Treatment of endophthalmitis due to molds
- Marlene L Durand, MD
Marlene L Durand, MD
- Associate Professor of Medicine
- Harvard Medical School
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
- Section Editors
- Kieren A Marr, MD
Kieren A Marr, MD
- Section Editor — Compromised Host Infections; Fungal Infections
- Professor of Medicine and Oncology
- Johns Hopkins University School of Medicine
- Jonathan Trobe, MD
Jonathan Trobe, MD
- Section Editor — Ophthalmology
- Professor of Ophthalmology and Visual Sciences
- Professor of Neurology
- University of Michigan Kellogg Eye Center
Endophthalmitis due to molds is uncommon in temperate climates but is common in tropical regions such as India. Fusarium and Aspergillus spp account for most cases of mold endophthalmitis. Mold endophthalmitis often results in loss of vision.
The treatment of endophthalmitis due to molds will be reviewed here. The epidemiology, clinical features, and diagnosis of fungal endophthalmitis are discussed elsewhere. The treatment of endophthalmitis caused by Candida and bacterial species are also presented separately. Fusarium keratitis is also discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis" and "Treatment of endogenous endophthalmitis due to Candida species" and "Treatment of exogenous endophthalmitis due to Candida species" and "Bacterial endophthalmitis" and "Treatment and prevention of Fusarium infection", section on 'Keratitis'.)
The term "endophthalmitis" means infection within the eye involving the vitreous and/or aqueous (figure 1).
Endogenous endophthalmitis results from bacterial or fungal seeding of the eye via the bloodstream. In most cases of endogenous mold endophthalmitis, the highly vascular choroid is seeded first, and the infection typically progresses from the "back" of the eye (posterior segment) anteriorly.
Exogenous endophthalmitis means the infection was introduced from the "outside," for example, following eye surgery, eye trauma, or extension of fungal infection of the cornea (termed "fungal keratitis" or "keratomycosis"). In exogenous endophthalmitis, the aqueous is typically infected first and, in some cases, the vitreous is not involved.
The treatment of mold endophthalmitis typically involves a combination of vitrectomy, intravitreal and/or intracameral (into the anterior chamber) injection of an antifungal agent, removal of foreign materials (eg, intraocular lens), and systemic antifungal therapy [1-3]. Corneal transplantation is indicated in some cases of mold keratitis (corneal infection) that have extended to the aqueous . No controlled trials of treatment regimens for mold endophthalmitis have been performed given its rarity. The evidence regarding the treatment of mold endophthalmitis comes from case reports and case series. Even with therapy, there is a high rate of loss of useful vision, but the prognosis may be improving with the availability of newer antifungal agents such as voriconazole. (See 'Prognosis' below.)
Vitrectomy and removal of foreign bodies — Surgical removal of the vitreous, or vitrectomy, is nearly always necessary in mold endophthalmitis [2-5]. Vitrectomy entails the use of a vitrector, an instrument inserted into the vitreous cavity that simultaneously cuts and aspirates some of the approximately 4 mL of gel-like vitreous into a canister (figure 2). During this process, a separate cannula infuses balanced salt solution into the vitreous cavity to maintain intraocular pressure. By the end of the case, the canister contains dilute vitreous "washings" (eg, 50 to 100 mL). Vitrectomy decreases the burden of fungi quickly by debriding the vitreous . Samples are obtained during vitrectomy for microbiologic studies, and intravitreal antibiotics are injected at the end of the case. A vitrectomy, which is typically performed with local anesthesia with sedation, may be difficult if there is so much inflammation that the retina surgeon cannot see the retina. In patients too ill for eye surgery, a needle aspiration of the vitreous (for stains and cultures) followed by an intravitreal antibiotic injection should be performed. If the aqueous is primarily involved, then needle aspiration of aqueous plus intracameral antibiotic injection should be performed.
- Riddell J 4th, Comer GM, Kauffman CA. Treatment of endogenous fungal endophthalmitis: focus on new antifungal agents. Clin Infect Dis 2011; 52:648.
- Durand ML. Endophthalmitis. In: Principles and Practice of Infectious Diseases, 8th edition, Bennett JE, Dolin R, Blaser MJ. (Eds), Elsevier Saunders, Philadelphia 2015. Vol 1, p.1415.
- Patel AV, Young LH. Endogenous endophthalmitis. In: Endophthalmitis, Durand ML, Miller JW, Young LH. (Eds), Springer International Publishing, Switzerland 2016. p.171.
- Kauffman CA. Exogenous fungal endophthalmitis. In: Endophthalmitis, Durand ML, Miller JW, Young LH. (Eds), Springer International Publishing, Switzerland 2016. p.185.
- Chakrabarti A, Shivaprakash MR, Singh R, et al. Fungal endophthalmitis: fourteen years' experience from a center in India. Retina 2008; 28:1400.
- Riddell Iv J, McNeil SA, Johnson TM, et al. Endogenous Aspergillus endophthalmitis: report of 3 cases and review of the literature. Medicine (Baltimore) 2002; 81:311.
- Güngel H, Eren MH, Pınarcı EY, et al. An outbreak of Fusarium solani endophthalmitis after cataract surgery in an eye training and research hospital in Istanbul. Mycoses 2011; 54:e767.
- Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol 2010; 149:916.
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1.
- Lin RC, Sanduja N, Hariprasad SM. Successful treatment of postoperative fungal endophthalmitis using intravitreal and intracameral voriconazole. J Ocul Pharmacol Ther 2008; 24:245.
- Kernt M, Neubauer AS, De Kaspar HM, Kampik A. Intravitreal voriconazole: in vitro safety-profile for fungal endophthalmitis. Retina 2009; 29:362.
- Wykoff CC, Flynn HW Jr, Miller D, et al. Exogenous fungal endophthalmitis: microbiology and clinical outcomes. Ophthalmology 2008; 115:1501.
- Sen P, Gopal L, Sen PR. Intravitreal voriconazole for drug-resistant fungal endophthalmitis: case series. Retina 2006; 26:935.
- Kramer M, Kramer MR, Blau H, et al. Intravitreal voriconazole for the treatment of endogenous Aspergillus endophthalmitis. Ophthalmology 2006; 113:1184.
- Vila Arteaga J, Suriano MM, Stirbu O. Intravitreal voriconazole for the treatment of Aspergillus chorioretinitis. Int Ophthalmol 2011; 31:341.
- Belenitsky MP, Liu C, Tsui I. Scedosporium apiospermum endopthalmitis treated early with intravitreous voriconazole results in recovery of vision. J Ophthalmic Inflamm Infect 2012; 2:157.
- Tabbara KF, al Jabarti AL. Hospital construction-associated outbreak of ocular aspergillosis after cataract surgery. Ophthalmology 1998; 105:522.
- Gao H, Pennesi ME, Shah K, et al. Intravitreal voriconazole: an electroretinographic and histopathologic study. Arch Ophthalmol 2004; 122:1687.
- Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al. Exogenous fungal endophthalmitis. Ophthalmology 1988; 95:19.
- Yilmaz S, Ture M, Maden A. Efficacy of intracameral amphotericin B injection in the management of refractory keratomycosis and endophthalmitis. Cornea 2007; 26:398.
- Yoon KC, Jeong IY, Im SK, et al. Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis. Cornea 2007; 26:814.
- Kuriakose T, Kothari M, Paul P, et al. Intracameral amphotericin B injection in the management of deep keratomycosis. Cornea 2002; 21:653.
- Kernt M, Kampik A. Intracameral voriconazole: in vitro safety for human ocular cells. Toxicology 2009; 258:84.
- Han SB, Shin YJ, Hyon JY, Wee WR. Cytotoxicity of voriconazole on cultured human corneal endothelial cells. Antimicrob Agents Chemother 2011; 55:4519.
- Shen YC, Wang MY, Wang CY, et al. Pharmacokinetics of intracameral voriconazole injection. Antimicrob Agents Chemother 2009; 53:2156.
- Vemulakonda GA, Hariprasad SM, Mieler WF, et al. Aqueous and vitreous concentrations following topical administration of 1% voriconazole in humans. Arch Ophthalmol 2008; 126:18.
- Senthilkumari S, Lalitha P, Prajna NV, et al. Single and multidose ocular kinetics and stability analysis of extemporaneous formulation of topical voriconazole in humans. Curr Eye Res 2010; 35:953.
- Qu L, Li L, Xie H. Corneal and aqueous humor concentrations of amphotericin B using three different routes of administration in a rabbit model. Ophthalmic Res 2010; 43:153.
- Goldblum D, Rohrer K, Frueh BE, et al. Ocular distribution of intravenously administered lipid formulations of amphotericin B in a rabbit model. Antimicrob Agents Chemother 2002; 46:3719.
- Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 2004; 122:42.
- Garbino J, Ondrusova A, Baglivo E, et al. Successful treatment of Paecilomyces lilacinus endophthalmitis with voriconazole. Scand J Infect Dis 2002; 34:701.
- Figueroa MS, Fortun J, Clement A, De Arévalo BF. Endogenous endophthalmitis caused by Scedosporium apiospermum treated with voriconazole. Retina 2004; 24:319.
- Scott IU, Cruz-Villegas V, Flynn HW Jr, Miller D. Delayed-onset, bleb-associated endophthalmitis caused by Lecythophora mutabilis. Am J Ophthalmol 2004; 137:583.
- Durand ML, Kim IK, D'Amico DJ, et al. Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin. Am J Ophthalmol 2005; 140:552.
- Tu EY, McCartney DL, Beatty RF, et al. Successful treatment of resistant ocular fusariosis with posaconazole (SCH-56592). Am J Ophthalmol 2007; 143:222.
- Sponsel WE, Graybill JR, Nevarez HL, Dang D. Ocular and systemic posaconazole(SCH-56592) treatment of invasive Fusarium solani keratitis and endophthalmitis. Br J Ophthalmol 2002; 86:829.
- Spriet I, Delaere L, Lagrou K, et al. Intraocular penetration of voriconazole and caspofungin in a patient with fungal endophthalmitis. J Antimicrob Chemother 2009; 64:877.
- Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2016; 387:760.
- Goldblum D, Fausch K, Frueh BE, et al. Ocular penetration of caspofungin in a rabbit uveitis model. Graefes Arch Clin Exp Ophthalmol 2007; 245:825.
- Suzuki T, Uno T, Chen G, Ohashi Y. Ocular distribution of intravenously administered micafungin in rabbits. J Infect Chemother 2008; 14:204.
- Cornely OA, Schmitz K, Aisenbrey S. The first echinocandin: caspofungin. Mycoses 2002; 45 Suppl 3:56.
- Essman TF, Flynn HW Jr, Smiddy WE, et al. Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 1997; 28:185.
- Dursun D, Fernandez V, Miller D, Alfonso EC. Advanced fusarium keratitis progressing to endophthalmitis. Cornea 2003; 22:300.
- Young LH, Bazari H, Durand ML, Branda JA. Case records of the Massachusetts General Hospital. Case 33-2010. A 22-year-old woman with blurred vision and renal failure. N Engl J Med 2010; 363:1749.
- Mithal K, Pathengay A, Bawdekar A, et al. Filamentous fungal endophthalmitis: results of combination therapy with intravitreal amphotericin B and voriconazole. Clin Ophthalmol 2015; 9:649.
- Vitrectomy and removal of foreign bodies
- Corneal transplantation
- Intravitreal antifungal therapy
- Intracameral antifungal therapy
- Topical antifungal therapy
- Systemic antifungal therapy
- Approach to treatment
- - Exogenous mold endophthalmitis
- Anterior segment involvement only
- Vitreous involvement
- - Endogenous endophthalmitis
- - Duration of therapy
- SUMMARY AND RECOMMENDATIONS