Page 10 - Advances in Biomechanics and Tissue Regeneration

4 1. PERSONALIZED CORNEAL BIOMECHANICS

Consequently, it is important to understand how these ocular factors are related to pathologies in order to improve
treatments. In order to do that different corneal features must be properly characterized:

• physiological conditions of the eye: IOP and interaction of the eyeball with the surrounding media;
• patient-specific corneal geometry; and
• patient-specific mechanical properties of the eye.
To date, IOP can be measured using contact tonometers (e.g., Goldmann Applanation Tonometry) [3, 4], whereas
corneal topography is obtained with corneal topographers (e.g., Pentacam or Sirius [5]). The availability of high-
resolution topographical data and a patient’s IOP have made it possible to reconstruct a patient’s specific geometric
model. In this regard, some patient-specific models have already been reported in the literature [6, 7]. However, the
workflow described in these studies cannot be automated in a straightforward manner so as to permit personalized
analysis on large populations in order to, for example, characterize the mechanical properties of the corneal tissue.
Noncontact tonometry (e.g., CorVis ST, Oculus Optikger€ ate GmbH [8]) has recently gained interest as a diagnostic
tool in ophthalmology as an alternative method for characterizing the mechanical behavior of the cornea. In a
noncontact tonometry test, a high-velocity air jet is applied to the cornea for a very short time (less than 30 ms), causing
the cornea to deform while the corneal motion is recorded by a high-speed camera. A number of biomarkers associated
with the motion of the cornea, that is, maximum corneal displacement and the time between the first and second
applications, among others, have been proposed to characterize preoperative and postoperative biomechanical
changes [8–16].
As the dynamic response is the result of the interplay between different corneal features (IOP, geometry, material), it
is reasonable to argue that a misunderstanding of the diagnostic tools is likely to be the cause of the unexpected clinical
results already occurring (e.g., a softer cornea with a higher IOP could show the same behavior as a stiffer cornea with a
lower IOP). Although geometry and IOP can already be measured accurately, the mechanical behavior of the cornea
cannot be directly characterized in vivo.
Precise knowledge about the underlying factors that affect the corneal mechanical response will allow establishing
better clinical diagnoses, monitoring the progression of different diseases (e.g., Keratoconus), or designing a priori
patient-specific surgical plans that may reduce the occurrence of unexpected outcomes.
The construction of predictors for real-time clinical applications must rely on mathematical tools that, given a set of
clinical biomarkers, can return the material parameters of a given constitutive model [17]. In the present study, a K-nn
(nearest neighbor) approach is used to determine the corneal material parameters using three clinical biomarkers: the
maximum corneal displacement measured during a noncontact tonometry test (U), the patient’s IOP, and the geomet-
rical features of the cornea.
This chapter explores methodologies to determine the patient-specific geometry and mechanical properties of the
cornea. Shedding light on patient-specific corneal biomechanics will allow performing a personalized assessment in
ocular surgeries and treatments. This is further demonstrated by two applications: the prediction of a patient-specific
refractive surgery (astigmatic keratotomy [AK]) in an animal model, and the qualitative assessment in the level of stres-
ses induced by an intracorneal ring segment implantation in humans that, clinically, is impossible to measure.

1.2 EYE ANATOMY

The eye is composed of different structures and layers (see Fig. 1.1). Among the most important macroscopic struc-
tures, those providing the eyeball’s shape are the cornea (i.e., the outermost transparent layer), the sclera (i.e., the white
layer protecting and shaping the eye), and the limbus (i.e., the transition between the cornea and sclera). Besides, the
cornea, which represents 45 of the 60 diopters of the optical power of a relaxed eye, and the crystalline, ciliary mus-
cles, retina, and optical nerve are the optical elements in charge of vision quality. Generally, ocular structures present
three main layers: the fibrous layer that protects and gives the shape (tunica externa bulbi), the vascular layer that
perfuses the organ (tunica vasculosa bulbi), and the nervous layer that provides the sensorial faculties (tunica interna
bulbi). The mechanical compliance of the human eye is mainly associated with the collagen fibrils embedded in the
fibrous layer (cornea, sclera, limbus, and lamina cribosa). Although human eye dimensions vary significantly between
patients, average measures can be set. Generally, the main dimensions of an emmetropic eye (nonrefractive errors) are

• an axial (sagittal) diameter of 24–25 mm (i.e., the distance between the corneal apex and the sclera);
• a transversal (i.e., nasal-temporal plane) diameter of 23.5 mm;
• a vertical (i.e., superior-inferior plane) diameter of 23 mm;
• a mean corneal diameter of 11–12 mm;

I. BIOMECHANICS