Range of surgical options growing for infectious keratitis patients

Medical treatments still work fairly well for bacteria, explains Jennifer R. RoseNussbaumer, MD. When infections do not respond to antimicrobials, thinning progresses, or perforation occurs, then surgery may be indicated.

Early surgical intervention may effectively treat cases of infectious keratitis that do not yield to medicine, according to Jennifer R. Rose-Nussbaumer, MD. “Medical therapy doesn’t always seem to be adequate at this time, particularly for fungal keratitis,” she said. Dr. Rose-Nussbaumer gave an overview of surgical interventions for infectious keratitis.

Infectious keratitis is “a big problem in tropical countries,” she said. Even in Florida, up to half of infectious keratitis may be fungal, she said.

“People are having devastating outcomes even though we are giving them everything we know how to do medically.” Medical treatments still work fairly well for bacteria, she said.

She cited the example of a recent patient with a Pseudomonas corneal ulcer who improved from 20/1200 to 20/25 vision in 12 months as infiltrates and scars cleared.

Natamycin is the most effective antifungal available for infectious keratitis, Dr. Rose-Nussbaumer said. But it doesn’t penetrate the cornea, and only prevents perforations or the need for a therapeutic keratoplasty about half the time in severe cases.

Oral voriconazole has proved disappointing, she noted. In the randomized controlled mycotic ulcer treatment trial II, Dr. Rose-Nussbaumer and her colleagues found that adding oral voriconazole to topical treatments did not reduce the risk of corneal perforation or the need for a therapeutic keratoplasty.

The risk of perforation or need for therapeutic penetrating keratoplasty was about 50% in both groups. In a secondary analysis of this data, they found that the risk doubled if the patients had a hypopyon at baseline, if the infection involved the posterior third or if the infiltrate was greater than 6.5 mm.

Almost all the patients with these risk factors had a perforation or needed a therapeutic keratoplasty, Dr. Rose-Nussbaumer said. They found that those with positive 6-day cultures had much worse visual acuity and larger scar sizes at 3 months, and were 7 times more likely to perforate or need therapeutic penetrating keratoplasty, she said.

The researchers graded infiltrate depth as 1) no infiltrate, 2) infiltrate involving the anterior one-third of the stroma, 3) infiltrate involving two-thirds of the stroma and 4) infiltrate involving the deepest third of the cornea.

For each step increase in the infiltrate depth as measured at baseline, there was 1.69 times the odds of the patient developing a full-thickness corneal perforation and/or needing a therapeutic penetrating keratoplasty.

At baseline, visual acuity was generally poor. The median was logMAR 1.7. For every line of worsening in baseline visual acuity, the odds of a perforation increased 1.06 times, but this was not statistically significant.

Epithelial defect size, baseline culture positivity, type of filamentous fungal organism, and duration of symptoms were not statistically significant predictors of progression, nor were demographic factors such as age, sex, and occupation.

The researchers noted that all the participants in the study were from Southeast Asia and it is possible that organisms in this area have different characteristics than those in other regions.

Turning to surgery

When infections do not respond to antimicrobials, thinning progresses, or perforation occurs, surgery is indicated. Cyanoacrylate glue arrests thinning before perforation, and after perforations can restore anatomic integrity, delaying the need for surgical intervention, said Dr. Rose-Nussbaumer.

It has antimicrobial properties and decreases the risk of endophthalmitis, she said. It can often improve visual acuity, but is best for perforations less than 3 mm. For larger perforations, Dr. Rose-Nussbaumer recommends a patch graft.

Compared with a therapeutic keratoplasty, a tectonic graft poses less risk of glaucoma and rejection. It is compatible with good vision, but leaves open the possibility of a later optical penetrating keratoplasty. But therapeutic grafts are not as successful on average as grafts for optical indications, Dr. Rose-Nussbaumer said.

Diving deeper

Researchers are still looking for new options to treat infectious keratitis. Among those being tested are corneal collagen crosslinking and intrastromal injection of voriconazole, she said.

Crosslinking is an interesting alternative because the procedure can be anti-microbial, anti-inflammatory and anti-collagenase. It may overcome such problems as drug resistance, toxicity and non-compliance.

Dr. Rose-Nussbaumer and colleagues have enrolled 110 patients in a 4-arm trial comparing natamycin alone, natamycin plus crosslinking, amphotericin alone, and amphotercin plus crosslinking.

They are expecting the study results soon. Among other outcomes, they are measuring repeat culture at 24 hours, best-corrected visual acuity at three months, infiltrate or scar size, the rate of penetration, astigmatism, corneal thickness, and vision-related quality of life

Disclosures:

Jennifer R. Rose-Nussbaumer, MDE: Jennifer.Rose-Nussbaumer@ucsf.edu This article was adapted from Dr. Rose-Nussbaumer’s presentation at Cornea Subspecialty Day during the 2017 meeting of the American Academy of Ophthalmology. Dr. Rose-Nussbaumer did not indicate any proprietary interest relevant to the subject matter.