Placement, severity determines corneal ulcer treatment

The choice of therapeutic and dosing schedule for corneal ulcer treatment will vary depending on the severity and location of the infiltrate, according to several practitioners.

Empirical treatment is sufficient for small, low-risk ulcers with one infiltrate located on the periphery of a healthy patient, Paul Karpecki, OD, FAAO, told Primary Care Optometry News.

“In light of the broad spectrum of activity in the more recently approved fluoroquinolones, you can manage [small ulcers] quite successfully with a single agent,” he said.

Peripheral corneal ulcer: NaFl stain and cobalt blue light show this epithelial defect overlying the stromal infiltrate. Image: Lonsberry B

“Studies presented at ARVO in 2009 showed that besifloxacin had extremely good MIC 90 data against all the pathogens,” Charles W. Ficco, OD, said in an interview. “I think besifloxacin is so strong right now because it’s brand new; there’s no systemic counterpart to it. The other fluoroquinolones have systemic counterparts that have been used for years, so the bacteria have adapted to them by now.”

For larger corneal ulcers located on the visual axis, more aggressive therapy must be used, according to Blair Lonsberry, MS, OD, MEd, FAAO.

“For central or severe keratitis where there is deep stromal involvement or an infiltrate larger than 2 mm with extensive suppuration, a loading dose is instilled every 5 to 15 minutes for the first 1 to 3 hours followed by frequent applications every 30 minutes to 1 hour around the clock,” he said in an interview.

Initial presentation: MRSA infiltrate under a LASIK flap. Image: Thimons JJ

MRSA: This corneal ulcer occurred in an 83-year-old nursing home resident. Image: Ficco CW

J. James Thimons, OD, is especially concerned with postoperative LASIK, PRK and corneal transplant patients who develop corneal ulcers. Considering the preoperative prophylaxis administered several days before surgery, the organism that broke through is more dangerous and aggressive than a typical pathogen, he said.

“A surgical eye has been traumatized, and the organism is allowed access to a space it never typically gets to,” Dr. Thimons told PCON. “In LASIK, the infection will be under the flap, so you have this perfect incubator where the organism is resting.”

Culture suspicious cases

Initial treatment for suspicious corneal ulcers also consists of ordering cultures. According to Dr. Karpecki, culturing helps identify the pathogen and select an appropriate treatment regimen.

“I would culture any ulcer greater than 3 mm in size, an ulcer with two or more infiltrates, an ulcer within a millimeter of the visual axis, all patients who come from a hospital setting where you’re worried about MRSA [methicillin-resistant Staphylococcus aureus], anyone who is immunocompromised and anyone who’s had recent surgery,” Dr. Karpecki said.

Joseph P. Shovlin, OD, said he would also culture any infiltrate occurring after a history of organic trauma, one with an atypical appearance, an infiltrate not responding to seemingly appropriate therapy, when there is 50% or greater corneal thinning or scleral extension with significant keratitis.

A large central bacterial corneal ulcer. Image: Karpecki PM

For treating severe keratitis until culture results are obtained, Dr. Shovlin recommends a fortified aminoglycoside or later-generation fluoroquinolone and fortified cephalosporin or vancomycin.

In cases where clinicians suspect growth other than bacterial, Dr. Thimons said it is important to advise the lab to initially plate for viral and fungal growth.

Evaluating success

Patient symptomatology and ulcer appearance is the best method to gauge success, Dr. Shovlin said.

“Measures of significant improvement include reduced pain; blunting of the perimeter of stromal suppuration; a reduction in the stromal edema, anterior chamber reaction and density of the infiltrate; and progressive re-epithelialization,” he told PCON. “Each organism will look different the next day. The patient will often look worse if the organism is Pseudomonas or a mixed infection, or the patient may look significantly improved after 24 to 48 hours in certain strands of Staphylococcus epidermidis. Organisms such as S. aureus and Streptococcus pneumoniae are generally unchanged at 24 hours and then improve rapidly.”

According to Dr. Lonsberry, if the ulcer is not progressing and is stabilized, the treatment is effective.

The initial therapeutic regimen should be modified when the eye shows a lack of improvement or stabilization after 48 hours or if culture and sensitivities dictate alternate therapy. Dr. Ficco recommends alternating therapy to battle both gram-positive and gram-negative bacteria in advanced corneal ulcers.

“I start with a newer-generation fluoroquinolone such as besifloxacin or Zymaxid (gatifloxacin 0.5%, Allergan) and alternate with tobramycin,” he said. “The newer studies such as Ocular TRUST [Asbell et al.] have shown that tobramycin still has a great deal of efficacy in most gram-negative pathogens, and the newer-generation fluoroquinolones handle both the gram-positive and -negative organisms.”

Atypical cases

When antibacterial treatment fails, Dr. Thimons uses multiple fortified therapies while waiting for culture results. All corneal ulcers look the same until about day 7, he said, when key traits of the ulcer begin to appear and they can be differentiated as fungus, Acanthamoeba or MRSA.

“Fungal lesions frequently produce an immune ring (Ring of Wessely), but they are also prone to develop satellite lesions not typically seen in bacterial disease,” he said. “A bacterial infection almost never spreads beyond the point of the lesion, while a fungal lesion may produce another lesion 3 mm away that’s now active.”

A classic sign of Acanthamoeba is radial neuritis, an inflammation of the corneal nerves that produces a spoke and wheel-like presentation, he said.

Dr. Shovlin added that oral agents such as doxycycline are a beneficial adjunct in cases of progressive corneal thinning. “If there is significant scleral involvement, especially with Pseudomonas, IV medication is essential,” he said.

Treating MRSA

MRSA is relatively uncommon in corneal ulcers. However, though MRSA was historically limited to those who worked or lived in hospital settings, today anyone could potentially have MRSA. According to a study by Blomquist, corneal ulcers made up 10% of MRSA ocular infections, Dr. Lonsberry said.

“The take-home message is that MRSA is present in ocular infections and not contained to hospital or institutional settings; it is increasingly a community acquired infection,” he said.

“Although community-acquired cases continue to grow, I would treat someone from a hospital setting with the worry of it being MRSA,” Dr. Karpecki added, “starting the patient on Besivance (besifloxacin 0.6%, Bausch + Lomb) and alternating Polytrim (polymyxin B-trimethoprim, Allergan) drops. If the cultures confirm MRSA or methicillin-resistant S. epidermidis, I would add fortified vancomycin.”

Err on the side of caution

These experts advised referral to a corneal specialist if a clinician does not feel comfortable treating an ulcer.

“Consider referring cases of central corneal ulcers that have a higher chance of being infectious and resulting in scarring and permanent loss of vision,” Dr. Lonsberry said.

“When there’s vision loss, you want to have a corneal specialist involved, from a logistic as well as protective level,” Dr. Karpecki added. – by Stephanie Vasta

References:

• Asbell PA, et al. Am J Ophthalmol. 2008;145:951-958.
• Blomquist PH. Trans Am Ophthalmol Soc. 2006;104:322-345.

• Charles W. Ficco, OD, is clinic director, Clayton Eye Care Center, Morrow, Ga.; (770) 968-8888; charficco@aol.com. Dr. Ficco is a paid consultant for Allergan.
• Paul M. Karpecki, OD, FAAO, is a PCON Editorial Board member and clinical director, Corneal Services and Ocular Surface Research, Koffler Vision Group, Lexington, Ky.; (859) 227-7781; paul@karpecki.com. Dr. Karpecki is a paid consultant for Allergan and Bausch + Lomb.
• Blair Lonsberry, MS, OD, MEd, FAAO, is clinic director, Portland Vision Center; (503) 352-2510; blonsberry@pacificu.edu.
• Joseph P. Shovlin, OD, FAAO, is a PCON Editorial Board member who practices at Northeastern Eye Institute in Scranton, Pa.; (570) 342-3145; jpshovlin@gmail.com. Dr. Shovlin has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• J. James Thimons, OD, is a PCON Editorial Board member who practices at Ophthalmic Consultants of Connecticut, Fairfield, Conn.; (203) 257-7336; jthimons@sbcglobal.net.