Development of a clinical multi-excitation optical coherence elastography system to interrogate corneal biomechanics for the detection and staging of normotensive glaucoma

In Peru, Glaucoma is the first cause of irreversible blindness characterized by progressive optic nerve damage and visual field loss. It is estimated that 50% of Glaucoma Peruvian patients are not aware they carry such a disease. The primary risk factor for Glaucoma detection is elevated intraocular pressure (IOP). However, normotensive Glaucoma (NTG) is a form of Glaucoma that develops in the eye despite its IOP being within the normal range of 12 to 21 mmHg. Therefore, early detection of NTG becomes a challenging task and it is crucial for timely intervention and preservation of vision. Currently, NTG diagnosis relies on IOP measurements through the cornea and visual field testing, which may miss the early stages of the disease. Corneas with abnormal (softer) biomechanics and topography (high astigmatism) may lead to inaccurate readings of IOP which, added to the assumptions made by each clinical tonometer, results in high variability in the estimation of IOP. Moreover, there is scientific evidence reporting that patients with NTG tend to have softer corneas compared to control patients.We propose the development of a clinical multi-excitation optical coherence elastography system to interrogate corneal biomechanics for the detection and staging of normotensive glaucoma. This system will be capable of measuring the topography of the cornea (structural B-mode frame information) and the corneal dynamic response (biomechanical information) from two simultaneous excitation sources: air-pulse macro deformation (AP-MD), and air-couple ultrasonic wave excitation (AC-US). The innovative integration of both excitation technologies together with a finite element model (FEM) of the eye will allow us to probe not only the shear modulus of the cornea through the propagation of Lamb waves, but the calculation of a true-biomechanically corrected IOP. The accuracy of the estimations of shear modulus and corrected IOP using measurements from the clinical system and the outcomes of the inverse FEM simulations will be tested using ex vivo animal models of the eye by modulating IOP with an artificial pressure-control system, and corneal stiffness with collagen enzymes. After a safety validation of the system in terms of acoustics, photonics, and air pressure for human use, a preliminary patient study will be carried out with 20 control patients, 20 patients with NTG, and 20 patients with high-tension Glaucoma (HTG). These measurements and estimations will be used to generate biomechanically inspired biomarkers of the corneal to detect early and advanced stages of NTG. We expect that shear modulus and the true-biomechanically correlated IOP can separate NTG from control and HTG patients. The impact of this research on the Peruvian ophthalmology healthcare system is fundamental since our proposed solution could catch NTG earlier and enable patient treatment to avoid further optical nerve damage and vision loss. This represents more than 80% in savings in the application of more invasive (costly) treatments and preserving vision quality. Finally, this technology can be used to understand the impact of unusual corneas (i.e., high astigmatism, low rigidity, and thin corneas) in the estimation of IOP, treatment monitoring, and the evaluation of other ocular diseases such as keratoconus.

The development of a clinical multi-excitation optical coherence elastography system to interrogate corneal biomechanics for the potential detection and staging of normotensive glaucoma.

- The development of a clinical Swept-Source OCT system integrated with two excitation modules: ACUS and APMD, capable of measuring the structural and biomechanical properties of human subjects. - The development of a FEM simulation based on a digital twin of a patient eye and integrating the system human measurements for the calculation of shear modulus of the cornea and the true-biomechanically corrected IOP. - The proposal of biomarkers and preliminary tests to separate NTG patients from control and HTG patients based on shear modulus and IOP measurements.

- A non-contact and non-invasive multi-excitation system capable of imaging Lamb wave propagation and corneal macro deflection for the mapping of cornea biomechanical properties both in vitro and in vivo with lateral and axial resolutions of 100 μm and 16 μm, respectively, in clinical environments. - A FEM package capable of simulating a patient’s cornea integrated with the experimental measurements for the accurate calculation of the shear modulus of the cornea and the true-biomechanically corrected IOP. - A set of potential biomarkers using the previous estimations for the detection and staging of NTG using a cohort of control, NTG, and HTG patients.

The impact of this research on the Peruvian ophthalmology healthcare system is fundamental  since our proposed solution could catch NTG earlier and enable patient treatment to avoid further  optical nerve damage and vision loss. This represents more than 80% in savings in the application  of more invasive (costly) treatments and preserving vision quality. Finally, this technology can be  used to understand the impact of unusual corneas (i.e., high astigmatism, low rigidity, and thin corneas) in the estimation of IOP, treatment monitoring, and the evaluation of other ocular diseases  such as keratoconus. Finally, this project represents one of the first stones in the development of  the areas of Biomedical Optics and Biophotonics in Peru which will allow the involvement of a new  generation of students in this discipline and the collaboration with the local industry, health  companies, and ophthalmology clinics.

Investigacion aplicada

Interdisciplinario

ADMINISTRADO

LIMA - LIMA - SAN MIGUEL

• 85 — Óptica aplicada

Ciencias médicas, Ciencias de la salud - Otras ciencias médicas - Otras ciencias médicas

INSTITUTO NACIONAL DE OFTALMOLOGÍA