Consider matrix therapy for corneal crosslinking

Topical regenerating agent eye drops speed up the corneal healing and reduce ocular discomfort after the epi-off crosslinking but more research is needed.

Take-home message: Topical regenerating agent eye drops speed up the corneal healing and reduce ocular discomfort after the epi-off cross-linking but more research is needed.

 Reviewed by Koray Gumus, MD

Kayseri, Turkey-A new matrix therapy (CACICOL20) may provide faster corneal healing after epithelial-off crosslinking with ultraviolet A and riboflavin, said Koray Gumus, MD.

Corneal crosslinking (CXL) has become a gold standard for slowing progression of keratoconus, but the debate continues about which technique-epithelial-on or epithelial-off (epi-on and epi-off, respectively)-is better, as there are advantages and disadvantages to both. Recent studies have shown that even the epi-on technique can cause epithelial damage, and result in ocular discomfort.

“Some complications might be related to the corneal wound healing,” said Dr. Gumus, Erciyes University School of Medicine, Kayseri, Turkey. “We need to promote better healing in these patients.”

Topical regenerating agent (RGTA) is a “promising agent,” he said, noting it is an engineered biopolymer, mimicking heparin sulfate as a protector and stabilizer of the actions of heparin binding growth factor. He presented results from an initial study on the agent.

What is RGTA?

According to Dr. Gumus, RGTA replaces endogenous glycosaminoglycans (GAGs) that have been degraded by the glycogenolysis. Their binding to matrix proteins, collagen, elastin, and fibronectin results in a mechanical protection against proteolytic degradation. Restoration of extracellular matrix scaffolding properties is then induced and so is the communication between cells.

These effects allow the recreation of a suitable microenvironment for cells to respond properly to the cascade of signals needed for the normal tissue regeneration process to take place.

Previous case series and animal model studies found RGTA “potentially useful in alternative noninvasive therapeutic approach in challenging cases, especially the resistant and the neurotrophic corneal ulcers,” Dr. Gumus said.

His group investigated whether RGTA would speed up the corneal healing and reduce ocular symptoms after epi-off accelerated CXL.

Study details


Study details

The prospective, randomized, single-masked clinical study enrolled 60 eyes-all of which underwent the epi-off accelerated CXL by one surgeon (KG). At the end of the procedure, eyes were randomly assigned to receive the topical RGTA eyedrop just prior to contact lens fitting or to the control group, which received just a contact lens fitting.

During the CXL procedure, “I kept the lid speculum throughout the procedure,” Dr. Gumus said. “I marked the cornea with the same size trephine to standardize the area and I touched the corneal surface with the tip of a triangle sponge soaked in 20% of ethanol.

“I used the same isotonic riboflavin solution, which has a very unique composition, helping to maintain or even slightly swell the cornea up to 5% so we did not need to use any hypotonic riboflavin solution,” Dr. Gumus added.

All patients received the same postop medication therapy and were monitored for three consecutive days. The contact lens was not removed on Day 1, and if there was incomplete healing by Day 2 or Day 3, the size of the corneal epithelial defect was measured at the slit lamp, he said.

At baseline, the mean age, gender, and corneal epithelial defect size were comparable between groups.

While 25 eyes (83.3%) with RGTA revealed complete healing on day 2, only 4 eyes (13.3%) revealed complete healing in the control group.

Conjunctival hyperemia and ocular pain scores


“The conjunctival hyperemia scores were also significantly lower in the RGTA group on Day 1 and 2,” he said. “When we look at the ocular pain scores on Days 0, 1 and 2, ocular pain scores were significantly lower in RGTA group. Similarly, the other symptoms also particularly were low on Day 2 in the RGTA group.”

At the time of his presentation, there was only one other paper published on the same topic with RGTA in the literature, but some substantial methodological differences between the two were noted, he said.

For one, Kymionis et al.1 randomly assigned 36 eyes (18 patients) to RGTA or artificial tears.

“While we used RGTA only once before fitting the contact lens, that group used 1 drop RGTA daily till complete re-epithelization,” Dr. Gumus said.

Similarly, Kymionis et al. concluded RGTA instillation seems to result in faster corneal re-epithelialization after CXL.

Differently, “our results showed complete healing one day earlier, on Day 2,” he said. “Frequent use of RGTA might have decreased its effect on wound healing.”

Additionally, the authors did not find any significant effect in subject pain or discomfort, Dr. Gumus said.

In that study, it may have been difficult for patients to discern ocular symptoms between their eyes since both were enrolled, he said.



1.     Kymionis GD, Liakopoulos DA, Grentzelos MA, et al. Effect of the regenerative agent poly(carboxymethylglucose sulfate) on corneal wound healing after corneal cross-linking for keratoconus. Cornea. 2015;34:928-931.


Koray Gumus, MD


This article was adapted from Dr. Gumus’ presentation at the 2015 meeting of the American Academy of Ophthalmology. Dr. Gumus has no financial interests to disclose.

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