Fungal Keratitis (Fungus Infection of the Cornea)

Definition

Fungal keratitis is an infection of the cornea caused by a fungus. Although keratitis (corneal inflammation) can occur for several reasons, a fungus is one of the more common causes of infectious keratitis. It can lead to severe damage of the eye and blindness if not diagnosed early or left untreated for long periods of time. Fungal keratitis can affect any person but it is more commonly seen among contact lens users. It has also become a significant indicator of HIV infection, particularly in Africa. Although the elderly and patients who are immunocompromised are more likely to be affected, fungal keratitis can also occur in the immunocompetent and young individuals.

Incidence

Fungal keratitis is not an uncommon eye infection. The incidence in the United States varies between 2% to 35% depending on the geographical location. Fusarium keratitis, a fungal corneal infection cause by the Fusarium species, has become more common in the United States particularly among contact lens users and in states such as Florida. Greater awareness about the condition since 2006 and better intervention has reduced the incidence and complications in recent years. Globally, the Aspergillus species of fungi is the most common pathogen in fungal keratitis. Males are more commonly affected than females.

Pathophysiology

The cornea is the clear outer part of the eye that is lined with a very thin membrane known as the conjunctiva. Light passes through the cornea and then through the anterior chamber to reach the pupil, which is the aperture formed by the iris. From here the light is focused by the lens to strike the retina optimally for visual acuity. It is the cornea itself that has a greater part to play in the refraction of light than the lens. However, the cornea’s refractive index, despite being higher, is fixed and the lens is therefore needed to ensure acuity since it can alter its refractive index. Damage to the cornea can affect both the entry of light and visual acuity depending on the severity of the injury. Blindness can occur.

Fungi reach the cornea directly from the external environment in most cases of fungal keratitis and not through the bloodstream to the eye. In most instances it arises after an injury to the eye. The outer corneal epithelium is fairly resistant to microbial invasion but any injury or defect can make it prone to an infection. Once a fungus reaches the cornea, some fungi release toxins and enzymes which damage the corneal structure. Other fungi may reside and grow within the corneal tissue without releasing any such substances. It may therefore delay the onset of inflammation and the action of the immune defenses which could possibly neutralize it in the early stages.

Inflammation leads to swelling (edema) and redness of the cornea. If the infection is treated adequately at this point it may preserve the corneal tissue sufficiently to allow for some degree of reversal of the damage. However, as the fungi multiply and invade more of the corneal tissue, as well as secrete toxins and enzymes, it destroys the healthy tissue of the cornea. Necrosis (tissue death) of the cornea leads to the formation of ulcers in some cases. In rare instances the infection can progress to the posterior aspect (back) of the eye and the fungal infiltration can cause widespread damage of the internal structures of the eye.

Symptoms

The symptoms of fungal keratitis is similar to many other eye disorders in the early stages. This includes :

  • Itching of the eye that may also feel like a gritty sensations as is experienced with a foreign body.
  • Discomfort in the eye that is initially present may progress to eye pain.
  • Excessive redness of the eye associated with concomitant conjunctivitis.
  • Watery eyes (tearing) and sometimes discharge oozing from the eye.
  • Light sensitivity (photophobia) that develops gradually.
  • Blurring of the vision which may initially be present from the preceding trauma and gradually worsens.

Appearance of the Eye

Apart from these non-specific eye symptoms, fungal keratitis also presents with :

  • Gray-white color of the cornea which is clearly visible.
  • Corneal surface appears rough and elevated.
  • Visible fine to coarse corneal infiltrate with rough edges.
  • White ring around the site of infection with smaller lesions in close proximity.

Complications

Severe fungal keratitis and untreated infections can lead to complications. Perforation of the cornea may occur and the infection may spread to the posterior aspect of the eye (endophthalmitis). Ultimately there may be very severe loss of vision and even blindness. Progressing infections in deep fungal keratitis can lead to loss of the eye.

Causes

There are over 70 species of fungi that have been implicated as possible causes of fungal keratitis. The most common of these fungi include :

  • Aspergillus species
  • Fusarium species
  • Candida species

Most fungal infections are preceded by trauma to the eye that allows for the fungus to infiltrate the cornea. It can affect a person who has healthy immune defenses. Aspergillus and Fusarium are commonly found in water, soil and on plants. People who sustain eye injuries while outdoors and farm workers are therefore at greater risk.

With yeasts like the Candida species, the fungus is normally present on the skin surface and can infiltrate the cornea even without trauma, particularly when there is pre-existing eye disease or lowered immunity. However, not every person who sustains an eye injury, has pre-existing eye disease or lowered immune defenses will develop fungal keratitis.

Eye Injury and Disease

  • Contact lenses
  • Foreign bodies
  • Corneal surgery
  • Penetrating injuries
  • Chronic keratitis
  • Exposure keratopathy

Risk Factors

  • Chronic keratitis
  • Corticosteroid eye drops
  • Long-term steroid use
  • Older patients
  • Immunocompromised patients (HIV/AIDS, anti-rejection drugs following transplants, uncontrolled diabetes mellitus)

Diagnosis

The symptoms alone of fungal keratitis are not sufficient for diagnosis. Although some of the features may be considered characteristic of the condition, further laboratory testing is necessary for a conclusive diagnosis. Corneal tissue is collected through a scraping or biopsy and is used for further investigations. This includes examination of the sample under microscope with staining to identify the type the fungus and growing the fungus on a medium in a laboratory (culture). An opthalmic B-scan ultrasound is another useful investigation to identify spread of the infection to the posterior aspect of the eye.

Treatment

Fungal keratitis is treated with antifungal agents – topical and oral. Sometimes injectable antifungals may be necessary. Surgery is only sometimes necessary and reserved for severe infections that do not respond to medication.

Medication

There are three classes of antifungal drugs that may be used depending on whether the infection is superficial or deep and based on the fungal species responsible for the keratitis.

  • Polyenes :
    – Amphotericin B
    – Natamycin
    – Nystatin
  • Azoles :
    – Fluconazole
    – Itraconazole
    – Ketoconazole
    – Miconazole
  • Fluorinated pyrimidines :
    – Flucytosine

Although topical corticosteroids can increase the risk of fungal keratitis and should not be used initially, it may be helpful after several weeks of antifungal therapy. It is only considered when there is persisting inflammation of the cornea.

Surgery

As many as 1 out of 4 patients with fungal keratitis may require surgical intervention. This includes procedures such as :

  • Corneal debridement to scrape off damaged tissue and some of the fungus on the surface.
  • Conjunctival flap to repair a corneal perforation until the tear heals.
  • Corneal transplantation for replacement of the damaged cornea.

Prognosis

The prognosis for fungal keratitis depends on several factors. As in many as 1 out of 3 cases, treatment with medication may fail and corneal perforation may arise. The prognosis is poorer in immunocompromised patients and the elderly. Mild infections and early diagnosis greatly improves the prognosis. However, the outlook deteriorates significantly if the infection spreads deeper into the eye or involves the sclera.

References :

www.cdc.gov/fungal/fungal-keratitis/

emedicine.medscape.com/article/1194167-overview

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