Top of FormBottom of FormFungal Keratitis BackgroundFungal 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. See the images below.Fungal corneal ulcer.Fungal ulcer in an elderly woman.Fungal keratitis.Fungal infection.Fungal infection.Fungal ulcer.Fungal corneal ulcer, with excessive vascularization.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.ClassificationOf 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 corneaFor the past 13 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 end. It joins a peripheral circular corneal channel, which is present in every eye, but becomes visible as a transparent line in all cases of arcussenilis. It is the lucid interval, which actually is a canal, the canal of Singh. The corneal network joins canal of Singh at about 36-40 points. If cases of arcussenilis are studied regularly with optical coherence tomography, the Singh canal and Schlemm canal will be visualized as being connected through connecting channels. This channel structure helps to understand and explain many observations in corneal infections and in glaucoma cases. Next Section: 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 corneo-scleral 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, Candida albicans 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.

Epidemiologi (USA) cari yang di Indonesia

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 Fusariumoxysporum was the most common isolate (37%), followed by, in order of decreasing frequency, Fusariumsolani (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 Fusariumkeratitis 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.

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 (See images below.) Fungal corneal ulcer, with excessive vascularizati Fungal corneal ulcer, with excessive vascularization. Marginal ulcer, fungus positive. Marginal ulcer, fungus positive. Epithelial defect Suppuration (See images below.) Fungal abscess. Fungal abscess. Fungal corneal abscess/ulcer. A proven case of fun Fungal corneal abscess/ulcer. A proven case of fungal infection, 5 days' duration. Intense infiltration around the abscess. Stromal infiltration Anterior chamber reactionHypopyon

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.

Mixed bacterial and fungal infections are common in the developing countries. The patients may present after many days or weeks. While antibacterial therapy is started in most clinics in the periphery, fungal infection may not be considered. The most practical approach in good clinics in developing countries is to examine a scraping from the ulcer, both for bacteria and fungi. If hyphae and/or spores are found, the treatment efforts are directed towards the fungus, but broad-spectrum antibiotics are also used to cover for bacteria.

Once a few fungal ulcers or fungal keratitis cases have been carefully examined, it becomes easy to make a presumptive diagnosis of fungus infection. In the developing countries and tropics, fungal cases are very common in the hot summer months.

Advanced severe filamentous fungal and yeast keratitis are indistinguishable and resemble keratitis caused by virulent bacteria, such as Staphylococcus aureus and Pseudomonas aeruginosa.

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