FEATURE MEDICINE PLUS SURGERY TREATS AN UNUSUAL CASE OF FUNGAL ENDOPHTHALMITIS Careful attention to the patient’s history and persistent follow-up made for a positive result.

BY ADITYA MEHTA, MD, and YU HYON KIM, MD

Extreme morning sickness, hyperemesis gravidarum requiring TPN. She returned 2 weeks or hyperemesis gravidarum, later with complaints of blurry vision in her right eye (OD). is a complication of The patient had no previous ocular history or history pregnancy characterized by of intravenous drug use. HIV test performed earlier in the severe nausea and vomit- pregnancy was negative. On presentation, visual acuity (VA) ing, weight loss, and even was 20/70 OD and 20/20 in her left eye (OS). Her intraocular dehydration. Whereas pressure (IOP) was 19 mm Hg OD and 20 mm Hg OS, and mild cases of hyperemesis there was no relative afferent pupillary defect. The external gravidarum can be treated with dietary changes, rest, and examination was unremarkable. Anterior chamber examina- antacids, more severe cases can require hospitalization and tion exhibited 1+ cell OD. intravenous nutrition. The following case report describes a young pregnant woman with fungal endophthalmitis in the setting of candidemia from fungal endocarditis after receiv- ing total parenteral nutrition (TPN).

CASE REPORT A 31-year-old black woman, at 24 weeks gestational age, was admitted to the San Antonio Military Medical Center for AT A GLANCE

• Ophthalmologic findings of C. albicans endophthalmitis have a strong association with disseminated candidiasis, especially in the setting of predisposing factors. • In this case report, prompt vitrectomy and intravitreal injection of amphotericin led to Figure 1. Fundus photo OD. A superior juxtafoveal lesion is rapid visual recovery. visible, and optic disc edema is apparent.

28 RETINA TODAY | OCTOBER 2017 FEATURE

A B A B

Figure 3. B-scan OD vertical anterior-posterior (A) and Figure 2. OCT macula 512x128 horizontal (A) and vertical (B) 9 o’clock transverse (B) sections with extensive vitritis. section OD.

A B A B

Figure 4. Postoperative day 5. OCT macula 512x128 Figure 5. Postoperative week 3. OCT macula 512x128 horizontal (A) and vertical (B) sections OD. horizontal (A) and vertical (B) sections OD.

Funduscopic examination OD revealed a solitary fluffy was administered after vitrectomy. The results of vitreous white juxtafoveal lesion that measured 1 disc diameter biopsy were positive for Candida albicans. with slight elevation. Overlying vitritis with small intrareti- On postoperative day 5, the patient’s VA was 20/100 OD, nal hemorrhage was seen adjacent to the lesion (Figure 1). and OCT revealed interval clearance of the VMA, resolving On scleral depression, numerous snowballs were present in intraretinal edema, and CFT of 392 μm (Figure 4). At 3 weeks the inferior vitreous. postoperative, the patient’s VA had improved to 20/40 OD, Ocular coherence tomography (OCT) of the macula and funduscopic examination revealed macular plaque, inter- revealed vitreomacular adhesion (VMA) with a hyperreflec- val clearance of white clumps, and improved vitritis (Figure 5). tive lesion superior to the fovea. Central fundus thickness Repeat blood cultures and biopsy from transesophageal echo- (CFT) was 552 μm (Figure 2). cardiogram revealed C. albicans. A systemic evaluation was performed, including echo- The patient underwent 6 weeks of antibiotic therapy and cardiogram, which revealed vegetation on the patient’s surgical resection of vegetation with annuloplasty of her tricuspid valve. Initial blood cultures were negative for bacte- tricuspid valve to address the endocarditis. At postoperative rial or fungal microorganisms, but Fungitell assay (Beacon month 5, she had returned to her baseline VA of 20/20 OD Diagnostics Laboratory) was positive for the presence of with a stable superior macular plaque. fungus. The patient had no previous cardiac history, but she did have a remote history of bacteremia from a central line DISCUSSION infection. Noncontrast magnetic resonance imaging of the Fungal endophthalmitis from Candida infections primar- brain and orbits was normal. ily develops from an endogenous source via hematogenous The patient was treated with intravenous liposomal spread to the choroid. Long-term indwelling central venous amphotericin B and daptomycin, in consultation with catheters increase the risk for bacteremia, particularly infectious disease specialists, due to concern for concurrent Staphylococcus aureus.1 Increased parenteral caloric intake is native-valve endocarditis and the previous history of a another independent risk factor for bloodstream infections, central line infection. Extensive lab workup was unremark- particularly those resulting from C. albicans.2,3 The differential able for rapid plasma reagin, cytomegalovirus (CMV), toxo- diagnosis for fungal endophthalmitis includes endogenous or plasmosis, immunoglobulin M and G antibodies, Brucella, exogenous bacterial endophthalmitis, toxoplasma retinocho- histoplasmosis, Cryptococcus, and Coxiella antigen. roiditis, primary intraocular lymphoma, and CMV retinitis.4 The next day, the patient’s VA had worsened to 20/200 Posterior uveitis from other inflammatory and infectious con- OD. Examination revealed worsening papillary optic disc ditions such as sarcoidosis, syphilis, tuberculosis, Lyme disease, edema and vitritis. B-scan demonstrated worsening vitritis and Brucellosis may also be considered. (Figure 3). Due to the extent of the vitritis and the location The diagnosis of fungal endophthalmitis is based on oph- of the retinitis, the patient underwent pars plana vitrectomy thalmologic appearance and high suspicion for fungemia in with removal of the hyaloid. Intravitreal amphotericin B 5 μg the setting of predisposing factors. Fungal endophthalmitis is

OCTOBER 2017 | RETINA TODAY 29 FEATURE associated with fluffy white chorioretinal lesions and vitritis CONCLUSION that is manifested by small, white, snowball-like opacities. A In the patient described here, vitrectomy was performed positive vitreous culture is the gold standard for diagnosis; and intravitreal amphotericin was administered due to wors- however, vitreous tap has a sensitivity of approximately ening VA, severe vitritis, and posterior pole involvement. 44%,5 whereas vitrectomy offers an increased diagnostic The rapid effectiveness of vitrectomy was highlighted by yield, ranging from 75% to 92%.6-8 improved VA, and postoperative OCT demonstrated drastic Fungal bacteremia may be initially missed on routine resolution of intraretinal edema and clearance of the VMA. blood cultures,9 as was the case with our patient. Various Severe inflammation from endophthalmitis and VMA are other serologic procedures have been employed to quickly independent risk factors that can lead to retinal detachment, identify a fungus source. In this case, the Fungitell assay but vitrectomy performed within 1 week of presentation is was used, which detects the (1→3)-β-D-glucan cell wall associated with a lower risk of retinal detachment.5,17 constituent and has a reported sensitivity of 93.3% and This case illustrates that ophthalmologic findings of C. albicans specificity of 77.2%.10 endophthalmitis have a strong association with disseminated Treatment of fungal endophthalmitis represents a unique candidiasis, especially in the setting of predisposing factors. challenge, given the presence of the blood-ocular barrier, Furthermore, early surgical treatment with vitrectomy and which can prevent the adequate concentration of antifungal intravitreal antifungal therapy in eyes with posterior pole and agents within the vitreous cavity. Due to the highly vascular vitreous involvement can lead to rapid visual recovery. n nature of the choroid and retina, chorioretinitis without 1. Benito N, Miro JM, de Lazzari E, et al; for the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) investiga- vitritis can be successfully treated with systemic therapy tors. Health care-associated native valve endocarditis: importance of non-nosocomial acquisition. Ann Intern Med. 2009;150(9):586-594. alone with either fluconazole and voriconazole or liposomal 2. Dissanaike S, Shelton M, Warner K, O’Keefe GE. The risk of bloodstream infections is associated with increased parenteral intake in patients receiving parenteral nutrition. Crit Care. 2007;11(5):R114. amphotericin B with or without flucytosine. Furthermore, 3. Chow JK, Golan Y, Ruthazer R, et al. Factors associated with candidemia caused by non-albicans candida species versus candida patients with a concern for S. aureus bacteremia due to albicans in the intensive care unit. Clin Infect Dis. 2008;46(8):1206-1213. 4. Skondra D, Eliott D. Fungal endophthalmitis. In: Yanoof M, Duker JS, eds. Ophthalmology. 4th ed. Philadelphia, PA: Saunders Elsevier; indwelling central lines can be treated with intravenous dap- 2014:733-737. tomycin, which has good intravitreal penetration.11 Vitreous 5. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal endophthalmitis: causative organisms, management strategies, and visual acuity outcomes. Am J Ophthalmol. 2012;153(1):162-166.e1. involvement requires intravitreal injection with either 6. Binder MI, Chua J, Kaiser P, et al. Endogenous endophthalmitis: an 18-year review of culture positive cases at a tertiary care center. amphotericin B deoxycholate (5-10 μg/0.1 mL) or voricon- Medicine (Baltimore). 2003;82(2):97-105. 7. William A, Spitzer M, Deuter C, et al. Outcomes of primary transconjunctival 23-gauge vitrectomy in the diagnosis and treatment of azole (100 μg/0.1 mL). The administration of intravitreal presumed endogenous fungal endopthalmitis. Ocul Immunol Inflamm. 2017;25(2):239-245. 8. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal endophthalmitis: causative organisms, management strategies, and antifungal agents, whether only through tap and inject or visual acuity outcomes. Am J Ophthalmol. 2012;153(1):162-166. combined with vitrectomy, is evolving. 9. Washington JA 2nd. The role of the microbiology laboratory in the diagnosis and antimicrobial treatment of infective endocarditis. Mayo Clin Proc. 1982;57(1):22-32. Historically, involvement of the posterior pole and vit- 10. Pickering JW, Sant HW, Bowles CAP, et al. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J reous has been treated with vitrectomy, with or without Clin Microbiol. 2005;43(12):5957-5962. 11. Sheridan KR, Potoski BA, Shields RK, Nau GJ. Presence of adequate intravitreal concentrations of daptomycin after systemic intrave- intravitreal amphotericin B (5-10 μg/0.1 mL) in an effort to nous administration in a patient with endogenous endophthalmitis. Pharmacotherapy. 2010;30(12):1247-1251. decrease infectious load and provide immediate delivery 12. Christmas NJ, Smiddy WE. Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic 12,13 Surg Lasers. 1996;27(12):1012-1018. of drug. Recently, small case series have advocated for 13. Peyman GA, Raichand M, Bennett TO. Management of endophthalmitis with pars plans vitrectomy. Br J Ophthalmol. early complete vitrectomy in addition to intravitreal anti- 1980;64(7):472-475. 14. Sallam A, Taylor SR, Khan A, et al. Factors determining visual outcome in endogenous candida endophthalmitis. Retina. fungal agents, with demonstration of favorable outcomes. 2012;32(6):1129-1134. A retrospective review of 44 eyes found that Candida 15. Kim DY, Moon HI, Joe SG, Kim JG, Yoon YH, Lee JY. Recent clinical manifestation and prognosis of fungal endopthalmi- tis: a 7-year experience at a tertiary referral center in Korea. J Korean Med Sci. 2015;30(7):960-964. endophthalmitis was associated with poor visual outcome, 16. Behera UC, Budhwani M, Das T, et al. Role of early vitrectomy in the treatment of fungal endophthalmitis [published online ahead of print May 23, 2017]. Retina. especially in patients with poor presenting VA and posteri- 17. Martinez-Vázquez C, Fernández-Ulloa J, Bordón J, et al. Candida albicans endophthalmitis in brown heroin addicts: or pole involvement (relative risk, 5.01; P <.05). Vitrectomy response to early vitrectomy preceded and followed by antifungal therapy. Clin Infect Dis. 1998;27(5):1130-1133. helped to significantly reduce the risk of retinal detach- ment (P = .02).14 Yu Hyon Kim, MD A recent 7-year retrospective review of 40 eyes with n retina specialist at the University Eye Institute, University Hospitals fungal endophthalmitis demonstrated that 71% of Cleveland Medical Center, in Ohio patients treated with vitrectomy plus an intravitreal n financial interest: none acknowledged antifungal agent have more than 2 lines of VA recovery, n [email protected] compared with 25% of patients treated with intravitreal antifungal injection alone (P = .034).15 A prospective anal- Aditya Mehta, MD ysis in a subset of patients with fungal endophthalmitis n ophthalmology resident at San Antonio Military Medical Center, who underwent early, complete vitrectomy with either Texas amphotericin B or voriconazole (n = 6) had statistically n financial interest: none acknowledged significant vision improvement as compared with diag- n [email protected] nostic vitrectomy with antifungal agents.16

30 RETINA TODAY | OCTOBER 2017