Collagen Crosslinking Shows Promise for Keratitis

Laird Harrison

November 15, 2020

Corneal collagen crosslinking, a procedure developed for keratoconus, could treat keratitis as effectively as antimicrobials, a new study suggests.

The procedure could prove particularly useful in treating drug-resistant pathogens, said Emilio Torres-Netto, MD, from the Center for Applied Biotechnology and Molecular Medicine (CABMM) at the University of Zurich, Switzerland.

"Crosslinking actually kills the microorganisms on the surface of the cornea," he told Medscape Medical News.

Torres-Netto presented the finding at the American Academy of Ophthalmology 2020 annual meeting.

In crosslinking, clinicians apply riboflavin to the cornea as a photosensitizer then shine ultraviolet light on it. The riboflavin generates reactive oxygen species, which induce the formation of covalent bonds linking collagen molecules to each other and to proteoglycans.

This stiffens the cornea, arresting the progression of keratoconus and other forms of corneal ectasia. Developed in Germany, the procedure has only come to the United States in recent years.

Ultraviolet light has long been used to treat blood infections, so the idea of using it for keratitis occurred early on to researchers developing crosslinking.

It might work in a few different ways: The same reactive oxygen species might disrupt the cell membranes of the pathogens causing keratitis. The ultraviolet light might damage their DNA or RNA. Or the altered cornea might become more resistant to digestion by the microbes.

To test the theory, Torres-Netto and colleagues recruited patients with bacterial infections, fungal infections, or a mixture of the two, causing infiltrates and early superficial ulcers up to 4 mm in diameter. The researchers assigned 21 patients to medication and 18 to crosslinking.

The crosslinking was done with 7.2 joules/cm2 of energy. Torres-Netto and colleagues have found that the cornea can withstand much more ultraviolet energy than the 5.4 J/cm2 typically used in crosslinking. This can help in treating fungal infections, which are particularly hard to cure, he said.

The infection continued progressing in two patients assigned to the crosslinking group, so clinicians treated them with antimicrobials. And in the medication group, two patients had penetrations that required surgery.

In both groups, the median time to epithelialization in the remaining patients was 7 days. Mean LogMAR corrected distance visual acuity scores improved from 0.73 to 0.54 in the medication group and from 0.76 to 0.53 in the crosslinking group — a statistically equivalent change.

The finding supports a need for a larger clinical trial, said Torres-Netto.

In practice, crosslinking might be combined with antimicrobials to achieve even greater efficacy, he said.

Although the study did not address this point, it appears that the treatment works best in early to moderate ulcers, he added.

The research group has had success treating corneas as thin as 250 µm, much thinner than the 400 µm that had been recommended in the past.

And the treatment could become more available because a new device called the C-Eye (EMAGine AG) can be mounted on a slit lamp for office use. The device is now on sale in Europe but is not yet available in the United States.

The new technique offers an advance in treating a condition offering little recent progress, said Sumit Garg, MD, a cornea surgeon at University of California, Irvine.

"It's really exciting as a cornea specialist because we know that despite proper identification of pathogens in the cornea, and proper treatment based on what we know, you don't always get resolution," he told Medscape Medical News.

Many infections require weeks of antimicrobial treatment, he said, and some of these treatments are themselves toxic to the cornea.

American Academy of Ophthalmology (AAO) 2020 Annual Meeting: Session PO076. Presented November 13, 2020. Available on demand November 2020.

Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on radio and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at www. or follow him on  Twitter: @LairdH .


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