SUBRETINAL CANDIDA ALBICANS ABSCESSES RESPONSIVE TO ORAL VORICONAZOLE Tony H. Huynh, MD, Mark W. Johnson, MD, Richard E. Hackel, MA, CRA, FOPS
Purpose: To report findings in a patient with bilateral Candida albicans subretinal abscesses responsive to oral voriconazole. Methods: Retrospective, case report. Results: A 62-year-old woman presented with bilateral C albicans subretinal abscesses secondary to chronic immunosuppression. The abscesses responded to oral voriconazole and resolved completely within 4 months of initial presentation. Conclusions: This case illustrates that oral voriconazole may be effective in the treatment of large subretinal abscesses in an immunocompromised patient. Additionally, this report suggests that a subretinal aspirate may have greater diagnostic sensitivity than a vitreous specimen in eyes with infectious subretinal abscesses. RETINAL CASES & BRIEF REPORTS 2:213–215, 2008
From the W.K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.
areas of retinitis overlying the larger subretinal infiltrates in each eye. The patient underwent diagnostic pars plana vitrectomy with subretinal aspiration biopsy on the left eye. Histologic examination of the vitreous and subretinal specimens revealed yeast and pseudohyphae. Vitreous cultures were negative, while subretinal infiltrate cultures yielded Candida albicans. Infectious disease evaluation yielded no evidence for involvement of other organ systems by fungal infection. The patient was treated with oral voriconazole (200 mg twice daily). One week postoperatively, examination of the right eye showed enlargement of the subretinal infiltrate with extension toward the macula. Amphotericin B (10 g) was injected intravitreally in the right eye. One week later, the right eye received a second injection of amphotericin B because of possible slight progression of the lesion toward the macula. Examination of the left eye during this time showed minimal progression of the subretinal infiltrates (Fig. 2). After 3 weeks of voriconazole treatment (1 week after reinjection of amphotericin B in the right eye), improvement in the subretinal infiltrates was evident in both eyes. Therapy with voriconazole was continued for an additional week, and then treatment was transitioned to oral fluconazole (400 mg twice daily). Three weeks later, best-corrected visual acuity was 20/25 in the right eye and 20/50 in the left eye. Examination showed near complete resolution of chorioretinitis and subretinal infiltrates in both eyes. Fluconazole treatment was continued for an additional 2 months during slow tapering of prednisone doses. The patient underwent vitrectomy repair of rhegmatogenous retinal detachment followed by cataract surgery on the left eye. Six months after discontinuing antifungal medication, best-corrected
Case Report A 62-year-old woman reported a 2-week history of bilaterally blurred vision. She denied ocular redness, pain, fevers, and chills. Medical history was notable for autoimmune hemolytic anemia treated for the previous 3 months with high doses of prednisone (100 –200 mg daily). The onset of anemia had followed intravenous pyelography and placement of a temporary ureteral stent for nephrolithiasis. Best-corrected visual acuity was 20/40 in both eyes. Anterior segment examination was remarkable for 1⫹ cell in the anterior chamber of the left eye. Right fundus examination revealed 1⫹ vitritis with inflammatory debris and a solitary, thick, subretinal inflammatory infiltrate with overlying retinitis and retinal hemorrhage located just superonasal to the optic disk (Fig. 1A). A single cotton-wool spot was present in the inferior macula. Left fundus examination showed 2⫹ vitritis with inflammatory debris. There was a large area of subretinal inflammatory infiltrate with overlying retinitis along with three small, separate foci of chorioretinitis (Fig. 1B). Fluorescein angiography confirmed the presence of smaller
None of the authors have any proprietary interest in the subject matter of this report. Reprint requests: Mark W. Johnson, MD, W.K. Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; e-mail:
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Fig. 1. Initial presentation. A, Fundus photograph of the right eye shows mild vitritis, a large subretinal inflammatory infiltrate with overlying retinitis and retinal hemorrhage, and a single cotton-wool spot in the macula. B, Fundus photograph of the left eye shows moderate vitritis, a large area of subretinal inflammatory infiltrate with overlying retinitis, and a small focus of chorioretinitis in the macula.
visual acuity was 20/20 in each eye. Fundus examination showed inactive chorioretinal scarring bilaterally (Fig. 3).
Discussion In immunocompromised patients, endogenous fungal endophthalmitis is a rare but potentially devastating condition that presents significant therapeutic challenges. The use of systemic amphotericin B in such cases is limited by poor intravitreal penetration and significant systemic side effects.1 These issues can by circumvented by intravitreal administration; however, this route of delivery is associated with its own risks, including the potential for retinal toxicity.2,3 The
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Fig. 2. After 2 weeks of voriconazole therapy. A, There is enlargement and extension toward the macula of the subretinal infiltrate in the right eye. B, Minimal enlargement of the subretinal infiltrates is seen in the left eye.
use of other agents, such as flucytosine, imidazole, ketoconazole, fluconazole, and itraconazole, has been limited by a narrow spectrum of activity, poor intraocular penetration, and/or side effects. Voriconazole is a newer antifungal agent derived from fluconazole that has recently gained attention in the ophthalmic community for its role in treating fungal intraocular infections.4 Given orally, voriconazole has been shown to have excellent bioavailability (⬎90%) and good intraocular penetration.5,6 Furthermore, the agent has been shown to have a broad spectrum of activity against multiple organisms including Aspergillus species (Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus), Candida species (C. albicans, Candida gla-
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properties make voriconazole an excellent candidate for the oral treatment of fungal endophthalmitis and chorioretinitis.4 Our case illustrates that oral voriconazole may be effective in the treatment of large subretinal abscesses in an immunocompromised patient. Although we briefly used intravitreal amphotericin B as adjunctive treatment of the right eye, this may have been unnecessary because the left eye had a similar response to voriconazole alone. It is possible that vitrectomy altered the pharmacodynamics of the left eye, resulting in greater intravitreal drug levels in the left eye than in the right eye. However, it is unlikely that the surgery significantly influenced choroidal and retinal levels of the drug in an already inflamed eye. Both eyes had resolution of the subretinal abscesses with medical therapy without the need for surgical drainage. Our case also illustrates the potential importance of performing subretinal aspiration on eyes with suspected infectious subretinal abscesses. For our patient, results of histologic examination of both vitreous and subretinal specimens were suggestive of fungal infection, but only cultures of the subretinal aspirate confirmed the presence of C. albicans. This suggests that a subretinal aspirate may have greater diagnostic sensitivity than a vitreous specimen from eyes with infectious subretinal abscesses. Key words: Candida albicans, endophthalmitis, chorioretinitis, fungus, subretinal abscess, voriconazole. References 1.
2. 3. Fig. 3. Six months after discontinuing antifungal agents. Inactive chorioretinal scarring is present in the right (A) and left (B) eyes. Scars from laser treatment placed during retinal detachment repair are evident in the left eye (B).
brata, Candida krusei, Candida parapsilosis, and Candida tropicalis), Scedosporium apiospermum, and Fusarium species, including Fusarium solani.5 These
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O’Day DM, Head WS, Robinson RD, et al. Intraocular penetration of systemically administered antifungal agents. Curr Eye Res 1985;4:131–134. Souri EN, Green WR. Intravitreal amphotericin B toxicity. Am J Ophthalmol 1974;78:77–81. Axelrod AJ, Peyman GA, Apple DJ. Toxicity of intravitreal injection of amphotericin B. Am J Ophthalmol 1973;76:578– 583. Breit SM, Hariprasad SM, Mieler WF, et al. Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol 2005;139:135–140. Sabo JA, Abdel-Rahman SM. Voriconazole: a new triazole antifungal. Ann Pharmacother 2000;34:1032–1043. Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentrations of orally administered voriconazole in humans. Arch Ophthalmol 2004;122: 42–47.