Predictors of Fungal Keratitis-related Corneal Perforation Identified

By Marilynn Larkin

August 25, 2017

NEW YORK (Reuters Health) – Baseline presence of hypopyon and infiltrate depth and size are significant predictors of corneal perforation and/or need for therapeutic penetrating keratoplasty (TPK) in patients with severe fungal keratitis, researchers say.

To determine which patients might be at higher risk of poor outcomes from infectious keratitis, Dr. Jennifer Rose-Nussbaumer of the University of California, San Francisco, and colleagues conducted a secondary analysis of the Mycotic Ulcer Treatment Trial (MUTT) II, a multicenter placebo-controlled trial that ran from 2010 to 2015.

The participants were 240 patients (mean age at enrollment, 49) with smear-positive filamentous fungal corneal ulcers. All were of Southeast Asian descent, and 43% were women.

At baseline, participants had visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or placebo. Both groups also received topical 1% voriconazole and, after results from MUTT I became available, topical 5% natamycin.

As reported in JAMA Ophthalmology, online August 17, about half of participants developed a full-thickness corneal perforation or needed to undergo TPK during the study period.

Patients with hypopyon at baseline were more than twice as likely to develop corneal perforation, need TPK, or both.

Participants with infiltrate involving the posterior third of the stroma had a 71.4% risk of developing corneal perforation, needing TPK, or both; each 1-mm increase in the geometric mean of the infiltrate increased those odds by a relative 37%. Patients whose baseline infiltrate size had a geometric mean >6.63 mm showed a 66.7% risk of developing corneal perforation, needing TPK, or both.

Clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism, duration of symptoms and demographic characteristics (e.g., gender, occupation) were not significant predictors.

The authors conclude that “risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK.”

However, they acknowledge some limitations of the study, including the fact that the characteristics of organisms causing fungal keratitis in Southeast Asia may differ from those in other regions, and that most infections were related to agricultural exposure and not contact lenses, the cause in most developed countries.

Dr. Rose-Nussbaumer told Reuters Health by email that the findings “may be particularly useful for allocating resources in resource-poor settings, although they are relevant to all patients with infectious keratitis.”

Dr. Uyen Tran, Division Chief, Cornea and Refractive Surgery at Vanderbilt Eye Institute, Nashville, Tennessee, told Reuters Health, “In my practice, we will not do a TPK unless the infection threatens the corneal limbus with spread to the sclera. We know that once the infection has spread to the sclera, the visual prognosis is extremely poor.”

“If this criterion is not met,” he said by email, “we will treat conservatively and wait to eradicate all infection and inflammation before performing surgery. This will give a better prognosis to the transplant with less risk of eventual complications.”


JAMA Ophthalmol 2017.