Nepal Journal of Epidemiology

eISSN 2091-0800

Short Communication Open Access

Fungal keratitis: study of increasing trend and common determinants

Yogesh Acharya1, Bhawana Acharya2, Priyanka Karki3

Abstract:
Fungal keratitis is one of the leading cause of ocular morbidity. Fungal keratitis possesses a clinical challenge
due to its slow pathologic process, overlapping features, diagnostic difficulty, and potential complications. Its
increasing trend can be attributed to the use of contact lens, non-judiciary corticosteroid, and vegetative
trauma. Early diagnosis and treatment is the cornerstone for its effective control. Knowledge of pathological
course and clinical characteristics of fungal keratitis will definitely add in early diagnosis and treatment, with
reduction in ocular morbidity. This review article explores the risk factor of fungal keratitis, its clinical course
and management strategy.

Keyword: Fungal eye Infections; contact lenses; risk factor; prevalence; complication.

Correspondence: Dr. Yogesh Acharya, MD, Assistant Professor, Research director, Department of
epidemiology and preventive health, Avalon University School of Medicine, Santa Rosaweg 122-124,
Willemstad, Curacao, Netherland Antilles
Email: [email protected]
Received 15 October 2016/Revised 20 May 2017/Accepted 30 May 2017
Citation: Acharya Y, Acharya B, Karki P. Fungal keratitis: study of increasing trend and common
determinants. Nepal J Epidemiol. 2017;7(2); 685-693.
This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2017 CEA& INEA. Published online by NepJOL-INASP.

www.nepjol.info/index.php/NJE

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 million dollar in health care [4]. Contact lens provides a direct
Introduction threat for microbial keratitis and around 26 million contact
Eye is the most beautiful thing in the world. Pure appreciation lens users have significant ocular health risk. Fungal keratitis
of beauty is only possible with the intact functioning eye. It is is also an important predictor of ocular health in developing
well said that vision controls the mind. We believe in what we countries and is a major cause of unilateral blindness.
see and we prefer to see what we believe in. Eye is a delicate Risk factors:
organ and is kept free of pathogens and harmful Eye is susceptible to microbial infection due to local and
microorganism by its natural protective mechanism. This systemic factors that invade the protective mechanism. These
natural check and balance is absolutely necessary for a healthy local factors like trauma to the eye ball, introduces and
eye. Breach of this delicate balance of protective environment inoculates various fungal members into the eye with or
can lead to ocular diseases with visual morbidity. without bacterial associates. Risk factors associated with
Cornea is the major refractive and protective outer layer of fungal keratitis are Male, Trauma, Contact lens use, Topical
eye. Inflammation of the cornea is known as keratitis. There corticosteroid use, Diabetes mellitus, and Low socioeconomic
are several causes of keratitis: infectious, physical or chemical. status.
Infectious or microbial keratitis is a predictor of general health Vegetative ocular trauma is undoubtedly the most common
due to its higher incidence in community and associated risk factor for fungal keratitis. Ocular trauma is essential to
complications. Microbial keratitis has long been a challenge breach an intact corneal epithelium for introduction of
for the physicians’ due to its varied presentation, overlapping microbial organism. Vegetative trauma predisposes to fungal
symptoms, and rapid progression. Bacterial keratitis is the infections being an important identifiable cause. It is
most prevalent amongst microbial keratitis. But there has been extremely rare to encounter a case of fungal keratitis in an
a constant surge in fungal keratitis in the recent times due to otherwise healthy eye, without any associated risk factors.
multiple overlaying factors. Despite being a slow process in This is because intact cornea is fairly resistant to microbial
comparison to bacterial counterpart fungal keratitis possesses infections. Trauma helps to introduce and inoculate fungi
considerable ocular morbidity. Fungal keratitis carries a directly into the cornea. Male are particularly more prone to
significant risk in developing countries and is one of the fungal keratitis, as outdoor activities and farming practices
leading causes of vision loss [1]. Vegetative trauma in predisposes to vegetative trauma.
agriculturist and sand particles are the most common causes of CL use has become widespread in recent times. With an
mycotic keratitis in developing countries [2]. Middle age increase in CL use in the general community, the overall cases
workingmen are more susceptible and constitutes majority of of fungal keratitis are also increasing. Although CL is
cases. Whereas, contact lens (CL) use is the leading cause in implicated for major proportion of fungal keratitis, the overall
developed countries. prognosis is better in contact lens induced keratitis [3]. Factors
Fungi are distinct group of microbial organism. They are associated with CL use and chances of fungal keratitis include
ubiquitous microbial eukaryotic pathogens. Fungal keratitis, nocturnal use during sleep, male gender, smoking history and
also known as keratomycosis, is an important cause of socioeconomic status, relating to unhygienic contact lens
microbial keratitis in the general population. Fungi are behavior [5]. Microbes have higher chance of adherence to
classified as yeasts or moulds. Yeasts ore oval or round cornea with CL. Hypoxia and hypercapnia are pathogenic
bodies, with blastoconidium. Moulds are filamentous changes associated with CL induced microbial keratitis [6].
structures, known as hyphae. Hyphae can form a large mass of Antibiotics and corticosteroids use also render the eye
filaments known as mycelium. These filaments can be septate susceptible to infections. Steroid has been the cornerstone of
or non-septate. Fungi are capable of reproducing sexually as medical management for inflammatory disease process in
well as asexually. Sexual reproduction takes place through modern medicine. Excessive steroid use leads to decrease in
formation of spores and asexual by conidia or host defense mechanism and creates a favorable environment
sporangiospores. Fungi infecting cornea are generally in for fungal inoculation. Systemic disease like diabetes mellitus
asexual phase of life cycle, when cultured. Yeast like fungi are has emerged as a major risk factor in the recent years. Diabetes
associated with the past history of ocular diseases, surgery and is becoming a global public health problem. Host defense is
steroid use with poor clinical outcome. Filamentous fungi are severely impaired in diabetes and high glucose provides a
usually found in patients with a history of ocular trauma [3]. suitable growth media for microbial organism.
Epidemiology:
There are more than 900,000 physician visit and 58,000
emergency visits related to keratitis and contact lens use in
US, accounting an estimated expenditure of around $175

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 Table-2: Commonly isolated fungi in microbial keratitis.

Fungi

Common Uncommon

1. Fusarium 1. Lophotrichus spp.

2. Aspergillus 2. Alternaria spp.
3. Candida 3. Acremonium spp.
4. Cladosporium 4. Cryptococcus albidus
5. Curvularia 5. Pythium insidiosum
6. Rhizopus 6. Other : Beauveria bassiana,
Paecilomyces,
Cunninghamella spinosum,
Scedosporium apiospermum,
Rhodotorula mucilaginosa,
Cylindrocarpon lichenicola,
Cladorrhinum bulbillosum.

Fig-1: Peripheral corneal fungal keratitis in slit-lamp Fig-2: Fungal keratitis with satellite lesions in slit-lamp
microscopy. microscopy.

Fig-3: Corneal fungal ulcer with Hypopyon in slit-lamp Fig-4: Corneal fungal abscess at periphery with infiltration
microscopy. in slit-lamp microscopy.

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Fungal species: feathery margins and endothelial plaques (Fig-1). Satellite
Apergillus and Fusarium are two major cause of fungal lesion is typically seen in fungal keratitis (Fig-2). Hypopyon is
keratitis. Aspergillus is associated with higher incidences of detected in most of the cases, which can lead to ocular
complications but shows better response with antifungal hypertension (Fig-3). The identified risk factor for hypopyon
medications. Fungal keratitis due to Candida species has the includes infection with Fusarium and Aspergillus, in
worst clinical outcome [7]. Common fungal isolates from particular; and long duration of symptoms with larger lesion
corneal scrapping of patients with clinically suspected keratitis size [23]. It is not uncommon to see deep stromal infiltration,
are listed in Table-2. corneal abscess and dissemination of infection.
Fusarium is mainly associated with contact lens induced Once the presumptive diagnosis is made, corneal scrapping
keratitis. It is necessary to recognize Fusarium keratitis early and corneal biopsy is taken as required for inoculation and
in the period of its progression and adequate measures should isolation of organism. There are different ways to illustrate the
be taken to minimize the ocular morbidity [8]. There have presence of fungal keratitis. These methods include Gram’s
been multiple reported incidences of Fusarium keratitis with stain, Potassium hydroxide (KOH) mount, and Calcofluor
CL and ReNu CL solution (Bausch & Lomb) for lens care. white fluorescent staining and finally culture. Common culture
This can be attributed to poor contact lens hygiene and media for fungus is Sabourauds Dextrose Agar. Direct
improper use habits. Some of these patients required visualization with KOH wet mount is commonly implicated
emergency penetrating keratoplasty for severe complicating followed by culture, being the most conclusive. (2) KOH is
keratitis despite the medical treatment [9]. There are different applied in corneal scrapping to dissolve epithelial strands. Use
Fusarium species and complexes responsible for keratitis; of 10% KOH better aids in fungal recognition and diagnosis.
Fusarium solani species complex, Fusarium oxysporum Definitive diagnosis lays on the foundation of culture and
species complex and Gibberella fujikuroi species complex. isolation. Culture facilitates the direct visualisation of fungi
Fusarium solani species complex is the most common [10]. under microscopy. Culture and sensitivity will also guide the
There are many other fungal species implicated in fungal use of appropriate anti-fungal therapy for superior clinical
keratitis. These fungal species are responsible for sporadic recovery.
cases of fungal keratitis and include: Lophotrichus spp. [11], Polymerase Chain Reaction [24] and dot hybridization [25] are
Alternaria spp. [12], Acremonium spp. [13], Cryptococcus newer rapid detection technique for sensitive and specific
albidus [14]), Pythium insidiosum [15], Beauveria bassiana diagnosis of fungal species. They have higher sensitivity than
[16], Paecilomyces [17], Cunninghamella spinosum [18], KOH wet mount and Gram smear [26] and are able to detect
Scedosporium apiospermum [19]), Rhodotorula mucilaginosa the fungus successfully in culture negative cases [27]. PCR
[20], Cylindrocarpon lichenicola [21], Cladorrhinum high-resolution melting analysis is a variant PCR technique
bulbillosum [22]. Lophotrichus species were isolated from the that is effective in differentiating between filamentous fungi
necrotic corneal sample complicating fungal keratitis after dog and yeast form [28].
paw traumatic injury [11]. Management:
Presentation: Management of fungal keratitis is directed by the objectives:
Keratitis usually presents with ocular pain, foreign body a) distinctive diagnostic procedure to correctly identify the
sensation and blurred vision. Affected eye will be red and the disease process, b) concurrent use of effective treatment
patient can have injection of the conjunctiva. Intense modalities, c) eradication of the disease process, d)
inflammatory process after infection usually results in copious minimizing the complication, and e) prevention of future
amount of ocular secretions but secretions in fugal keratitis are recurrences. This is achieved by the use of topical antifungal
usually scanty in contrast to other microbial infections. medication with or without surgical interventions. It is
Diagnosis: absolutely necessary to halt the disease progression early in
Diagnosis of fungal keratitis starts with strong clinical the pathogenic process to reduce the overall complications and
suspicion with concurrent presence of risk factors. Diagnosis associated ocular morbidity.
is strongly supported by suggestive clinical presentations and Pharmacological management:
fungal isolation from corneal sample. Antibiotic Pharmacological treatment of fungal keratitis rest on topical
unresponsiveness provides a clinical clue for diagnosis. Direct anti-fungal medications. There are currently no available
microscopic examination of cornea with subsequent of corneal antifungal recommendations in accordance with specific
sample culture, still remains the gold standard for fungal fungal isolation. Many of these anti-fugal differ in their
diagnosis. corneal penetration activity and effectiveness. Topical
Keratitis is best examined under slit lamp microscopy. Slit instillation of the active antimicrobial pharmacological agents
lamp microscopy will show dry, thick and raised corneal is still remains the gold standard treatment protocol. There are
surface. Majority of cases will have stromal infiltrates with
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conflicting reports of intra-stromal injections but it has not keratitis with corneal melting. They decrease corneal
shown proven added benefit over topical instillation [29]. perforation and recurrences in majority of patient [38]. CXL-
Natamycin remains the cornerstone of anti-fungal therapy. PACK is safer procedure but it can increase the likelihood of
Natamycin (5%) is the treatment of choice for filamentous bacterial keratitis in the patient because of epithelial removal
fungi. Poor response to natamycin is directly related to necessary for the procedure. In addition to to it there are other
increase infiltrate, larger scar size and perforation probability potential factors responsible for causing keratitis, which can
[30]. For candida species topical amphotericin B (0.1-0.3%) is range from use of contact lens after local corticosteroid after
frequently implicated with superior response [31]. There has the procedure. It is necessary for the physician to properly
been increasing evidence of topical voriconazole use in fungal counsel the patient about this complication and caution should
keratitis with favourable clinical outcome. Topical be taken to avoid them [39, 40].
voriconazole is especially useful in fungal keratitis not Complications:
responding to natamycin [29]. Topical voriconazole is also Fungal keratitis can result in several complications leading to
effective against Cladosporium species [32]. There are visual disability. These complications can range from
different patterns of drug susceptibility in different groups of formation of abscess and mild to severe corneal scarring with
fungi. Therefore it is warranted that fungal specimen is taken loss of vision due to dissemination (Fig-4). Severe long-term
and culture grown, for identification and antimicrobial disease process can lead to corneal perforation and
sensitivity, if no response is visible after initiation of treatment dissemination of infection. Fungal infection also facilitates
[33]. other superadded microbial keratitis. Patient can have an
Some fungal infection responds to topical fluoroquinolones, anterior segment disruption with increased intraocular pressure
namely moxifloxacin [34]. This initial response leads to leading to glaucoma. Similarly it can result in endophthalmitis
assumption of bacterial infection and eventually accounts for resulting in evisceration making the patient visually handicap.
higher chances of complications with delay in diagnosis. It is Recent developments:
necessary to understand that fluoroquinolone monotherapy There are newer approaches for diagnosis of fungal corneal
will not be able to control most of the fungal infection and in infection and treatment methods. Dot hybridization assay has
turn can lead to prolongation of the disease course with been used successfully to diagnose Cryptococcus albidus, a
chances of relapse. rare fungi which and treated with intra-stromal injection of
Surgical management: Amphotericin B [14]. MicroRNAs (MiRNAs) are RNA
Surgery is definitely a choice for fungal keratitis, when molecules in humans that do not code. They are responsible
response to pharmacological agent is poor and there is for regulation of functions in the human cell and show very
imminent threat of perforation. Surgery will eliminate the high tissue specificity. They can be identified by PCR
necrotic, infectious and antigenic source of ocular insult with technique. They are evidences of increased MiRNA expression
creation of favourable environment for pharmacological agents in fungal keratitis, indicating its role in pathologic process and
to act and fastens healing [35]. potential target for modifications in the future [41].
Periodic debridement is an excellent procedure to remove dead Calprotectin is a neutrophil derived protein with potent
and necrotic tissues from cornea. Debridement helps to antimicrobial property. Calprotectin uses Zn and Mn chelation
improve the blood circulation, increase topical drug to inhibit fungal growth. It has proven beneficial effect in
effectiveness and finally decrease the overall microbial load Aspergillus fumigatus growth inhibition in experimental mice
for speedy recovery. Conjunctival flap and lamellar or model and awaits further work in humans [42]. Lectin-like
penetrating keratoplasty is applied in severe keratitis where a oxidized low-density lipoprotein receptor 1 (LOX-1) [43],
pharmacological agent fails. Patch graft and transplant can be spleen-tyrosine kinase (Syk) [44, 45] and intracellular
used as final resort to restore the cornea and normal vision, nucleotide-binding oligomerization domain-containing protein
whenever possible. (NOD)-like receptors [46] have also been isolated from
Corneal crosslinking: Aspergillus infected corneal epithelial cells. LOX-1, Syk and
Corneal crosslinking is an effective approach to control NOD have basic role in modification of signalling pathways
microbial keratitis. It is proven to have an excellent ulcer and its inhibitors can be used to regulate fungal growth in the
healing properties and induce overall reduction in hypopyon future.
formation. There are few incidences of opacification of lens Photodynamic therapy with rose Bengal has been successful in
after crosslinking procedure [36]. Its efficacy is limited in viral restriction of certain fungal growth [47]. Riboflavin/UV-A has
keratitis due to incidences of corneal melting and tectonic also been effective in Fusarium, Aspergillus and Candida after
keratoplasty [37]. Corneal collagen cross-linking with pre treatment with amphotericin B [48]. Combination therapy
photoactivated riboflavin (CXL-PACK) has shown a of antifungal medication with UV-A can prove safe and
promising outcome in-patient with advanced microbial alternative to single therapy [49].
689
Discussion 7. Spleen-tyrosine kinase (Syk)
There has been progressive incline in microbial keratitis in the 8. Nucleotide-binding oligomerization domain (NOD)
recent time. Fungal keratitis, in particular, has the highest risk Authors’ contributions:
and possesses a significant threat for increased ocular YA and BA conceived the idea. YA, BA, and PK reviewed the
morbidity owing to its slower course and diagnostic difficulty. literature and drafted the manuscript. All authors reviewed,
This rapid surge can be attributed to increased contact lens edited and agreed on the final version of this manuscript.
use, and non judiciary antimicrobial and corticosteroid use, Authors’ affiliations:
1
complicated by systemic disease interfering with immune Assistant professor, Avalon University School of Medicine,
status. Most of the cases in western world can be attributed to Willemstad, Curacao, Netherland Antilles.
2
unhygienic contact lens use, whereas vegetative trauma in Registered nurse, VHA home health care, Toronto, Ontario,
working class is the major cause in developing countries. Male Canada.
3
has higher incidences of fungal keratitis but corneal re- Medical officer, Nobel Medical College and Hospital,
epithelialization time is higher in female in comparison with Biratnagar, Morang, Nepal.
males, accounting higher recovery period [50]. Conflict of interest:
Fusarium and Aspergillus are the common isolates from The authors hereby announce that they have no conflict of
corneal scrapping, Fusarium associated with CL use. Healthy interest arising from the study.
eye is relatively immune to fungal infection and ocular trauma Source of Support:
provides an excellent opportunity for pathologic fungal Nil
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