Fungal Endophthalmitis Workup

Updated: Mar 14, 2023
  • Author: Lihteh Wu, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Laboratory Studies

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. Vitrectomy samples are more sensitive for fungal cultures than vitreous needle biopsies. However, low yields from vitrectomy samples make diagnosing fungal endophthalmitis accurately quite challenging. Typically fungemia ranges from 0 to 33% of cases. [14]

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. [23]

Serum fungal markers such as beta-d-glucan and galactomannan may aid in the diagnosis. Directly testing intraocular fluids with these markers may increase the identification of fungal endophthalmitis but needs to be further validated. [14, 24, 25, 26]

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 often are 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.


Imaging Studies

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). [27]

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.


Histologic Findings

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.