Biomechanical Optimization Of Lenticules For The Treatment Of Advanced Keratoconus

Tissue additive procedures have been shown to be effective for treating Keratoconus (KC) and providing visual improvement for patients. Current options utilize tissue from human or porcine origin. Both provide biocompatible scaffolds, and as the tissue can be decellularised, carry no risk of immune rejection, making porcine tissue an attractive option to overcome human tissue shortages. Additionally, tissue can be processed to optimise mechanical properties to best counteract the effects of KC. Here, we use optical methods to characterize mechanical properties of porcine-derived Xenia® lenticules, and determine the scope for standardization and customization, in addition to the implications of flap and keyhole-based insertion procedures.

All lenticular implants were produced by Gebauer Medizintechnik GmbH, Neuhausen, DE. Imaging was conducted by Abby Wilson at UCL Mechanical Engineering and UCL Institute of Ophthalmology, London, UK. LASIK and SMILE procedures were performed by Dan Reinstein at The London Vision Clinic, London, UK.

Corneal lenticules (diameter = 9mm, thickness = 150µm) were extracted from the central anterior stroma of porcine corneas (< 24hrs post-mortem). 12 samples were not subjected to further processing, the remaining 12 samples underwent a 4-stage processing procedure involving decellularisation, washing, compression and crosslinking. Interferometry was used to quantify the stiffness of the lenticules in terms of Young’s modulus, via evaluating the deformation of the lenticules in response to pressure variations. Additionally, % change in corneal resistance to IOP variations for 8 porcine corneas, before vs after LASIK(4) and SMILE(4), was evaluated via interferometry to assess the biomechanical implications of insertion protocols.

The average stiffness of processed lenticules was approximately double the stiffness of lenticules that had not undergone processing (21.9 MPa (range 16.2 – 23.9) vs 10.9 MPa (range 9.7 – 12.8)). Variability in the stiffness of the processed lenticules was over 2-fold greater than variability in the stiffness of the unprocessed lenticules, however the stiffness of all processed lenticules was higher than unprocessed tissue. LASIK resulted in a 21.4 % decrease in corneal resistance to intraocular pressure variations vs 7.6 % decrease in SMILE.

Both LASIK and SMILE procedures reduce the overall resistance of the cornea to IOP variations, with SMILE better preserving the biomechanical integrity of the cornea, suggesting that keyhole approaches to lenticule insertion have biomechanical advantages over flap-based. The processing procedure used to manufacture Xenia® lenticules enhances tissue stiffness on average by 100%, sufficient to counteract the biomechanical weakening from flap or keyhole-based procedures. Further work is required to identify sources of variability in lenticule processing to achieve better standardization of lenticule properties.