Mycotic Keratitis

Mahendra Rai, Marcelo Luis Occhiutto, Mahendra Rai, Marcelo Luis Occhiutto

• Publisher: CRC Press
• Year: 2019
• eBook ISBN: 9780429664557
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

Mycotic keratitis, also known asfungal keratitis, is commonly defined as an inflammation of the cornea. Globally, mycotic keratitis is more common as compared to others eye disorders. Though it occurs in all parts of the world it is more prevalent in tropical and subtropical areas. Mycotic Keratitis emphasizes novel perspectives on mycotic keratitis treatments and addresses different therapies used in treatment. The book is designed to be immensely useful for the students and teachers of microbiology, medicine, mycology, ophthalmology, biotechnology and nanotechnology. Medical microbiology researchers in general and medical mycology in particular will find it a valuable user-friendly book.

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Mycotic Keratitis

An Old Disease with Modern Nanotechnological Solutions

Mahendra Rai,^1,* Avinash P. Ingle,² Indarchand Gupta,³ Pramod Ingle,¹ Priti Paralikar¹ and Marcelo Luís Occhiutto⁴

INTRODUCTION

Mycotic Keratitis (MK) is also known as fungal keratitis and is considered as one of the major causes of corneal blindness, especially in tropical and subtropical environments (Maharana et al. 2016). MK caused by Aspergillus sp. was for the first time described in Germany by Leber in 1879 in a 54-year-old farmer, who had a mild corneal injury due to oat chaff while working with a shredder (Dreschmaschine) (Leber 1879). It is a condition which is usually manifested by severe inflammation, the formation of a corneal ulcer, and hypopyon, with the presence of fungal hyphae within the corneal stroma (Thomas and Kaliamurthy 2013, Venkatesh et al. 2018). It is observed that among all the cases of microbial keratitis, MK accounts for about 1–4%, depending upon the geographic conditions (Gower et al. 2010, Garg 2012).

It is proposed that the frequency of MK is more in developing countries as compared to developed countries (Acharya et al. 2017). As far as the statistics are concerned, no information is available about recent MK cases. But, Thomas and Kaliamurthy (2013) presented some analysis based on old information available. According to them a single institution (L.V. Prasad Eye Institute, Hyderabad) in India reported about 1360 cases of MK during February 1991 and June 2001 (Gopinathan et al. 2009) and Shandong Eye Institute, Qingdao in Northern China reported 654 MK patients from January 1999 to December 2004 (Xie et al. 2006). On the contrary, Royal Victorian Eye and Ear Hospital, Melbourne, Australia documented only 56 cases of MK between July 1996 to May 2004 (Bhartiya et al. 2007) and according to clinical and microbiology records of the New York Eye and Infirmary, USA only 61 cases were recorded during January 1, 1987 and June 1, 2003 (Ritterband et al. 2006). From the above mentioned data, it is clear that number of MK cases in developing countries are considerably higher than that of developed countries.

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¹ Nanobiotechnology Laboratory, Department of Biotechnology, SGB Amravati University, Amravati-444602, Maharashtra, India.

² Department of Biotechnology, Engineering School of Lorena, University of Sao Paulo, Estrada municipal do Campinho, sn, 12602-810 Lorena, SP, Brazil.

³ Department of Biotechnology, Government Institute of Science, Nipatniranjan Nagar, Caves Road, Aurangabad-431004, Maharashtra, India.

⁴ Instituto de Oftalmologia Tadeu Cvintal, University of Campinas, São Paulo, Brazil.

^* Corresponding author: [email protected], [email protected]

The most common fungal genera responsible for mycotic infections include Fusarium, Aspergillus, Curvularia, Bipolaris and Candida (Gower et al. 2010, Revankar and Sutton 2010, Garg 2012, Paty et al. 2018). Worldwide it was observed that Aspergillus species are most frequently associated with MK; however, as mentioned above, it varies greatly depending on geographic regions. In one of the studies performed, it was reported that in India Aspergillus species is the most common causative agent (27 to 64%), followed by Fusarium (6 to 32%) and Penicillium (2 to 29%) recovered from patients suffering from MK. However, in another study performed with 275 patients, 198 patients were diagnosed with MK. From these patients, about 210 fungal isolates were recovered and identification confirmed that these isolates belong to 17 genera and 29 species. Among these isolates, Fusarium was found to be most common genus (49.5%), followed by Aspergillus (18.6%), Candida (12.4%), and other genera (19.5%) such as Alternaria, Acremonium, Cladosporium and Beauveria (Al-Hatmi et al. 2018, Castano and Mada 2018). Moreover, other causative agents of MK are listed in Table 1.1.

Although, various approaches such as pharmacological treatment, surgery and corneal crosslinking are investigated for the management of MK, unfortunately none of these approaches are very effective in the management for MK. Pharmacological agents are topical antifungal medications and each of them showed varied corneal penetration activity and effectiveness. Topical use of antifungal agents is still considered as a gold standard treatment protocol because other therapies like the use of intra-stromal injections did not show any proven benefit over topical pharmacological treatment (Acharya et al. 2017). It is postulated that delay in diagnosis and treatment of MK can result in many mild complications like formation of abscess and severe complications like corneal scarring which may lead to visual disability. In addition, such infections may lead to disruption of the anterior segment of the eye with increased intraocular pressure leading to glaucoma and endophthalmitis which is sufficient to make the patient visually handicapped (Acharya et al. 2017). Considering the severity of MK and unavailability of effective treatment strategies, it is necessary to expedite the scientific efforts by the researchers in this particular field, so as to develop effective management strategies with no or negligible side effects.

In this chapter, we have focused on various important topics related to MK, which mainly include worldwide severity and epidemiology of disease, existing methods for diagnosis, various management approaches and toxicological issues.

Epidemiology and Severity of MK

MK is mostly observed in male outdoor workers (Bharathi et al. 2003, Raval et al. 2014). It is proposed that occupation plays an important role in the appearance of infectious keratitis (Raval et al. 2014). Veena et al. (2017) reported keratitis in 380 out of 450 (84.4%) corneal scrapings from patients, which include a vast range of fungi viz. Asperigillus, Fusarium, Yeast, Paecillomysis, Acremonium, Curvularia spp. and Scytidilia spp. In addition, the studies performed by Leck et al. (2002) and Bajpai et al. (2016) also demonstrated the severity of MK. Apart from these, some other isolates were found to be responsive to topical antifungals but some were responsive to oral administration of drugs along with a topical one.

Table 1.1: Various causative agents in mycotic keratitis (Adapted and modified from Thomas and Kaliamurthy 2013; with a copyright permission from European Society of Clinical Microbiology and Infectious Diseases Published by Elsevier Ltd.).

Fungal keratitis in rigorous conditions penetrate Descemet’s membrane and invades the anterior chamber and pupillary spaces (Pleyer et al. 1995) thus showing feathery margins, raised surface, satellite lesions, and non-yellow infiltrate colour along with moderate-to-large ulcers (Thomas et al. 2005, Dalmon et al. 2012, Chidambaram et al. 2018). The severity of fungi causing keratitis is a result of certain characteristics like the adherence capacity of the fungus to cells, enzyme and toxin production which destroys anatomical defence (Gopinath et al. 2009, Nath et al. 2011). MK is sometimes followed by an autoimmune condition known as Sympathetic Ophthalmia (SO), which is a result of retinal antigen reaction to conjunctival or orbital lymphatics. In the period of 15 months, 23 new cases were identified in a study by British Ophthalmic Surveillance Unit with the incidence of SO as 0.3/100000 (Kilmartin et al. 2000, Buller et al. 2006). SO is characterized by the sudden outbreak of immune responsive reaction involving exposure of retinal antigens and the concurrent appearance of corneal infections (Liddy and Stuart 1972).

Wu and colleagues (2004) established a mouse model for the demonstration of corneal fusariosis caused by F. solani, permitting assessment of fungal infection and pathogenesis. Topical corneal inoculations of F. solani were performed in immunocompetent and cyclophosphamide-treated adult BALB/c (i.e., immunosuppressed) mice and observed daily for 2 weeks. Histopathological examination following quantitative fungal recovery was carried out at regular intervals. The dose dependent responses were observed in immunosuppressed mice, which resulted in increased disease severity and deferred fungal pathogen clearance. Under severe conditions, fungal hyphae, stromal edema, and inflammatory cells were evident in corneal tissue. Although immunosuppressed mice showed infection after corneal surface scarification which was assessed both in vivo and in vitro methods (Wu et al. 2004).

In another study, the MK mouse model was generated by intrastromal injections of A. fumigatus, which were then divided into different groups on the basis of treatment to be given, such as PBS treated (group I), voriconazole treated (group II), FK506, i.e., tacrolimus treated (group III), and voriconazole and FK506 treated (group IV). After the zymosan stimulation (10 mg/ml for 8 hours) the mRNA and protein expression levels of type I and II INFs were found to be profoundly elevated in macrophages, neutrophils, lymphocytes, and corneal epithelial cells (A6(1) cells). Also, the inflammatory cytokines were quantitatively analyzed at regular time intervals by quantitative real-time PCR (qRT-PCR) and western blotting (Zhong et al. 2018).

Epidemiology refers to the study of the distribution and determinants of a disease in a given population at a given period of time. Whereas prevalence is the rate or frequency with which the disease is found in a group or population under study at a particular point in time, and the incidence is the frequency with which new cases of a disease arise over a defined period of time (Sommer 1980). There are no previous reports on the prevalence of the disease. The prevalence of disease and severity can be estimated on the basis of infection cases presented to the hospitals (Tuft and Tullo 2009).

Microbial keratitis was mainly reported from North America, Australia, the Netherlands and Singapore and MK was largely reported in India (Shah et al. 2011). In Brazil, epidemiological study was performed on the basis of sales distribution of antifungal eye drops, which showed the linear regression relationship between reduction of humidity and antifungal eye drop sales, i.e., more cases of MK observed during the third quarter of the year when the agricultural activities are at the peak (Ibrahim et al. 2012).

Keratitis caused due to filamentous fungi is primarily observed in people continuously working in an outdoor environment like agriculture, where the penetration and invasion by fungal conidia is secondary to trauma (Gopinath et al. 2009, Nath et al. 2011). Fungal conidia and other traumatizing materials from plant and animal origin or the dust particles are responsible for intrastromal and intracameral invasion (Thomas 2007, Arora et al. 2011, Hu et al. 2016, Veena et al. 2017). The fungal species isolated from patients is primarily dependant on environmental factors like wind, humidity and rainfall. For example, Curvularia spp. are more frequent along the Gulf of Mexico during hotter and moister summers because of more airborne spores of Curvularia spp. in this period (Leck et al. 2002, Thomas 2007). The yeast-like non-filamentous fungi mainly include Candida albicans and related fungi which causes keratitis in the situations where there is insufficient tear secretion, defective eyelid closure or systemic causes includes diabetes mellitus and immunosuppression (Sun et al. 2007).

Current methods for diagnosis of MK

The diagnosis has been a vital part in the tr...

Table of contents

• Cover
• Title Page
• Copyright Page
• Foreword
• Preface
• Table of Contents
• 1. Mycotic Keratitis: An Old Disease with Modern Nanotechnological Solutions
• 2. Fungal Keratitis Due to Fusarium
• 3. Mycotic Keratitis Caused by Dematiaceous Fungi
• 4. Microbiological Diagnosis of Fungal Keratitis
• 5. Special Cases in the Diagnosis and Treatment of Fungal Keratitis
• 6. Diagnosis and Treatment of Fungal Keratitis
• 7. Presentation, Clinical Signs and Prognostic Factors of Mycotic Keratitis
• 8. Management of Fungal Keratitis
• 9. Pathogenesis of Fungal Keratitis
• 10. Epidemiology of Mycotic Keratitis
• 11. Exploring Potential of Nanocarriers for Therapy of Mycotic Keratitis
• 12. Novel Perspectives in Treatment of Fungal Keratitis
• 13. Therapeutic Approach in Fungal Keratitis
• 14. Surgical Management of Mycotic Keratitis
• Index
• Color Plate Section