Coccidioides immitis Chorioretinitis

Coccidioides immitis is a dimorphic fungus. The disease is endemic in the semiarid areas of the southwestern United States and Mexico. The area affected most heavily is the San Joaquin valley of central California. Cases of coccidioidomycosis, however, have been found in almost every state in the United States in persons who have at one time lived or traveled through an endemic area. The disease has also been reported in Hawaii, Canada, Central and South America, Italy, and the Balkan countries. The disease is transmitted to humans by inhalation of the arthroconidia stages in the saprophytic phase of the organism’s life cycle

Fig. 9.27 Light microscopy reveals cryptococcal organisms with their characteristic mucopolysaccharide capsule. (Reprinted with permission from Khodadoust, AA, Payne JW. Cryptococcal “torular” retinitis: a clinicopathologic case report. Am J Ophthalmol. 1969,67:745–750)

from dry dust arising from contaminated soil [42]. Coccidioides immitis has rarely been proved to cause ocular disease.

Risk Factors

The general population is susceptible to coccidioidomycosis because the major risk factor is exposure to the arthroconidia of the mycelial phase of C. immitis. However there are some risk factors for ocular compromise including:

•Dissemination of primary coccidioidal lesion. Systemic coccidioidomycosis becomes manifest as an asymptomatic subclinical infection, an acute self-limited pulmonary flu-like disease (primary pulmonary), a chronic pulmonary disease (persistent pulmonary), or a disseminated condition with involvement of the lungs and extrapulmonary lesions in skin, joints, bones, and meninges.

•Pregnant women contracting coccidioidomycosis are at significant risk of developing severe or disseminated disease.

•Patients with immunosuppression [43].

Pathogenesis

Coccidioides immitis produces pyogenic, granulomatous, and mixed reactions [44]. Fibrosis, necrosis, and calcification can occur. Miliary retinal and choroidal granulomas may result by distribution of the endospores via the ophthalmic artery (Fig. 9.28).

Fig. 9.28 (a) Focal granuloma in the fundus of a man who died of disseminated coccidioidomycosis. (b) Multiple spherule-containing endospores (arrow). (Modified and

reprinted with permission from Boyden BS, Yee D. Trans Am Acad Ophthalmol Otolaryngol, 1971; 75:1006–1100)

Fig. 9.29 (a) Right fundus photograph shows a small choroidal lesion superotemporal to the fovea (arrow) and mild papilledema. (b) Left fundus photograph shows two choroidal lesions, one superonasal to the optic nerve head and one inferotemporal to the fovea

(arrows). Mild papilledema is also evident. (Modified and reprinted with permission from Cunningham ET Jr, Seiff SR, Berger TG, et al. Intraocular coccidioidomycosis diagnosed by skin biopsy. Arch Ophthalmol. 1998;116:674–677)

Clinical Features

Approximately 40% of infected individuals are symptomatic. The vast majority of symptomatic patients present upper respiratory tract infection. Ocular coccidioidomycosis is rare and may affect either the anterior or posterior segment of the eye producing blepharitis, phlyctenular conjunctivitis, episcleritis, scleritis, iridocyclitis, choroiditis, and chorioretinitis. The typical posterior infection is a multifocal choroiditis with numerous scattered, discrete, yellow-white lesions less than a disk diameter in size [44]. Large juxtapapillary choroidal infiltrates with variable involvement of the overlying retina may be associated with retinal edema and hemorrhage, and small peripheral chorioretinal scars with central hypopigmentation resembling presumed ocular histoplasmosis scars (Fig. 9.29). Miliary retinitis with multiple retinal granulomata has also been reported. Vitritis may be associated with vitreous cells and infiltrates overlying the chorioretinal lesion. C. immitis may also primarily affect the optic nerve.

Diagnosis

A history of travel to an endemic area may provide a clue to the diagnosis. If the diagnosis is highly suspected, the laboratory workup includes characterization and quantification of anticoccidioidal antibodies in serum and a coccidioidin skin test. Skin and serologic testing provide strong evidence for prior exposure to C. immitis but

alone do not confirm the presence of disseminated or intraocular disease.

Histopathologic or culture identification of C. immitis in anterior chamber, vitreous, or chorioretinal specimens is the most direct method to diagnose intraocular infection, but intraocular biopsy is not without risk. In contrast, biopsy of skin lesions has low morbidity and can provide definitive evidence for disseminated disease [45].

Antibodies to two antigens of C. immitis are of particular interest: a tube-precipitating (TP) reacting seroprotein (an IgM) and a complement fixing (CF) antibody (an IgG). The level of CF antibody is directly proportional to the extent of the disease. A positive CF antibody test in dilutions greater than 16-fold indicates extrapulmonary disseminated disease. Rising titers of both antibodies indicate a worsening prognosis, and falling titers indicate improvement.

Treatment

Amphotericin B is the drug of choice for treatment of chronic pulmonary and disseminated coccidioidomycosis [45]. With isolated vision-threaten- ing ocular infections, more aggressive treatment may be warranted, including intracameral or intravitreal injection of amphotericin B and pars plana vitrectomy. Ketoconazole, fluconazole, and itraconazole can also be used in combination with or following treatment with amphotericin B.