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Fungal, Mycobacterial, and Nocardia Infections and The Eye (2012) 26, 245–251 & 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12 www.nature.com/eye Fungal, P Garg CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM Mycobacterial, and Nocardia infections and the eye: an update Abstract blindness, especially in tropical countries.3–5 An overwhelming number of fungal genera and Although relatively uncommon, fungi, species have been implicated as causes of atypical Mycobacteria, and Nocardia have ophthalmic mycoses, and this number is steadily been isolated from a variety of infections of increasing. Table 1 highlights some of the eye including keratitis, scleritis, canaliculitis, important genera and species isolated from dacryocystitis, endophthalmitis and orbital various ophthalmic mycoses cases. cellulites. The organisms typically cause a slowly progressive disease. The diseases caused by the organisms can pose both Keratitis diagnostic and therapeutic challenges. In this manuscript we will describe updates Keratitis is by far the most frequent fungal 3,4 on important aspects of the ocular infections infection of eye. Trauma is the most important 5 caused by these organisms. predisposing factor. Other predisposing factors Eye (2012) 26, 245–251; doi:10.1038/eye.2011.332; include corneal surgery, prolonged use of published online 16 December 2011 corticosteroids or antibiotics, pre-existing ocular diseases, systemic diseases such 3,4,6,7 Keywords: fungi; non-tubercular Mycobacteria; as diabetes mellitus, and contact lenses. Nocardia; keratitis; scleritis; endophthalmitis Fungi produce a slowly progressive disease characterized by localized infiltrate. Classical clinical features are shown in Figures 1a and b. Although several features are characteristic, Cornea and Anterior Introduction not all patients present with these features. Ring Segment Services, LV Prasad Eye Institute, Banjara Hills, Infectious diseases of the eye have long been infiltrate mimicking acanthamoeba or frank Hyderabad, India recognized as important causes of blindness. suppuration mimicking bacterial keratitis or While Chlamydia trachomatis, Neisseria dendritic lesions, and even mutton fat Correspondence: P Garg, gonorrhoea, and Onchocerca volvulus are endothelial lesions mimicking HSV endothelitis Cornea and Anterior important causes of global blindness,1,2 many are not uncommon presentations in fungal Segment Services, other organisms can cause serious ocular keratitis. Further, non-fungal microorganisms Kallam Anji Reddy Campus, LV Prasad Eye Institute, morbidity. Although relatively uncommon, such as acanthamoeba, nocardia and Gram- Banjara Hills, ocular infections caused by fungi, atypical positive bacteria can present with clinical Hyderabad 500034, India Mycobacteria, and Nocardia can pose both features resembling fungal infection.8,9 Tel: þ 91 40 30612345; diagnostic and therapeutic challenges. In this Therefore, no clinical feature can be considered Fax: þ 91 40 23548271. manuscript we will describe updates on absolutely pathognomonic of fungal aetiology.10 E-mail: [email protected] important aspects of the ocular infections caused by these organisms. Received: 10 October 2011 Challenges with laboratory diagnosis Accepted in revised form: Although microscopic examination of smear 8 November 2011 using various stain and inoculation on culture Published online: 16 Fungal infections of the eye media helps in identification of fungal December 2011 Although fungi are recognized as opportunistic infections, laboratory diagnosis can be This work was presented at pathogens, ocular fungal infections or challenging, especially in patients with deep- the Cambridge ophthalmic mycoses are being increasingly seated keratitis. In such cases, corneal biopsy Ophthalmological recognized as important causes of morbidity and helps to establish the diagnosis.11 Although this Symposium. Fungi, atypical Mycobacteria, and Nocardia are important causes of ocular infections P Garg 246 Table 1 Important fungi isolated from ocular infections Fungi group Fungal genus and species Important ocular diseases Hyaline filamentous Fusarium (F. solani, F. dimerum, F. oxysporum) Keratitis, scleritis, endophthalmitis Aspergillus (A. fumingatus, A. terrus, A. terreus) Keratitis, scleritis, endophthalmitis, oribital cellulitis Dacryocystitis Scedosporium (S. apiospermum, S. prolificanc) Keratitis, scleritis, endophthalmitis Orbital cellulitis Paecilomyces (P. lilacinus, P. variotii) Keratitis, endophthalmitis Acremonium (A. kilience, A. potronii) Keratitis, endophthalmitis Dematiaceous Bipolaris (B. specifera, B. hawaiiensis) Keratitis, scleritis Curvularia (C. lunata, C. geniculata) Keratitis, scleritis Exserohilum (E. rostratum) Keratitis, scleritis Exophiala (E. dermatitidis) Keratitis, scleritis Lasiodiplodia theobromae Keratitis Yeasts and zygomycetes Yeasts Candida (C. albicans, C. parapsilosis, Keratitis, infectious crystalline keratopathy, scleritis, C.guilliermondii) endophthalmitis, orbital cellulitis Cryptococcus (C. neoformans, C. laurentii) Keratitis, blepharitis, endophthalmitis Zygomycetes Rhizopus, Mucor, Rhizomucor Orbital cellulitis, scleritis Thermally Paracoccidioides brasiliensis, Blastomyces Eye lid infection, conjunctivitis, keratitis, dimorphic fungi dermatitidis, Sporothrix schenckii endophthalmitis Histoplasma capsulatum Figure 1 Fungal infections of eye. (a) Shows fungal keratitis with dry gray to dirty white infiltrate and raised edges. (b) Shows keratitis with pigmented infiltrate. (c) Shows pigmented fungal growth on the surface of scleral buckle in a case of fungal scleritis. (d) Shows ulcerated scleritis lesion. technique allows direct visualization of organisms, it has microscopy, a non-invasive, in-vivo technique for limitation of being less sensitive, involving tissue examination of cornea, offers an alternative and has been destruction and having a high sampling error. Confocal found to be useful in diagnosis of fungal and Eye Fungi, atypical Mycobacteria, and Nocardia are important causes of ocular infections P Garg 247 acanthamoeba infections.12 However, the technique is not patients with advanced keratitis, as fungal filaments without limitations; besides the cost of the instrument, it were found to penetrate Descemet’s membrane in is not easy to get good-quality images in painful inflamed 61.5% specimens from advanced keratitis cases eyes, and experience is required for interpretation of (unpublished data). images.13,14 Although penetrating keratoplasty seems to be a better option in patients with deep keratitis, the procedure is Therapeutic challenges associated with several challenges.24 It is not surprising Fungal keratitis cases pose several therapeutic that 35% of the keratoplasty procedures performed for challenges. Only limited numbers of drugs are active fungal keratitis fail within the first month and 50% commercially available for ophthalmic use. Most of the by the end of first year.25 drugs are fungistatic, have limited spectrum of activity, and have poor penetration through ocular structures. Scleritis Therefore, medical treatment fails to control infection in a Fungi are important aetiological agents of infective scleritis significant proportion of cases.15 Some of the new in tropical regions.26,27 In a report published by us, 38% molecules investigated in recent past include azoles cases of infective scleritis were caused by fungi.26 The (voriconazole and posaconazole) and eccinocanidines fungal infection of sclera commonly occurs following (caspofungin and micafungin).16,17 While the accidental trauma or following variety of surgical pharmacological properties, in-vitro susceptibility, as well procedures, but can also occur as an extension from cornea as the anecdotal reports suggest superiority of or choroid and rarely as an endogenous infection.27 voriconazole over other antifungal agents,16 a Fungal scleritis usually presents as slowly progressive randomized clinical trail in South India comparing scleral necrosis with suppuration. Figures 1c and d natamycin with voriconazole in treatment of mycotic document various features of fungal scleritis. keratitis did not find any difference in the scar size, The diagnosis of fungal scleritis is often delayed visual acuity, and perforation rate.18 Therefore, more because the disease in initial stage appears identical to clinical trials are required to provide rigorous evidence that caused by immune-mediated disease. Further, as the basis to guide using these molecules. organisms lie deep in the stroma, negative microbiology is not rare in these cases. The outcome of medical therapy Can we increase drug concentration at the site of infection? alone is usually poor due to poor penetration of topical As penetration into ocular tissues is a major limiting factor, and systemic antifungal agents into avascular sclera. attempts have been made to push the antifungal It is therefore important to: drugs directly into the site of infection. The group from the Bascom Palmer Eye Institute (BPEI) used Consider infective aetiology in differential diagnosis of iontophoresis to deliver amphotericin B into the corneal all cases of suppurative scleritis, especially if there is stroma.19 More recently, clinicians have tried intrastromal history of accidental or surgical trauma or debilitating injection of water-soluble molecules such as amphotericin B systemic disease. and voriconazole. Sharma et al20 published a case series Remember that the negative microbiology does not demonstrating the successful use of this technique in the rule out infection. Such cases
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