Fungal Endophthalmitis Workup
- Author: Lihteh Wu, MD; Chief Editor: Hampton Roy, Sr, MD more...
The diagnosis of endogenous fungal endophthalmitis should be considered in patients who present with vitritis accompanied by a chorioretinal focus in the clinical setting of a recent or current debilitating illness. Clinical suspicion plays an important role in identifying patients who may have fungal endophthalmitis.
A presumptive diagnosis of fungal endophthalmitis can be made if the fungus is isolated from anywhere in the body and the typical intraocular findings are present.
Blood cultures, urine cultures, sputum cultures, and cerebrospinal fluid (CSF) cultures should be obtained in patients suspected of endogenous endophthalmitis. In addition, direct examination of fungi with Giemsa, Gomori-methenamine-silver (GMS), and periodic-acid Schiff (PAS) stains should be obtained.
Culture of the fungus confirms the diagnosis. However, the fungus may not always be detected, even clinically, in certain cases or in cases where the fungus has grown from another site. Fungal cultures can be positive in 44-70% of patients diagnosed clinically. Vitrectomy samples are more sensitive for fungal cultures than vitreous needle biopsies.
Part of the delay in making a diagnosis is because many laboratory isolates are considered contaminants by laboratory personnel. Laboratory personnel should be told to consider all fungal growth as significant and to report these findings. In addition, the culture must be kept at the laboratory for at least 4-6 weeks to ensure that slow-growing or fastidious fungal organisms are not missed.
A useful, recently introduced diagnostic tool for fungal endophthalmitis is the polymerase chain reaction (PCR). The main advantages of PCR over conventional fungal cultures are the higher sensitivity and the rapid results obtained with PCR. Although PCR does not replace conventional mycologic methods, it helps to make an early differentiation between bacterial endophthalmitis and fungal endophthalmitis.
Where available, DNA microarray analysis may be useful for obtaining a rapid diagnosis.
Candida species grow well on Sabouraud media without cycloheximide. The colonies are white and pasty. PCR has been used successfully to identify Candida species from an intraocular sample.
Aspergilli species are observed best with GMS or PAS stains. Culture is the most reliable means of identification. The fungus grows readily in Sabouraud and Czapek solutions. Aspergilli cultures are initially flat, white, and filamentous. Within 48 hours, conidia are produced with a concomitant change in pigmentation. Blood cultures are often negative for aspergilli organisms.
Cryptococci also grow well in Sabouraud agar. Cryptococci may be identified by India ink. C immitis can be diagnosed using a 10% KOH mount and identifying endospores that contain spherules.
Fluorescein angiography: The chorioretinal lesions appear hypofluorescent in the early phases of the study; leakage occurs in the later phases.
Anterior chamber tap
Anterior chamber (AC) specimens are unreliable in the diagnosis of Candida species.
Coccidioidomycosis has been diagnosed in a handful of cases by analyzing the AC taps.
Pars plana vitrectomy
Pars plana vitrectomy is important in obtaining undiluted specimens for culture and sensitivity. Primary 23-gauge vitrectomy can be used to confirm the diagnosis of endogenous fungal endophthalmitis. A retrospective analysis of 19 eyes in 15 patients demonstrated that 23-gauge vitrectomy confirmed diagnosis in 75% of the eyes (12 of 16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes).
Vitreous samples should be concentrated either by centrifugation or by millipore filtration.
If C neoformans is suspected, the sample should be stained with mucicarmine and undergo membrane filtration cytology.
Candida endophthalmitis: Candida organisms can be seen as budding yeasts with pseudohyphae within the lesions. The lesions contain few organisms, but they are surrounded by an intense granulomatous and suppurative inflammatory reaction.
Aspergillus endophthalmitis: Identification of branching septate hyphae in the choroid, retina, and vitreous characterizes Aspergillus endophthalmitis. Vessel thrombosis characterized by perivasculitis and necrotizing vasculitis often is observed in the retina and the choroid. Acute and chronic inflammatory cells are present in the anterior chamber and the vitreous.
Cryptococcus endophthalmitis: Cryptococci organisms usually are found in the choroid. They also have been identified in the retina, subretinal space, vitreous, and optic nerve. Typically, a diffuse or focal granulomatous inflammatory reaction that leads to a noncaseating necrosis is elicited. However, the number of inflammatory cells involved is much less than the expected given inflammatory reaction.
Coccidioides endophthalmitis: C immitis has been isolated from the limbus, iris, ciliary body, retina, choroid, and optic nerve. Typically, a granulomatous inflammatory reaction is present.
Essman TF, Flynn HW Jr, Smiddy WE, Brod RD, Murray TG, Davis JL. Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers. 1997 Mar. 28(3):185-94. [Medline].
Klotz SA, Penn CC, Negvesky GJ, Butrus SI. Fungal and parasitic infections of the eye. Clin Microbiol Rev. 2000 Oct. 13(4):662-85. [Medline].
Sridhar J, Flynn HW Jr, Kuriyan AE, Miller D, Albini T. Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections. J Ophthalmic Inflamm Infect. 2013. 3(1):60. [Medline].
Sridhar J, Flynn HW Jr, Kuriyan AE, Miller D, Albini T. Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections. J Ophthalmic Inflamm Infect. 2013 Sep 20. 3 (1):60. [Medline].
Smith TC, Benefield RJ, Kim JH. Risk of Fungal Endophthalmitis Associated with Cataract Surgery: A Mini-Review. Mycopathologia. 2015 Dec. 180 (5-6):291-7. [Medline].
Mikosz CA, Smith RM, Kim M, Tyson C, Lee EH, Adams E. Fungal endophthalmitis associated with compounded products. Emerg Infect Dis. 2014 Feb. 20(2):248-56. [Medline].
Schiedler V, Scott IU, Flynn HW, Davis JL, Benz MS, Miller D. Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes. Am J Ophthalmol. 2004 Apr. 137(4):725-31. [Medline].
Shah CP, McKey J, Spirn MJ, Maguire J. Ocular candidiasis: a review. Br J Ophthalmol. 2008 Apr. 92(4):466-8. [Medline].
Rao NA, Hidayat A. A comparative clinicopathologic study of endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared to aspergillosis. Trans Am Ophthalmol Soc. 2000. 98:183-93; discussion 193-4. [Medline].
Lundquist O, Osterlin S. Glucose concentration in the vitreous of nondiabetic and diabetic human eyes. Graefes Arch Clin Exp Ophthalmol. 1994 Feb. 232(2):71-4. [Medline].
Paulus YM, Cheng S, Karth PA, Leng T. PROSPECTIVE TRIAL OF ENDOGENOUS FUNGAL ENDOPHTHALMITIS AND CHORIORETINITIS RATES, CLINICAL COURSE, AND OUTCOMES IN PATIENTS WITH FUNGEMIA. Retina. 2015 Dec 11. [Medline].
Lalwani GA, Flynn HW Jr, Scott IU, Quinn CM, Berrocal AM, Davis JL, et al. Acute-onset endophthalmitis after clear corneal cataract surgery (1996-2005). Clinical features, causative organisms, and visual acuity outcomes. Ophthalmology. 2008 Mar. 115(3):473-6. [Medline].
Anand A, Madhavan H, Neelam V, Lily T. Use of polymerase chain reaction in the diagnosis of fungal endophthalmitis. Ophthalmology. 2001 Feb. 108(2):326-30. [Medline].
Sakai T, Kohzaki K, Watanabe A, Tsuneoka H, Shimadzu M. Use of DNA microarray analysis in diagnosis of bacterial and fungal endophthalmitis. Clin Ophthalmol. 2012. 6:321-6. [Medline].
William A, Spitzer MS, Deuter C, Blumenstock G, Partsch M, Voykov B, et al. Outcomes of Primary Transconjunctival 23-Gauge Vitrectomy in the Diagnosis and Treatment of Presumed Endogenous Fungal Endophthalmitis. Ocul Immunol Inflamm. 2016 Jan 30. 1-7. [Medline].
Khan FA, Slain D, Khakoo RA. Candida endophthalmitis: focus on current and future antifungal treatment options. Pharmacotherapy. 2007 Dec. 27(12):1711-21. [Medline].
Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002 Dec 19. 347(25):2020-9. [Medline].
Gauthier GM, Nork TM, Prince R, Andes D. Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis. Clin Infect Dis. 2005 Aug 1. 41(3):e27-8. [Medline].
Mikosz CA, Smith RM, Kim M, Tyson C, Lee EH, Adams E, et al. Fungal endophthalmitis associated with compounded products. Emerg Infect Dis. 2014 Feb. 20 (2):248-56. [Medline].
Sallam A, Taylor SR, Khan A, McCluskey P, Lynn WA, Manku K. FACTORS DETERMINING VISUAL OUTCOME IN ENDOGENOUS CANDIDA ENDOPHTHALMITIS. Retina. 2012 Jan 31. [Medline].
Tanaka H, Ishida K, Yamada W, Nishida T, Mochizuki K, Kawakami H. Study of ocular candidiasis during nine-year period. J Infect Chemother. 2016 Mar. 22 (3):149-56. [Medline].
Akler ME, Vellend H, McNeely DM, Walmsley SL, Gold WL. Use of fluconazole in the treatment of candidal endophthalmitis. Clin Infect Dis. 1995 Mar. 20(3):657-64. [Medline].
Blumenkranz MS, Stevens DA. Therapy of endogenous fungal endophthalmitis: miconazole or amphotericin B for coccidioidal and candidal infection. Arch Ophthalmol. 1980 Jul. 98(7):1216-20. [Medline].
Breit SM, Hariprasad SM, Mieler WF et al. Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol. 2005 Jan. 139(1):135-40. [Medline].
Brod RD, Flynn HW, Clarkson JG, Pflugfelder SC, Culbertson WW, Miller D. Endogenous Candida endophthalmitis. Management without intravenous amphotericin B. Ophthalmology. 1990 May. 97(5):666-72; disc: 672-4. [Medline].
Brooks RG. Prospective study of Candida endophthalmitis in hospitalized patients with candidemia. Arch Intern Med. 1989 Oct. 149(10):2226-8. [Medline].
Christmas NJ, Smiddy WE. Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers. 1996 Dec. 27(12):1012-8. [Medline].
Cornely OA, Schmitz K, Aisenbrey S. The first echinocandin: caspofungin. Mycoses. 2002. 45 Suppl 3:56-60. [Medline].
Crump JR, Elner SG, Elner VM, Kauffman CA. Cryptococcal endophthalmitis: case report and review. Clin Infect Dis. 1992 May. 14(5):1069-73. [Medline].
Donahue SP, Greven CM, Zuravleff JJ, Eller AW, Nguyen MH, Peacock JE Jr, et al. Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study. Ophthalmology. 1994 Jul. 101(7):1302-9. [Medline].
Edwards JE Jr, Foos RY, Montgomerie JZ, Guze LB. Ocular manifestations of Candida septicemia: review of seventy-six cases of hematogenous Candida endophthalmitis. Medicine (Baltimore). 1974 Jan. 53(1):47-75. [Medline].
Gao H, Pennesi ME, Shah K, Qiao X, Hariprasad SM, Mieler WF, et al. Intravitreal voriconazole: an electroretinographic and histopathologic study. Arch Ophthalmol. 2004 Nov. 122(11):1687-92. [Medline].
Griffin JR, Pettit TH, Fishman LS, Foos RY. Blood-borne Candida endophthalmitis. A clinical and pathologic study of 21 cases. Arch Ophthalmol. 1973 Jun. 89(6):450-6. [Medline].
Gross JG. Endogenous Aspergillus-induced endophthalmitis. Successful treatment without systemic antifungal medication. Retina. 1992. 12(4):341-5. [Medline].
Henderson DK, Edwards JE Jr, Montgomerie JZ. Hematogenous candida endophthalmitis in patients receiving parenteral hyperalimentation fluids. J Infect Dis. 1981 May. 143(5):655-61. [Medline].
Hunt KE, Glasgow BJ. Aspergillus endophthalmitis. An unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology. 1996 May. 103(5):757-67. [Medline].
Luttrull JK, Wan WL, Kubak BM, Smith MD, Oster HA. Treatment of ocular fungal infections with oral fluconazole. Am J Ophthalmol. 1995 Apr. 119(4):477-81. [Medline].
Martinez-Vazquez C, Fernandez-Ulloa J, Bordón J, Sopena B, de la Fuente J, Ocampo A, et al. Candida albicans endophthalmitis in brown heroin addicts: response to early vitrectomy preceded and followed by antifungal therapy. Clin Infect Dis. 1998 Nov. 27(5):1130-3. [Medline].
McDonald HR, De Bustros S, Sipperley JO. Vitrectomy for epiretinal membrane with Candida chorioretinitis. Ophthalmology. 1990 Apr. 97(4):466-9. [Medline].
Naoi N, Sawada A. Effect of vitrectomy on epiretinal membranes after endogenous fungal endophthalmitis. Jpn J Ophthalmol. 1996. 40(3):434-8. [Medline].
Okhravi N, Adamson P, Mant R, Matheson MM, Midgley G, Towler HM, et al. Polymerase chain reaction and restriction fragment length polymorphism mediated detection and speciation of Candida spp causing intraocular infection. Invest Ophthalmol Vis Sci. 1998 May. 39(6):859-66. [Medline].
Okhravi N, Dart JK, Towler HM, Lightman S. Paecilomyces lilacinus endophthalmitis with secondary keratitis: a case report and literature review. Arch Ophthalmol. 1997 Oct. 115(10):1320-4. [Medline].
Ozdamar A, Aras C, Ozturk R, Akin E, Karacorlu M, Ercikan C. In vitro antimicrobial activity of silicone oil against endophthalmitis-causing agents. Retina. 1999. 19(2):122-6. [Medline].
Parke DW 2nd, Jones DB, Gentry LO. Endogenous endophthalmitis among patients with candidemia. Ophthalmology. 1982 Jul. 89(7):789-96. [Medline].
Scherer WJ, Lee K. Implications of early systemic therapy on the incidence of endogenous fungal endophthalmitis. Ophthalmology. 1997 Oct. 104(10):1593-8. [Medline].
Sheu SJ, Chen YC, Kuo NW, et al. Endogenous cryptococcal endophthalmitis. Ophthalmology. 1998 Feb. 105(2):377-81. [Medline].
Smiddy WE. Treatment outcomes of endogenous fungal endophthalmitis. Curr Opin Ophthalmol. 1998 Jun. 9(3):66-70. [Medline].
Smith SR, Kroll AJ, Lou PL, Ryan EA. Endogenous bacterial and fungal endophthalmitis. Int Ophthalmol Clin. 2007. 47(2):173-83. [Medline].
Weishaar PD, Flynn HW, Murray TG, Davis JL, Barr CC, Gross JG, et al. Endogenous Aspergillus endophthalmitis: clinical features and treatment outcomes. Ophthalmology. 1998 Jan. 105(1):57-65. [Medline].
Weissgold DJ, Maguire AM, Brucker AJ. Management of postoperative acremonium endophthalmitis. Ophthalmology. 1996 May. 103(5):749-56. [Medline].
Zakka KA, Foos RY, Brown WJ. Intraocular coccidioidomycosis. Surv Ophthalmol. 1978 Mar-Apr. 22(5):313-21. [Medline].
Zhang YQ, Wang WJ. Treatment outcomes after pars plana vitrectomy for endogenous endophthalmitis. Retina. 2005 Sep. 25(6):746-50. [Medline].