Scleral biomechanics and myopia development and control
- Autores: Lupe Ivette Villegas Lopez
- Directores de la Tesis: Susana Marcos Celestino (dir. tes.), Francisco Javier Rojo Pérez (tut. tes.)
- Lectura: En la Universidad Politécnica de Madrid ( España ) en 2025
- Idioma: inglés
- Tribunal Calificador de la Tesis: Juan Gonzalo Carracedo Rodríguez (presid.), Gustavo Ramón Plaza Baonza (secret.), Sabine Kling (voc.), Juan Manuel Bueno García (voc.), Maria Viñas Peña (voc.)
- Programa de doctorado: Programa de Doctorado en Ingeniería Biomédica por la Universidad Politécnica de Madrid
- Calificación: Sobresaliente Cum Laude
- Materias:
- Enlaces
- Tesis en acceso abierto en: Archivo Digital UPM
- Resumen
The sclera is the main supporting tissue of the internal structures of the eye. Biomechanical changes in the scleral tissue can be related to ocular diseases such as myopia. Myopia is a global public health problem that is currently considered a new pandemic due to its enormous magnitude. At present, the role of scleral remodeling as a modulator of myopia and potential moderator of myopia progression is not fully understood. The main objective of the work described in this thesis is to develop new methods to determine the role of the sclera and its modulation in the development and control of myopia. The biomechanical responses of porcine and rabbit scleral tissues were studied using deformation imaging and elastography. Air-puff Optical Coherence Deformation Imaging revealed that scleral deformation changed across species (porcine or rabbit) and geographically at different locations on the same eye globe. In porcine eyes, maximum scleral deformation occurred in the superior and inferior sclera, and in rabbit eyes in the equatorial nasal and inferior sclera, for the same air-pulse configuration. Multi-directional Optical Coherence Elastography allowed radial mapping of mechanical properties at different locations and orientations of the eye globes and showed that the sclera was stiffer circumferentially and anteriorly than meridionally and posteriorly. The highest shear modulus values were found in the superior circumferential sclera. These results demonstrate that the tissue response depends on the internal structure (biochemical composition and collagen fibers organization), which varies between animal models and scleral regions. Cross-linking has been proposed as a potential treatment for myopia, by stiffening the scleral tissue and halting axial elongation. The effects of Rose Bengal-green light and Riboflavin-ultraviolet light cross-linking on the biomechanical and swelling properties of rabbit sclera were investigated. Rose Bengal-green light cross-linking induced scleral stiffness to the same extent as riboflavin-ultraviolet light cross-linking. In addition, non-crosslinked tissue swelled more rapidly than crosslinked scleral tissue, and an inverse relationship between swelling and scleral stiffness was observed. Changes in the scleral collagen organization were examined by Second Harmonic Generation microscopy. The results suggest that Rose Bengal-green light cross-linking has potential for future in vivo studies as a method for the treatment of myopia, if the challenge of the photoinitiator and light irradiation reaching the posterior sclera is overcome. Several pharmacological treatments have been proposed for myopia control. In particular, we tested in vivo latanoprost (an ocular hypotensive agent) and atropine (a dopamine-releasing agent) in monocular form-deprived myopia-induced guinea pigs. Myopic eyes were instilled daily with saline, latanoprost, or atropine for nine weeks. Ocular biometry, scleral biomechanics and collagen fiber organization were measured. The results suggest that latanoprost was as effective as atropine in inhibiting myopia progression by reducing axial length and refractive error. Both treatments attenuated the decrease in Young's modulus in myopic eyes, but only atropine increased the shear modulus. Consistent with these biomechanical differences, scleral collagen organization appeared to be at least partially restored in pharmacologically treated eyes. In summary, this thesis used custom-developed technologies to characterize mechanically and structurally the sclera of common animal models. The scleral changes observed in myopia suggest that the sclera is a target tissue to prevent myopia progression.
