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Small Case Series
May 11, 2009

Intraocular Cryptococcoma

Arch Ophthalmol. 2009;127(5):700-702. doi:10.1001/archophthalmol.2008.620

Cryptococcus neoformansis a ubiquitous, encapsulated fungus that can enter the body through inhalation and spread hematogenously to end organs, most commonly the brain. The most common ophthalmic manifestation of cryptococcosis is secondary to cryptococcal meningitis or meningoencephalitis.1Cryptococcusneoformanscan also cause conjunctivitis, iritis, choroiditis, chorioretinitis, vitritis, and endophthalmitis.2In this article, we describe the presentation, ultrasound characteristics, and management of 2 patients with subretinal cryptococcal mass lesions, cryptococcomas.

Report of Cases
Case 1

A 63-year-old Honduran man who did not have human immunodeficiency virus was referred for redness, photophobia, pain, and decreased vision of the right eye for 5 months, which had been followed by progressive anorexia, weight loss, and high fevers. He was diagnosed as having disseminated cryptococcosis with associated skin, central nervous system, and bilateral adrenal abscesses. At the time of referral, he had been an inpatient for 2 of the previous 3 months and had received intravenous liposomal-soluble amphotericin B and flucytosine.

Visual acuity was light perception in the right eye and 20/20 OS. There was a relative afferent pupillary defect in the right eye. The right eye revealed moderate conjunctival injection, as well as moderate anterior chamber cell and posterior synechiae. There was diffuse vitritis with a creamy yellow, indistinct mass in the posterior pole. Examination of the left eye was unremarkable. Ultrasonography of the right eye confirmed the presence of diffuse vitreous opacities and a dome-shaped, subretinal lesion involving the choroid with regular structure and low reflectivity that measured 5.5 mm × 6.5 mm × 9.5 mm and an associated localized retinal detachment (Figure 1A and B). Systemic antifungal therapy with intravenous liposomal-soluble amphotericin B (4 mg/kg/d) and flucytosine (100 mg/kg/d) was continued. A vitrectomy was performed with intravitreal injection of 5 μg of amphotericin B. The vitreous aspirate contained multiple oval yeast forms that stained positively with periodic acid–Schiff, Gomori methanamine silver, and mucicarmine (Figure 2A); immunohistochemical analysis was also positive for Cneoformans(Figure 2B). Vitreous microbiological cultures were negative. After vitrectomy, a clearer view of the macular mass lesion was obtained and revealed associated multifocal smaller subretinal lesions (Figure 1C). The eye continued to be painful. Another pars plana vitrectomy was performed 10 days after initial vitrectomy with retinal biopsy, debridement of the subretinal abscess, and intravitreal injection of amphotericin B (5 μg). Microbiological cultures were negative, but pathological analysis revealed diffuse encapsulated yeast forms within the abscess.

Figure 1.
Ultrasonography of the right eye. A, B-scan ultrasonogram demonstrates vitreous opacities and a dome-shaped mass with overlying retinal detachment. B, A-scan ultrasonogram demonstrates regular structure and low reflectivity. C, Fundus photograph shows vitritis and a large macular mass with many smaller subretinal lesions. D, Fundus photograph taken after treatment shows scarring without active inflammation.

Ultrasonography of the right eye. A, B-scan ultrasonogram demonstrates vitreous opacities and a dome-shaped mass with overlying retinal detachment. B, A-scan ultrasonogram demonstrates regular structure and low reflectivity. C, Fundus photograph shows vitritis and a large macular mass with many smaller subretinal lesions. D, Fundus photograph taken after treatment shows scarring without active inflammation.

Figure 2.
A, Oval yeast forms with a mixed inflammatory cell infiltrate and vitreous strands (periodic acid–Schiff, original magnification ×1000). B, Positive immunohistochemical labeling of cryptococcal organisms (anti-Cryptococcuspolyclonal antibody, original magnification ×1000).

A, Oval yeast forms with a mixed inflammatory cell infiltrate and vitreous strands (periodic acid–Schiff, original magnification ×1000). B, Positive immunohistochemical labeling of cryptococcal organisms (anti-Cryptococcuspolyclonal antibody, original magnification ×1000).3

Intravitreal injections of amphotericin B (5 μg) were given approximately twice a week for 2 months until the vitreous inflammation decreased, the mass lesions subsided, and the eye was no longer painful. In addition, the patient completed a 12-week course of intravenous liposomal-soluble amphotericin B and flucytosine. Near the completion of this treatment course, the posterior pole lesion was fibrotic (Figure 1D), and vision had improved to counting fingers at 1 ft.

Case 2

A 74-year-old man was referred after a routine evaluation for spectacles revealed a retinal mass in his left eye. Seven months previously, he underwent chemotherapy and a lobectomy for lung cancer. Three months previously, he was hospitalized for cryptococcal meningitis and treated with intravenous fluconazole for 2 weeks followed by oral fluconazole for 2 weeks. Best-corrected visual acuity was 20/25 OD and 20/40 OS. There was no afferent pupillary defect. Results of anterior segment evaluation were unremarkable in both eyes, except for early cataracts present in both eyes. A dilated fundus examination revealed an unremarkable right eye. In the left eye, there was moderate vitritis with a creamy yellow, subretinal mass at the 10:30-clock position posterior to the equator that extended into the far periphery (Figure 3A). The optic nerve head and macula in the left eye were unremarkable. Ultrasonography showed a regularly structured dome-shaped lesion with low to medium reflectivity that measured 2.3 mm × 8.0 mm × 9.5 ×mm (Figure 3B and C). Given the patient's recent cryptococcal meningitis, an infectious process was considered as a possible cause. A metastatic lesion and decolorized subretinal hemorrhage were also considered as diagnoses.

Figure 3.
A, Fundus photograph shows vitritis and a subretinal mass. B, B-scan ultrasonogram demonstrates a dome-shaped mass. C, A-scan ultrasonogram demonstrates regular structure and low to medium reflectivity. D, Fundus photograph taken after treatment shows scarring without active inflammation.

A, Fundus photograph shows vitritis and a subretinal mass. B, B-scan ultrasonogram demonstrates a dome-shaped mass. C, A-scan ultrasonogram demonstrates regular structure and low to medium reflectivity. D, Fundus photograph taken after treatment shows scarring without active inflammation.

A pars plana vitrectomy with biopsy of the lesion was performed. The inner surface was a thin membrane continuous with the retina. The underlying retinal pigment epithelium and choroid appeared intact. The abscess was debrided by cutting and aspiration. After demarcation with endolaser, a partial fluid-air exchange was performed and 50 μg of voriconazole was injected intravitreally. Microbiological cultures yielded C neoformanssensitive to voriconazole, amphotericin B, fluconazole, and ketoconazole. The patient then completed a 6-week course of oral fluconazole (400 mg daily) without recurrence. Three months postoperatively, visual acuity was 20/50 OS, and a fundus examination revealed clear media with a large, inactive chorioretinal scar with surrounding fibrosis and atrophic laser scars (Figure 3D).

Comment

Ocular cryptococcal mass lesions are rare and have been described involving the conjunctiva, limbus,4and iris. In 1976, an article in the German literature2described an enucleated eye with a large cryptococcoma involving the vitreous, ciliary body, iris, and lens with total retinal detachment.

The current series describes cryptococcal mass lesions within the subretinal space treated successfully without enucleation. Although ultrasonographic examination revealed characteristics similar to those seen with choroidal melanoma, with regular structure and low to medium internal reflectivity on an A-scan ultrasonogram, the cryptococcoma reflectivities were less than those classically observed with choroidal melanomas. In addition, the cryptococcoma in patient 1 was similar to a choroidal melanoma because it demonstrated a collar-button shape with adjacent localized retinal detachment.

In contrast to treatment of multifocal choroiditis caused by Cneoformans,5surgical debridement of mass lesions of the subretinal space may be indicated to eradicate the disease. In both of the current cases, systemic medical antifungal therapy was insufficient. Both patients underwent abscess drainage during pars plana vitrectomy. In addition, this allowed definitive diagnosis by microbiological cultures in one case and histopathological analysis in the other, as has been reported previously.1,4In cases in which debridement of the abscess and systemic treatment do not resolve the infection, as in patient 1, supplementary intravitreal injections of antifungal medication may be helpful.

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Article Information

Correspondence: Dr Albini, Bascom Palmer Eye Institute, 900 NW 17th St, Miami, FL 33136 (TAlbini@med.miami.edu).

Financial Disclosure: None reported.

Funding/Support: This study was supported by an unrestricted grant to the University of Miami from Research to Prevent Blindness.

References
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Ehrhorn  JGrosse  GStaib  FWollensak  J Intraocular cryptococcosis [in German]. Klin Monatsbl Augenheilkd 1976;168 (4) 577- 583
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Moskowitz  LBGanjei  PZiegels-Weissman  JCleary  TJPenneys  NSNadji  M Immunohistologic identification of fungi in systemic and cutaneous mycoses. Arch Pathol Lab Med 1986;110 (5) 433- 436
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Fine  HFChang  MADunn  JP  Jr Bilateral cryptococcal choroiditis. Arch Ophthalmol 2004;122 (11) 1726- 1727
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