96 results on '"Birkenfeld, J."'
Search Results
2. Estimation of the full shape of the crystalline lens in-vivo from OCT images using eigenlenses
- Author
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European Commission, Ministerio de Ciencia e Innovación (España), Polish National Agency for Academic Exchange, Foundation for Polish Science, L'Oréal-UNESCO For Women in Science, Ministerio de Ciencia, Innovación y Universidades (España), Flaum Eye Institute, National Institutes of Health (US), Florida Lions Eye Bank, Beauty of Sight Foundation, Hyderabad Eye Research Foundation, Martínez-Enríquez, Eduardo, Curatolo, Andrea, Castro, Alberto de, Birkenfeld, J., González-Ramos, Ana M., Mohamed, Ashik, Ruggeri, Marco, Manns, Fabrice, Fernando, Zvietcovich, Marcos, Susana, European Commission, Ministerio de Ciencia e Innovación (España), Polish National Agency for Academic Exchange, Foundation for Polish Science, L'Oréal-UNESCO For Women in Science, Ministerio de Ciencia, Innovación y Universidades (España), Flaum Eye Institute, National Institutes of Health (US), Florida Lions Eye Bank, Beauty of Sight Foundation, Hyderabad Eye Research Foundation, Martínez-Enríquez, Eduardo, Curatolo, Andrea, Castro, Alberto de, Birkenfeld, J., González-Ramos, Ana M., Mohamed, Ashik, Ruggeri, Marco, Manns, Fabrice, Fernando, Zvietcovich, and Marcos, Susana
- Abstract
Quantifying the full 3-D shape of the human crystalline lens is important for improving intraocular lens power or sizing calculations in treatments of cataract and presbyopia. In a previous work we described a novel method for the representation of the full shape of the ex vivo crystalline lens called eigenlenses, which proved more compact and accurate than compared state-of-the art methods of crystalline lens shape quantification. Here we demonstrate the use of eigenlenses to estimate the full shape of the crystalline lens in vivo from optical coherence tomography images, where only the information visible through the pupil is available. We compare the performance of eigenlenses with previous methods of full crystalline lens shape estimation, and demonstrate an improvement in repeatability, robustness and use of computational resources. We found that eigenlenses can be used to describe efficiently the crystalline lens full shape changes with accommodation and refractive error.
- Published
- 2023
3. Poster Session: Experimental assessment of scleral anisotropy using multi-meridian air-coupled ultrasonic optical coherence elastography
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European Commission, Ministerio de Ciencia e Innovación (España), Research to Prevent Blindness, Consejo Superior de Investigaciones Científicas (España), L'Oréal-UNESCO For Women in Science, Foundation for Polish Science, #NODATA#, Villegas, Lupe, Zvietcovich, Fernando, Varea, Alejandra, Curatolo, Andrea, Birkenfeld, J., Marcos, Susana, European Commission, Ministerio de Ciencia e Innovación (España), Research to Prevent Blindness, Consejo Superior de Investigaciones Científicas (España), L'Oréal-UNESCO For Women in Science, Foundation for Polish Science, #NODATA#, Villegas, Lupe, Zvietcovich, Fernando, Varea, Alejandra, Curatolo, Andrea, Birkenfeld, J., and Marcos, Susana
- Abstract
Scleral biomechanics plays a key role in the understanding of myopia progression. In this study, we characterized the elastic properties of sclera using an air-coupled ultrasonic (ACUS) optical coherence elastography (OCE) system. New Zealand rabbit eyes (n=7) were measured (<24hr postmortem) in four scleral locations: superior/inferior temporal (ST, IT), and superior/inferior nasal (SN, IN) maintaining an intraocular pressure of 15 mmHg. Elastic waves were induced in the sclera, and wave propagation velocity and shear modulus were measured along two directions: circumferential (superior-inferior) and meridional (nasal-temporal). Wave velocity in scleral tissue ranged from 6 to 24 m/s and shear modulus from 11 to 150 kPa. Velocity was significantly higher (p<.001) in the circumferential vs. meridional directions in the following locations: ST:15.83±2.85 vs 9.43±1.68 m/s, IT:15.00±3.98 vs 8.93±1.53 m/s; SN:16.79±4.30 vs 9.27±1.47 m/s; and IN:13.92±3.85 vs 8.57±1.46 m/s. The average shear modulus in the circumferential was also significantly higher (p<.001) than in the meridional direction for all locations: 65.37±6.04 vs 22.55±1.36 kPa. These results show that the rabbit sclera is mechanically anisotropic with higher rigidity in the circumferential direction compared to the meridional direction. ACUS-OCE is a promising non-invasive method to quantify the biomechanical changes in scleral tissue for future studies involving myopia treatments.
- Published
- 2023
4. Poster Session: Estimation of scleral biomechanical properties from air-puff-coupled optical coherence tomography
- Author
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European Commission, Ministerio de Ciencia e Innovación (España), Foundation for Polish Science, Research to Prevent Blindness, #NODATA#, Birkenfeld, J., Villegas, Lupe, Hoz, A. de la, Bronte-Ciriza, David, Varea, Alejandra, Martínez-Enríquez, Eduardo, Curatolo, Andrea, Germann, James A., Marcos, Susana, European Commission, Ministerio de Ciencia e Innovación (España), Foundation for Polish Science, Research to Prevent Blindness, #NODATA#, Birkenfeld, J., Villegas, Lupe, Hoz, A. de la, Bronte-Ciriza, David, Varea, Alejandra, Martínez-Enríquez, Eduardo, Curatolo, Andrea, Germann, James A., and Marcos, Susana
- Abstract
Progression of myopia is usually accompanied by axial overgrowth of the eyeball, which affects scleral biomechanics (BM). To study scleral biomechanics, we propose the use of air-puff deformation swept-source OCT imaging. Air-puff deformation imaging was performed at different sites of ex vivo porcine (n=5) and rabbit (n=3) eyes, (<24hr postmortem): Nasal/temporal equatorial and posterior sclera (NE, NP, TE, TP), superior (S) and inferior (I) sclera, and cornea (C). Intraocular pressure was kept at 15mmHg. Deformation data were used as input to inverse finite element model (FEM) algorithms to reconstruct BM properties. Experimental deformation amplitudes showed dependence on the animal model, with porcine scleras exhibiting greater inter-site variation (displacement of S, I was up to four times greater than that of N, T), while rabbit scleras exhibited at most 40% of displacement differences between all sites. Both models showed significant (p<.001) differences in the temporal deformation profile between sclera and (C), but similarities in all scleral locations, suggesting that the scleral temporal profile is independent of scleral thickness variations. The FEM estimated an elastic modulus of 1.84 ± 0.30 MPa (I) to 6.04 ± 2.11 MPa (TE) for the porcine sclera. The use of scleral air-puff imaging is promising for noninvasive investigation of structural changes in the sclera associated with myopia and for monitoring possible modulation of scleral stiffness with myopia treatment.
- Published
- 2023
5. Noninvasive Monitoring to Detect Dehydration: Are We There Yet?
- Author
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Massachusetts Institute of Technology, National Institutes of Health (US), Massachusetts General Hospital, #NODATA#, Gray, Martha, Birkenfeld, J., Butterworth, Ian, Massachusetts Institute of Technology, National Institutes of Health (US), Massachusetts General Hospital, #NODATA#, Gray, Martha, Birkenfeld, J., and Butterworth, Ian
- Abstract
The need for hydration monitoring is significant, especially for the very young and elderly populations who are more vulnerable to becoming dehydrated and suffering from the effects that dehydration brings. This need has been among the drivers of considerable effort in the academic and commercial sectors to provide a means for monitoring hydration status, with a special interest in doing so outside the hospital or clinical setting. This review of emerging technologies provides an overview of many technology approaches that, on a theoretical basis, have sensitivity to water and are feasible as a routine measurement. We review the evidence of technical validation and of their use in humans. Finally, we highlight the essential need for these technologies to be rigorously evaluated for their diagnostic potential, as a necessary step to meet the need for hydration monitoring outside of the clinical environment.
- Published
- 2023
6. Prospective observational pilot study of quantitative light dosimetry in erythropoietic protoporphyria
- Author
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National Center for Advancing Translational Sciences (US), Massachusetts General Hospital, National Institutes of Health (US), Harvard University, Dickey, Amy K., Rebeiz, Lina, Raef, Haya, Leaf, Rebecca K., Elmariah, Sarina, Naik, Hetanshi, Anderson, Karl, Conley, Jared, Iyasere, Christiana, Zhao, Sophia, Birkenfeld, J., Arroyo-Gallego, Teresa, Wheeden, Kristen, Ducamp, Sarah, Christiani, David C., Fleming, Mark D., Kochevar, Irene, National Center for Advancing Translational Sciences (US), Massachusetts General Hospital, National Institutes of Health (US), Harvard University, Dickey, Amy K., Rebeiz, Lina, Raef, Haya, Leaf, Rebecca K., Elmariah, Sarina, Naik, Hetanshi, Anderson, Karl, Conley, Jared, Iyasere, Christiana, Zhao, Sophia, Birkenfeld, J., Arroyo-Gallego, Teresa, Wheeden, Kristen, Ducamp, Sarah, Christiani, David C., Fleming, Mark D., and Kochevar, Irene
- Published
- 2022
7. Co-axial acoustic-based optical coherence vibrometry probe for the quantification of resonance frequency modes in ocular tissue
- Author
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European Research Council, Agencia Estatal de Investigación (España), University of Rochester, L'Oréal-UNESCO For Women in Science, Polish National Agency for Academic Exchange, McAuley, Ryan, Nolan, Andrew, Curatolo, Andrea, Alexandrov, Sergey, Zvietcovich, Fernando, Varea, Alejandra, Marcos, Susana, Leahy, Martin, Birkenfeld, J., European Research Council, Agencia Estatal de Investigación (España), University of Rochester, L'Oréal-UNESCO For Women in Science, Polish National Agency for Academic Exchange, McAuley, Ryan, Nolan, Andrew, Curatolo, Andrea, Alexandrov, Sergey, Zvietcovich, Fernando, Varea, Alejandra, Marcos, Susana, Leahy, Martin, and Birkenfeld, J.
- Abstract
We present a co-axial acoustic-based optical coherence vibrometry probe (CoA-OCV) for vibro-acoustic resonance quantification in biological tissues. Sample vibrations were stimulated via a loudspeaker, and pre-compensation was used to calibrate the acoustic spectrum. Sample vibrations were measured via phase-sensitive swept-source optical coherence tomography (OCT). Resonance frequencies of corneal phantoms were measured at varying intraocular pressures (IOP), and dependencies on Young¿s Modulus (E), phantom thickness and IOP were observed. Cycling IOP revealed hysteresis. For E = 0.3 MPa, resonance frequencies increased with IOP at a rate of 3.9, 3.7 and 3.5 Hz/mmHg for varied thicknesses and 1.7, 2.5 and 2.8 Hz/mmHg for E = 0.16 MPa. Resonance frequencies increased with thickness at a rate of 0.25 Hz/µm for E = 0.3 MPa, and 0.40 Hz/µm for E = 0.16 MPa. E showed the most predominant impact in the shift of the resonance frequencies. Full width at half maximum (FWHM) of the resonance modes increased with increasing thickness and decreased with increasing E. Only thickness and E contributed to the variance of FWHM. In rabbit corneas, resonance frequencies of 360–460 Hz were observed. The results of the current study demonstrate the feasibility of CoA-OCV for use in future OCT-V studies.
- Published
- 2022
8. Hysteresis in vibrational resonance modes of model corneas measured with Optical Coherence Tomography Vibrography utilizing a co-axial acoustic stimulation technique and pre-compensation
- Author
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McAuley, Ryan, primary, Nolan, A., additional, Curatolo, A., additional, Alexandrov, S., additional, Zvietcovich, F., additional, Varea, A., additional, Marcos, S., additional, Birkenfeld, J. S., additional, and Leahy, M., additional
- Published
- 2022
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9. Method and system for biomechanically characterising ocular tissue through deformation thereof
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Nolan, Andrew, McAuley, Ryan, Alexandrov, Sergey, Leahy, Martin, Birkenfeld, J., Curatolo, Andrea, Marcos, Susana, Elsheikh, A., Abass, A., Eliasy, A., Nolan, Andrew, McAuley, Ryan, Alexandrov, Sergey, Leahy, Martin, Birkenfeld, J., Curatolo, Andrea, Marcos, Susana, Elsheikh, A., Abass, A., and Eliasy, A.
- Abstract
The present disclosure relates to a method and a system for biomechanically characterising ocular tissue (C) through deformation of the ocular tissue. The method comprises: - generating an acoustic stimulus for delivery onto the ocular tissue in a collinear manner with an axis of a measuring device, for producing vibration of the ocular tissue; - measuring ocular tissue displacement with the measuring device at a plurality of locations of the ocular tissue; - obtaining at least a biomechanical parameter by processing the ocular tissue displacements at the plurality of locations. The disclosure also relates to a method and a system for screening biomechanical abnormality of ocular tissue (C).
- Published
- 2021
10. System and method for obtaining biomechanical parameters of ocular tissue through deformation of the ocular tissue
- Author
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Curatolo, Andrea, Marcos, Susana, Birkenfeld, J., Wojtkowski, Maciej, Karnowski, Karol, Elsheikh, A., Abass, A., Eliasy, A., Curatolo, Andrea, Marcos, Susana, Birkenfeld, J., Wojtkowski, Maciej, Karnowski, Karol, Elsheikh, A., Abass, A., and Eliasy, A.
- Abstract
The invention relates to a system for obtaining biomechanical parameters of ocular tissue (C), the system comprising: - an air-puff module (200) configured to deliver at least one air-puff stimulus onto the ocular tissue; - an imaging device (100, 100') operatively coupled to the air-puff module (200); characterised in that - the air-puff module comprises a transparent window (PW) at its front thereof, the transparent window having a transparent through hole (OD) for delivering the at least one air-puff stimulus, the hole configured to be aligned with an optical axis of the imaging device, such that the air-puff stimulus delivered onto the ocular tissue can be centred on an apex of the ocular tissue and can be made collinear with the optical axis of the imaging device, the transparent window (PW) and its transparent through hole further allowing continuity of imaging of the ocular surface; - the imaging device (100, 100') being configured to capture the three-dimensional coordinates of a plurality of points distributed on a surface of the ocular tissue, captured in groups of at least two simultaneous points; the system further comprising: - means for selecting and changing the location and distribution of the plurality of captured points on a surface of the ocular tissue; - processing means configured to process the plurality of points provided by the imaging device for obtaining biomechanical parameters of the ocular tissue. The invention also relates to a method for obtaining biomechanical parameters of ocular tissue, especially, corneal biomechanical parameters.
- Published
- 2021
11. System and method for obtaining biomechanical parameters of ocular tissue through deformation of the ocular tissue
- Author
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Curatolo, A., Marcos, Susana, Birkenfeld, J., Wojtkowski, Maciej, Karnowski, Karol, Elsheikh, A., Abass, A., and Eliasy, A.
- Subjects
genetic structures ,sense organs ,eye diseases - Abstract
The invention relates to a system for obtaining biomechanical parameters of ocular tissue (C), the system comprising: - an air-puff module (200) configured to deliver at least one air-puff stimulus onto the ocular tissue; - an imaging device (100, 100') operatively coupled to the air-puff module (200); characterised in that - the air-puff module comprises a transparent window (PW) at its front thereof, the transparent window having a transparent through hole (OD) for delivering the at least one air-puff stimulus, the hole configured to be aligned with an optical axis of the imaging device, such that the air-puff stimulus delivered onto the ocular tissue can be centred on an apex of the ocular tissue and can be made collinear with the optical axis of the imaging device, the transparent window (PW) and its transparent through hole further allowing continuity of imaging of the ocular surface; - the imaging device (100, 100') being configured to capture the three-dimensional coordinates of a plurality of points distributed on a surface of the ocular tissue, captured in groups of at least two simultaneous points; the system further comprising: - means for selecting and changing the location and distribution of the plurality of captured points on a surface of the ocular tissue; - processing means configured to process the plurality of points provided by the imaging device for obtaining biomechanical parameters of the ocular tissue. The invention also relates to a method for obtaining biomechanical parameters of ocular tissue, especially, corneal biomechanical parameters., Consejo Superior de Investigaciones Científicas (CSIC), Instytut Chemii Fizycznej, The University of Liverpool, A1 Solicitud de patente con informe sobre el estado de la técnica
- Published
- 2020
12. Method and system for biomechanically characterising ocular tissue through deformation thereof
- Author
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Nolan, Andrew, McAuley, Ryan, Alexandrov, Sergey, Leahy, Martin, Birkenfeld, J., Curatolo, A., Marcos, Susana, Elsheikh, A., Abass, A., and Eliasy, A.
- Subjects
genetic structures ,sense organs ,eye diseases - Abstract
The present disclosure relates to a method and a system for biomechanically characterising ocular tissue (C) through deformation of the ocular tissue. The method comprises: - generating an acoustic stimulus for delivery onto the ocular tissue in a collinear manner with an axis of a measuring device, for producing vibration of the ocular tissue; - measuring ocular tissue displacement with the measuring device at a plurality of locations of the ocular tissue; - obtaining at least a biomechanical parameter by processing the ocular tissue displacements at the plurality of locations. The disclosure also relates to a method and a system for screening biomechanical abnormality of ocular tissue (C)., National University of Ireland Galway, Consejo Superior de Investigaciones Científicas, University of Liverpool, A1 Solicitud de patente con informe sobre el estado de la técnica
- Published
- 2020
13. Assessing collagen microstructural changes in an ex vivo keratoconic eye model with Stokes polarization-sensitive optical coherence tomography
- Author
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Uribe-Patarroyo, Néstor, Birkenfeld, J., Curatolo, A., Cannon, Taylor M., Germann, James, Villiger, Martin, Marcos, Susana, and Bouma, Brett E.
- Abstract
ARVO Annual Meeting Abstract , June 2020
- Published
- 2020
14. Customized swept-source optical coherence tomography system for air-puff induced corneal deformation imaging on multiple meridians
- Author
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Curatolo, A., Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Palací, J., Pascual, Daniel, Muralidharan, Geethika, Solarski, J., Karnowski, Karol, Wojtkowski, Maciej, and Marcos, Susana
- Abstract
PIE BiOS, San Francisco, California, United States, 17 Marzo 2020. -- SPIE Proceedings Vol. 11218: Ophthalmic Technologies XXX . -- https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11218/2546050/Customized-swept-source-optical-coherence-tomography-system-for-air-puff/10.1117/12.2546050.full?SSO=1
- Published
- 2020
15. Assessment of asymmetries in biomechanical properties from corneal deformation imaging
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Birkenfeld, J., Germann, James, Castro, Alberto de, Hoz, A. de la, Curatolo, A., Marcos, Susana, European Commission, and Ministerio de Economía y Competitividad (España)
- Abstract
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019, Support European Project Multiply H-2020-MSCA-COFUND-2015 Ref. 713694, Spanish Government Grant FIS2017-84753-R, European Project Presbyopia ERC-2011-AdG Ref. 294099, European Project Imcustomeye H2020-ICT-2017 Ref. 779960, BES-2015-072197
- Published
- 2019
16. Crystalline lens accommodation through multifocal corrections
- Author
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Muralidharan, Geethika, Birkenfeld, J., Viñas, María, Curatolo, A., Martínez-Enríquez, Eduardo, Castro, Alberto de, and Marcos, Susana
- Abstract
Vancouver Convention Centre, Vancouver, B.C., April 28 – May 2 (2019)
- Published
- 2019
17. Customized swept-source optical coherence tomography system for air-puff induced corneal deformation imaging on multiple meridians
- Author
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Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Palací, J., Pascual, Daniel, Muralidharan, Geethika, Solarski, J., Karnowski, Karol, Wojtkowski, Maciej, Marcos, Susana, Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Palací, J., Pascual, Daniel, Muralidharan, Geethika, Solarski, J., Karnowski, Karol, Wojtkowski, Maciej, and Marcos, Susana
- Published
- 2020
18. Investigation of the corneal frequency response to modulated sound excitation
- Author
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Birkenfeld, J., Curatolo, Andrea, Nolan, Andrew, McAuley, Ryan, Abass, A., Eliasy, A., Leahy, Martin, Elsheikh, A., Marcos, Susana, Birkenfeld, J., Curatolo, Andrea, Nolan, Andrew, McAuley, Ryan, Abass, A., Eliasy, A., Leahy, Martin, Elsheikh, A., and Marcos, Susana
- Published
- 2020
19. Detecting deformation asymmetries on multiple meridians in an ex vivo keratoconic eye model
- Author
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European Commission, Ministerio de Economía y Competitividad (España), Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Palací, J., Pascual, Daniel, Muralidharan, Geethika, Eliasy, A., Abass, A., Solarski, J., Karnowski, Karol, Wojtkowski, Maciej, Elsheikh, A., Marcos, Susana, European Commission, Ministerio de Economía y Competitividad (España), Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Palací, J., Pascual, Daniel, Muralidharan, Geethika, Eliasy, A., Abass, A., Solarski, J., Karnowski, Karol, Wojtkowski, Maciej, Elsheikh, A., and Marcos, Susana
- Published
- 2020
20. In vivo measurement of shear modulus of the human cornea using optical coherence elastography
- Author
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National Institutes of Health (US), National Science Foundation (US), Ramier, A., Eltony, A.M., Chen, Y.T., Clouser, F., Birkenfeld, J., Watts, A., Yun, S.H., National Institutes of Health (US), National Science Foundation (US), Ramier, A., Eltony, A.M., Chen, Y.T., Clouser, F., Birkenfeld, J., Watts, A., and Yun, S.H.
- Abstract
Corneal stiffness plays a critical role in shaping the cornea with respect to intraocular pressure and physical interventions. However, it remains difficult to measure the mechanical properties noninvasively. Here, we report the first measurement of shear modulus in human corneas in vivo using optical coherence elastography (OCE) based on surface elastic waves. In a pilot study of 12 healthy subjects aged between 25 and 67, the Rayleigh-wave speed was 7.86 ± 0.75 m/s, corresponding to a shear modulus of 72 ± 14 kPa. Our data reveal two unexpected trends: no correlation was found between the wave speed and IOP between 13–18 mmHg, and shear modulus decreases with age (− 0.32 ± 0.17 m/s per decade). We propose that shear stiffness is governed by the interfibrillar matrix, whereas tensile strength is dominated by collagen fibrils. Rayleigh-wave OCE may prove useful for clinical diagnosis, refractive surgeries, and treatment monitoring.
- Published
- 2020
21. Multi-meridian corneal imaging of air-puff induced deformation for improved detection of biomechanical abnormalities
- Author
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European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Foundation for Polish Science, Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Muralidharan, Geethika, Palací, J., Pascual, Daniel, Eliasy, A., Abass, A., Solarski, J., Karnowski, K., Wojtkowski, M., Elsheikh, A., Marcos, Susana, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Foundation for Polish Science, Curatolo, Andrea, Birkenfeld, J., Martínez-Enríquez, Eduardo, Germann, James, Muralidharan, Geethika, Palací, J., Pascual, Daniel, Eliasy, A., Abass, A., Solarski, J., Karnowski, K., Wojtkowski, M., Elsheikh, A., and Marcos, Susana
- Abstract
Corneal biomechanics play a fundamental role in the genesis and progression of corneal pathologies, such as keratoconus; in corneal remodeling after corneal surgery; and in affecting the measurement accuracy of glaucoma biomarkers, such as the intraocular pressure (IOP). Air-puff induced corneal deformation imaging reveals information highlighting normal and pathological corneal response to a non-contact mechanical excitation. However, current commercial systems are limited to monitoring corneal deformation only on one corneal meridian. Here, we present a novel custom-developed swept-source optical coherence tomography (SSOCT) system, coupled with a collinear air-puff excitation, capable of acquiring dynamic corneal deformation on multiple meridians. Backed by numerical simulations of corneal deformations, we propose two different scan patterns, aided by low coil impedance galvanometric scan mirrors that permit an appropriate compromise between temporal and spatial sampling of the corneal deformation profiles. We customized the air-puff module to provide an unobstructed SSOCT field of view and different peak pressures, air-puff durations, and distances to the eye. We acquired multi-meridian corneal deformation profiles (a) in healthy human eyes in vivo, (b) in porcine eyes ex vivo under varying controlled IOP, and (c) in a keratoconus-mimicking porcine eye ex vivo. We detected deformation asymmetries, as predicted by numerical simulations, otherwise missed on a single meridian that will substantially aid in corneal biomechanics diagnostics and pathology screening.
- Published
- 2020
22. System and method for obtaining ocular tissue biomechanical parameters
- Author
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Marcos, Susana, Birkenfeld, J., and Yun, S.H.
- Subjects
genetic structures ,sense organs ,eye diseases - Abstract
The invention refers toa system (lOO) for obtaining biomechauical properties of ocular tissue, the system comprising: -an air-puff generator (lO) configured to generate a stepped-frequency train of air-pnff pulses of dífferent frequencies for delivery onto the ocular tissue; -an imaging device (20) operatively coupled to the air-pnff generator, the imaging device being configured to capture a plurality of axial positions of a region of the ocular tissue; -processing means (30) configured to: -process the plurality of axial positions provided by the imaging device for obtaining displacement and velocity of the region of the ocular tissue at the dífferent frequencies; and to -carry out frequency domain analysis of the obtained displacements and velocities of the region of the ocular tissue at the dífferent frequencies to at least derive a mechauical resonance frequency of the ocular tissue; and to -perform inverse calculation and obtain biomechanical parameters and intraocular pressure of the ocular tissue using the displacement, velocity and mechanical resonance frequency as inputs in a Fine-Element-Model based calculation. The invention also relates toa method for obtaining biomechauical parameters of ocular tissue., Consejo Superior de Investigaciones Científicas (España), Wellman Center for photomedicine, A1 Solicitud de patente con informe sobre el estado de la técnica
- Published
- 2019
23. Assessment of ocular mechanical resonances using phase-sensitive OCT and frequency-domain air puff stimulation
- Author
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Birkenfeld, J., Ramier, A., Tavakol, Behrouz, Marcos, Susana, Yun, S., and National Institutes of Health (US)
- Abstract
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018., Support NIH Grant 228599 P41, Marie Curie Actions
- Published
- 2018
24. Off-axis optical coherence tomography imaging of the crystalline lens to reconstruct the gradient refractive index using optical methods
- Author
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European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), National Eye Institute (US), Castro, Alberto de, Birkenfeld, J., Heilman, B.M., Ruggeri, M., Arrieta, E., Parel, Jean Marie, Manns, Fabrice, Marcos, Susana, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), National Eye Institute (US), Castro, Alberto de, Birkenfeld, J., Heilman, B.M., Ruggeri, M., Arrieta, E., Parel, Jean Marie, Manns, Fabrice, and Marcos, Susana
- Abstract
Earlier studies have shown that the gradient index of refraction (GRIN) of the crystalline lens can be reconstructed in vitro using Optical Coherence Tomography (OCT) images. However, the methodology cannot be extended in vivo because it requires accurate measurements of the external geometry of the lens. Specifically, the posterior surface is measured by flipping the lens so that the posterior lens surface faces the OCT beam, a method that cannot be implemented in vivo. When the posterior surface is imaged through the lens in its natural position, it appears distorted by the unknown GRIN. In this study, we demonstrate a method to reconstruct both the GRIN and the posterior surface shape without the need to flip the lens by applying optimization routines using both on-axis and off-axis OCT images of cynomolgous monkey crystalline lenses, obtained by rotating the OCT delivery probe from -45 to +45 degrees in 5 degree steps. We found that the GRIN profile parameters can be reconstructed with precisions up to 0.009, 0.004, 1.7 and 1.1 (nucleus and surface refractive indices, and axial and meridional power law, respectively), the radius of curvature within 0.089 mm and the conic constant within 0.3. While the method was applied on isolated crystalline lenses, it paves the way to in vivo lens GRIN and posterior lens surface reconstruction.
- Published
- 2019
25. Morphological changes of human crystalline lens in myopia
- Author
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European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Muralidharan, Geethika, Martínez-Enríquez, Eduardo, Birkenfeld, J., Velasco Ocaña, Miriam, Pérez Merino, Pablo, Marcos, Susana, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Muralidharan, Geethika, Martínez-Enríquez, Eduardo, Birkenfeld, J., Velasco Ocaña, Miriam, Pérez Merino, Pablo, and Marcos, Susana
- Abstract
Ocular biometric parameters, including full shape crystalline lens, were assessed in myopes and emmetropes using 3-D optical coherence tomography. The anterior chamber depth, the radius of the curvature of the anterior cornea, anterior lens, and posterior lens, lens thickness, lens equatorial diameter, surface area, equatorial position, volume, and power, were evaluated as functions of refractive errors and axial lengths while controlling for age effects. The crystalline lens appears to change with myopia consistent with lens thinning, equatorial, and capsular stretching while keeping constant volume. Axial elongation appears counteracted by a crystalline lens power reduction, while corneal power remains unaffected.
- Published
- 2019
26. Assessment of asymmetries in biomechanical properties from corneal deformation imaging
- Author
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European Commission, Ministerio de Economía y Competitividad (España), Birkenfeld, J., Germann, James, Castro, Alberto de, Hoz, A. de la, Curatolo, Andrea, Marcos, Susana, European Commission, Ministerio de Economía y Competitividad (España), Birkenfeld, J., Germann, James, Castro, Alberto de, Hoz, A. de la, Curatolo, Andrea, and Marcos, Susana
- Published
- 2019
27. Assessment of ocular mechanical resonances using phase-sensitive OCT and frequency-domain air puff stimulation
- Author
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National Institutes of Health (US), Birkenfeld, J., Ramier, A., Tavakol, Behrouz, Marcos, Susana, Yun, S., National Institutes of Health (US), Birkenfeld, J., Ramier, A., Tavakol, Behrouz, Marcos, Susana, and Yun, S.
- Published
- 2018
28. Full OCT-based pseudophakic custom computer eye mode
- Author
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Sun, M., Pérez Merino, Pablo, Castro, Alberto de, Birkenfeld, J., Ortiz, Sergio, and Marcos, Susana
- Abstract
World Meeting in Visual and Physiological Optics, Wroclaw, Poland, 25-27 August 2014
- Published
- 2014
29. Lens Spherical Aberrations in Cynomolgus Monkeys: Comparison of Laser Ray Tracing Measurements and Reconstructed GRIN Model Predictions
- Author
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Castro, Alberto de, Birkenfeld, J., and Marcos, Susana
- Subjects
Physics::Optics - Abstract
Orlando, United States, 4–8 May 2014, To compare the spherical aberration of cynomolgus monkey lenses measured with a laser ray tracing (LRT) system and the spherical aberration estimated from numerical ray-trace through a model of the lens with the measured lens shape and a reconstructed gradient refractive index (GRIN).
- Published
- 2014
30. Crystalline lens volume, diameter and equator estimates from OCT images: impact on future paradigms of cataract surgery
- Author
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European Commission, Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), Martínez-Enríquez, Eduardo, Sun, M., Birkenfeld, J., Pérez Merino, Pablo, Velasco Ocaña, Miriam, Marcos, Susana, European Commission, Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), Martínez-Enríquez, Eduardo, Sun, M., Birkenfeld, J., Pérez Merino, Pablo, Velasco Ocaña, Miriam, and Marcos, Susana
- Published
- 2016
31. Optical coherence tomography based estimates of crystalline lens volume, equatorial diameter, and plane position
- Author
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European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Educación y Ciencia (España), Martínez-Enríquez, Eduardo, Sun, M., Velasco Ocaña, Miriam, Birkenfeld, J., Pérez Merino, Pablo, Marcos, Susana, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Educación y Ciencia (España), Martínez-Enríquez, Eduardo, Sun, M., Velasco Ocaña, Miriam, Birkenfeld, J., Pérez Merino, Pablo, and Marcos, Susana
- Abstract
PURPOSE. Measurement of crystalline lens geometry in vivo is critical to optimize performance of state-of-the-art cataract surgery. We used custom-developed quantitative anterior segment optical coherence tomography (OCT) and developed dedicated algorithms to estimate lens volume (VOL), equatorial diameter (DIA), and equatorial plane position (EPP). METHODS. The method was validated ex vivo in 27 human donor (19-71 years of age) lenses, which were imaged in three-dimensions by OCT. In vivo conditions were simulated assuming that only the information within a given pupil size (PS) was available. A parametric model was used to estimate the whole lens shape from PS-limited data. The accuracy of the estimated lens VOL, DIA, and EPP was evaluated by comparing estimates from the whole lens data and PS-limited data ex vivo. The method was demonstrated in vivo using 2 young eyes during accommodation and 2 cataract eyes. RESULTS. Crystalline lens VOL was estimated within 96% accuracy (average estimation error across lenses ± standard deviation: 9.30 ± 7.49 mm). Average estimation errors in EPP were below 40 ± 32 lm, and below 0.26 ± 0.22 mm in DIA. Changes in lens VOL with accommodation were not statistically significant (2-way ANOVA, P = 0.35). In young eyes, DIA decreased and EPP increased statistically significantly with accommodation (P < 0.001) by 0.14 mm and 0.13 mm, respectively, on average across subjects. In cataract eyes, VOL = 205.5 mm3, DIA = 9.57 mm, and EPP = 2.15 mm on average. CONCLUSIONS. Quantitative OCT with dedicated image processing algorithms allows estimation of human crystalline lens volume, diameter, and equatorial lens position, as validated from ex vivo measurements, where entire lens images are available.
- Published
- 2016
32. Imaging crystalline lens microscopic structures of intact in vitro mammal lenses using confocal microscopy
- Author
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Birkenfeld, J., Lamela, J., Ortiz, Sergio, and Marcos, Susana
- Abstract
Spanish Government Grant FIS2011- 25637 to SM; European Research Council ERC-AdG-294099 to SM; CSIC JAEPre Program to JB; CSIC i-LINK+ 2012, i-LINK+0609 to SM.
- Published
- 2014
33. Three-dimensional biometry and alignment in eyes implanted with Accommodative IOLs as a function of accommodative demand
- Author
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Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Velasco Ocaña, Miriam, Sun, M., Birkenfeld, J., Durán, Sonia, and Jiménez-Alfaro, Ignacio
- Abstract
ARVO Annual Meeting 2013, Washington State Convention Center, May 5-9, 2013
- Published
- 2013
34. Astigmatism of the isolated human crystalline lens: Surface shape and gradient refractive index contributions
- Author
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Birkenfeld, J., Castro, Alberto de, Marcos, Susana, Birkenfeld, J., Castro, Alberto de, and Marcos, Susana
- Published
- 2015
35. Astigmatism of the ex vivo human lens: Surface and gradient refractive index age-dependent contributions
- Author
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Consejo Superior de Investigaciones Científicas (España), European Commission, Ministerio de Ciencia e Innovación (España), Birkenfeld, J., Castro, Alberto de, Marcos, Susana, Consejo Superior de Investigaciones Científicas (España), European Commission, Ministerio de Ciencia e Innovación (España), Birkenfeld, J., Castro, Alberto de, and Marcos, Susana
- Abstract
© 2015 The Association for Research in Vision and Ophthalmology, Inc. PURPOSE. We estimated the contribution of the gradient refractive index (GRIN) and lens surfaces to lens astigmatism and lens astigmatic angle as a function of age in human donor lenses. METHODS. Human lenses were imaged, ex vivo, with 3D-spectral optical coherence tomography (OCT) and their back focal length was measured using laser ray tracing. The contribution of lens surfaces and GRIN to lens astigmatism were evaluated by computational ray tracing on the GRIN lens and a homogenous equivalent index lens. Astigmatism magnitude and relative astigmatic angle of and between lens surfaces, GRIN lens, and lens with homogeneous refractive index were evaluated, and all results were correlated with age. RESULTS. The magnitude of astigmatism in the anterior lens surface decreased with age (slope = -0.005 diopters [D]/y; r = 0.397, P =0.018). Posterior surface astigmatism and lens astigmatism were not age-dependent. Presence of GRIN did not alter significantly the magnitude or axis of the lens astigmatism. The astigmatism of GRIN lens and lens with homogeneous refractive index correlated with anterior lens surface astigmatism (GRIN, P = 3.9E - 6, r = 0.693; equivalent refractive index lens, P = 4.1E - 4, r = 0.565). The astigmatic angle of posterior surface, GRIN lens, and homogeneous refractive index lens did not change significantly with age. CONCLUSIONS. The axis of lens astigmatism is close to the astigmatic axis of the anterior lens surface. Age-related changes in lens astigmatism appear to be related to changes in the anterior lens astigmatism. The influence of the GRIN on lens astigmatism and the astigmatic axis is minor.
- Published
- 2015
36. Aberrometry in patients implanted with accommodative intraocular lenses
- Author
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Pérez Merino, Pablo, Birkenfeld, J., Dorronsoro, Carlos, Ortiz, Sergio, Durán, Sonia, Jiménez-Alfaro, Ignacio, Marcos, Susana, Pérez Merino, Pablo, Birkenfeld, J., Dorronsoro, Carlos, Ortiz, Sergio, Durán, Sonia, Jiménez-Alfaro, Ignacio, and Marcos, Susana
- Abstract
Purpose To evaluate the objective accommodative response, change of aberrations, and depth of focus in eyes implanted with the Crystalens accommodative intraocular lens (IOL) at different accommodative demands. Design Prospective, observational study. Methods Eleven cataract patients (22 eyes) who underwent implantation of a Crystalens accommodative IOL, and control groups of 9 normal subjects (17 eyes) and 17 pseudophakic patients (17 eyes) implanted with monofocal IOLs were evaluated. A custom-developed laser ray tracing aberrometer was used to measure the optical aberrations. The monochromatic wave aberrations were described using a sixth-order Zernike polynomial expansion. Measurements were obtained under dilated and natural viewing conditions (for accommodative efforts ranging from 0 to 2.5 diopters [D]). The accommodative response was obtained by analyzing changes in paraxial defocus (associated to changes in defocus) and by evaluating the differences in the effective defocus (associated with defocus, spherical aberrations, and pupil diameter) with the accommodative demand. Depth of focus was estimated from through-focus objective optical quality. Results Wave aberration measurements were highly reproducible. Vertical trefoil (Z3 -3) was the predominant higher-order aberration in the Crystalens group and significantly higher (P <.0001) than in the young group, but similar to the monofocal IOL group. The coma root mean square also was higher (P <.005) in the Crystalens group than in the young group. On average, the defocus term (Z2 0), astigmatism, or higher-order aberrations did not change systematically with accommodative demand in Crystalens eyes. As found for paraxial defocus, the effective defocus in Crystalens eyes did not show significant differences between conditions: 0.34 ± 0.48 D (far), 0.32 ± 0.50 D (intermediate), and 0.34 ± 0.44 D (near). Depth of focus was statistically significantly higher in the Crystalens eyes than in the control groups. Concl
- Published
- 2014
37. Crystalline lens gradient refractive index and posterior surface shape from multiple orientations OCT imaging: towards a reconstruction in vivo?
- Author
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Castro, Alberto de, Birkenfeld, J., Maceo, B. M., Ruggeri, Marco, Arrieta, Esdras, Parel, Jean Marie, Manns, Fabrice, Marcos, Susana, Castro, Alberto de, Birkenfeld, J., Maceo, B. M., Ruggeri, Marco, Arrieta, Esdras, Parel, Jean Marie, Manns, Fabrice, and Marcos, Susana
- Published
- 2014
38. Lens Spherical Aberrations in Cynomolgus Monkeys: Comparison of Laser Ray Tracing Measurements and Reconstructed GRIN Model Predictions
- Author
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Maceo, B. M., Castro, Alberto de, Birkenfeld, J., Arrieta, Esdras, Parel, Jean Marie, Marcos, Susana, Manns, Fabrice, Maceo, B. M., Castro, Alberto de, Birkenfeld, J., Arrieta, Esdras, Parel, Jean Marie, Marcos, Susana, and Manns, Fabrice
- Published
- 2014
39. OCT 3-D surface topography of isolated human crystalline lenses
- Author
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Sun, M., Birkenfeld, J., Castro, Alberto de, Ortiz, Sergio, Pérez Merino, Pablo, Velasco Ocaña, Miriam, Marcos, Susana, Sun, M., Birkenfeld, J., Castro, Alberto de, Ortiz, Sergio, Pérez Merino, Pablo, Velasco Ocaña, Miriam, and Marcos, Susana
- Published
- 2014
40. Three-dimensional evaluation of accommodating intraocular lens shift and alignment in vivo
- Author
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Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Birkenfeld, J., Durán, Sonia, Jiménez-Alfaro, Ignacio, Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Birkenfeld, J., Durán, Sonia, and Jiménez-Alfaro, Ignacio
- Abstract
Objective To quantify 3-dimensionally the anterior segment geometry, biometry, and lens position and alignment in patients before and after implantation of the Crystalens-AO (Bausch & Lomb, Rochester, NY) accommodating intraocular lens (A-IOL). Design Prospective, observational study. Participants Ten patients (20 eyes) with cataract before and after implantation of the Crystalens-AO A-IOL. Methods Custom full anterior segment 3-dimensional (3-D) spectral optical coherence tomography (OCT) provided with quantification tools was used to image the cornea, iris, and natural lens preoperatively and intraocular lens postoperatively. Measurements were obtained under phenylephrine preoperatively and under natural viewing conditions and phenylephrine (for accommodative efforts ranging from 0 to 2.5 diopters [D]) and pilocarpine postoperatively. Main Outcome Measures Three-dimensional quantitative anterior segment images, corneal geometry and power, anterior chamber depth (ACD), lens thickness, pupil diameter, A-IOL shift with accommodative effort or drug-induced accommodation, and A-IOL alignment. Results Crystalline lens and IOLs were visualized and quantified 3-dimensionally. The average ACD were 2.64±0.24 and 3.65±0.35 mm preoperatively and postoperatively (relaxed state), respectively, and they were statistically significantly correlated (although their difference was not statistically correlated with lens thickness). The A-IOL did not shift systematically with accommodative effort, with 9 lenses moving forward and 11 lenses moving backward (under natural conditions). The average A-IOL shift under stimulated accommodation with pilocarpine was -0.02±0.20 mm. The greatest forward shift occurred bilaterally in 1 patient (-0.49 mm in the right eye and -0.52 mm in the left eye, under pilocarpine). The high right/left symmetry in the horizontal tilt of the crystalline lens is disrupted on IOL implantation. Accommodative IOLs tend to be slightly more vertically tilted than the
- Published
- 2014
41. Intraocular lens alignment from an en face optical coherence tomography image Purkinje-like method
- Author
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Sun, M., Castro, Alberto de, Ortiz, Sergio, Pérez Merino, Pablo, Birkenfeld, J., Marcos, Susana, Sun, M., Castro, Alberto de, Ortiz, Sergio, Pérez Merino, Pablo, Birkenfeld, J., and Marcos, Susana
- Abstract
Measurement of intraocular lens (IOL) alignment implanted in patients in cataract surgery is important to understand their optical performance. We present a method to estimate tilt and decentration of IOLs based on optical coherence tomography (OCT) images. En face OCT images show Purkinje-like images that correspond to the specular reflections from the corneal and IOL surfaces. Unlike in standard Purkinjeimaging, the tomographic nature of OCT allows unequivocal association of the reflection with the corresponding surface. The locations of the Purkinje-like images are linear combinations of IOL tilt, IOL decentration, and eye rotation. The weighting coefficients depend on the individual anterior segment geometry, obtained from the same OCT datasets. The methodology was demonstrated on an artificial model eye with set amounts of lens tilt and decentration and five pseudophakic eyes. Measured tilt and decentration in the artificial eye differed by 3.7% and 0.9%, respectively, from nominal values. In patients, average IOL tilt and decentration from Purkinje were 3.30 ± 4.68 deg and 0.16 ± 0.16 mm, respectively, and differed on average by 0.5 deg and 0.09 mm, respectively, from direct measurements on distortion-corrected OCT images. Purkinje-based methodology from anterior segment en face OCT imaging provided, therefore, reliable measurements of IOL tilt and decentration. © The Authors.
- Published
- 2014
42. Contribution of shape and gradient refractive index to the spherical aberration of isolated human lenses
- Author
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Birkenfeld, J., Castro, Alberto de, Marcos, Susana, Birkenfeld, J., Castro, Alberto de, and Marcos, Susana
- Abstract
Purpose. To estimate the contribution of 3-dimensional (3D) lens geometry and gradient refractive index (GRIN) to the lens spherical aberration (SA) with age. Methods. A total of 35 donor human lenses (19-71 years) were imaged with 3D-spectral optical coherence tomography (sOCT). Paraxial and nonparaxial back focal length were measured with laser ray tracing (LRT). The parameters of a 4-variable 3D GRIN model were reconstructed from the data using a global search algorithm. Spherical aberration was calculated for GRIN lenses and their corresponding homogeneous lenses. Results. Lens thickness and radii of curvature increased significantly with age. Negative anterior conic constant shifted toward more-positive values (slope: 0.228, P < 0.001), whereas posterior values remained almost constant (slope: 0.0275, P = 0.002). We found a minor decrease and a small significant increase of nucleus and surface refractive index, respectively. The GRIN meridional power exponent had a tendency to increase, indicating a flattening of GRIN distribution, whereas the axial exponent remained almost constant. We did not find a significant age-dependence of the equivalent index. The back focal length had a significant increase with age (P < 0.001). The SA shifted toward less-negative values (slope: 0.0249, P < 0.001) at higher rates when considering the reconstructed GRIN (slope: 0.041, P < 0.001). Conclusions. Three-dimensional sOCT and LRT allowed reconstruction of lens geometry and GRIN in isolated lenses. The constancy of the GRIN axial power exponent, and the opposite slopes of surface and nucleus indices with age, explain the minor variations of the average index. Both geometrical changes and increase in the GRIN meridional power exponent contribute to the age-dependent shift of negative SA. © 2014 The Association for Research in Vision and Ophthalmology, Inc.
- Published
- 2014
43. Three dimensional biometry and alignment in eyes implanted with Accommodative IOLs as a function of accommodative demand
- Author
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Ministerio de Educación y Ciencia (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Velasco Ocaña, Miriam, Sun, M., Birkenfeld, J., Durán, Sonia, Jiménez-Alfaro, Ignacio, Ministerio de Educación y Ciencia (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Velasco Ocaña, Miriam, Sun, M., Birkenfeld, J., Durán, Sonia, and Jiménez-Alfaro, Ignacio
- Published
- 2013
44. Influence of shape and gradient refractive index in the accommodative changes of spherical aberration in nonhuman primate crystalline lenses
- Author
-
Ministerio de Educación y Ciencia (España), European Commission, Consejo Superior de Investigaciones Científicas (España), National Eye Institute (US), Florida Lions Eye Bank, Henri and Flore Lesieur Foundation, Vision Cooperative Research Centre (Australia), Castro, Alberto de, Birkenfeld, J., Maceo, B. M., Manns, Fabrice, Arrieta, Esdras, Parel, Jean Marie, Marcos, Susana, Ministerio de Educación y Ciencia (España), European Commission, Consejo Superior de Investigaciones Científicas (España), National Eye Institute (US), Florida Lions Eye Bank, Henri and Flore Lesieur Foundation, Vision Cooperative Research Centre (Australia), Castro, Alberto de, Birkenfeld, J., Maceo, B. M., Manns, Fabrice, Arrieta, Esdras, Parel, Jean Marie, and Marcos, Susana
- Abstract
Purpose. To estimate changes in surface shape and gradient refractive index (GRIN) profile in primate lenses as a function of accommodation. To quantify the contribution of surface shape and GRIN to spherical aberration changes with accommodation. Methods. Crystalline lenses from 15 cynomolgus monkeys were studied in vitro under different levels of accommodation produced by a stretching system. Lens shape was obtained from optical coherence tomography (OCT) cross-sectional images. The GRIN was reconstructed with a search algorithm using the optical path measured from OCT images and the measured back focal length. The spherical aberration of the lens was estimated as a function of accommodation using the reconstructed GRIN and a homogeneous refractive index. Results. The lens anterior and posterior radii of curvature decreased with increasing lens power. Both surfaces exhibited negative asphericities in the unaccommodated state. The anterior surface conic constant shifted toward less negative values with accommodation, while the value of the posterior remained constant. GRIN parameters remained constant with accommodation. The lens spherical aberration with GRIN distribution was negative and higher in magnitude than that with a homogeneous equivalent refractive index (by 29% and 53% in the unaccommodated and fully accommodated states, respectively). Spherical aberration with the equivalent refractive index shifted with accommodation toward negative values (-0.070 lm/diopter [D]), but the reconstructed GRIN shifted it farther (-0.124 lm/ D). Conclusions. When compared with the lens with the homogeneous equivalent refractive index, the reconstructed GRIN lens has more negative spherical aberration and a larger shift toward more negative values with accommodation. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
- Published
- 2013
45. Contribution of shape and gradient index to the spherical aberration of donor human lenses
- Author
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Birkenfeld, J., Castro, Alberto de, Marcos, Susana, Birkenfeld, J., Castro, Alberto de, and Marcos, Susana
- Published
- 2013
46. Full OCT anterior segment biometry: An application in cataract surgery
- Author
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Ortiz, Sergio, Pérez Merino, Pablo, Duran, Sonia, Velasco Ocaña, Miriam, Birkenfeld, J., Castro, Alberto de, Jiménez-Alfaro, Ignacio, Marcos, Susana, Ortiz, Sergio, Pérez Merino, Pablo, Duran, Sonia, Velasco Ocaña, Miriam, Birkenfeld, J., Castro, Alberto de, Jiménez-Alfaro, Ignacio, and Marcos, Susana
- Abstract
In vivo three-dimensional (3-D) anterior segment biometry before and after cataract surgery was analyzed by using custom highresolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT). The system was provided with custom algorithms for denoising, segmentation, full distortion correction (fan and optical) and merging of the anterior segment volumes (cornea, iris, and crystalline lens or IOL), to provide fully quantitative data of the anterior segment of the eye. The method was tested on an in vitro artificial eye with known surfaces geometry at different orientations and demonstrated on an aging cataract patient in vivo. Biometric parameters CCT, ACD/ILP, CLT/ILT Tilt and decentration are retrieved with a very high degree of accuracy. IOL was placed 400 οm behind the natural crystalline lens, The IOL was aligned with a similar orientation of the natural lens (2.47 deg superiorly), but slightly lower amounts (0.77 deg superiorly). The IOL was decentered superiorly (0.39 mm) and nasally (0.26 mm). © 2013 Optical Society of America.
- Published
- 2013
47. Inhibition of neurite extension by overexpression of individual domains of LIM kinase 1.
- Author
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Birkenfeld, J., Betz, H., and Roth, D.
- Subjects
- *
NEUROCHEMISTRY , *CELLS , *MICE - Abstract
Lin-11, Isl-1 and Mec-3 (LIM) kinases are serine/threonine kinases that phosphorylate cofilin, an actin depolymerizing protein. LIM kinases have a highly modular structure composed of two N-terminal LIM domains (LIM 1/2), a PSD-95, Dlg and ZO-1 (PDZ) domain and a C-terminal protein kinase domain. Here, we overexpressed individual domains of mouse LIM kinase 1 (LIMK1) in PC12 cells and investigated their effects on neurite outgrowth. Although none of the LIMK1 domains had an effect on spontaneous neurite outgrowth, the N-terminal LIM 1/2 domains strongly inhibited differentiation of PC12 cells after stimulation with both nerve growth factor (NGF) and the Rho-kinase inhibitor Y-27632. In contrast, the overexpressed PDZ domain reduced neurite outgrowth only when differentiation had been induced by Y-27632, but not by NGF. Our data suggest that the different non-catalytic N-terminal domains of LIMK1 contribute to the regulation of neurite extension by using distinct signal transduction pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
48. High-Throughput and Format-Agnostic Mispairing Assay for Multispecific Antibodies Using Intact Mass Spectrometry.
- Author
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Ziegengeist T, Orth J, Kroll K, Schneider M, Spindler N, Dimova D, Handschuh S, Brandenburg A, Ossola R, Furtmann N, Birkenfeld J, Beil C, Hoffmann D, Schmidt T, Sendak R, Fischer M, Hölper S, and Kühn J
- Subjects
- Mass Spectrometry, Epitopes, Antibodies
- Abstract
Multispecific antibodies have gained significant importance in a broad indication space due to their ability to engage multiple epitopes simultaneously and to thereby overcome therapeutic barriers. With growing therapeutic potential, however, the molecular complexity increases, thus intensifying the demand for innovative protein engineering and analytical strategies. A major challenge for multispecific antibodies is the correct assembly of light and heavy chains. Engineering strategies exist to stabilize the correct pairing, but typically individual engineering campaigns are required to arrive at the anticipated format. Mass spectrometry has proven to be a versatile tool to identify mispaired species. However, due to manual data analysis procedures, mass spectrometry is limited to lower throughputs. To keep pace with increasing sample numbers, we developed a high-throughput-capable mispairing workflow based on intact mass spectrometry with automated data analysis, peak detection, and relative quantification using Genedata Expressionist. This workflow is capable of detecting mispaired species of ∼1000 multispecific antibodies in three weeks and thus is applicable to complex screening campaigns. As a proof of concept, the assay was applied to engineering a trispecific antibody. Strikingly, the new setup has not only proved successful in mispairing analysis but has also revealed its potential to automatically annotate other product-related impurities. Furthermore, we could confirm the assay to be format-agnostic, as shown by analyzing several different multispecific formats in one run. With these comprehensive capabilities, the new automated intact mass workflow can be applied as a universal tool to detect and annotate peaks in a format-agnostic approach and in high-throughput, thus enabling complex discovery campaigns.
- Published
- 2023
- Full Text
- View/download PDF
49. Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.
- Author
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Promsote W, Xu L, Hataye J, Fabozzi G, March K, Almasri CG, DeMouth ME, Lovelace SE, Talana CA, Doria-Rose NA, McKee K, Hait SH, Casazza JP, Ambrozak D, Beninga J, Rao E, Furtmann N, Birkenfeld J, McCarthy E, Todd JP, Petrovas C, Connors M, Hebert AT, Beck J, Shen J, Zhang B, Levit M, Wei RR, Yang ZY, Pegu A, Mascola JR, Nabel GJ, and Koup RA
- Subjects
- Animals, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Virus Latency, HIV Antibodies, HIV Infections, HIV-1
- Abstract
Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4
+ and CD8+ T cells. Co-culturing CD4+ with autologous CD8+ T cells from ART-suppressed HIV+ donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8+ T cells. This trispecific antibody mediates CD4+ and CD8+ T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)- Published
- 2023
- Full Text
- View/download PDF
50. An end-to-end automated platform process for high-throughput engineering of next-generation multi-specific antibody therapeutics.
- Author
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Furtmann N, Schneider M, Spindler N, Steinmann B, Li Z, Focken I, Meyer J, Dimova D, Kroll K, Leuschner WD, Debeaumont A, Mathieu M, Lange C, Dittrich W, Kruip J, Schmidt T, and Birkenfeld J
- Subjects
- Escherichia coli, HEK293 Cells, Humans, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins immunology, Antibodies, Bispecific chemistry, Antibodies, Bispecific genetics, Antibodies, Bispecific immunology, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal genetics, Antibodies, Monoclonal immunology, Automation, Laboratory, Gene Library, Protein Engineering
- Abstract
Next-generation multi-specific antibody therapeutics (MSATs) are engineered to combine several functional activities into one molecule to provide higher efficacy compared to conventional, mono-specific antibody therapeutics. However, highly engineered MSATs frequently display poor yields and less favorable drug-like properties (DLPs), which can adversely affect their development. Systematic screening of a large panel of MSAT variants in very high throughput (HT) is thus critical to identify potent molecule candidates with good yield and DLPs early in the discovery process. Here we report on the establishment of a novel, format-agnostic platform process for the fast generation and multiparametric screening of tens of thousands of MSAT variants. To this end, we have introduced full automation across the entire value chain for MSAT engineering. Specifically, we have automated the in-silico design of very large MSAT panels such that it reflects precisely the wet-lab processes for MSAT DNA library generation. This includes mass saturation mutagenesis or bulk modular cloning technologies while, concomitantly, enabling library deconvolution approaches using HT Sanger DNA sequencing. These DNA workflows are tightly linked to fully automated downstream processes for compartmentalized mammalian cell transfection expression, and screening of multiple parameters. All sub-processes are seamlessly integrated with tailored workflow supporting bioinformatics. As described here, we used this platform to perform multifactor optimization of a next-generation bispecific, cross-over dual variable domain-Ig (CODV-Ig). Screening of more than 25,000 individual protein variants in mono- and bispecific format led to the identification of CODV-Ig variants with over 1,000-fold increased potency and significantly optimized production titers, demonstrating the power and versatility of the platform.
- Published
- 2021
- Full Text
- View/download PDF
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