See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/341869442

Fungal Keratitis

Chapter · June 2020

CITATIONS READS
7 1,022

3 authors:

Ayman Elnahry Gabriel Castaño

Bascom Palmer Eye Institute Los Andes University (Colombia)
85 PUBLICATIONS 369 CITATIONS 6 PUBLICATIONS 23 CITATIONS

SEE PROFILE SEE PROFILE

Pradeep Kumar Mada

Comanche County Memorial Hospital
32 PUBLICATIONS 101 CITATIONS

SEE PROFILE

All content following this page was uploaded by Ayman Elnahry on 09 July 2020.

The user has requested enhancement of the downloaded file.

7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.

Fungal Keratitis
Gabriel Castano; Ayman G. Elnahry; Pradeep Kumar Mada.

Author Information

Authors

Gabriel Castano1; Ayman G. Elnahry2; Pradeep Kumar Mada3.

Affiliations
1 UT Health San Antonio
2 Cairo University, Faculty of Medicine
3 Louisiana State University Shreveport

Last Update: June 2, 2020.

Introduction
Bacteria, viruses, fungi, and protozoa are all causes of microbial keratitis. Fungal keratitis
(FK) was first documented in 1879, and its incidence has been increasing for the past 30 years.
It accounts for about 40% to 50% of all microbial keratitis cases.[1][2][1] FK is a serious
condition that if not properly treated can lead to corneal destruction and endophthalmitis with
severe loss of vision. Early diagnosis and management are, therefore, essential to prevent long-
term complications including blindness.[3][4]

More than 100 different fungal species are capable of causing FK.[5] Monomorphic fungi can be
classified into yeast and filamentous fungi and both are responsible for cases of FK. The specific
type of fungus responsible for FK depends on several factors including personal risk factors,
regional temperature, climate conditions, geographic location, and urbanization.[6]

Trauma, immunocompromised state, ocular surface disease, and contact lens wear are the most
prevalent personal risk factors associated with FK and may predispose to different types of
fungal infections.[6][7][6]

Clinically, it may be challenging to diagnose a fungal infection as a cause for keratitis and
diagnostic delays are common with negative or delayed culture results. A high index of suspicion
is, therefore, usually required depending on the presence of specific risk factors for FK. Even if
the diagnosis is made, management is still challenging as many antifungal agents have poor
penetration into the cornea.

Etiology
Many fungal species can result in FK, however, the most commonly implicated are Fusarium,
Aspergillus, and Candida species.[5] The causative organism of FK may differ according to
several factors including regional temperature, climate, and urbanization. In a study performed in
India on FK, Aspergillus species were the most commonly isolated species followed by
Fusarium.[8] This was also confirmed in several other studies from India, with one study
showing that Aspergillus was responsible for more than 55% of all FK cases, suggesting that
Aspergillus species are the most common cause of FK in the Indian subcontinent.[9] Other
studies, however, have shown that Fusarium was the most common etiology of FK in other parts
of the world including south India.[10][11] In a large study from the USA over a 7 year period,
39% of FK cases were caused by Fusarium, while 22% were caused by yeasts including

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 1/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

Candida.[7] In another study of 2065 cases of confirmed fungal keratitis in central China, the
predominant fungal species was also Fusarium (>50%), followed by Aspergillus (>9%) and
Alternaria (>7%).[12] This was similar to findings from a study performed in north China.[1] In
a study from the United Kingdom, however, Candida (57%) was the most prevalent causative
fungus followed by Aspergillus (17%).[6] This indicates that the causative organism of FK may
differ according to the geographic location.

The prevalence of specific types of fungi causing FK also depends on specific patient-related risk
factors. For example, Fusarium species are found more commonly in association with trauma
and contact lens use,[7][13][7] while Candida species are found more in association with ocular
surface disease and topical steroid use.[6] Trauma, especially with vegetative matter, is an
important risk factor for filamentary fungal infections in general, including Fusarium,
however, it may also result in bacterial infections.[14][12][14] Accordingly, certain occupations,
like those involving agriculture, may carry an increased risk of microbial keratitis including
fungal keratitis.[12] The risk of corneal fungal infections may also be increased with a lack of
personal hygiene including poor hand hygiene and overnight contact lens wear.[15]

Corneal refractive surgery including laser in situ keratomileusis (LASIK) may also rarely be a
cause of fungal keratitis that could lead to severe consequences if not properly treated.[16]
Various fungal species responsible for post-LASIK FK have been isolated including Candida,
Fusarium, Aspergillus, and Alternaria species.[17][18][19][20] This could be due to
inappropriate operative room sterilization techniques or poor postoperative hygiene.[17]

Epidemiology
Like most infectious diseases, geographical location, and socioeconomic status influence the
prevalence and cause of FK. In the United States, warm places in southern locations like Florida
have a higher incidence of FK compared to colder places in the north.[21][22]
[21] Fusarium, Candida, and Aspergillus are the most frequently isolated species causing FK in
the USA,[7] while in India, Aspergillus is the most common cause.[9] Fusarium is a particularly
common cause of FK in warm climates such as Brazil,[23] while Candida may be more common
in temperate climates.[22]

The overall incidence of FK seems to be markedly higher in certain parts of the world. In a study
of FK in Hyderabad India, 1360 patients with FK were seen over a period of 10 years in a single
institute, while in a study from central China, 2065 cases were documented over a 9 year period.
[12] In a study in Melbourne Australia, however, only 56 cases were seen in 8 years,[24] while in
a study from New York, only 61 eyes with FK were documented over a 16 year period.[25] This
may be due to climate, environmental, occupational, or behavioral differences.

An estimated 45 million residents in the USA use contact lenses.[26] Contact lens use can lead to
microbial keratitis, especially if not properly used, and it is estimated that more than 80% of
contact lens users in the USA in different age groups have at least one behavior that makes them
at risk for developing a contact lens-associated eye infection.[27] These risky behaviors include
wearing contact lenses overnight and washing contact lenses with tap water. In a major outbreak
of Fusarium keratitis across the USA and many other countries of the world between 2005 and
2006, however, cases were eventually traced back to a specific brand of multipurpose contact
lens disinfecting solution, indicating the importance of the continuous monitoring of these
products and their components to decrease the risk of future outbreaks of contact lens-associated
eye infections.[28]

Several studies have shown a higher incidence of FK in young adult males, possibly due to more
outdoor activities and higher incidence of trauma.[29] In a large study of Chinese patients with
https://www.ncbi.nlm.nih.gov/books/NBK493192/ 2/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

FK, more than 60% were males, and more than 75% were aged between 30 and 60 years.[12]

Pathophysiology
FK commonly results from fungal access into the corneal stroma through a defect in the corneal
epithelium; this is probably the reason behind the increased risk of FK in association
with trauma and foreign bodies that lead to loss of the integrity of the protecting epithelium.
Injury with vegetative matter may result in direct inoculation of fungal conidia present on their
surface into the corneal stroma leading to initiation of infection or injure the overlying corneal
epithelium permitting fungal invasion.[1][13] Once in the tissue, fungi start to replicate in the
stroma spreading circumferentially with satellite lesions and penetrating deeply into the stroma
to reach Descemet's membrane and eventually the anterior chamber. This may eventually lead to
corneal perforation and endophthalmitis if the infection is not overcome by the natural body
defenses or if proper treatment is not administered. Fungi can also spread from the cornea into
the sclera and surrounding structures, leading to severe consequences such as scleritis and
panophthalmitis.

The cornea is avascular, and on top of its barrier capacity, is immune privileged with restricted
defense mechanisms, dendritic cells, immune cells, and immunoglobulins, making it easy to be
colonized by fungi. Fungi also secrete various toxins and enzymes including serine proteases and
matrix metalloproteinases that help in corneal invasion and colonization.[2] The associated
inflammatory reaction from immune cells in the cornea, especially polymorphonuclear
leukocytes, may result in further damage to corneal tissue.[2]

Histopathology
Gross granular infiltration of the corneal epithelium and the anterior stroma is the main finding in
FK with collagen destruction, coagulative necrosis, and stromal fungal infiltration seen on
microscopy. FK is usually associated with less purulent inflammatory cellular infiltration
compared to bacterial keratitis.[30] Having low neutrophil infiltration in the cornea is a positive
finding as they are the ones that contribute the most to the destruction of the cornea with the
intent to control the causative organism.[2] Lymphocytes and plasma cells are also often seen in
FK.

Various stains can be used to detect fungi in corneal tissue or scrapings including potassium-
hydroxide, gram staining, Giemsa staining, lactophenol cotton blue, methenamine silver, and
calcofluor white.[22] This allows visualization of both fungal hyphae and yeast cells and helps in
the early differential diagnosis of the causative organism before the results of cultures are
available.[31] It may also allow the detection of a mixed fungal and bacterial infection. Different
hyphal growth patterns have been observed histopathologically and may also help in the
differential diagnosis of the specific filamentous fungus responsible for the condition including
Fusarium hyphae that lay parallel to the lamellae of the corneal stroma, and Aspergillus hyphae
that grow vertically.[32]

History and Physical

The history and clinical picture of FK may differ according to the causative organism, depending
on whether it is a filamentous fungus or yeast.[22] General features of microbial keratitis are
usually present including blurring of vision, pain, redness, discharge, and blepharospasm. In
addition to corneal infiltration, patients may have signs of inflammation of the anterior chamber
with hypopyon. In cases of FK due to filamentous fungi, there may be a history of trauma with
vegetative matter, and patients usually present with an ulcer characterized by elevated firm
slough, hyphate lines that extend beyond the edge of the central ulcer, and feathery satellite
https://www.ncbi.nlm.nih.gov/books/NBK493192/ 3/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

stromal lesions. Patients with FK due to yeast fungi may have a history of an ocular surface
disease or immunosuppression with a clinical picture that resembles more bacterial keratitis but
with a slower progression. Although it may sometimes be possible to differentiate a fungal
etiology from a bacterial etiology of microbial keratitis based on the clinical picture alone, this
may not always be the case, and prediction of the causative fungal genus or species responsible
for the condition may be even more challenging and inaccurate.[33]

Evaluation
Laboratory evaluation of a case of FK begins with the collection of an appropriate sample for
testing. These specimens are used for direct examination by microscopy using various stains
such as Giemsa and Gomori methenamine silver stains, culture, histologic testing, and other
tests.[34] Because fungi have the predilection to penetrate deep into the cornea, tissue swabbing
is usually inadequate in confirming a fungal infection and deep corneal scrapings are usually
needed.[35][36] A corneal biopsy may sometimes be needed to obtain an adequate sample.
Ideally, every sample should be sent for polymerase chain reaction (PCR) and culture, especially
if corneal scraping stains are negative.[35][36] Fungal cultures usually take from 1 to 35 days for
fungal growth and include Sabouraud glucose neopeptone agar, blood agar, thioglycolate broth,
and brain heart infusion, which allow isolation of different types of fungi.[34][36] A major
disadvantage of fungal cultures, however, is the relatively low sensitivity with false-negative
results possibly due to the small amount of material available from corneal scrapings.[35]
[36] This is especially true for cases that have been treated with antifungal agents. PCR testing
has been proposed as a more sensitive method of diagnosing FK that allows accurate species
identification and takes about 4 to 8 hours, however, it may be less specific with false-positive
results possibly due to the amplification of non-pathogenic organisms in the sample.[22][34]
[36] Targets used for PCR amplification include fungal 18S rRNA and 28S rRNA. PCR can be
performed from a small sample of ocular tissues or fluids like tears or aqueous
humor but requires very specialized equipment that is expensive and may not always be
available.

Beta-D-glucan is a component of the cell wall of many fungal species that can be detected in
blood samples of patients with invasive fungal infections.[37] Previously, it has been shown that
beta-d-glucan testing is a more rapid and more sensitive method of diagnosing systemic fungal
infections than fungal cultures especially in organisms that do not grow in blood cultures such as
Aspergillosis.[38] Beta-D-glucan may be detected in tear samples of patients with fungal keratitis
facilitating early and rapid diagnosis.[39] It can also be detected in intraocular fluids of cases
complicated by fungal endophthalmitis.[40]

Non-invasive methods, including confocal microscopy and anterior segment optical coherence
tomography (AS-OCT), can also be used to detect microorganisms responsible for microbial
keratitis, including fungi, using in vivo examination techniques. Confocal microscopy may allow
detection of hyphae-like branching white lines in the area of infiltration in cases of filamentous
fungi,[41] while AS-OCT may show early localized and diffuse areas of necrotic stromal cystic
spaces in cases of infection by Aspergillus species.[42] Both modalities can also be used in the
follow up of the response to treatment.[43]

Ophthalmic B-scan ultrasonography can be useful in the diagnosis and follow up of cases
suspected of developing endophthalmitis especially if corneal fungal infiltration precludes
examination with ophthalmoscopy.

Treatment / Management

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 4/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

Medical Treatment

All the currently available antifungal agents are fungistatic but not fungicidal, which necessitates
a prolonged period of treatment until the body defenses can completely eradicate the fungal
organism. Topical natamycin 5% is usually the first treatment of choice for FK especially
filamentous fungi,[44][45] although primary treatment failure has previously been reported in
31.3% of cases.[46]

Other topical agents used in the treatment of FK include amphotericin B 0.15-0.3%, voriconazole
1%, econazole 1%, itraconazole 1%, and miconazole 1%. Amphotericin B is the preferred
treatment of choice for yeasts. Voriconazole 1% has better penetration into the eye and is
purported to be a superior alternative to natamycin. It can also be used as intrastromal or
intracameral injections.[47]

Subconjunctival injections of antifungal agents such as miconazole and fluconazole may be used
in patients with poor compliance and those with severe keratitis.

Systemic treatment can also be used in the form of intravenous amphotericin B or oral
itraconazole or fluconazole.

Decisions to continue therapy as based on the following biomicroscopic findings:

A decrease in pain and size of infiltrate

A decrease in satellite lesions

A decrease in the density of suppuration

Blunting of the infiltrate edges

A decrease in inflammation in the anterior chamber

Continued reepithelialization

Recently published clinical trials have reported equal or inferior efficacy of topical 1%
voriconazole (reconstituted from injection vial) compared with topical 5% natamycin eye drops
in FK especially in that caused by Fusarium. These results, however, are contradictory to
experimental and in vitro data. Sharma et al conducted a study of 118 patients where 58 patients
were treated with voriconazole and 60 patients with natamycin. Despite the frequency of healed
or resolving ulcers being similar on day 7 (natamycin 35/54, 65%; voriconazole 34/50, 68%), at
the final visit the percentage of patients who had healed corneal ulcer were significantly higher in
the group treated with natamycin (50/56, 89.2% versus 34/51, 66.6%; p=0.005).[48]

A Cochrane Database systematic review of the medical treatment of fungal keratitis was
performed in 2015 and also concluded that natamycin may be more effective than voriconazole
in the treatment of fungal keratitis but that also most studies were underpowered with variable
quality.[49] The randomized controlled trials analyzed included many comparisons including
topical 5% natamycin versus topical 1% voriconazole, topical 1% voriconazole vs intrastromal
voriconazole, and topical 1% natamycin versus topical 2% econazole.

Surgical Treatment

Patients who fail to respond to medical therapy may require surgical intervention, including
therapeutic penetrating and lamellar keratoplasty.[12][50][12] Therapeutic keratoplasty, however,
can be associated with complications including recurrence of infection, endophthalmitis, and
graft rejection.[50]

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 5/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

A recently available treatment modality is corneal collagen cross-linking which may sometimes
be useful in medically resistant corneal ulcers or even in some early cases of fungal infection.
[51][52][53][52] A recent randomized controlled clinical trial, however, did not show any benefit
of this modality in fungal keratitis with an increased incidence of complications.[54]
Conjunctival flaps can also rarely be used but may increase the incidence of graft rejection
following keratoplasty due to corneal vascularization.[12]

If a corneal perforation occurs, a tectonic or therapeutic keratoplasty is usually required to save

the eye. Cases complicated by endophthalmitis may require intravitreal injections of antifungal
agents or even pars plana vitrectomy which can be performed using endoscopy in cases with
poor posterior segment visualization due to extensive corneal infiltration.[55][56][57]
Enucleation, however, may eventually be the last resort in a blind and painful eye with
uncontrollable inflammation.

Healing of FK may result in central corneal scarring and opacification which may require
penetrating or lamellar keratoplasty for the restoration of visual acuity.

Differential Diagnosis

Bacterial keratitis

Acanthamoeba keratitis

Necrotizing herpetic keratitis

Prognosis
The prognosis depends on the causative organism, depth and extent of the infection, development
of complications, and timing of treatment initiation. Some patients can be cured
microbiologically by topical antifungals alone, but in some patients, therapeutic keratoplasty may
be needed. The Descemet membrane, an interior basement membrane near the aqueous humor, is
usually impermeable to bacteria but can be breached by fungal hyphae, leading to
endophthalmitis; endophthalmitis is a rare consequence of fungal keratitis that has a poor
prognosis. About 30% of fungal infections fail to respond to drug therapy and/or result in corneal
perforation. Successful healing of FK usually results in central corneal scarring and opacification
which may require penetrating or lamellar keratoplasty for the restoration of visual acuity.

Complications

Corneal perforation

Corneal melting

Corneal scarring

Scleritis

Endophthalmitis

Panophthalmitis

Permanent blindness

Deterrence and Patient Education

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 6/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

Patients should be educated about the proper use of contact lenses and their cleaning products in
order to decrease the risk of contact-lens associated corneal infections. Proper hygienic measures
should be emphasized including frequent hand washing especially before handling contact lenses
and avoiding overnight contact lens wear.

Pearls and Other Issues

Fusarium, Candida, and Aspergillus species are the most common isolates in fungal
keratitis worldwide.

Elevated edges, branching ulcers, feathery margins, rough texture, and satellite lesions are
features suggestive of fungal keratitis.

The diagnosis is by corneal scrapings. Samples should be sent for PCR and cultures.

Natamycin eye drops are frequently initially used.

Enhancing Healthcare Team Outcomes

The majority of patients with fungal keratitis present to the emergency department or their
primary care provider; in order to expedite the referral process to an ophthalmologist, an
interprofessional approach in diagnosis and care is vital. Any delay can lead to vision loss and
permanent blindness. The majority of patients with fungal keratitis are managed as outpatients
and treated with antifungal therapy for at least 12-16 weeks.

Patient education is vital in the prevention of fungal keratitis. Contact lens wearers need to be
educated about hand washing, use of appropriate cleaning solution, and avoiding sleeping and
swimming while wearing contact lenses. Contact lens wearers should also regularly follow up
with the optician or ophthalmologist and get their eyes checked. All contact lens wearers should
be informed of symptoms of eye infections and the need to immediately see an ophthalmologist
if they experience pain, redness, or loss of vision. Ophthalmology nurses should educate patients,
arrange for follow up, and ensure communication between the team members. Pharmacists
should review medication dosages, check for drug interactions, and review methods of
administration with patients.

Close follow up during treatment is required to ensure that the condition is not worsening. The
eventual outcome depends on factors like overall patient health, the status of the immune system,
and other comorbidities. Patients with a mild infection who are promptly treated have a good
outcome, but in patients with an infection that has spread into the sclera, the prognosis is
guarded. Data indicate that at least 30% of patients with fungal keratitis develop corneal
perforation or fail to respond to drug therapy.[58][59] The evidence regarding the management of
FK varies and ranges from large randomized controlled clinical trials with clear-cut results in
certain aspects of its management (Level 1 evidence) to case series and expert opinion in other
aspects (Level 5 evidence).

Questions
To access free multiple choice questions on this topic, click here.

References
1. Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology.
2006 Nov;113(11):1943-8. [PubMed: 16935335]
2. Gopinathan U, Ramakrishna T, Willcox M, Rao CM, Balasubramanian D, Kulkarni A,

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 7/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

Vemuganti GK, Rao GN. Enzymatic, clinical and histologic evaluation of corneal tissues in
experimental fungal keratitis in rabbits. Exp. Eye Res. 2001 Apr;72(4):433-42. [PubMed:
11273671]
3. Tena D, Rodríguez N, Toribio L, González-Praetorius A. Infectious Keratitis:
Microbiological Review of 297 Cases. Jpn. J. Infect. Dis. 2019 Mar 25;72(2):121-123.
[PubMed: 30381686]
4. Mittal R, Ahooja H, Sapra N. Corneal "Plaque" formation after anti-acanthamoeba therapy in
acanthamoeba keratitis. Indian J Ophthalmol. 2018 Nov;66(11):1623-1624. [PMC free
article: PMC6213680] [PubMed: 30355882]
5. Xie L, Zhai H, Zhao J, Sun S, Shi W, Dong X. Antifungal susceptibility for common
pathogens of fungal keratitis in Shandong Province, China. Am. J. Ophthalmol. 2008
Aug;146(2):260-265. [PubMed: 18547535]
6. Tuft SJ, Tullo AB. Fungal keratitis in the United Kingdom 2003-2005. Eye (Lond). 2009
Jun;23(6):1308-13. [PubMed: 18836409]
7. Gower EW, Keay LJ, Oechsler RA, Iovieno A, Alfonso EC, Jones DB, Colby K, Tuli SS,
Patel SR, Lee SM, Irvine J, Stulting RD, Mauger TF, Schein OD. Trends in fungal keratitis in
the United States, 2001 to 2007. Ophthalmology. 2010 Dec;117(12):2263-7. [PubMed:
20591493]
8. Tilak R, Singh A, Maurya OP, Chandra A, Tilak V, Gulati AK. Mycotic keratitis in India: a
five-year retrospective study. J Infect Dev Ctries. 2010 Mar 29;4(3):171-4. [PubMed:
20351459]
9. Saha R, Das S. Mycological profile of infectious Keratitis from Delhi. Indian J. Med. Res.
2006 Feb;123(2):159-64. [PubMed: 16575115]
10. Bharathi MJ, Ramakrishnan R, Vasu S, Meenakshi. Palaniappan R. Aetiological diagnosis
of microbial keratitis in South India - a study of 1618 cases. Indian J Med Microbiol. 2002
Jan-Mar;20(1):19-24. [PubMed: 17657018]
11. Bharathi MJ, Ramakrishnan R, Vasu S, Meenakshi R, Palaniappan R. Epidemiological
characteristics and laboratory diagnosis of fungal keratitis. A three-year study. Indian J
Ophthalmol. 2003 Dec;51(4):315-21. [PubMed: 14750619]
12. Wang L, Sun S, Jing Y, Han L, Zhang H, Yue J. Spectrum of fungal keratitis in central
China. Clin. Experiment. Ophthalmol. 2009 Nov;37(8):763-71. [PubMed: 19878220]
13. Gopinathan U, Sharma S, Garg P, Rao GN. Review of epidemiological features,
microbiological diagnosis and treatment outcome of microbial keratitis: experience of over
a decade. Indian J Ophthalmol. 2009 Jul-Aug;57(4):273-9. [PMC free article:
PMC2712695] [PubMed: 19574694]
14. Galarreta DJ, Tuft SJ, Ramsay A, Dart JK. Fungal keratitis in London: microbiological and
clinical evaluation. Cornea. 2007 Oct;26(9):1082-6. [PubMed: 17893539]
15. Lim CH, Carnt NA, Farook M, Lam J, Tan DT, Mehta JS, Stapleton F. Risk factors for
contact lens-related microbial keratitis in Singapore. Eye (Lond). 2016 Mar;30(3):447-55.
[PMC free article: PMC4791703] [PubMed: 26634710]
16. Taylan Sekeroglu H, Erdem E, Yar K, Yağmur M, Ersoz TR, Uguz A. A rare devastating
complication of LASIK: bilateral fungal keratitis. J Ophthalmol. 2010;2010:450230. [PMC
free article: PMC2990860] [PubMed: 21113441]
17. Moshirfar M, Welling JD, Feiz V, Holz H, Clinch TE. Infectious and noninfectious keratitis
after laser in situ keratomileusis Occurrence, management, and visual outcomes. J Cataract
Refract Surg. 2007 Mar;33(3):474-83. [PubMed: 17321399]
18. Chen WL, Tsai YY, Lin JM, Chiang CC. Unilateral Candida parapsilosis interface keratitis
after laser in situ keratomileusis: case report and review of the literature. Cornea. 2009
Jan;28(1):105-7. [PubMed: 19092419]
19. Kocatürk T, Pineda R, Green LK, Azar DT. Post-LASIK epithelial dendritic defect
https://www.ncbi.nlm.nih.gov/books/NBK493192/ 8/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

associated with Alternaria. Cornea. 2007 Oct;26(9):1144-6. [PubMed: 17893555]

20. Sun Y, Jain A, Ta CN. Aspergillus fumigatus keratitis following laser in situ keratomileusis.
J Cataract Refract Surg. 2007 Oct;33(10):1806-7. [PubMed: 17889780]
21. Estopinal CB, Ewald MD. Geographic Disparities in the Etiology of Bacterial and Fungal
Keratitis in the United States of America. Semin Ophthalmol. 2016;31(4):345-52.
[PubMed: 27101474]
22. Thomas PA, Kaliamurthy J. Mycotic keratitis: epidemiology, diagnosis and management.
Clin. Microbiol. Infect. 2013 Mar;19(3):210-20. [PubMed: 23398543]
23. Godoy P, Cano J, Gené J, Guarro J, Höfling-Lima AL, Lopes Colombo A. Genotyping of
44 isolates of Fusarium solani, the main agent of fungal keratitis in Brazil. J. Clin.
Microbiol. 2004 Oct;42(10):4494-7. [PMC free article: PMC522331] [PubMed: 15472299]
24. Bhartiya P, Daniell M, Constantinou M, Islam FM, Taylor HR. Fungal keratitis in
Melbourne. Clin. Experiment. Ophthalmol. 2007 Mar;35(2):124-30. [PubMed: 17362452]
25. Ritterband DC, Seedor JA, Shah MK, Koplin RS, McCormick SA. Fungal keratitis at the
new york eye and ear infirmary. Cornea. 2006 Apr;25(3):264-7. [PubMed: 16633023]
26. Konne NM, Collier SA, Spangler J, Cope JR. Healthy Contact Lens Behaviors
Communicated by Eye Care Providers and Recalled by Patients - United States, 2018.
MMWR Morb. Mortal. Wkly. Rep. 2019 Aug 16;68(32):693-697. [PMC free article:
PMC6818704] [PubMed: 31415490]
27. Cope JR, Collier SA, Nethercut H, Jones JM, Yates K, Yoder JS. Risk Behaviors for
Contact Lens-Related Eye Infections Among Adults and Adolescents - United States, 2016.
MMWR Morb. Mortal. Wkly. Rep. 2017 Aug 18;66(32):841-845. [PMC free article:
PMC5657667] [PubMed: 28817556]
28. Epstein AB. In the aftermath of the Fusarium keratitis outbreak: What have we learned?
Clin Ophthalmol. 2007 Dec;1(4):355-66. [PMC free article: PMC2704532] [PubMed:
19668512]
29. Manikandan P, Abdel-Hadi A, Randhir Babu Singh Y, Revathi R, Anita R, Banawas S, Bin
Dukhyil AA, Alshehri B, Shobana CS, Panneer Selvam K, Narendran V. Fungal Keratitis:
Epidemiology, Rapid Detection, and Antifungal Susceptibilities of Fusarium and
Aspergillus Isolates from Corneal Scrapings. Biomed Res Int. 2019;2019:6395840. [PMC
free article: PMC6360544] [PubMed: 30800674]
30. Agrawal V, Biswas J, Madhavan HN, Mangat G, Reddy MK, Saini JS, Sharma S,
Srinivasan M. Current perspectives in infectious keratitis. Indian J Ophthalmol. 1994
Dec;42(4):171-92. [PubMed: 10576995]
31. Punia RS, Kundu R, Chander J, Arya SK, Handa U, Mohan H. Spectrum of fungal keratitis:
clinicopathologic study of 44 cases. Int J Ophthalmol. 2014;7(1):114-7. [PMC free article:
PMC3949470] [PubMed: 24634875]
32. Xie L, Zhai H, Shi W, Zhao J, Sun S, Zang X. Hyphal growth patterns and recurrence of
fungal keratitis after lamellar keratoplasty. Ophthalmology. 2008 Jun;115(6):983-7.
[PubMed: 17919731]
33. Dahlgren MA, Lingappan A, Wilhelmus KR. The clinical diagnosis of microbial keratitis.
Am. J. Ophthalmol. 2007 Jun;143(6):940-944. [PMC free article: PMC1973090] [PubMed:
17408586]
34. Thomas PA. Current perspectives on ophthalmic mycoses. Clin. Microbiol. Rev. 2003
Oct;16(4):730-97. [PMC free article: PMC207127] [PubMed: 14557297]
35. Eleinen KG, Mohalhal AA, Elmekawy HE, Abdulbaki AM, Sherif AM, El-Sherif RH,
Abdul Rahman EM. Polymerase chain reaction-guided diagnosis of infective keratitis - a
hospital-based study. Curr. Eye Res. 2012 Nov;37(11):1005-11. [PubMed: 22746322]
36. Ferrer C, Alió JL. Evaluation of molecular diagnosis in fungal keratitis. Ten years of
experience. J Ophthalmic Inflamm Infect. 2011 Feb 23;1(1):15-22. [PMC free article:
https://www.ncbi.nlm.nih.gov/books/NBK493192/ 9/11
7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

PMC3062769] [PubMed: 21475656]

37. Obayashi T, Yoshida M, Tamura H, Aketagawa J, Tanaka S, Kawai T. Determination of
plasma (1-->3)-beta-D-glucan: a new diagnostic aid to deep mycosis. J. Med. Vet. Mycol.
1992;30(4):275-80. [PubMed: 1432487]
38. Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, Ketchum PA, Finkelman
MA, Rex JH, Ostrosky-Zeichner L. Beta-D-glucan as a diagnostic adjunct for invasive
fungal infections: validation, cutoff development, and performance in patients with acute
myelogenous leukemia and myelodysplastic syndrome. Clin. Infect. Dis. 2004 Jul
15;39(2):199-205. [PubMed: 15307029]
39. Kaji Y, Hiraoka T, Oshika T. Increased level of (1,3)-beta-D-glucan in tear fluid of mycotic
keratitis. Graefes Arch. Clin. Exp. Ophthalmol. 2009 Jul;247(7):989-92. [PubMed:
19151994]
40. Kolomeyer AM, Murphy KM, Traband A, Frank I, Kim BJ. BETA-D-GLUCAN TESTING
IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS. Retina (Philadelphia, Pa.). 2018
Apr;38(4):650-659. [PubMed: 29370030]
41. Mitani A, Shiraishi A, Uno T, Miyamoto H, Hara Y, Yamaguchi M, Ohashi Y. In vivo and
in vitro investigations of fungal keratitis caused by Colletotrichum gloeosporioides. J Ocul
Pharmacol Ther. 2009 Dec;25(6):563-5. [PubMed: 20028265]
42. Soliman W, Fathalla AM, El-Sebaity DM, Al-Hussaini AK. Spectral domain anterior
segment optical coherence tomography in microbial keratitis. Graefes Arch. Clin. Exp.
Ophthalmol. 2013 Feb;251(2):549-53. [PubMed: 22729467]
43. Martone G, Pichierri P, Franceschini R, Moramarco A, Ciompi L, Tosi GM, Balestrazzi A.
In vivo confocal microscopy and anterior segment optical coherence tomography in a case
of alternaria keratitis. Cornea. 2011 Apr;30(4):449-53. [PubMed: 21099420]
44. Farrell S, McElnea E, Moran S, Knowles S, Murphy CC. Fungal keratitis in the Republic of
Ireland. Eye (Lond). 2017 Oct;31(10):1427-1434. [PMC free article: PMC5639195]
[PubMed: 28524886]
45. Sun CQ, Lalitha P, Prajna NV, Karpagam R, Geetha M, O'Brien KS, Oldenburg CE, Ray
KJ, McLeod SD, Acharya NR, Lietman TM., Mycotic Ulcer Treatment Trial Group.
Association between in vitro susceptibility to natamycin and voriconazole and clinical
outcomes in fungal keratitis. Ophthalmology. 2014 Aug;121(8):1495-500.e1. [PMC free
article: PMC4122634] [PubMed: 24746358]
46. Lalitha P, Prajna NV, Kabra A, Mahadevan K, Srinivasan M. Risk factors for treatment
outcome in fungal keratitis. Ophthalmology. 2006 Apr;113(4):526-30. [PubMed: 16581414]
47. Narayana S, Krishnan T, Ramakrishnan S, Samantaray PP, Austin A, Pickel J, Porco T,
Lietman T, Rose-Nussbaumer J. Mycotic Antimicrobial Localized Injection: A Randomized
Clinical Trial Evaluating Intrastromal Injection of Voriconazole. Ophthalmology. 2019
Aug;126(8):1084-1089. [PMC free article: PMC6646068] [PubMed: 30904540]
48. Sharma S, Das S, Virdi A, Fernandes M, Sahu SK, Kumar Koday N, Ali MH, Garg P,
Motukupally SR. Re-appraisal of topical 1% voriconazole and 5% natamycin in the
treatment of fungal keratitis in a randomised trial. Br J Ophthalmol. 2015 Sep;99(9):1190-5.
[PubMed: 25740805]
49. FlorCruz NV, Evans JR. Medical interventions for fungal keratitis. Cochrane Database Syst
Rev. 2015 Apr 09;(4):CD004241. [PubMed: 25855311]
50. Anshu A, Parthasarathy A, Mehta JS, Htoon HM, Tan DT. Outcomes of therapeutic deep
lamellar keratoplasty and penetrating keratoplasty for advanced infectious keratitis: a
comparative study. Ophthalmology. 2009 Apr;116(4):615-23. [PubMed: 19243833]
51. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/riboflavin corneal cross-
linking for infectious keratitis associated with corneal melts. Cornea. 2008 Jun;27(5):590-4.
[PubMed: 18520510]
https://www.ncbi.nlm.nih.gov/books/NBK493192/ 10/11
View publication stats

7/9/2020 Fungal Keratitis - StatPearls - NCBI Bookshelf

52. Tabibian D, Richoz O, Riat A, Schrenzel J, Hafezi F. Accelerated photoactivated chromophore

for keratitis-corneal collagen cross-linking as a first-line and sole treatment in early fungal
keratitis. J Refract Surg. 2014 Dec;30(12):855-7. [PubMed: 25437486]
53. Zhu Z, Zhang H, Yue J, Liu S, Li Z, Wang L. Antimicrobial efficacy of corneal cross-
linking in vitro and in vivo for Fusarium solani: a potential new treatment for fungal
keratitis. BMC Ophthalmol. 2018 Mar 02;18(1):65. [PMC free article: PMC5833033]
[PubMed: 29499665]
54. Uddaraju M, Mascarenhas J, Das MR, Radhakrishnan N, Keenan JD, Prajna L, Prajna VN.
Corneal Cross-linking as an Adjuvant Therapy in the Management of Recalcitrant Deep
Stromal Fungal Keratitis: A Randomized Trial. Am. J. Ophthalmol. 2015 Jul;160(1):131-
4.e5. [PubMed: 25841317]
55. Chee YE, Eliott D. The Role of Vitrectomy in the Management of Fungal Endophthalmitis.
Semin Ophthalmol. 2017;32(1):29-35. [PubMed: 27792412]
56. Gao Y, Chen N, Dong XG, Yuan GQ, Yu B, Xie LX. Surgical management of fungal
endophthalmitis resulting from fungal keratitis. Int J Ophthalmol. 2016;9(6):848-53. [PMC
free article: PMC4916141] [PubMed: 27366686]
57. De Smet MD, Carlborg EA. Managing severe endophthalmitis with the use of an
endoscope. Retina (Philadelphia, Pa.). 2005 Dec;25(8):976-80. [PubMed: 16340526]
58. Fontana L, Moramarco A, Mandarà E, Russello G, Iovieno A. Interface infectious keratitis
after anterior and posterior lamellar keratoplasty. Clinical features and treatment strategies.
A review. Br J Ophthalmol. 2019 Mar;103(3):307-314. [PMC free article: PMC6579547]
[PubMed: 30355718]
59. McElnea E, Power B, Murphy C. Interface Fungal Keratitis After Descemet Stripping
Automated Endothelial Keratoplasty: A Review of the Literature With a Focus on
Outcomes. Cornea. 2018 Sep;37(9):1204-1211. [PubMed: 29781928]

Copyright © 2020, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in
any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the
Creative Commons license, and any changes made are indicated.

Bookshelf ID: NBK493192 PMID: 29630244

https://www.ncbi.nlm.nih.gov/books/NBK493192/ 11/11