Artificial cornea implantation: High postop infectious keratitis rate

Reviewed by Anthony J. Aldave, MD

Infectious keratitis is a “bugaboo” associated with implantation of the Boston Type I Keratoprosthesis (KPro), the most widely used artificial cornea worldwide, and develops in approximately 17% of cases, according to Anthony J. Aldave, MD, professor of Ophthalmology and chief of the Cornea and Uveitis Division at UCLA’s Stein Eye Institute in Los Angeles California.

Considering the potentially devastating effects of infectious keratitis, Aldave and colleagues looked retrospectively at patients who underwent KPro implantation at Stein Eye Institute and the Centre Hospitalier of the University of Montreal between May 1, 2004, and December 31, 2018.

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They sought to determine the incidence, associated organisms, risk factors, and clinical course of infectious keratitis after KPro implantation and develop evidence-based guidelines for postoperative patient management.

Postoperative antibiotic regimen
All procedures had been performed by Aldave In Los Angeles and Mona Harissi-Dagher, MD, in Montreal.

Slightly different postoperative antimicrobial regimens were used at the 2 surgical sites: topical fourth-generation fluoroquinolones 4 times daily indefinitely (and vancomycin 4 times daily for approximately 4 months before 2013) in Los Angeles and topical fourth-generation fluoroquinolones 4 times daily and tapered to once or twice daily indefinitely in Montreal. No topical antifungal prophylaxis was used.

At both institutions, the postoperative regimen included a topical steroid (prednisolone acetate) used between 4 times daily and every 2 hours and then tapered to once or twice daily; this was stopped when no intraocular or ocular surface inflammation was present.

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A therapeutic soft contact lens was used postoperatively when needed to keep the corneal epithelium intact, relieve discomfort, or maintain sufficient quality of vision.

The lens was replaced every 1 to 3 months and discontinued when an indication was no longer present or if the lens could not be maintained on the eye, Aldave explained.

Results
The KPro was implanted during 349 procedures in 295 eyes of 268 patients (mean age, 62.7 years; mean follow-up, 51.6 months).

Graft failure was the primary indication for the initial KPro procedure and was a significantly more frequent indication in Los Angeles than in Montreal (64.7% vs 46.4%, respectively; P < .01).

Significantly more patients in Los Angeles underwent repeated implantations compared with those in Montreal (21.0% vs 9.6%, respectively; P = .005).

Related: Confocal microscopy key to diagnosing infectious keratitis

Familial aniridia was present significantly more often in Montreal (15.2%) compared with Los Angeles (3.1%; P < .01) as the indication for the KPro implantation, he said.

“Fifty-seven cases of presumed infectious keratitis developed after 53 procedures (15.2%) in 50 eyes (16.9%) of 49 patients (18.3%).

This equates to an annual incidence of 0.035 cases per year, with annual incidence of culture-positive bacterial keratitis of 0.014 and culture-positive fungal keratitis of 0.004,” Aldave said.

The annual incidence of presumed infectious keratitis corresponded to development of 1 case of infectious keratitis each 29 years of follow-up.

The incidence of bacterial keratitis corresponded to 1 case per 71 years of follow-up and was significantly higher than that of fungal keratitis, which corresponded to 1 case for every 250 years of follow-up.

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The mean time to development of infectious keratitis was 20.4 months (15.3 months in Los Angeles vs 33.5 months in Montreal; P < .01).

No significant difference was seen between the 2 sites in the time to development of bacterial keratitis (average time, 15.5 months) or to the time to development of fungal keratitis (mean time, 38.2 months).

The annual incidence of infectious keratitis was highest during the first and second years postoperatively.

Clinical presentation
“The typical presentation of a corneal infiltrate in patients with a KPro is the presence of an opacity under the edge of the front plate next to the optic in 78% of cases,” Aldave said. “The donor cornea peripheral to the edge of the front plate was involved in 63%, and the infiltrate was confined to under the edge of the front plate in 14%.”

Bacterial keratitis developed more often than fungal keratitis at both institutions, with bacterial keratitis seen in 43% and 44%, respectively, in Los Angeles and Montreal, and fungal keratitis in 14% and 6%, respectively.

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The most common bacteria were coagulase-negative Staphylococcus and Streptococcus species at both centers, at 68.4% and 87.5%, respectively.

The most common fungal isolates were Candida parapsilosis and Alternaria, in 15.8% and 12.5%, respectively.

The demographic risk factors for infectious keratitis were location (with a lower incidence in Montreal) and cicatricial disease.

Postoperative risk factors for presumed infectious keratitis overall and culture-positive bacterial keratitis and fungal keratitis evaluated separately included development of a persistent corneal epithelial defect (P < .01 for all comparisons).

Prolonged topical steroid use was associated with a significantly decreased risk of development of infectious keratitis overall and when bacterial and fungal keratitis were evaluated separately (P < .01 for all comparisons).

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Topical vancomycin resulted in a higher incidence of fungal keratitis (P < .01). Contact lens use was not associated with bacterial or fungal keratitis; however, prolonged use was associated with a decreased risk of infectious keratitis.

Management of infections
Medical management was successful for the bulk of the cases (34 of 53 cases), with an average time to infection resolution of 3.1 months.

In 30 cases for which the visual outcomes were known, 9 eyes lost 2 or more lines of corrected distance vision.

Surgical management was needed in 19 cases: 11 underwent penetrating keratoplasty, 6 KPro removal and replacement, and 2 evisceration.

“Infectious keratitis was associated with a significantly increased risk of KPro explanation, with a mean time to removal of 2.3 months after diagnosis of infectious keratitis,” Aldave said.

Infectious keratitis was associated with a significantly increased incidence of endophthalmitis, idiopathic vitritis, corneal stromal necrosis, retroprosthetic membrane formation, retinal detachment, hypotony, and cystoid macular edema compared with eyes in which infectious keratitis did not develop.

Related: Snapshot: Managing endogenous endophthalmitis in patients

What follows are take-home messages from the findings:

> Infectious keratitis is one of the most common complications following KPro implantation, developing in approximately 17% of eyes, with an annual incidence rate of 0.035 per year.

> A preoperative history of cicatrizing conjunctivitis and development of persistent epithelial defects following surgery are risk factors for infectious keratitis after KPro implantation.

> Bacterial keratitis caused by Streptococcus and Staphylococcus species is more common than fungal keratitis, which results most often from Candida species.

> Failed medical therapy required explanation of the KPro in approximately one-third of cases.

> Infectious keratitis is associated with increased incidence rates of postoperative complications, including endophthalmitis, idiopathic vitritis, corneal stromal necrosis, retinal detachment, and hypotony.

> The significantly increased risk of KPro retention failure and complications associated with infectious keratitis underscore the importance of topical antimicrobial prophylaxis, aggressive management of persistent corneal epithelial defects, and prompt diagnosis and treatment of suspected infectious keratitis.

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Anthony J. Aldave, MD
e:aldave@jsei.ucla.edu
This article is adapted from Aldave’s presentation during Subspecialty Day at the American Academy of Ophthalmology 2020 virtual annual meeting. He has no financial interest in this subject matter.