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Unravelling the role of scleral events on a novel treatment for Myopia using microscopy techniques

Periodic Reporting for period 2 - MYOMICRO (Unravelling the role of scleral events on a novel treatment for Myopia using microscopy techniques)

Reporting period: 2022-09-16 to 2023-09-15

Myopia prevalence has increased dramatically in the last few decades. It has reached 30% among young population in Europe and U.S.A. and over 80% in Asia. However, refractive correction remains the only option for treatment. Myopia has been linked to the shifting balance between far- and near-vision activities and the resulting abnormal axial growth of the eye, but many key questions remain unanswered, which are critical for exploring new treatments. The eye grows in a coordinated manner during normal development so that the ocular optics projects focused images on the retinal plane. However, in myopic eyes, it is commonly found that the eye grows excessively in the axial direction, causing images to be focused in front of the retina. This results in blurred images on the retina and poor vision. Studies have suggested that severe, also called pathologic, Myopia, with a refractive error of -6 D or more, may negatively affect the individual’s social, educational, and athletic development. People with less severe Myopia are currently managed by concave-lens eye glasses or surgical refractive corrections (i.e. LASIK). While these methods can improve vision, the more profound problem of Myopia is that it is linked to other eye diseases. Patients with high Myopia have an increased risk for glaucoma and retinal detachment. However, we do not know what causes the increasing risk, and furthermore even the underlying structural and physiological mechanisms of Myopia are not fully understood. This lack of understanding is frustrating the efforts of developing treatments of Myopia and lowering the Myopia-induced risks in potentially sight-threatening eye diseases.

Although some genetic associations and environmental factors for Myopia have been identified, debates are ongoing as to whether and how much these factors intervene. On the other hand, strong phenomenological correlations have been found between Myopia and the morphology and tissue-structure of the eye. A stablished fact is that during ocular growth, scleral development critically determine eye size and thus the refractive status of the eye. This project has been designed to better understand the collagen structures and biomechanical properties of the sclera in both normal and myopic eyes and to devise novel therapies aiming at promoting natural collagen-matrix deposition and/or improving scleral strength to resist abnormal ocular elongation. Analysis of the myopic eye morphology, will shed light into the structural changes occurring in Myopia progression, and clarify the role of scleral events in its development.

MYOMICRO is as a collaborative project, lead by Dr. María Vinas-Pena, between two host institutions (HIs) the EU beneficiary (VioBio Lab, CSIC, Spain), and the partner organization (Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, USA), with a short research stay at the Center for Visual Sciences, University of Rochester, USA). The goal of my research is to advance our understanding of Myopia and help to develop new treatments. As an important step, I propose to develop new innovative optical instruments to characterize myopic eyes in unprecedented details to gain novel insights, and to assess treatment effects objectively and comprehensively beyond conventional vision tests. Specifically, I aim to accomplish the following: (a) substantial advances in the understanding of physical changes underlying Myopia, (b) quantitative assessment of optical, structural, and mechanical properties of the eye during Myopia development, and (c) anatomical- & structural-level assessment of novel interventions to stop Myopia progression.
Despite the high prevalence of Myopia, several key questions remain, in part because of the unavailability of quantitative techniques to characterize optical/morphological properties of the myopic eye, and structural changes produced by intervention. The primary research questions are: (1) How does the sclera change at the biomechanical/microstructural level when Myopia develops? (2) How the newest Myopia stopping treatments work and can they be improved? (3) Can SCXL be an effective technique for Myopia treatment?

During the first 24 months, the outgoing phase and the short research stay happened, and focussed on research objectives RO1 and 2.
RO1: Development of innovative imaging methods for the quantitative assessment of optical, structural, and mechanical properties of the sclera. We will develop AO-ocular-multiphoton and Brillouin microscopy techniques, focused on myopic scleral properties and subsequent SCXL treatments.
RO2: Understanding the role of scleral collagen packing and CXL strategies. We will study collagen organization/ biomechanical properties of the sclera in normal/myopic eyes, and CXL, thus new optical models will be developed.

RO1 and 2 were tackled via work packages 1 and 2 during the outgoing phase and the short research stay.
WP1(RO1) Development of innovative imaging methods for Myopia. The development of custom AO-SGH and Brillouin microscopy techniques for the sclera, by modifying already existing custom-developed systems, was the target of WP1.

WP2 (RO2) Scleral collagen packing and SCXL strategies. Brillouin microscopy was replaced by Optical Coherence elastography (OCE) with excellent results. In combination with tensile tests, SHG microscopy, and fluorescence life time imaging, we were able to study scleral collagen organization & biomechanical properties in normal eyes (WP2.1) and in treated eyes (WP2.2).
The proposal aims to develop new imaging technologies in ophthalmology, thus is presented in the Life Sciences call; it focuses on the prioritary topic on Medical Imaging Techologies with emphasis on Prevalent Conditions, and Photonics as a key enabling technology. The prososal follows a multidisciplinary approach involving researchers in the fields of optics, physics, optical engineering, bioengineering, electrical engineering, mechanical engineering, visual sciences, ocular biology and clinical ophhalmology. The new technology will have a high impact in how Myopia is understood and treated. The social and economic burden of Myopia is high, and increasing at a high rate in urban areas Understanding Myopia will lead to a better clinical management. Besides, research on emerging solutions for Myopia prevention will help to assess their potential and propose improved interventions, potentially reaching millions.

Myopia is a very active research area, due to the lack of consensus on its etiology and moderate success of interventions to stop its progression. With high prevalence of Myopia in developed countries and increasing dramatically, and high economic and social costs associated to Myopia, the topic has raised interest in the scientific, clinical and industrial communities for many years. Since 1980, > 10.000 papers address Myopia etiology/treatment. However, a general weakness is the lack of state-of-the art 3D biometry tools, high resolution imaging techniques and visual simulators, which would allow a more accurate assessment of structural and perceptual changes of Myopia and its treatment. In general, technology-oriented groups have not tackled Myopia as a research question. The development of novel imaging techniques for the sclera will have a significant impact in the way the study scleral events in the eye, and consequently Myopia development, are studied.
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