Clinicopathologic Reports, Case Reports, and Small Case Series
December 2002

Endogenous Fungal Retinitis in a Patient With Acute Lymphocytic Leukemia Manifesting as Uveitis and Optic Nerve Lesion

Author Affiliations

Copyright 2002 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2002

Arch Ophthalmol. 2002;120(12):1754-1756. doi:

Ocular infections continue to be an increasingly common complication in immunosuppressed patients. Endophthalmitis has been reported in immunosuppressed patients and patients who use intravenous drugs. Candida albicans is the most frequent cause of endogenous mycotic endophthalmitis.1 Other organisms include the Aspergillus and Fusarium species, Cryptococcus neoformans, Coccidioides immitis, Sporotrichum schenckii, Blastomyces dermatitidis, and Histoplasma capsulatum.1 Nonfungal organisms, such as the Pseudomonas and Salmonella species, may also cause endophthalmitis in immunosuppressed individuals.2

Ocular signs may be the first manifestation of leukemia or may be a manifestation of relapsed leukemia. Although the choroid is the most frequently affected ocular site in histopathologic studies,3 choroidal involvement may not be evident clinically. Leukemic retinopathy, infiltrates, microaneurysms, orbital and eyelid involvement,3,4 leukemic hypopyon,5 retinal detachment,6 and optic nerve head infiltration by leukemic cells7 have also been reported. Optic nerve involvement occurs mainly in children with acute lymphocytic leukemia.3 It is occasionally seen on routine examination without ocular complaints such as pain.7 Edema, hemorrhage, and retrolaminar infiltration of the optic nerve head may be present. In the case of leukemic optic nerve involvement, radiation therapy should be initiated promptly.7

Report of a Case

A 3-year-old boy was referred to the Bascom Palmer Eye Institute (Miami, Fla) for decreased vision in the left eye and esotropia of 2 days. Two months prior to this examination, the patient was diagnosed as having acute lymphocytic leukemia without central nervous system involvement. He had undergone 2 uneventful courses of induction therapy, including dexamethasone and intrathecal methotrexate. During the course of treatment, the patient was hospitalized for fever and pneumonia and candidal skin infections. The results of all fever work-ups were negative.

Four weeks prior to our examination, at the end of his induction course, the patient had a red, painless left eye. He was diagnosed as having anterior uveitis of the left eye and was treated with 1% topical prednisolone acetate. The patient started receiving systemic dexamethasone. The day prior to our examination, the patient was noted to have esotropia and stated that he could not see from his left eye. The patient did not have any systemic complaints. He denied headache, nausea, or vomiting.

On examination, the child was afebrile, with a visual acuity of 20/25 OD and no light perception OS. Twenty prism diopters of esotropia was noted with full motility. An amaurotic 4+ relative afferent pupillary defect of the left eye was present. The left cornea disclosed mild, diffuse anterior stromal haze with 360° of posterior synechia. There was no hypopyon. The right eye was unremarkable.

Indirect ophthalmoscopy of the left eye through a small pupil disclosed 3+ vitreous haze. The right eye was unremarkable. Echography revealed dense vitreous opacities and a pedunculated retinal lesion anterior to the optic nerve head, with subretinal extension (Figure 1). Results of magnetic resonance imaging of the brain and orbits, using gadolinium contrast medium, were consistent with a lesion anterior to the left optic nerve head without central nervous system involvement.

Figure 1.
Image not available

Echography of the left eye reveals a pedunculated lesion anterior to the optic nerve head. Adjacent subretinal involvement is present.

Examination with the patient anesthetized revealed a yellow, creamy pedunculated retinal lesion adjacent to the anterior optic nerve head, with a dense overlying vitritis (Figure 2). Fungal endophthalmitis was suspected, and enucleation of the left eye with implantation of a hydroxyapatite implant was performed.

Figure 2.
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Examination under anesthesia reveals a yellow pedunculated retinal lesion adjacent to the optic nerve head, with a dense vitritis in the left eye (RetCam 120, Massey Research, Dublin, Calif).

A specimen of the enucleated eye and the lesion were sent for culture. Enucleation was selected as the diagnostic, therapeutic surgery of choice because of the absence of light perception and the possibility of an intraocular malignancy. The remainder of the tissue was placed in 10% neutral buffered formalin, processed, and sectioned serially through the retinal lesion. Blood cultures were obtained.

Gross examination of the left eye disclosed an endophytic yellow retinal mass in the posterior pole anterior to the optic nerve head (Figure 3). Light microscopic examination of the left eye disclosed an endophytic peripapillary retinal lesion measuring 5.0 mm in height and 4.0 mm in base. The lesion contained fungal elements, a focus of central necrosis, and an acute and chronic inflammatory cell infiltrate. An acute and chronic inflammatory cell infiltrate was present over the apex of the lesion, with extension into the vitreous. No leukemic cells were identified (Figure 4A and B). The iris, angle, ciliary body, and lens were unremarkable. The inner retina contained a chronic inflammatory cell infiltrate in the area of the lesion. Retinal vasculitis was focally present. The choroid, sclera, and optic nerve were unremarkable.

Figure 3.
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Gross examination after enucleation discloses a yellow retinal mass anterior to the optic nerve head.

Figure 4.
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A, Histopathologic examination of the left eye discloses an endophytic fungating retinal lesion with superficial extension into the optic nerve (hematoxylin-eosin; original magnification ×2). B, At the apex of the lesion, a moderate number of acute inflammatory cells extends into the vitreous cavity (hematoxylin-eosin; original magnification ×10). C, A dense collection of fungal elements within the retinal lesion was present (gomori methenamine silver; original magnification ×4). D, High-power micrograph of the fungal elements within the retinal lesion (gomori methenamine silver; original magnification ×40).

Gomori methenamine silver stain disclosed a dense collection of fungal elements suggestive of candidal infection (Figure 4C and D). Cultures of the intraocular contents at the time of enucleation were negative for organisms as were 2 blood cultures. A systemic work-up for possible sources of fungus was negative, with the exception of a resolved cutaneous candidal infection.


Intraocular fungal infections are uncommon. Fungal endophthalmitis has been most commonly reported in immunosuppressed individuals and patients who use intravenous drugs. The most common organisms are from the Candida species. Candida endophthalmitis has been reported as a complication of disseminated fungal infection in a patient with acute nonlymphocytic leukemia.8

Leukemic recurrences are rare and may be indicated by retinal vessel changes, hemorrhages, and leukemic infiltration. Of 657 children diagnosed as having acute leukemia, 52 (9%) had ocular abnormalities. Retinal hemorrhages were present in 19 (37%) of 52 patients. Invasion of the optic nerve, retina, iris, or orbit occurred in 29 (56%) of those patients.4

In our patient, the presence of a retinal lesion with overlying vitritis was discovered after a thorough ocular examination. This patient had retinal infiltration with fungal elements, retinal, and subretinal infiltration of acute and chronic inflammatory cells, necrosis, and retinal vasculitis. Optic nerve infiltration has been reported to occur mainly in children with acute leukemia, particularly in acute lymphocytic leukemia.9,10 Because of the vitritis and the intraocular mass in an immunocompromised patient, an opportunistic ocular infection was suspected.

A diagnostic enucleation was performed to determine whether the ocular mass contained leukemic cells, infectious organisms, such as fungus, or both. A globe-conserving biopsy would likely not have revealed positive cultures and would have been interpreted as nondiagnostic, leading to a therapeutic dilemma (in the face of negative cultures from direct enucleation of a portion of the lesion and surrounding ocular tissue). A patient with acute lymphocytic leukemia with both endogenous Fusarium endophthalmitis and leukemic ocular infiltrates has been reported.1

Our patient showed no evidence of central nervous system leukemic involvement and no evidence of leukemic recurrence. He had a history of a skin rash secondary to Candida, which presumptively was felt to be the source of infection.

This case demonstrates the importance of careful ophthalmic examination of immunosuppressed patients, particularly those undergoing chemotherapy for hematologic malignancies. Distinguishing between infectious and neoplastic recurrence in patients with hematologic malignancies may be difficult and requires careful clinical evaluation as well as systemic work-up to ascertain the cause.

Corresponding author and reprints: Timothy Murray, MD, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, PO Box 016880, Miami, FL 33101.

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