Ocular Coccidioidomycosis

Ocular Coccidioidomycosis

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Coccidioidomycosis is a disease caused by Coccidioides immitis, a dimorphic fungus that thrives in the lower Sonoran Desert ecozone of the Western hemisphere. Coccidioidal uveitis should be considered in any patient with apparent idiopathic iritis who has lived or traveled through endemic areas, including Arizona, New Mexico, west Texas, parts of Central America, Argentina, northwest Mexico, and the San Joaquin Valley in California. [1]

The warm, dry climate and sandy, saline soil are ideal for growth of the mycelial phase of the fungus. The mold forms hyphae of 2-4 mm, which consist of chains of arthroconidia that later germinate under moist conditions. During dry seasons, winds spread the highly infectious arthrospores and infection occurs through inhalation of contaminated dust. No documented cases of animal-to-human or human-to-human transmission have occurred.

Ocular involvement occurs secondary to dissemination and is considered rare. [2] The eyelids and conjunctiva are the most common sites. The skin of the eyelids may contain granulomatous foci of Langerhans giant cells and coccidioidal spherules. [3] Phlyctenular conjunctivitis may be seen and represents a hypersensitivity reaction. [1] True mycotic granulomas of the conjunctiva are less common than hypersensitivity conjunctivitis and usually are seen in the presence of skin lesions.

The uvea is the most common site of intraocular disease. A granulomatous iridocyclitis with iris nodules and posterior synechiae may be seen. [4] However, the typical infection is a multifocal choroiditis with many discrete, yellow-white lesions less than a disc diameter in size. [5, 6, 7, 8, 9]

Also see Coccidioidomycosis and Dermatologic Manifestations of Coccidioidomycosis.

Vitreitis, vasculitis, serous retinal detachment, and retinal haze may occur in the acute phase. Typical coccidioidal granulomas with spherules are seen in the choroid on histopathology. [10] Lesions also have been noted within the optic nerves. One histopathologically documented case of intraretinal granulomas and organisms that occurred in a previously healthy 12-year-old child has been reported. [11]

Choroidal neovascularization may occur in areas of scarring. Secondary glaucoma may occur from inflammation and its sequelae. Retinal seeding from anterior disease may occur following vitrectomy. [12]

Presenting visual acuity of patients reported in the literature ranges from 20/20 to 20/200. [13, 3] Final visual acuity ranges from 20/20 to no light perception, depending on severity, time to diagnosis, and patient compliance with medical therapy and follow-up care.

The true incidence of ocular coccidioidomycosis is unknown. [14] However, in one series of 10 patients with disseminated coccidioidomycosis, 4 developed evidence of choroidal infection over a 12-month period of observation. [1]

The prognosis depends on the degree of choroidal involvement and seems to be related to initial visual acuity and initial systemic severity of disease. Typical choroidal scars have been found in patients with mild respiratory infection and in those with more extensive disease. [2] The prognosis in patients with severe ocular coccidioidomycosis is often poor. Most eyes require enucleation due to pain and blindness despite aggressive treatment. [15]

Patients must be made aware that ocular coccidioidomycosis may reactivate years later. Additionally, because choroidal neovascularization can occur in areas of scarring and may lead to blindness, patients must understand the importance of yearly follow-up care, including a dilated fundus examination.

Ocular history includes the following:

Pain

Redness

Photophobia

Decreased vision

Tearing

Foreign body sensation

Floaters

Lid swelling

Scotoma

The physical examination should include the following:

Eyelids – Lid granuloma

Conjunctiva – Phlyctenular or follicular conjunctivitis, conjunctival granuloma

Sclera – Episcleritis or scleritis

Cornea – Keratitis, granulomatous mutton-fat keratic precipitates

Anterior chamber – Cell and flare

Iris – Nodules

Lens – Cataract, seclusio pupillae (complete adhesion along the pupillary margin)

Intraocular pressure – Elevation (secondary glaucoma)

Vitreous – Vitreitis

Retina – Edema, exudate, hemorrhage, serous retinal detachment

Retinal vessels – Vascular sheathing

Several groups of findings have been reported for the choroid, as follows:

Diffuse choroiditis (usually seen in preterminal patients)

Large (400-1000 µm) juxtapapillary infiltrates involving the choroid, with variable involvement of the overlying retina

Medium (150-400 µm) spherical opacities at the level of the Bruch membrane and sensory retina

Small (100-200 µm) peripheral chorioretinal scars of variable elevation and pigmentation with central hypopigmentation

Differentials to consider in the diagnosis of ocular coccidioidomycosis include the following:

Endophthalmitis, Fungal

Episcleritis

Presumed Ocular Histoplasmosis Syndrome

Intermediate uveitis

Actinomycosis

Conjunctivitis, allergic

Glaucoma, uveitic

Herpes simplex

Retinal detachment, exudative

Sarcoidosis

Scleritis

Tuberculosis

Anterior granulomatous uveitis

Disseminated Candida

Disseminated cryptococcosis

Disseminated blastomycosis

Ocular manifestations of syphilis

Aspergillus endophthalmitis

Fluorescein angiography (FA) is not recommended in the initial workup, because it will not help in the differential or initial management. However, if performed, active lesions show late staining.

FA is helpful in evaluating choroidal neovascularization that may develop over time in areas of scars where the Bruch membrane is compromised.

Tissue biopsy with fungal smears and culture can be valuable. Biopsy of skin lesions, if present, carries a lower morbidity than aqueous or vitreous aspiration or chorioretinal biopsy. Therapeutic vitrectomy may be performed in conjunction with biopsy, depending on the severity of the vitreous involvement.

Patients with uveitis often have pulmonary or disseminated coccidioidomycosis disease and are typically hospitalized for intravenous antifungal therapy.

The treatment of intraocular coccidioidomycosis typically consists of intravenous amphotericin B therapy. The role of intraocular injections of this agent remains unclear. With systemic disease, much higher doses of intravenous amphotericin B may be needed. The role of systemic itraconazole in the treatment of intraocular coccidioidomycosis is unclear. Involvement of an infectious disease specialist is essential in these cases because it is often difficult to determine when systemic therapy may be discontinued. [15] Once the patient shows a clinical response to therapy, one may consider changing to an oral antifungal and outpatient management.

If an aqueous or vitreous tap is performed for diagnostic purposes, injection of an intraocular antifungal agent should be considered. Intracameral amphotericin B also should be considered in cases with vision-threatening uveitis.

Since ocular coccidioidomycosis represents disseminated disease, obtaining a thorough systemic evaluation in conjunction with an infectious disease specialist is paramount. This is especially true if neurologic impairment is suspected.

Patients with uveitis should be seen frequently. Check visual acuity, intraocular pressure, and activity of choroidal lesions and grade anterior chamber and vitreous inflammation. Follow-up care may be spaced according to clinical improvement.

Patients should receive follow-up care at yearly intervals to screen for active lesions. One case report in the literature documents ocular coccidioidomycosis occurring 22 years after primary infection and 9 years after a unilateral pars planitis that had been treated with cryotherapy.

Rodenbiker HT, Ganley JP. Ocular coccidioidomycosis. Surv Ophthalmol. 1980 Mar-Apr. 24(5):263-90. [Medline].

Rodenbiker HT, Ganley JP, Galgiani JN, Axline SG. Prevalence of chorioretinal scars associated with coccidioidomycosis. Arch Ophthalmol. 1981 Jan. 99(1):71-5. [Medline].

Cunningham ET Jr, Seiff SR, Berger TG, Lizotte PE, Howes EL Jr, Horton JC. Intraocular coccidioidomycosis diagnosed by skin biopsy. Arch Ophthalmol. 1998 May. 116(5):674-7. [Medline].

Bell R, Font RL. Granulomatous anterior uveitis caused by Coccidioides immitis. Am J Ophthalmol. 1972 Jul. 74(1):93-8. [Medline].

Boyden BS, Yee DS. Bilateral coccidioidal choroiditis. A clinicopathologic case report. Trans Am Acad Ophthalmol Otolaryngol. 1971 Sep-Oct. 75(5):1006-10. [Medline].

Holland GN. Endogenous fungal infections of the retina and choroid. Retina. 1989. 2:631-2.

Lamer L, Paquin F, Lorange G, Bayardelle P, Ojeimi G. Macular coccidioidomycosis. Can J Ophthalmol. 1982 Jun. 17(3):121-3. [Medline].

Morse PH. Coccidioidomycosis. Vitreoretinal Disease: A Manual for Diagnosis and Treatment. Mosby-Year Book; 1979. 370-1.

Zakka KA, Foos RY, Brown WJ. Intraocular coccidioidomycosis. Surv Ophthalmol. 1978 Mar-Apr. 22(5):313-21. [Medline].

Francois J, Rysselaere M. Coccidioidomycosis. Oculomycoses. Charles C Thomas Publisher: Springfield, Ill; 1972. 216-28.

Glasgow BJ, Brown HH, Foos RY. Miliary retinitis in coccidioidomycosis. Am J Ophthalmol. 1987 Jul 15. 104(1):24-7. [Medline].

Mondino KM, Holland GN, Glasgow BJ. Retinal seeding from anterior segment coccidioidomycosis after vitrectomy. Br J Ophthalmol. 2007 Jun. 91(6):837-8. [Medline].

Blumenkranz MS, Stevens DA. Endogenous coccidioidal endophthalmitis. Ophthalmology. 1980 Oct. 87(10):974-84. [Medline].

Increase in reported coccidioidomycosis–United States, 1998-2011. MMWR Morb Mortal Wkly Rep. 2013 Mar 29. 62(12):217-21. [Medline].

Moorthy RS, Rao NA, Sidikaro Y, Foos RY. Coccidioidomycosis iridocyclitis. Ophthalmology. 1994 Dec. 101(12):1923-8. [Medline].

Mark Ventocilla, OD, FAAO Adjunct Clinical Professor, Michigan College of Optometry; Editor, American Optometric Association Ocular Surface Society Newsletter; Chief Executive Officer, Elder Eye Care Group, PLC; Chief Executive Officer, Mark Ventocilla, OD, Inc; President, California Eye Wear, Oakwood Optical

Mark Ventocilla, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Optometric Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, University of Tennessee College of Medicine

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Retina Society, American College of Healthcare Executives, American Uveitis Society

Disclosure: Nothing to disclose.

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

L Raymond DeBarge, MD Assistant Professor, Department of Ophthalmology, University of Tennessee College of Medicine at Chattanooga

L Raymond DeBarge, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Physicians, American Medical Association, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Cynthia A Self, MD Eastern Maine Eye Associates, Bangor, ME

Cynthia A Self, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Cornea Society, Maine Medical Association, and Maine Society of Eye Physicians and Surgeons

Disclosure: Nothing to disclose.

Ocular Coccidioidomycosis

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