Managing infections in artificial cornea

Improvements in the Boston Keratoprosthesis device have resulted in fewer complications after implantation, but they still occur. Surgeons should be alert to development of infectious keratitis and endophthalmitis postoperatively.

Reviewed by Kathryn Colby, MD, PhD

Chicago-Corneal specialists have turned to a keratoprosthesis (Boston keratoprothesis [KPro], Massachusetts Eye and Ear) with increasing frequency over the past decade to address corneal blindness.

Kathryn Colby, MD, PhD, attributes the increase in implantations to changes in the postoperative management-and in the device itself, which has been in use since the 1960s-for the decrease in device extrusion and endophthalmitis. Currently, about 11,000 devices have been implanted.

However, infectious keratitis and endophthalmitis may still develop in up to 18% of cases for several factors, she explained.

“The device is a foreign body without biointegration into the eye that connects the outside world to the interior of the eye,” said Dr. Colby, who is the Louis Block professor and chairman, Department of Ophthalmology and Visual Science, University of Chicago.

Courtesy of Kathryn Colby, MD, PhD

“Second, use of low-dose topical antibiotics and topical steroids in the setting of continuous bandage lens wear predisposes the eye to infection,” she added. “Finally, many of these patients have severe ocular surface disease that has been shown to be risk factors for infections.”

Infections associated with its implantation can be bacterial or fungal and the risk factors are persistent epithelial defects, a history of autoimmune ocular surface diseases, i.e., Stevens-Johnson syndrome and mucous membrane pemphigoid, and chemical injury.

Infectious keratitis

Dr. Colby advised that ophthalmologists maintain a high index of suspicion for possible infectious keratitis.

“Don’t ignore subtle infiltrates, and be wary of deposits on bandage lenses because these may indicate the presence of fungus,” she said.

“Performing cultures is the mainstay of therapy to establish the diagnosis but cultures can be challenging,” said Dr. Colby, recommending imaging, corneal biopsies, or passing a suture through the area of a deep infiltrate to make the diagnosis.

The first step in management is removing the bandage contact lens, which can either be replaced or left off. Steroids can be tapered or stopped and topical antibiotics that cover gram-negative and gram-positive organisms should be prescribed.

Administration of a topical antifungal drug, usually amphotericin B, is a consideration. Most fungal infections that develop after device implantation are identified as Candida, Dr. Colby said.

Other considerations are the role of systemic therapy, removal of the KPro, and replacement with tectonic penetrating keratoplasty. In all scenarios, the patients should be followed closely.

Possible complications after infectious keratitis include corneal melting that exposes the back plate of the device. A retroprosthetic membrane is another possibility after infectious keratitis.

Infectious endophthalmitis

Infectious endophthalmitis occurs in up to 12.5% of patients who are implanted with the device, despite using prophylactic antibiotics postoperatively. Gram-positive organisms are mostly responsible for the endophthalmitis.

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However, Dr. Colby noted that recently surgeons are seeing an uptick in gram-negative and fungal infections. The management in these patients is the standard tap and inject and physicians can consider a pars plana vitrectomy.

The endophthalmitis risk factors include patient non-compliance with antibiotic therapy.

“It is very important to underscore the importance of instilling the antibiotics in patients implanted with KPro,” she said.

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As with infectious keratitis, risk factors include Stevens-Johnson syndrome, mucous membrane pemphigoid, and infectious keratitis itself.

“Early diagnosis and management of infectious keratitis will decrease the chance of progression to endophthalmitis,” Dr. Colby said.

Conjunctival erosion has also been reported as a risk factor for endophthalmitis.

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A pitfall in these patients is the difficulty in differentiating idiopathic vitritis, which can develop in up to 14.5% of patients, from infectious endophthalmitis. The vision in patients with vitritis can decrease acutely. The clue to the diagnosis is that the eye is “quiet” and painless, and administration of topical steroids or a sub-Tenon’s depot injection results in rapid visual improvement.

Dr. Colby advised seeing patients a few days after steroid treatment to determine if the vision has improved.

When in doubt

When in doubt, however, these cases should be treated as infectious endophthalmitis, she said. When considering prophylaxis against infection in patients with KPro, there is no level I evidence for an ideal regimen.

“We know that a broad-spectrum agent should be used,” Dr. Colby said. “Some investigators advocate the use of vancomycin, especially in monocular patients or those with an autoimmune disorder.”

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Specifics about what the optimal timing and duration of the therapy, and how many times the drug should be administered daily, are still under discussion.

Future therapeutic directions include antibiotic-eluting contact lenses or sutures, an antimicrobial coating on the KPro materials, and antibiotic-eluting synthetic corneal carrier tissue.

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Kathryn Colby, MD, PhD

E: kcolby@bsd.uchicago.edu

Dr. Colby has no financial interest in the subject matter.