macular scars are noted. In addition, there is a complete absence of vitreous inflammation.

Because chorioretinal scars are usually asymptomatic, it is usually not until CNV compromises the fovea that individuals seek ophthalmologic attention. The presenting symptoms in most patients are blurred central vision, metamorphopsia, micropsia, and central scotomas.

attempts at treating the disease with antimycotics failed and were abandoned. Although systemic corticosteroids were widely used at one time, oral steroids have not shown to be beneficial in treating CNV associated with ocular histoplasmosis and this type of treatment is not routinely used.

Ocular

Laser photocoagulation

In randomized clinical trials, the Macular Photocoagulation Study demonstrated that argon and krypton laser photocoagulation is effective in treating extrafoveal and juxtafoveal CNV lesions secondary to ocular histoplasmosis. From 1 year through 5 years of follow-up, 10% of eyes treated with laser photocoagulation versus approximately 40% of observed eyes had visual acuity that was six or more lines worse than at baseline. Thermal laser photocoagulation is not recommended for subfoveal CNV lesions given the immediate visual loss that results from a foveal scotoma.

Photodynamic therapy with verteporfin

Photodynamic therapy with verteporfin (Visudyne©; Norvartis Ophthalmics, Basel, Switzerland), termed verteporfin therapy, was developed as an alternative to thermal photocoagulation for the treatment of subfoveal CNV. A large randomized clinical trial confirmed the benefit of verteporfin therapy for CNV in age-related macular degeneration. Unlike laser photocoagulation, verteporfin therapy has been shown to selectively occlude vessels of experimentally induced CNV in animal models with minimal effects on the overlying retina and underlying choroid. Two-year results from an uncontrolled clinical study of 26 patients with ocular histoplasmosis revealed improvement of visual acuity from baseline as well as an absence of serious adverse events.

Surgery

The Submacular Surgery Trials (SST) Group H Trial was a randomized trial to compare surgical removal vs observation of subfoveal CNV lesions due to ocular histoplasmosis or idiopathic causes. Although the findings from the SST Group H do not support submacular surgery in similar patients with an initial visual acuity of 20/100 or better, surgery should be considered when presenting visual acuity is worse than 20/100. Quality-of-life findings were consistent with a beneficial affect of surgery.

Laboratory findings

In a large portion of the Ohio and Mississippi River valleys, 60% or more of the adult population reacts positively to histoplasmin skin testing; thus a positive skin test is not proof of ocular histoplasmosis. Additional ancillary studies, such as serologic testing, are also not helpful, and the diagnosis is primarily made clinically when the patient presents with visual symptoms and ocular findings that are consistent with ocular histoplasmosis. Fluorescein angiography is used to assess for CNV and guide the physician with clinical treatment.

TREATMENT

Systemic

Although H. capsulatum is postulated but not proven to play a direct role in the development of ocular histoplasmosis,

SUMMARY

The diagnosis of presumed ocular histoplasmosis is made primarily by finding the typical clinical findings of peripapillary scarring, chorioretinal scars, and a serous or hemorrhagic detachment of the macula. Loss of central vision is caused by the development of CNV. Laser photocoagulation has proved to be effective in the treatment of extrafoveal and juxtafoveal CNV lesions, and verteporfin therapy has been effective and safe in a small case series of subfoveal CNV patients.

Although the risk of CNV in the second eye is less than 2% per year, there is no evidence that the risk diminishes over time. Patients who have CNV in one eye should be counseled regarding the lifetime risk of CNV developing in the second eye and the need to consult the ophthalmologist if any visual symptoms are noted in the fellow eye.

infections. Medications that have been used, depending on patient symptoms, include:

●Artificial tears;

●Antihistamine drops as needed for severe itching;

●Antibiotics if mucopurulent discharge or uncertain diagnosis;

●Non-steroidal anti-inflammatory drops (diclofenac, ketorolac);

●Cidofovir (shown effective in early studies, but with concerning lacrimal stenosis toxicity, thus development was abandoned in the US and not FDA approved).

Supportive

This is the usual treatment of choice in most cases. It generally consists of:

●Patient education regarding the expected time course until resolution of symptoms and the rare occurrence of serious complications;

●Cold compresses to the eyelids as needed;

●Antipyretics as needed;

●Hand washing before and after contact with the eye or other respiratory secretions;

●Cleaning or disposal of pillow cases, towels, tissues or other surfaces that contact the eye.

Kaye SB, Lloyd M, Williams H, et al: Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis. J Med Virol 77:227– 231, 2005.

Kinchington PR, Romanowski EG, Gordon YJ: Prospects for adenovirus antivirals. J Antimicrobial Chemotherapy 55:424–429, 2005.

Koidl C, Bozic M, Mossböck G, et al: Rapid diagnosis of adenoviral keratoconjunctivitis by a fully automated molecular assay. Ophthalmology 112:1521–1527, 2005.

Kojaoghlanian T, Flomenberg P, Horwitz MS: The impact of adenovirus infection of the immunocompromised host. Rev Med Virol 13:155–171, 2003.

Hillenkamp J, Reinhard T, Ross RS, et al: The effects of cidofovir 1% with and without cyclosporin A 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study. Ophthalmology 109:845–850, 2002.

Pavan-Langston D: Viral diseases of the cornea and external eye. In: Albert DM, Jakobiec FA, eds. Principles and practices of ophthalmology. 2nd edn. Philadelphia, WB Saunders, 2000:878–879.

Shenk T: Adenoviridae. In: Knipe DM, Howley PM, eds: Fields virology. Philadelphia, Lippincott-Williams & Wilkins, 2001:2265–2228.

Uchio E, Ishiko H, Aoki K, Ohno S: Adenovirus detected by polymerase chain reaction in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis. Am J Ophthalmol 134:618–619, 2002.

Vastine DW, Wilner BI: Adenoviridae. In: Darrell RW, ed: Viral diseases of the eye. Philadelphia, Lea & Febiger, 1985:131–146.

PRECAUTIONS

Human adenoviral infections are highly contagious and have been implicated in several epidemic outbreaks.

Concern for chronic infections and delayed transmission of viral pathogens are supported by isolation of different serotypes of adenovirus in feces or tear secretions of patients months to years after onset of symptoms. These patients tended to have a more severe presentation and were more likely to have been prescribed topical steroids early on in their disease course.

Topical ophthalmic medication bottles may provide an additional mechanism for viral spread, especially to patient family members. This may be a reason to limit the use of topical medication according to the patient’s symptoms and to counsel patients regarding the high transmissibility of virus. In addition, patients should be counseled to consider a leave of absence for at least 2 weeks, especially those with close contact with coworkers (schools, nursing homes, military housing or summer camps) or those providing healthcare to immune-compromised patients.

36 PNEUMOCOCCUS 041.2

(Streptococcus pneumoniae)

F. Hampton Roy, MD, FACS

Little Rock, Arkansas

ETIOLOGY/INCIDENCE

Commonly known as pneumococcus, Streptococcus pneumoniae is a gram-positive, lancet-shaped coccus characteristically appearing as diplococcus but occasionally appearing singly or as short chains. The normal habitat of the pneumococcus is the upper respiratory tract of humans; it is also present in the eyes of a small percentage of healthy individuals.

Pneumococcus is the primary etiologic agent in all types of pneumonia and the most frequent cause of otitis media in children; the organism also has been implicated in meningitis and septicemia. Pneumococcal infection is spread through aerosol dispersal of droplets released by infected persons.

SUMMARY

Pharyngoconjunctival fever (PCF) is one of several disease presentations of ocular adenoviral infection that tends to be selflimited and typically responds well to supportive treatment alone. Consistent hand washing and other hygiene methods seem to be the most effective ways to reduce the incidence and spread of PCF to close contacts.

REFERENCES

Elnifro EM, Cooper RJ, Klapper PE, et al: Diagnosis of viral and chlamydial keratoconjunctivitis: which laboratory test? Br J Ophthalmol 83:622– 627, 1999.

DIAGNOSIS

Clinical signs and symptoms

Pneumococcal pneumonia is often preceded by an upper respiratory infection.

Systemic

●Sudden onset.

●Shaking chills.

●Fever.

●Sharp pain in the involved hemithorax.

●Cough with early sputum production.

●Headache.

●Gastrointestinal symptoms.