Background

Fungal keratitis was first described by Leber in 1879. This entity is a very
common cause of corneal infection in developing countries, although it is not
common in Western countries. If not diagnosed and treated promptly and
effectively, significant damage can occur.

Fungal corneal ulcer.

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Fungal ulcer in an elderly

woman.
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 Fungal keratitis.
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Fungal infection.
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 Fungal infection.
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Fungal ulcer.
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 Fungal corneal ulcer, with
excessive vascularization.
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Keratitis is a general term meaning any inflammation of the cornea. The term
fungal keratitis refers to a corneal infection caused by fungi. One type of
fungus that can infect the cornea is Fusarium. When Fusarium infects the
cornea, the eye disease is referred to as Fusarium keratitis.
The early stage of fungal keratitis remains a diagnostic and therapeutic
challenge to the ophthalmologist. There is difficulty in establishing the clinical
diagnosis, isolating the etiologic fungal organism in the laboratory, and
treating the keratitis effectively with topical antifungal agents. Unfortunately,
delayed diagnosis is common, primarily because of lack of suspicion. When a
diagnosis has been made, management remains a challenge because of the
poor corneal penetration of antifungal agents.
The incidence of fungal keratitis has increased over the past 30 years. This
increased occurrence of fungal keratitis is a result of the frequent use of
topical corticosteroids along with antibacterial agents in treating patients with
keratitis. With better laboratory facilities, the awareness about fungal keratitis
has increased.
Classification
Of the 70 different fungi that have been implicated as causing fungal keratitis,
the 2 medically important groups responsible for corneal infection are yeast
and filamentous fungi (septate and nonseptate).
Yeast produces characteristic creamy, opaque, pasty colonies on the surface
of culture media. Candida is the most representative pathogen in this group,
primarily affecting those corneas already compromised by topical steroids,
surface pathology, or both.
A feathery or powdery growth on the surface of culture media is produced by
septate filamentary fungi, which are the most common cause of fungal
keratitis.
Fluid movement in the cornea
For the past 15 years, the author (Singh) has been studying the possibility of
fluid channels existing in the cornea. Some of the observations are
summarized below.
The channels in the cornea are normally invisible. However, if it becomes
semiopaque for some reason, the channels tend to stand out.
The question arises as to where the corneal network of channels ends. It joins
a peripheral circular corneal channel, which is present in every eye, but
becomes visible as a transparent line in all cases of arcus senilis. It is the
“lucid interval,” which actually is a canal, the canal of Singh. The corneal
network joins canal of Singh in multiple layers all around the limbus.
If cases of arcus senilis are studied regularly with optical coherence
tomography, the Singh canal and Schlemm canal will be visualized as being
connected through ”aqueducts.” The corneal channel structure helps to
understand and explain many observations in corneal infections.
Pathophysiology
Many fungal organisms associated with ocular infections are ubiquitous,
saprophytic organisms and have been reported as causes of infection only in
the ophthalmic literature. Fungal isolates have been classified into the
following groups: Moniliaceae (nonpigmented filamentary fungi,
including Fusarium and Aspergillus species), Dematiaceae (pigmented
filamentary fungi, including Curvularia and Lasiodiplodia species), and yeasts
(including Candida species).
Fungi gain access into the corneal stroma through a defect in the epithelium,
then multiply and cause tissue necrosis and an inflammatory reaction. The
epithelial defect usually results from trauma (eg, contact lens wear, foreign
material, prior corneal surgery). The organisms can penetrate an intact
Descemet membrane and gain access into the anterior chamber or the
posterior segment. Mycotoxins and proteolytic enzymes augment the tissue
damage.
Fungal keratitis also has been described to occur secondary to fungal
endophthalmitis. In these cases, fungal organisms extend from the posterior
segment through the Descemet membrane and into the corneal stroma.
Another possibility is entry through corneoscleral trabeculae in to the many
channels in the cornea that exist as a network.
In the advanced countries of the West, fungi are not a common cause of
microbial keratitis. However, in the developing countries, fungal infections are
extremely common. Farm injuries are the most important cause. Fungi cannot
penetrate the intact corneal epithelium. They need a penetrating injury or a
previous epithelial defect to enter the cornea. Once within the cornea,
however, they are able to proliferate and spread through the corneal
channels.
Organisms that infect preexisting epithelial defects belong to the normal
microflora of the conjunctiva and adnexa. The most common pathogen that
invades a preexisting epithelial defect is Candida. Filamentous fungi are the
principal causes of posttraumatic infection. The intrinsic virulence of fungi
depends on the fungal substances produced and the host response
generated.
Filamentous fungi proliferate within the corneal stroma without release of
chemotactic substances, thereby delaying the host immune/inflammatory
response. In contrast, Candidaalbicans produces phospholipase A and
lysophospholipase on the surface of blastospores, facilitating the entrance to
the tissue. Fusariumsolani, which is a virulent fungus, is able (as are other
filamentous fungi), to spread within the corneal stroma and penetrate the
Descemet membrane.
Corneal trauma is the most frequent and major risk factor for fungal keratitis.
In fact, the physician should have a high level of suspicion in a patient with a
history of corneal trauma, particularly with plant or soil matter.
The trauma that accompanies contact lens wear is miniscule; contact lenses
are not a common risk factor of fungal keratitis. Candida is the principal cause
of keratitis associated with therapeutic contact lenses, and filamentous fungi
are associated with refractive contact lens wear. Photorefractive keratectomy
and laser in-situ keratomileusis (LASIK) cases, on a rare occasion, can
develop fungal infection, which may result in severe damage to the cornea,
even loss of an eye. Infections may develop in a series of patients if an
infected fluid is used in a number of patients at one session.
Topical steroid use has definitively been implicated as a cause of increased
incidence, development, and worsening of fungal keratitis. Other risk factors
to consider are foreign bodies, and immunosuppressive diseases.
Epidemiology
Frequency
United States
The incidence of fungal keratitis varies according to geographical location and
ranges from 2% of keratitis cases in New York to 35% in warm weather
Florida. Fusarium species are the most common cause of fungal corneal
infection in the southern United States (45-76% of fungal keratitis),
while Candida and Aspergillus species are more common in northern states.
In a large series of fungal keratitis from south Florida, Rosa et al reported
that Fusarium oxysporum was the most common isolate (37%), followed by, in
order of decreasing frequency, Fusarium solani (24%), Candida,
Curvularia, and Aspergillus species. [1]
Fusarium species are commonly found in soil, in water, and on plants
throughout the world, particularly in warmer climates. Past studies
of Fusarium keratitis have found that most incidences of Fusarium keratitis
have been caused by an eye injury with vegetative matter (eg, being hit in the
eye with a palm branch).
An estimated 30 million persons in the United States wear soft contact lenses.
The annual incidence of microbial keratitis is estimated to be 4-21 per 10,000
soft contact lens users, depending on whether users wear lenses overnight.
A number of individuals have contracted Fusarium keratitis from contact lens
wear, especially through the use of the Bausch & Lomb ReNu with Moisture
Lock contact lens solution. This number is generally very small, particularly in
the northern part of the United States.
On March 8, 2006, the Centers for Disease Control and Prevention (CDC)
received a report from an ophthalmologist in New Jersey regarding 3 patients
with contact lens-associated Fusarium keratitis during recent months. Initial
contact with several corneal disease specialty centers in the United States
revealed that other centers also had seen recent increases
in Fusarium keratitis.
The CDC began an investigation of the Fusarium keratitis outbreak. There
were 130 confirmed cases of Fusarium keratitis. Over 60% of people with
confirmed Fusarium keratitis had used Bausch & Lomb ReNu with Moisture
Lock contact lens solution, and 37 of these cases resulted in cornea
transplant surgery.
The US Food and Drug Administration (FDA) recalled Bausch & Lomb ReNu
with Moisture Lock contact lens solution.
According to Bausch & Lomb, "unique characteristics of the formulation of the
ReNu with Moisture Lock product in certain unusual circumstances can
increase the risk of Fusarium infection."
International
Aspergillus species is the most common isolate in fungal keratitis worldwide.
Large series of fungal keratitis from India report that Aspergillus species is the
most common isolate (27-64%), followed by Fusarium (6-32%)
and Penicillium (2-29%) species.
Mortality/Morbidity
Fungal organisms can extend from the cornea into the sclera and intraocular
structures. Fungi can cause severe infections, such as scleritis,
endophthalmitis, or panophthalmitis. These infections are usually very difficult
to treat and may result in severe visual loss or even loss of the eye.
Sex
Fungal keratitis is more common in males than in females and often occurs in
patients with a history of outdoor ocular trauma.
Prognosis
Prognosis depends on several factors, including the extent of corneal
involvement upon presentation, the patient's health status (eg,
immunocompromised), and the timing of establishing a clinical diagnosis
confirmed by culture in the laboratory.
Patients with mild infections and an early microbiologic diagnosis have a good
prognosis; however, controlling or eradicating an infection that spreads into
the sclera or the intraocular structures is very difficult.
Approximately one third of fungal infections result in either medical treatment
failure or corneal perforation.
Patient Education
Patients who wear contact lenses should consult their eye care professional
concerning use of an appropriate cleaning/disinfecting product. (Patients
should discontinue use of Bausch & Lomb ReNu with Moisture Lock contact
lens solution.)
Patients should consider performing a “rub and rinse” lens cleaning method,
rather than a no rub method, regardless of which cleaning/disinfecting solution
used, in order to minimize the number of germs and to reduce the chances of
infection.
Patients should continue to follow proper lens care practices. Wash their
hands with soap and water and dry (lint-free method) them before handling
lenses. Wear and replace lenses according to the schedule prescribed by
their eye care professional. Follow the specific lens cleaning and storage
guidelines from their eye care professional and the solution manufacturer.
Keep the contact lens case clean and replace every 3-6 months.
Patients should remove the lenses and consult their eye care professional
immediately if they experience symptoms, such as redness, pain, tearing,
increased light sensitivity, blurry vision, discharge, or swelling.