Serious corneal infections still lack effective treatment regimens

Latest-generation fluoroquinolones are effective, but other modalities are needed to curb these infections.

Corneal infections that present the greatest risk to ocular health are those that lack safe and effective treatment modalities, such as Acanthamoeba keratitis and corneal fungal infections, according to experts who spoke with Ocular Surgery News.

“The outbreaks of Fusarium and Acanthamoeba keratitis among contact lens wearers, attributable to the use of specific lens care solutions, has now fortunately abated, but these devastatingly difficult to treat infectious agents are still lurking opportunistically,” Kenneth R. Kenyon, MD, OSN Cornea/External Disease Editor Emeritus, said.

Acanthamoeba and fungal infections of the cornea, including Fusarium keratitis, pose the greatest risk, followed corneal infections with unusual bacteria and viral infections that lack appropriate treatment, Eduardo C. Alfonso, MD, OSN Cornea/External Disease Board Member, said

Bacterial infections such as methicillin-resistant Staphylococcus aureus and epidermis (MRSA and MRSE) also present serious risks because of the extent of ocular damage from those infections.

Acanthamoeba

In 2007, the U.S. Centers for Disease Control and Prevention (CDC) issued an alert announcing an increase in cases of Acanthamoeba (a protozoa) keratitis infections. The CDC published data showing an increased risk with use of Complete MoisturePlus contact lens solutions (Abbott Medical Optics). AMO recalled the contact lens product.

The infection remains an issue because of both the difficulty in treating it and lack of an established cause for it. Theories abound about the cause of the infection, including environmental factors such as water that has high levels of amoeba, Francis S. Mah, MD, OSN Cornea/External Board Member, said.

“Obviously, [Acanthamoeba] was a major concern to the public just a couple of years ago, with its associations with AMO’s contact lens solutions, and I think a lot of the concern decreased with a probable false sense of security once there was a [U.S. Food and Drug Administration] recall,” Dr. Mah said. “A lot of people identified Acanthamoeba with the AMO contact lens solution; however, there are many ocular laboratory reports showing that the recall really did not stem the tide of Acanthamoeba infections.”

Contact lens wear itself remains one of the biggest factors in the increased risk of certain serious corneal infections, Dr. Kenyon said. He took part in a case-control study examining the infection risk in daily-wear vs. extended-wear of contact lenses and found a 10 times increased risk of ulcerative keratitis among extended-wear contact lens users as opposed to those who did not wear lenses overnight, independent of actual lens type of manufacturer.

“Bacterial infections occur in contact wearers, even if they have perfectly healthy eyes and good lens hygiene. The risk remains,” Dr. Kenyon said.

He said physicians should also be watchful for polymicrobial keratitis in the setting of Acanthamoeba because infectious crystalline keratopathy (usually streptococcal) or other bacterial infection can often coexist with the protozoal infestation, presenting additional issues.

Bacterial infections

A major issue in corneal infections is resistance to existing medication, Dr. Alfonso said. Of most immediate concern is how gram-positive bacterial infections are developing resistance to fourth-generation fluoroquinolones Zymar (gatifloxacin, Allergan), Vigamox (moxifloxacin, Alcon) and Iquix (levofloxacin, Vistakon).

“For the treatment of severe corneal ulcers, we are supplementing the fourth-generation fluoroquinolones with topical vancomycin because of its better coverage against Streptococcus pneumoniae and methicillin-resistant Staphylococcus,” he said. “We’re looking forward to development of newer antibiotics that will hopefully better cover the gram positives.”

Dr. Kenyon said fourth-generation fluoroquinolones continue to be “effective and potent anti-infectives” with “one drop stopping capability” against gram-positive and gram-negative bacterial infections. They are effective in treating ocular infections, including conjunctivitis and keratitis, and do not require special fortified antibiotic preparations, such as vancomycin.

“The activity of [fluoroquinolones], in particular against pseudomonas and other gram negatives, as well as atypical mycobacteria, is also critically advantageous in treating contact lens-related microbial keratitis, where grams negatives tend to be selectively more prevalent,” he said.

Fungal infections

A fungal infection was also linked to contact lens wear: In 2006, Bausch & Lomb recalled its ReNu with MoistureLoc solution after a CDC-confirmed link to Fusarium keratitis outbreaks.

Dr. Alfonso said options for fungal treatment are limited, with either poor corneal penetration or major toxicity. Natacyn (natamycin, Alcon) is the only commercially available antifungal topical treatment, but other drugs are in development, including Vfend (voriconazole, Pfizer), which appears to be safe, with well-tolerated intraocular and topical results. However, the organisms studied did not all have the same response to the drug.

“We’re still trying to figure out if all the organisms that we would like to cover are responding well to this treatment,” he said. “Information from my laboratory and others shows that not all organisms respond well to it, especially the Fusarium solani.”

It appears that Fusarium solani does not respond to treatment as well as Fusarium oxysporum, showing variability in response within the same group of organisms.

“We’re looking for and hoping we can come up with more alternatives in the antifungal area,” Dr. Alfonso said.

Treatment possibilities

In order to best treat all ocular infections, researchers and physicians may need to change some practice patterns, Dr. Alfonso said. Of key importance is an emphasis on what devices, drugs or contact lenses are placed in the eye and how they are placed to best minimize the microorganisms that are introduced to the eye.

“We need to be smarter about things that we do to change the micro-environment in which our eye exists,” he said.

Improved diagnostic tools are also needed to more accurately identify infections. Techniques using DNA could enhance diagnostic abilities, he said.

Pre-treating lid disease is especially important because the eyelids are the source of most ocular infections. “Pre-treating lid disease with new antibiotics, such as AzaSite (azithromycin, Inspire Pharmaceuticals), can improve meibomian gland dysfunction … and reduce colonization of the lid margins,” Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member, said. “I think more attention is going to be paid to blepharitis as a source of these bacteria than has been paid in the past.”

After diagnosis, safe and effective treatments are vital to halting the damage of ocular infections, according to Dr. Alfonso. Prevention might not be the most realistic way to halting microbial infections. Instead, controlling how the infections act in the eye may be the more effective means of treatment.

“If you have a bacteria, like pseudomonas, it is not the pseudomonas in itself that’s causing the damage but all the enzymes that are producing and how our immune response modulates those enzymes,” he said. “So we can leave the pseudomonas there living, we don’t have to kill it, if we can control the interaction of these enzymes with our bodies. If we come up with better treatment and modulation techniques for these microorganisms, I think we’re going to do much better.” – by Erin L. Boyle

Click here to see the Guide to Anti-Infective Medications.

Reference:

• Schein OD, Glynn RJ, Poggio EC, Seddon JM, Kenyon KR. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med. 1989;321(12):773-778.

• Eduardo C. Alfonso, MD, can be reached at Bascom Palmer Laser Vision Center, 900 NW 17th St., Miami, FL 33136; 305-326-6366; fax: 305-326-6337; e-mail: ealfonso@med.miami.edu. Dr. Alfonso is a lecturer, on the advisory board and provides research support for Alcon, Allergan, Bausch & Lomb and Vistakon.
• Eric D. Donnenfeld, MD, can be reached at OCLI, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; fax: 516-766-3714; e-mail: eddoph@aol.com. Dr. Donnenfeld is a consultant to Allergan, AMO, Bausch & Lomb, Alcon and Inspire.
• Kenneth R. Kenyon, MD, can be reached at Eye Health Vision Centers, 51 State Road, North Dartmouth, MA 02747; 508-994-1400; fax: 508-992-7701; e-mail: kenrkenyon@cs.com.
• Francis S. Mah, MD, can be reached at University of Pittsburgh Medical Center, Eye and Ear Institute, 203 Lothrop St., Eighth Floor, Pittsburgh, PA 15213; 412-647-2200; fax: 412-647-5119; e-mail: mahfs@upmc.edu. Dr. Mah is a consultant to Alcon, Allergan and Inspire.