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South East Asia is growing at an impressive pace with its GDP having increased by about 350% in ten years , ri sing from 650 Billion $ in 2002 to about 2300 Billion $ in 2012. Regional governments actively promote infrastructure, logistics and service development to create a favourable environment fo r sustainable growth. Within this framework, GNSS applications play a vital role. In particular, the increasing demand for better services , in both the public and private sector , and logistics is going to require increasingly reliable and trusted GNSS appl ications. South East Asia has the highest multi - GNSS coverage in the world, and is therefore the ideal place to test and compare performance and opportunities offered by the different g lobal n avigation s atellite s ystems. On the one hand, an active promotio n of E U GNSS (EGNSS) technology in this region, rising awareness on its main features while on the other hand facilitating the linking of European enterprises with South East Asian GNSS stakeholders, are extremely important so as to establish and maintain global European scientific and industrial leadership in this crucial sector. Indeed, it is also fundamental to encourage the penetration of EGNSS industry in to the South East Asian market taking into account all potential applications of EGNSS. Therefore, the BELS project exploits the opportunities presented by the NAVIS Centre, an International Collaboration Centre for Research and Development on Satellite Navigation Technology in South East Asia based in Hanoi, Vietnam, to promote visibility and to raise awareness o f EGNSS technology in the region. The next three years will be crucial for pav ing the way for Galileo services, both for European companies that can enter a new growing market and for the South East Asian countries that can discover the capabili ties of the EGNSS technology. Consequently, BELS facilitates and supports the visits of European companies for such purposes a s carrying out tests, South East Asia is growing at an impressive pace with its GDP having increased by about 350% in ten years , ri sing from 650 Billion $ in 2002 to about 2300 Billion $ in 2012. Regional governments actively promote infrastructure, logistics and service development to create a favourable environment fo r sustainable growth. Within this framework, GNSS applications play a vital role. In particular, the increasing demand for better services , in both the public and private sector , and logistics is going to require increasingly reliable and trusted GNSS appl ications. South East Asia has the highest multi - GNSS coverage in the world, and is therefore the ideal place to test and compare performance and opportunities offered by the different g lobal n avigation s atellite s ystems. On the one hand, an active promotio n of E U GNSS (EGNSS) technology in this region, rising awareness on its main features while on the other hand facilitating the linking of European enterprises with South East Asian GNSS stakeholders, are extremely important so as to establish and maintain global European scientific and industrial leadership in this crucial sector. Indeed, it is also fundamental to encourage the penetration of EGNSS industry in to the South East Asian market taking into account all potential applications of EGNSS. Therefore, the BELS project exploits the opportunities presented by the NAVIS Centre, an International Collaboration Centre for Research and Development on Satellite Navigation Technology in South East Asia based in Hanoi, Vietnam, to promote visibility and to raise awareness o f EGNSS technology in the region. The next three years will be crucial for pav ing the way for Galileo services, both for European companies that can enter a new growing market and for the South East Asian countries that can discover the capabili ties of the EGNSS technology. Consequently, BELS facilitates and supports the visits of European companies for such purposes a s carrying out tests, Peer Reviewed, Postprint (author's final draft)

Esta tesis aborda la medición de las propiedades biomecánicas de la córnea. Se desarrollaron técnicas para medir la rigidez de la córnea in vitro con el fin de estudiar el comportamiento de la córnea como una función de diferentes factores (tales como la hidratación, la geometría, la presión intraocular y la rigidez de la córnea). Los datos experimentales se utilizaron para construir modelos numéricos capaces de reproducir la respuesta biomecánica observada de la córnea. Se aplicaron modelos numéricos para recuperar los parámetros biomecánicos de mediciones de deformación in vivo y para estudiar el efecto de la implantación de segmentos de anillos intraestromales. En particular, se utilizaron el método de inflación en ojos enteros y botones córneales, la extensiometría bídimensional, un soplo de aire combinado con tomografía de coherencia óptica (OCT), microscopía de Brillouin y OCT-vibrografía para las mediciones experimentales. Para el análisis numérico, se construyeron modelos de elementos finitos para estudiar la inflación de ojos enteros y botones córneales, la respuesta de la córnea después de un soplo de aire, el comportamiento del ojo bajo vibración y los cambios refractivos después de la implantación de anillos intraestromales. This thesis addresses the measurement of the corneal biomechanical properties. Techniques were developed to measure the corneal stiffness in vitro in order to study the corneal behavior as a function of different factors (such as hydration, geometry, intraocular pressure, corneal stiffness). Experimental data were used to build numerical models, which were able to reproduce the observed biomechanical response of the cornea. Numerical models were applied to retrieve biomechanical parameters from in vivo deformation measurements and to study the outcome with implantation of intrastromal ring segments. In particular whole-eye / corneal inflation, 2D extensiometry, an air-puff technique combined with optical coherence tomography (OCT), B

Most techniques measuring corneal biomechanics in vivo are biased by side factors. We demonstrate the ability of optical coherence tomographic (OCT) vibrography to determine corneal material parameters, while reducing current prevalent restrictions of other techniques (such as intraocular pressure (IOP) and thickness dependency). Modal analysis was performed in a finite-element (FE) model to study the oscillation response in isolated thin corneal flaps/eye globes and to analyse the dependency of the frequency response function on: corneal elasticity, viscoelasticity, geometry (thickness and curvature), IOP and density. The model was verified experimentally in flaps from three bovine corneas and in two enucleated porcine eyes using sound excitation (100¿110 dB) together with a phase-sensitive OCT to measure the frequency response function (range 50¿510 Hz). Simulations showed that corneal vibration in flaps is sensitive to both, geometrical and biomechanical parameters, whereas in whole globes it is primarily sensitive to corneal biomechanical parameters only. Calculations based on the natural frequency shift revealed that flaps of the posterior cornea were 0.8 times less stiff than flaps from the anterior cornea and cross-linked corneas were 1.6 times stiffer than virgin corneas. Sensitivity analysis showed that natural vibration frequencies of whole globes were nearly independent from corneal thickness and IOP within the physiological range. OCT vibrography is a promising non-invasive technique to measure corneal elasticity without biases from corneal thickness and IOP

PURPOSE. Air puff systems have been presented recently to measure corneal biomechanical properties in vivo. In our study we tested the influence of several factors on corneal deformation to an air puff: IOP, corneal rigidity, dehydration, presence of sclera, and in vivo versus in vitro conditions. METHODS. We used 14 freshly enucleated porcine eyes and five human donor eyes for in vitro experiments; nine human eyes were used for in vivo experiments. Corneal deformation was studied as a function of: IOP ranging from 15 to 45 mm Hg (in vitro); dehydration after riboflavin-dextran instillation (in vitro); corneal rigidity after standard ultraviolet (UV) corneal crosslinking (CXL, in vitro); boundary conditions, that is effect of the presence of the sclera (comparing corneal buttons and whole globes in vitro in pigs); and effect of ocular muscles (comparing human whole globes in vitro and in vivo). The temporal corneal deformation was characterized by the apex indentation across time, the maximal indentation depth, and the temporal symmetry (comparing inward versus outward deformation). The spatial corneal profile was characterized by the peak distance at maximal deformation. RESULTS. Temporal and spatial deformation profiles were very sensitive to the IOP (P < 0.001). The sclera slightly affected the temporal symmetry, while the ocular muscles drastically changed the amount of corneal recovery. CXL produced a significant (P=0.001) reduction of the cornea indentation (by a factor of 1.41), and a change in the temporal symmetry of the corneal deformation profile (by a factor of 1.65), indicating a change in the viscoelastic properties with treatment. CONCLUSIONS. Corneal deformation following an air puff allows the measurement of dynamic properties, which are essential for the characterization of corneal biomechanics. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Purpose. Corneal collagen crosslinking (CXL) is designed to halt the progression of keratoconus and corneal ectasia by inducing corneal stiffening. However, it currently is difficult to monitor and evaluate CXL outcome objectively due to the lack of suitable methods to characterize corneal mechanical properties. We validated noncontact Brillouin microscopy to quantify corneal mechanical properties before and after CXL. Methods. CXL was performed on fresh porcine eyes using various presoaking times and light doses, with or without epithelial debridement. From Brillouin maps of corneal elastic modulus, stiffness and average modulus of anterior, middle, and posterior stroma were analyzed. Corneal stiffening index (CSI) was introduced as a metric to compare the mechanical efficacy of a given CXL protocol with respect to the standard protocol (30-minute riboflavin presoak, 3 mW/cm2 ultraviolet illumination for 30 minutes). Results. Brillouin corneal stiffness increased significantly (P < 0.001) by epi-off and epi-on CXL. The increase of Brillouin modulus was depth-dependent, indicating that anterior stromal stiffening contributes the most to mechanical outcome. The increase of anterior Brillouin modulus was linearly proportional to the light dose (R2 > 0.98). Compared to the standard epi-off procedure, a typical epi-on procedure resulted in a third of stiffness increase in porcine corneas (CSI = 33). Conclusions. Brillouin microscopy allowed imaging and quantifying CXL-induced mechanical changes without contact in a depth-dependent manner at high spatial resolution. This technique may be useful to evaluate the mechanical outcomes of CXL procedures, to compare different crosslinking agents, and for real-time monitoring of CXL in clinical and experimental settings. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

A new technique is presented for the non-invasive imaging of the dynamic response of the cornea to an air puff inducing a deformation. A spectral OCT instrument combined with an air tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal evolution of the corneal apex. The entire deformation process can be dynamically visualized. A quantitative analysis allows direct extraction of several deformation parameters, such as amplitude, diameter and volume of the maximum deformation, as well as duration and speed of the increasing deformation period and the recovery period. The potential of the technique is demonstrated on porcine corneas in vitro under constant IOP for several conditions (untreated, after riboflavin instillation and under cross-linking with ultraviolet light), as well as on human corneas in vivo. The new technique has proved very sensitive to detect differences in the deformation parameters across conditions. We have confirmed non-invasively that Riboflavin and UV-cross-linking induce changes in the corneal biomechanical properties. Those differences appear to be the result of changes in constituent properties of the cornea, and not a consequence of changes in corneal thickness, geometry or IOP. These measurements are a first step for the estimation of the biomechanical properties of corneal tissue, at an individual level and in vivo, to improve diagnosis and prognosis of diseases and treatments involving changes in the biomechanical properties of the cornea. © 2012 Optical Society of America.

PURPOSE: Understanding corneal biomechanics is important to refractive or therapeutic corneal treatments. The authors studied the corneal response to variable intraocular pressure (IOP) in porcines eyes after UV collagen cross-linking (CXL), in comparison with untreated eyes. METHODS: Twenty-three enucleated eyes were treated with standard CXL conditions (365 nm, 3 mW, 30 minutes), and 15 contralateral eyes served as control. Eyes (within a humidity- and temperature-monitored wet chamber) were measured by Scheimpflug corneal three-dimensional topographer. Images were obtained automatically while IOP either remained constant (14 eyes) or increased (24 eyes) by 40 mm Hg and then decreased (4-mm Hg steps). Measurements were performed immediately after treatment and 24 hours later. Corneal geometry was analyzed as a function of IOP, and whole globe stress-strain curves were calculated. RESULTS: Instillation of riboflavin-dextran solution reduced corneal thickness (by 281 +/- 5 microm). Cross-linking produced a 1.54x reduction in corneal thinning and 2.8x reduction in corneal apical rise with increased IOP. Anterior and posterior cornea flattened with increased IOP (less flattening in CXL eyes) and became steeper with decreased IOP. The horizontal meridian flattened significantly (P < 0.01) more than the vertical meridian. Young's modulus was higher in cross-linked eyes (1.096 +/- 0.30 kN/m(2)) than in non-cross-linked eyes (0.692 +/- 0.30 kN/m(2)). Hysteresis in nontreated eyes was also larger than in cross-linked eyes. CONCLUSIONS: Cross-linking stiffened porcine corneas significantly. Both experimental data and stress-strain analysis are valuable for finite element models to improve understanding of CXL and its predictability. Although differences are expected between human corneas in vivo and porcine corneas ex vivo, the results are consistent with clinical data found in patients. The apparent biomechanical anisotropy of pig corneas must be confirmed in humans. © Ass