Any saprophytic fungi found in natural habitats may cause exogenous fungal endophthalmitis. It is associated with a variety of species: common pathogens include Aspergillus species and Candida species (predominantly in postoperative cases) [7–10] and Fusarium species (predominantly following trauma and keratitis) [11]. The other mycotic agents include Paecilomyces species and Acremonium species [12]. One of the large case series from north India [7] reported Aspergillus species as the most common (54.4%) isolated fungus, followed by yeasts (24.6%) and melanised fungi (10.5%).

Direct microscopy of the ocular specimen is the most commonly followed method of identifying fungal pathogens as it is rapid and cost effective. Microscopic examination under 10% potassium hydroxide (KOH) preparations can identify the fungal structure and the distinctive morphology. KOH dissolves the human tissue and allows visualisation of the alkali -resistant fungal structures. Special stains like calcofluor white and Fontana-Masson stain are used to stain the cell wall and presence of melanin in the smear, respectively. Nevertheless, a direct microscopy is less sensitive than culture, and a negative smear does not rule out fungal infection [13].

When cultured, at least two different media are chosen for pathogen identification—selective (Sabouraud agar) and non-selective (chocolate, blood agar and brain heart infusion broth). They are incubated in room temperature as the growth is optimum between 25 and 37°C. The specimen is incubated for at least 4 weeks before reporting it negative. The yeasts and the moulds are distinguished from each other under direct microscopy. The main characteristics of commonly isolated fungal species are described in Table 11.2 and illustrated in Fig. 11.3.

Polymerase chain reaction (PCR) is invaluable in the diagnosis of fungal endophthalmitis. It has a high degree of specificity and sensitivity, reduces laboratory diagnosis time and is particularly useful in those cases where cultures have not yielded any growth. The routine use of PCR for the detection of fungal DNA, using pan-fungal primers ITS1 and ITS4 for the diagnosis of fungal pathogens on specimens as an adjunct to conventional microscopy and culture, is likely to increase diagnostic yield [15–17]. In one of the traumatic endophthalmitis studies PCR identified the organism in all the specimens when the cultures were all negative [18].

Treatment of fungal endophthalmitis has unique challenges, principally because of the following reasons: the diagnosis is often challenging, the choices of available therapies are limited, and the outcomes are frequently unfavourable. As the disease incidence is low and because there is no randomised control trial, the treatment protocol is still not optimised.

The management of the condition begins with collection of aqueous and vitreous sample for pathogen identification. Because of better recovery of fungi, the vitreous sample is considered more valuable than an aqueous tap [19]. An ultrasonography of the vitreous is mandatory to assess the vitreous involvement and associated ocular tissue damage. A standard two-/three-port vitrectomy at high cut rate and low vacuum for biopsy is considered safe. Presence of choroidal or retinal detachment should not deter a surgeon to sample the vitreous. A meticulous clearing of anterior segment exudates through a corneal paracentesis may improve visualisation of the anterior vitreous to allow direct view of the vitreous cutter at the anterior vitreous face. In rare instances when anterior vitreous face cannot be viewed due to poor corneal clarity, one may restrict to an aqueous tap alone, which can be done by aspirating anterior chamber fluid transcorneally by a 26G hypodermic needle mounted on a tuberculin syringe. Approximately 0.2–0.3 ml of vitreous sample or 0.2 ml of aqueous sample is collected for microbiological culture and microscopy. Depending on the proximity of the microbiology laboratory, the sample may either be sent in a sterile closed box or may be directly plated in the operating room. In addition to the culture, wet mount preparations of the sample with 10% KOH help identify fungal hyphae. The sensitivity of the test is higher when calcofluor white is added to KOH and the specimen is observed under fluorescent microscope [13].

Achieving adequate concentrations of antifungal antibiotic in the infected tissues is crucial to treatment success. The choroid and retina are highly vascular compared to the vitreous, and the vascular compartments are separated from intraocular structures by the blood-ocular barrier. Thus, infection localised to the chorioretinal layers, which are not protected by this barrier, can be treated with systemic antifungal agents, but treatment of other intraocular infections requires penetration of the antifungal agent through this relatively impermeable barrier.

Before the availability of newer triazoles, the most common antifungal treatment for fungal endophthalmitis was intravenous and/or intravitreal amphotericin B. It is effective against a wide range of fungal pathogens, but its utility in treating fungal endophthalmitis is limited by poor ocular penetration and the potential intraocular toxicity such as intense intraocular inflammation, retinal necrosis, and cataract formation [20, 21]. It would cause chills, fever, nausea, vomiting, diarrhoea, dyspnea, malaise, anaemia, arrhythmia, hypokalemia, hearing loss and renal failure when administered systemically [22].

With the availability of newer triazoles such as fluconazole, itraconazole, voriconazole, posaconazole and ravuconazole, the choice of treatment has moved away from the traditional use of amphotericin B. These newer drugs are less toxic and have a better bioavailability in vitreous when administered orally [23]. Fluconazole, an older-generation triazole, has been used systemically as a supplement or alternative to amphotericin B, but it lacks the broad spectrum of coverage necessary for the most commonly encountered fungal infections in the eye. Furthermore, intraocular penetration is marginal. Itraconazole is rarely used in the treatment of ocular fungal eye infections, as it lacks a broad spectrum of coverage, specifically against Fusarium species [24].

Voriconazole is the most preferred among the azoles currently in use for treatment of fungal endophthalmitis. It is a second-generation azole derived from fluconazole and can be administered intravitreally, orally and intravenously. It is effective against most Candida species, Aspergillus and Cryptococcus [25]. It has excellent intravitreal penetration after systemic administration, and the toxicities include visual disturbances like photophobia and elevation of hepatic enzymes [26].

After the large outbreak of Fusarium keratitis in contact lens wearers in 2005, interest in voriconazole to treat fungal eye infections increased among ophthalmologists, who realised the benefits of this broad-spectrum triazole agent in treating the difficult problem. Many studies on the distribution of voriconazole within ocular compartments were performed during treatment of complicated Fusarium keratitis. Most studies on voriconazole are from humans. The rationale for injection of voriconazole lies in its better safety profile than amphotericin B and its ability to achieve high levels of drug concentration in the vitreous. The details of common antifungals used in treatment of endophthalmitis are listed in Table 11.3.

Use of corticosteroids is controversial in the management of fungal endophthalmitis. The anti-inflammatory properties of corticoosteroid help modulate the inflammatory response to infection and maintain the structural integrity of the globe. While this is often considered in bacterial endophthalmtis, the mode of application in fungal endophthalmitis is a matter of debate. Topical corticosteroids are contraindicated in fungal keratitis, but intravitreal dexamethasone injection could be considered in fungal endophthalmitis [28].