CORNEAL REINFORCEMENT

While many investigators are focusing on modifications to the standard CXL technique, Jorge F Alio MD, PhD, Alfredo Vega-Estrada MD, MSc and colleagues at Vissum Corporacion Oftalmologica, Universidad Miguel Hernandez, Alicante, Spain, are developing a novel “lightfree” tissue engineering approach to reinforce the corneal tissue using carbon nanomaterials. Speaking during the Expert Meeting on the Surgical Management of Keratoconus, Dr Alio described the technology, presented outcomes of an initial preclinical study, and talked about the next steps for its development.

“The results from our first in vivo study show biocompatibility of our product with corneal tissue and a positive trend for an increase in tissue rigidity. Now we are working to enhance the properties and chemical structure of our nanoplatform as well as its delivery,” said Dr Alio. The carbon nanomaterials product developed by the Vissum group is a mixture of graphene and carbon nanotubes dispersed in an original registered vehicle. Dr Alio noted that these and other carbon nanomaterials have several physicochemical and mechanical properties that make them attractive as a platform technology for strengthening the cornea. They are biologically inert, almost completely transparent and have high elasticity, hardness and resistance.

The first in vivo study was designed primarily to test the safety of the carbon nanomaterials product for use in the cornea and also to obtain some preliminary information on its potential to affect corneal mechanical properties. The study involved New Zealand white rabbits and evaluated two different concentrations of the graphene/carbon nanotubes suspension (0.1 and 1.0 mg/ mL) compared with a control group.

Strong adhesion observed

Post-mortem examination of the corneal tissue after three months found no evidence that the carbon nanomaterials induced any reactivity. There was no fibrous scarring, vessel formation, inflammatory reaction, giant body cell reaction or alterations of the mucopolysaccharides of the corneal stroma. Strong adhesion of the tissue in the area surrounding the carbon nanomaterials was observed. A stress-strain analysis showed no statistically significant differences comparing the mean Young’s modulus value for any of the operated groups with the controls. However, the outcome for the eyes injected with the higher concentration of carbon nanomaterials showed a trend for a benefit of increasing rigidity.

“In this initial investigation we were aiming to find that there was at least a beneficial trend for a treatment effect, and we achieved that goal. Furthermore, our results are in coherence with data from other investigators showing adsorption and interaction of carbon nanomaterials with collagen fibrils and improvement in mechanical properties,” Dr Alio said. The investigators proposed several reasons why their study was unable to demonstrate a statistically significant effect on corneal biomechanics. Insufficient power due to small sample size may be one factor. In addition, the chosen endpoint of Young’s modulus may not have been sensitive enough to identify a treatment effect on corneal biomechanics.

However, the most important issue may be that the method of treatment, ie, injection into a stromal pocket, impregnated the cornea with only a single layer of the carbon nanomaterials, whereas more widespread tissue distribution may be more ideal. Based on the latter concept, Dr Alio and colleagues are now developing new methods for delivering the carbon nanomaterials, and they have achieved promising results in early testing.