October 2018


Presentation spotlight
How to treat corneal ulcers unresponsive to fluoroquinolones

by Lauren Lipuma EyeWorld Contributing Writer

An ulcer caused by Streptococcus pneumoniae infection. Most corneal ulcers are bacterial and Gram positive.

An ulceration caused by pseudomonas bacteria that has spread to the sclera

Fungal keratitis present under a LASIK flap

Keratitis caused by Acanthamoeba infection
Source (all): Brandon Ayres, MD

Experts recommend identifying the infectious agent and modifying treatment

Corneal ulcers are common but can be difficult for ophthalmologists to diagnose. It is not always easy to identify the underlying infection, and when the ulcer is unresponsive to the first line of treatment—a fluoroquinolone—physicians may be unsure what to do next.
Cornea specialists addressed this issue during the “Cornea Essentials” symposium at the 2018 ASCRS•ASOA Annual Meeting. The purpose of the session was to run through common cornea scenarios and discuss some of the questions that come up when treating these patients, said Francis Mah, MD, Scripps Clinic Medical Group, La Jolla, California, who moderated the session.
Brandon Ayres, MD, cornea service, Wills Eye Hospital, Philadelphia, described a two-pronged approach for treating corneal ulcers that are unresponsive to fluoroquinolones. First, identify the infectious agent, if possible; second, modify your treatment based on what you find.
Ophthalmologists can’t always identify which kind of microbe is causing the infection, but culturing a sample of the cornea may offer some clues, according to Dr. Ayres.
“There is no way you can look at a corneal ulcer and say, ‘I know what this is,’ because you will get tricked,” Dr. Ayres said. “But you can get a general sense of the infectious agent. It does help you steer what you’re going to do.”

Identifying the infectious agent

At the slit lamp, use topical anesthesia and a sterile spatula or calcium alginate swab to get a tissue sample from the cornea, Dr. Ayres said. Culture the sample in several types of culture medium, like blood, chocolate, Sabouraud, and thioglycollate. Use the cultures to perform multiple smears; do a Gram stain to see if the bacteria is Gram positive or negative, a calcofluor stain to see if it is fungal, and a hematoxylin and eosin stain to look for Acanthamoeba.
“If you don’t have access to culture medium, it’s because you haven’t tried to get access to culture medium,” said John Berdahl, MD, Vance Thompson Vision, Sioux Falls, South Dakota. “Get a fridge, talk to your local hospital. It’s on you if you don’t have access to it.”
Also look for clues in the patient’s history, like contact lens wear, exposure to vegetative matter, or swimming in lakes or rivers, Dr. Ayres said. Minimize steroid use until the infectious agent is identified and do a careful history and exam, looking for neurotropism and lid abnormality, he added.
If you’re having trouble getting a tissue sample or culturing the organism, take the patient to the operating room (OR), pass a microsuture through the stroma and let it grow in thioglycollate broth, said Kenneth Beckman, MD, Comprehensive Eye Care of Central Ohio, Columbus.
“You may not have access to cultures, but you do have access to an OR,” Dr. Beckman said. “That’s a good way to get a sample, even for someone who’s been on drops.” I typically reserve this for patients where the cultures were unrevealing, the ulcer is not responding, and the infection is deeper in the cornea. This allows me to access tissue within the actual infection. If this does not work, a corneal biopsy may be needed.”
Elizabeth Yeu, MD, Virginia Eye Consultants, Norfolk, Virginia, recommended using confocal microscopy to look for hyphae to determine whether the infection is fungal.
“Confocal microscopy in the setting of looking for hyphae is so helpful,” Dr. Yeu said. “The hyphae are often abundant and clumped together, with a more classic appearance that looks like branching or unbranching bamboo. It is not uncommon for the fungal smear to be negative, and the fungal culture can take 5–20 days for final results. I will initiate oral and topical anti-fungal therapy based on the confocal microscopy. Acanthamoeba can be more challenging to identify. The double-walled cysts of Acanthamoeba are often sparse and can be difficult to highlight among other debris and white cells within the infectious infiltrate.”

Treatment recommendations

Once you have an idea of what the infectious agent is, you’ll need to modify your treatment, according to Dr. Ayres. The majority of corneal ulcers are bacterial and Gram positive; fungi and Acanthamoeba make up only a few percent of infections.
If the fluoroquinolone antibiotic is not working, adding a second agent may help. Penicillin derivatives may not be effective when treating Gram positive bacteria, however, because methicillin resistance is growing among ocular pathogens and many organisms resistant to methicillin will be multi-drug resistant, Dr. Ayres said.
Vancomycin is a good choice, if you have easy access to it, but consider trimethoprim if you don’t, he said. Chloro-fluoroquinolones like besifloxacin are also a good option. Besifloxacin has a lower mean inhibitory concentration than other antibiotics and has never been used systemically, so there is little chance of resistance, he said.
It’s important to remember that not all ulcers are the same; the treatment may depend on the ulcer’s size and how much of an inflammatory reaction is present, according to Dr. Ayres.
For smaller ulcers that are less than 2.5 millimeters in diameter, have a minimal anterior chamber reaction, and are not threatening the visual axis, culturing the tissue is a good idea but not essential, he said. Add a second antibiotic to kill any methicillin-resistant organisms, consider using besifloxacin, and continue using drops hourly until you see a clinical improvement, Dr. Ayres said. Be aware that the ulcer may progress for 24–48 hours even with appropriate management.
Absolutely get a culture for large ulcers, where there is a deep, vision-threatening ulceration and a large inflammatory response, Dr. Ayres continued. But don’t hold off on treatment if you can’t culture the organism; change your treatment from a fluoroquinolone to fortified antibiotics hourly around the clock until you see an improvement, he said.

Editors’ note: Dr. Ayres has financial interests with Bausch + Lomb (Bridgewater, New Jersey). Dr. Beckman has no financial interests related to his comments. Dr. Berdahl has financial interests with Alcon (Fort Worth, Texas), Allergan, (Dublin, Ireland), and Bausch + Lomb. Dr. Mah has financial interests with Allergan, Bausch + Lomb, and Novartis (Basel, Switzerland). Dr. Yeu has financial interests with Johnson & Johnson Vision (Santa Ana, California).

Contact information

: bfast33@comcast.net
Beckman: kenbeckman22@aol.com
Berdahl: johnberdahl@gmail.com
Mah: Mah.Francis@Scrippshealth.org
Yeu: eyeulin@gmail.com

How to treat corneal ulcers unresponsive to fluoroquinolones How to treat corneal ulcers unresponsive to fluoroquinolones
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