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Woman referred for retinal lesion, sudden decrease in vision
Dilated fundus exam revealed a large, slightly elevated macular lesion with retinal whitening, serous retinal detachment, edema and hemorrhage.
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A 40-year-old woman was referred to our office for decreased vision and a retinal lesion in her left eye. She reported decreased central vision and pain in her left eye for the past 24 hours but otherwise denied any significant ocular history and had not been seen for regular eye exams in the past.
Her medical history included hepatitis C, which had been identified on routine lab work and was otherwise asymptomatic, as well as depression and anxiety. She was an active smoker, drank socially and admitted active intravenous heroin use. Her only medication was Klonopin (clonazepam, Genentech).
Examination
In our office, the patient’s vision was 20/20 in the right eye and count fingers eccentrically in the left eye. Confrontation visual fields were full in the right eye and notable for a central defect in the left eye. Extraocular motility was full, and IOP was normal in both eyes. The patient was pharmacologically dilated at the time of presentation. Her anterior segment examination was notable for diffuse conjunctival injection of the left eye and mild pigmented anterior chamber cell in both eyes that was symmetric and likely secondary to dilation. Dilated fundus exam revealed a large, slightly elevated macular lesion with associated retinal whitening, serous retinal detachment, edema and hemorrhage (Figure 1a). A layered subretinal hypopyon was observed along the inferior extent of the lesion (Figure 1b).
Figure 1a. Yellow-white subretinal/retinal infiltrate with associated serous retinal detachment in the macula with edema and hemorrhage.
Images: Tawse KL, Duker JS
Figure 1b. Layered subretinal hypopyon at the inferior aspect of the serous retinal detachment.
Figure 2. Vertical cuts through the macular lesion on OCT demonstrated the subretinal nature of the lesion.
Optical coherence tomography confirmed the subretinal location of the lesion but failed to capture the layered hypopyon (Figure 2).
What is your diagnosis?
Subretinal infiltrate
The differential diagnosis for a subretinal infiltrate is large, but given the sudden onset, appearance of the lesion, degree of inflammation and patient’s active history of intravenous drug use, an infectious etiology, specifically endogenous bacterial or fungal endophthalmitis, was suspected.
Figure 3. PAS stain of the vitreous biopsy showed acute and chronic inflammatory cells as well as pseudohyphae without definite septations and a wide-angle branching pattern consistent with Candida.
On initial presentation, a vitreous tap was performed, and intravitreal voriconazole, vancomycin and ceftazidime were administered. The patient was admitted to the hospital, and blood cultures were sent before the initiation of broad-spectrum intravenous antibiotics. The initial vitreous tap remained culture negative, and no organisms were identified on Gram stain. Several indurated skin lesions were noted on the patient’s extremities during hospitalization. The tissue of one of these lesions on the left forearm was biopsied and sent for culture, which grew 2+ Klebsiella pneumoniae, 1+ other gram negative rods and 1+ Candida. Pathology from that biopsy revealed a deep fungal infection with visualization of round budding spores. Blood cultures remained negative.
During the course of the hospitalization, the patient’s vision continued to decline, and the initially minimal vitritis became much more impressive. She was taken to the operating room on the third day of hospitalization for pars plana vitrectomy, at which time vitreous and retinal biopsies were obtained and sent for both pathology and culture. Pathology of the vitreous biopsy revealed acute and chronic inflammatory cells with fungi present. Specifically, pseudohyphae without septations were visualized on PAS stain, consistent with Candida (Figure 3). Vitreous culture again was negative.
Discussion
Candida accounts for 75% to 80% of endogenous fungal endophthalmitis and is much more common in tropical climates. Risk factors for developing candidal endophthalmitis include, most commonly, intravenous drug use, as well as a recent history of gastrointestinal surgery, hyperalimentation, diabetes mellitus or indwelling catheters. Postpartum women and premature infants are also at risk. Clinically, patients with ocular candidiasis can be asymptomatic with small peripheral lesions or present with eye pain, redness, photophobia and decreased vision. The classic finding is the presence of indistinct yellow-white choroidal lesions with overlying vitreous inflammation that progresses to form fluffy balls of vitreous opacities linked by opalescent strands, giving a “string of pearls” appearance. The differential diagnosis for candidal endophthalmitis includes other fungal infections including Aspergillus and Coccidioides, as well as bacterial endophthalmitis, Nocardia, ocular tuberculosis, primary intraocular lymphoma, syphilitic chorioretinitis and cytomegalovirus retinitis. Vitreous tap and inject should be performed in all cases of suspected candidal endophthalmitis, and a low threshold for vitrectomy should be kept in cases of sight-threatening lesions or significant vitritis.
Our patient did not have the significant vitritis on presentation that is classic for Candida but rather presented with a yellow subretinal infiltrate and subretinal hypopyon, features that are typically more classic for Aspergillus. However, the pathology demonstrated pseudohyphae without septations and a wide-angle branching pattern that were characteristic of Candida. Furthermore, although vitreous culture was negative, tissue from the patient’s left forearm grew Candida, making systemic candidemia likely.
Clinical course
The patient received intravenous broad-spectrum antibiotics and antifungals throughout her hospitalization and was discharged to a rehabilitation facility on intravenous voriconazole after the results of the biopsy were obtained. Her vision was hand motion in the affected eye at the time of discharge, and her fellow eye remained unaffected. Unfortunately, the patient signed out from the rehab facility against medical advice and has been lost to follow-up since that time.