Cornea
September 2022

by Ellen Stodola
Editorial Co-Director

When talking about infectious keratitis in the U.S., Francis Mah, MD, said this usually refers to bacterial keratitis, which has a higher incidence than fungal keratitis. However, he noted that there are reportedly 30,000–40,000 new cases of fungal keratitis annually, so it’s a significant number.

There are several issues associated with fungal keratitis, he added. The first is that there is generally a slight delay in making the correct diagnosis. Second, there are not many commercially available treatments. “We need to utilize compounding much more frequently for fungal keratitis, which adds to the delay in correct therapy,” Dr. Mah said.

He pointed out that fungal keratitis, in general, takes longer to resolve and can lead to more visual morbidities, scarring, and long-term vision issues. “In general, although it’s less than bacterial keratitis, 30,000–40,000 new cases a year is not insignificant, and it can lead to significant visual morbidity.”

Different areas will see higher prevalence of fungal keratitis. “The people across the U.S. seeing more fungal keratitis are those in hotter, more humid areas,” Dr. Mah said. However, he noted that many corneal specialists think there has been an increase in fungal keratitis across the U.S.

Dr. Mah had several thoughts as to why this may be, including contact lens wear. Contact lenses are always going to be a significant etiology for infectious keratitis, he said, adding that contact lens materials and comfort have gotten better over the years, so more people are able to be fit and wear lenses. This could contribute to the increase in keratitis among contact lens wearers.

Dr. Mah also pointed to dry eye as a potential reason for the increase. Many agents for dry eyes are anti-inflammatories. “If you alter the immune system, that may be a possible cause for more infections in the cornea,” he said.

Beeran Meghpara, MD, agreed that the incidence of fungal keratitis varies significantly around the world, with climate as the key factor. “The incidence is higher in warmer tropical/subtropical climates versus in cooler climates like here in the Northeast,” he said. However, he noted that he still sees a number of these cases at Wills Eye Hospital because it is a large referral center.

Depending on the study, Dr. Meghpara said that reported incidence ranges from about 3–800 per 100,000 individuals, so the range is wide. “Anecdotally, it feels like we are seeing more of these in Philadelphia,” he said. “We haven’t discovered a clear reason for this, but it is likely a combination of less-than-responsible contact lens use, trauma from vegetation, and corticosteroid drop use.”

How it presents

Dr. Meghpara noted that fungal keratitis patients usually present with a slowly progressing corneal infection. “Patients often come to us after seeing multiple eyecare providers and having been on multiple treatments (typically topical antibiotics for a suspected bacterial infection),” he said. “Usually this means they are presenting to us in the later stages of the disease, which is not ideal.”

Dr. Meghpara said that fungal keratitis can be very serious and may not be easy to treat. “Often, the infection is in the deeper layers of the cornea, making it less accessible to topical antifungals,” he said.

There also may be significant visual risks. “Even if we can successfully treat the fungus, these patients are often left with corneal scars than can affect vision, and they may need a corneal transplant,” Dr. Meghpara said. “The worst-case scenario is we cannot get the fungus under control, and this could lead to corneal perforation or even invasion of fungus into the eye, leading to endophthalmitis. This can be devastating.”

Dr. Mah noted that presentation for fungal keratitis is usually the same as with bacterial keratitis. Patients will typically report acute onset of pain, light sensitivity, discharge, change in vision, redness, and if they’re a contact lens wearer, they may associate it with contact lens issues.

When they do eventually see a physician, most will start with a topical antibiotic, he said, adding that there are more commercially available topical antibiotics than antifungals.

Patients with fungal keratitis may look a little better after this treatment, but ultimately, the problem will persist and further testing will be necessary to diagnose the problem of fungal keratitis, Dr. Mah said. In general, he said two main types of fungi causing infections are classified as filamentous and non-filamentous.

Dr. Meghpara said that the three big risk factors for fungal keratitis are trauma from vegetation (like a tree branch), contact lens use, and topical corticosteroid use. When looking for warning signs, he suggested that it’s important to keep these three factors in mind for all patients who come in with a corneal infection.

“It takes a high level of suspicion to make the diagnosis early,” he said. “We also look at the characteristics of the infiltrate. Classically, fungal keratitis presents with a gray/white infiltrate with ‘feathery’ edges. Sometimes there are satellite lesions.” However, he noted that the appearance can vary.

Treatment options

Dr. Mah said, there’s only one FDA-approved, commercially available topical antifungal for fungal keratitis, natamycin. He said this treatment works well but added that it tends to work better against filamentous forms of fungal keratitis.

The other agents that can be used for treatments are typically compounded, Dr. Mah said, and these include amphotericin B and voriconazole. He noted that amphotericin B might work slightly better with non-filamentous types of fungal keratitis, while voriconazole works well for both types.

Dr. Mah noted several challenges with treatment options. The first is that these antifungals are large molecules and generally don’t get through the corneal epithelium very well. So as the epithelium heals, it’s hard for the drugs to get through.

Another challenge is that fungi usually mutate quickly and become resistant quickly. For this reason, Dr. Mah said it’s better to treat with two agents so that resistance doesn’t become an issue.

When beginning to treat these patients, Dr. Meghpara said you need to start by performing a corneal culture. “We culture most of our suspected corneal infections anyway, but we always culture patients in whom we are suspicious of fungus,” he said.

“If we get a positive culture with sensitivity results, we can tailor our treatment to what the fungus is most susceptible to,” he said. “If the drops are not working as well as we would like, sometimes we use oral medication.”

Dr. Meghpara utilizes oral voriconazole but said it’s important to be careful with this, as it can cause liver toxicity. He noted the importance of monitoring the patient’s liver enzymes. “Sometimes the infection remains uncontrolled, and we have to do a therapeutic corneal transplant to essentially cut out the infection,” he added.

Dr. Meghpara said the earlier the treatment is started, the more successful the result. However, even with resolution of the infection, patients can still be left with significant corneal scars.

Treatment for fungal keratitis can take a very long time, Dr. Meghpara said, so it’s important to counsel patients about this. It may take several weeks at minimum and up to months to treat.

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About the physicians

Francis Mah, MD
Scripps Clinic
La Jolla, California

Beeran Meghpara, MD
Wills Eye Hospital
Philadelphia, Pennsylvania

Relevant disclosures

Mah: Santen
Meghpara: Santen

Contact

Mah: Mah.Francis@scrippshealth.org
Meghpara: bmeghpara@willseye.org