Introduction
Background
Fungal keratitis was first described by Leber in 1879. This entity is not a common cause of corneal infection, but it represents one of the major causes of infectious keratitis in tropical areas of the world. Considering fungus as a possible cause of infectious keratitis is important because devastating ocular damage can result if it is not diagnosed and treated promptly and effectively.
Fungal keratitis is a general term meaning any inflammation of the cornea. Fungi can infect (and therefore inflame) 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.
Fungal keratitis remains a diagnostic and therapeutic challenge to the ophthalmologist. Difficulties are related to establishing a 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; even if the diagnosis is made accurately, management remains a challenge because of the poor corneal penetration and the limited commercial availability of antifungal agents.
Moreover, 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 and antibacterial agents in treating patients with keratitis, the rise in the number of patients who are immunocompromised, and better laboratory diagnostic techniques that aid in its diagnosis.
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.
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.Fungi are not a common cause of microbial keratitis. Fungi cannot penetrate the intact corneal epithelium and do not enter the cornea from episcleral limbal vessels. They need a penetrating injury or a previous epithelial defect to enter the cornea. Once within the cornea, however, they are able to proliferate.
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, Candida albicans produces phospholipase A and lysophospholipase on the surface of blastospores, facilitating the entrance to the tissue. Fusarium solani, 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.
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.
Clinical
History
- A history of outdoor eye trauma often is reported.
- In patients presenting with possible fungal keratitis, inquire about possible risk factors (see Causes).
- Symptoms include the following:
- Foreign body sensation
- Increasing eye pain or discomfort
- Sudden blurry vision
- Unusual redness of the eye
- Excessive tearing and discharge from the eye
- Increased light sensitivity
Physical
The clinical diagnosis of fungal keratitis is based on risk factor analysis and characteristic corneal features.
- The most common signs on slit lamp examination are nonspecific and include the following:
- Conjunctival injection
- Epithelial defect
- Suppuration
- Stromal infiltration
- Anterior chamber reaction
- Hypopyon
- Presenting clinical features that are specific to fungal keratitis include an infiltrate with feathery margins, elevated edges, rough texture, gray-brown pigmentation, satellite lesions, hypopyon, and endothelial plaque.
- Fine or coarse granular infiltrate within the epithelium and anterior stroma
- Gray-white color, dry, and rough corneal surface that may appear elevated
- Typical irregular feathery-edged infiltrate
- White ring in the cornea and satellite lesions near the edge of the primary focus of the infection
- In advanced cases, suppurative stromal keratitis associated with conjunctival hyperemia, anterior chamber inflammation, hypopyon, iritis, endothelial plaque, or possible corneal perforation
- Although these highly characteristic signs may be present, obtaining a sample of the lesion by scraping or corneal biopsy is important before initiating treatment with antifungal therapy (see Procedures). Several unfortunate cases have been reported in which antifungal therapy had been initiated before fungi were seen or isolated, with resultant misdiagnosis and progression of the process.
- A deep stromal infiltrate with an intact epithelium also may be present. However, many fungal ulcers demonstrate no striking morphologic pattern, and it often is not possible to differentiate clinically between fungal keratitis and bacterial keratitis.
- Advanced severe filamentous fungal and yeast keratitis are indistinguishable and resemble keratitis caused by virulent bacteria, such as Staphylococcus aureus and Pseudomonas aeruginosa.
Causes
- Aspergillus is the most common cause of fungal keratitis worldwide. However, the epidemiology of fungal keratitis is climate specific. In the southern United States, Fusarium species are the most common cause of fungal keratitis, with an especially high incidence in Florida. In contrast, Candida and Aspergillus species are the most common pathogens in the northern United States.
- Common risk factors for the development of fungal keratitis include the following:
- Trauma (eg, contact lenses, foreign body); in a study of fungal keratitis from south Florida, trauma with vegetable matter was the major risk factor in 44% of patients.
- Topical corticosteroid use
- Corneal surgery such as penetrating keratoplasty, clear cornea (sutureless) cataract surgery, or laser in situ keratomileusis (LASIK)
- Chronic keratitis due to herpes simplex, herpes zoster, or vernal keratoconjunctivitis
- Young males
- Healthy
- No significant ocular disease
- Previous history of trauma (vegetable matter)
- Agricultural occupations
- Risk factors for Candida keratitis are as follows:
- Older patients
- Preexisting ocular disease
- Exposure keratopathy
- Chronic keratitis
- Long-term steroid use
- Immunosuppressive disease
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Further Reading
Keywords
fungal keratitis, fungal ulcer, infectious corneal infiltrate, corneal ulcer, fungal endophthalmitis, keratitis, keratomycosis
