Fungal Keratitis

Updated: May 20, 2015
  • Author: Daljit Singh, MBBS, MS, DSc; Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

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. See the images below.

Fungal corneal ulcer. Fungal corneal ulcer.
Fungal ulcer in an elderly woman. Fungal ulcer in an elderly woman.
Fungal keratitis. Fungal keratitis.
Fungal infection. Fungal infection.
Fungal infection. Fungal infection.
Fungal ulcer. Fungal ulcer.
Fungal corneal ulcer, with excessive vascularizati Fungal corneal ulcer, with excessive vascularization.

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.

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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.

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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 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.

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