Ophthalmology

Refractive interventions are widespread techniques for vision correction such as myopia or astigmatism. The cornea of the patient is reshaped by surgical intervention like incisions and laser ablation of stromal tissue. The amount of tissue to remove is traditionally estimated based on experimental nomograms or geometrical approaches. Unfortunately, the change of corneal power is frequently over- or under-estimated.

We proposed an opto-mechanical simulation framework to quantify the optical outcome induced by alteration of the corneal biomechanics. This numerical framework was used to perform personalized simulations of different surgical procedures such as corneal ring implantation and arcuate keratotomy. For example, arcuate keratotomy is a surgical technique used to correct astigmatism following cataract interventions. Our numerical simulation framework could estimate the outcome of different planning options before the surgery. Based on this numerical approach, we were also able to propose optimization algorithms to automatically determine the surgical parameters optimal for each specific patient. The patient-specific optimization of the surgery proved to better control the outcome of the intervention, leads to more reliable postoperative astigmatism, and limits the risks of overcorrection.

Refractive effects of local corneal stiffening

Optical coherence tomography (OCT) has become widely used in ophthalmology over the past two decades and has become a valuable tool for visualization of ocular tissue structures, playing a critical role in the evaluation and ongoing monitoring of various ocular diseases. Based on phase-sensitive deformation tracking algorithms, OCT elastography has emerged as a novel method for studying the mechanical deformations of tissues under controlled loading conditions.

We used state-of-the-art OCT imaging technique to determine the optomechanical changes caused by local corneal crosslinking (CXL) on ex vivo tissues. Different patterns were used to induce local corneal stiffening, e.g., in the shape of a bow tie or a half disk (Figure 1). Our results show that the cornea also undergoes geometric changes during stiffening, which in turn affect its refractive properties. We have quantified the relationship between the energy delivered to the tissue and the resulting refractive change. In addition, we have shown that OCE is an effective tool for studying high-resolution dynamic mechanical processes that the tissue undergoes during CXL.

The experimental data collected demonstrate that OCE is an innovative approach to quantify the mechanical properties of the cornea. When combined with biomechanical models of the tissue, this information provides new insights into the mechanical characterization of this tissue and could be useful in planning CXL treatments and refractive surgery.

 

Fig. 1: Optical changes in the cornea are achieved by local stiffening using structured cross-linking. Optical coherence tomography was used to quantify corneal strain 30 minutes (A-C) and 36 hours (D-F) after treatment. Different irradiation patterns were used, such as circular (A), bow-tie (B), or semi-disc (C).

Depth-Dependent properties of the human cornea

The prevalence of myopia is rising sharply, leading to an increase in elective refractive surgery. Since the cornea accounts for about two-thirds of the optical power of the eye, small changes in its shape or curvature have a significant impact on vision. Each person has unique corneal structure and biomechanics, making general surgical planning ineffective for predicting the outcomes of refractive surgery. Currently, these surgeries still result in double-digit under- or overcorrections. Therefore, numerical modeling is proposed to improve surgical planning and optimize the results of laser vision correction, which requires an accurate biomechanical characterization of the human cornea.

Over the past year, we have used different approaches to quantify corneal biomechanics. First, corneal samples were taken from young patients undergoing laser vision correction. The corneal lenticules taken during surgical correction were used in a uniaxial test setup to characterize their properties. As these samples were taken from the most anterior part of the cornea, an additional sample source was required to quantify the properties of the posterior cornea. For this evaluation, corneal grafts that were not intended for transplantation were used (Figure 2). In this case, femtosecond lasers were used to cut thin samples at different depths of the cornea so that the depth dependence of corneal biomechanics could be investigated. Our results show that the stiffness of the cornea decreases linearly with the depth of the human cornea, with the anterior part of the tissue being about 40 % stiffer than the posterior part.

In addition to the uniaxial tensile test, we quantified the mechanical properties of the cornea using tissue indentations (Figure 3). In this technique, a small spherical indenter is pressed onto the corneal surface to record the relationship between the force exerted by the indenter on the tissue and its displacement. Specimens were subjected to physiological intraocular pressure during indentation to account for the natural preload of the cornea, and both dynamic and cyclic loads were used to characterize the viscoelastic response of the human cornea.

This information is used to create numerical tissue models that take into account the known orientation of collagen fibers in the tissue, which are isotropically distributed in the corneal plane, while they are oriented along the corneal curvature and have little dispersion outside the corneal plane. Accurate characterization and modeling of the human cornea is essential to explore better refractive surgery for the population undergoing these treatments, to develop in silico models that account for corneal biomechanics when planning refractive surgery, and to provide a basis for improving visual outcomes in the rapidly growing population undergoing these treatments.

Fig. 2: Samples prepared with a laser at different depths of the human cornea were characterized mechanically. Fig. 3: The viscoelastic properties of the human cornea under physiological conditions were quantified by indentation.