The ROx is a retinal oximeter under development with the purpose of non-invasively and accurately measuring oxygen saturation (SO₂) in vivo. It is novel in that it utilizes the blue-green oximetry technique with on-axis illumination. ROx calibration tests were performed by inducing hypoxia in live anesthetized swine and comparing ROx measurements to SO₂ values measured by a CO-Oximeter. Calibration was not achieved to the precision required for clinical use, but limiting factors were identified and improved. The ROx was used in a set of sepsis experiments on live pigs with the intention of tracking retinal SO₂ during the development of sepsis. Though conclusions are qualitative due to insufficient calibration of the device, retinal venous SO₂ is shown to trend generally with central venous SO₂ as sepsis develops. The novel sepsis model developed in these experiments is also described. The method of cecal ligation and perforation with additional soiling of the abdomen consistently produced controllable severe sepsis/septic shock in a matter of hours. In addition, the ROx was used to collect retinal images from a healthy human volunteer. These experiments served as a bench test for several of the additions/modifications made to the ROx. This set of experiments specifically served to illuminate problems with various light paths and image acquisition. The analysis procedure for the ROx is under development, particularly automating the process for consistency, accuracy, and time efficiency. The current stage of automation is explained, including data acquisition processes and the automated vessel fit routine. Suggestions for the next generation of device minimization are also described.

Introduction: Oxygen delivery, or utilization, is a function of retinal blood flow and blood oxygen saturation. The retinal pigment epithelium (RPE), in particular, has been shown to have the highest levels of metabolic activity within the human body. Oxygen delivery is therefore of extreme importance to the maintenance of the health and integrity of the retina. Animal models presuppose that the oxygen tension in the retina is highest in the innermost layers at the level of the choriocapillaris, less in the photoreceptors and further decreases throughout the outer retinal structures. The choroid provides by far the largest component of the oxygen for consumption by the photoreceptors. A lack of oxygen stores in the inner retina therefore makes a constant supply crucial for its normal functioning. Blood flow dysfunction and subsequent hypoxia are both a feature in the pathogenesis of several major ocular diseases such as retinopathy of prematurity (ROP), age-related macular degeneration (ARMD), diabetic retinopathy (DR) and glaucoma. The development of methods to measure retinal blood flow and blood oxygen saturation is crucial to improve understanding of the patho-physiology of major ocular diseases. Purpose: The aims of this work were, firstly, to determine the least variable (range ± standard deviation) wavelength combination (610/548, 600/569 and 605/586) and subsequent ODR with the prototype HRC device. Secondly, using the ODR with the lowest measurement variability, we sought to quantify retinal blood SO2 in arterioles and venules and investigate the relationship between retinal blood SO2 and total retinal blood flow (TRBF) in response to stepwise changes in PETO2 in healthy participants. Retinal blood SO2 and TRBF were assessed using the IRIS HRC (Photon etc. Inc. Montreal, Canada) and the RTvue Doppler Fourier Domain OCT (Optovue Inc, Freemont, CA) instruments, respectively. Methods: Ten healthy participants between the ages of 23 and 37, with an average age of 28.3 years were evaluated in two descriptive cross-sectional studies. Two gas provocation protocols; hyperoxia (end-tidal oxygen; PETO2 of 100, 200, 300, 400mmHg) and hypoxia (PETO2 of 100, 80, 60, 50mmHg) were administered in a fixed sequential order. In each phase of gas provocation (via modulation of PETO2), retinal blood SO2 and TRBF measurements were acquired with the HRC and Doppler FD-OCT. The precise and repeated control of the partial end tidal pressures of oxygen (PETO2) and carbon dioxide (PETCO2) over the pre-determined phase duration, irrespective of the individuals’ respiratory rate, was made possible with the RespirAct (Thornhill Research Inc., Toronto, Canada); a sequential re-breathing gas delivery Results: In arterioles, the group range (±SD) of ODR values for baseline measurements (PETO2 of 100mmHg) was 0.169±0.061 for the 605/586 wavelength combination, 0.371±0.099 for the 600/569 wavelength combination and 0.340±0.104 for the 610/548 wavelength combination. In venules, the group range (±SD) of ODR values was 0.600±0.198 for the 605/586 wavelength combination, 0.569±0.169 for the 600/569 wavelength combination and 0.819±0.274 for the 610/548 wavelength combination. With the 605/586 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.607 ± 0.224 and 0.619 ± 0.158, respectively (p = 0.370), while in venules the group range (±SD) of ODR at baseline 1 and 2 was 0.289±0.750 and 0.284 ± 0.729, respectively (p = 0.714). For the 600/569 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.747±0.350 and 0.761±0.391, respectively (p = 0.424) while in venules the group range (±SD) of ODR at baseline 1 and 2 was 0.329±0.675 and 0.366±0.659, respectively (p = 0.372). For the 610/548 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.604±0.263 and 0.685±0.450, respectively (p = 0.056) while in venules, the group range (±SD) of ODR at baseline 1 and 2 was 0.292±0.746 and 0.285±1.009, respectively (p = 0.131). There was no statistical difference found between baseline ODR values (baseline 1 and 2) across all three wavelength combinations in both arterioles and venules. The mean retinal blood SO2 value at baseline in arterioles for 4 participants was 95.19% ± 31.04% and venules was 53.89% ± 17.24% (p = 0.115). There was a negative linear relationship between group retinal blood SO2 and TRBF values in the 10 participants studied, although the results of any of the 10 individuals did not show evidence of such a relationship using the described methodology. The Pearson’s correlation coefficient (r) between TRBF and SaO2 was r = -0.354 and p = 0.001 and between TRBF and SvO2 was r = - 0.295, p = 0.008 Conclusion: Of the three wavelength combinations investigated (605/586, 600/569 and 610/548), the 605/586 combination was shown to have the overall least variability. It would be unwise at this stage to adopt this wavelength combination for clinical usage, however, since it is presupposed that the 605/586 combination is also the most reliable combination to detect change in retinal blood SO2 i.e. lower variability of the 605/586 combination may be irrelevant if this combination proves to be insensitive to change in retinal blood SO2. The absolute mean ± SD retinal blood SO2 in the arterioles (SaO2) was 95.19% ± 31.04% and in the venules (SvO2) was 53.89% ± 17.24%. These values fell within the range expected and described in the literature. The magnitude of the difference between the SaO2 and SvO2 was also consistent with the literature. These findings were all appropriate for a low flow, high oxygen exchange vascular network typical of the inner retinal vascular system. Using group rather than individual data, TRBF was found in this study to relate inversely with SaO2 (r = -0.354 and p = 0.001) and SvO2 (r = – 0.295 and p=0.008), respectively. This relationship between TRBF and SaO2 and SvO2, was as expected based upon data derived primarily from animal models. This study is ground-breaking and unique, in that, it is the first study to concomitantly measure both retinal blood SO2 and TRBF in human participants. Individual data showed extensive variability and noise, thus limiting the strength of the association between TRBF and SaO2 and SvO2..

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 13, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 126-138).

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, 2007. / Bibliyografya var.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [145]-174).

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-11-10T16:30:55Z No. of bitstreams: 2 Dissertação - Luizmar Adriano Júnior - 2011.pdf: 4167499 bytes, checksum: 4e36a5a1dc0e88a79a75b9cc835c5185 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2014-11-10T16:31:04Z (GMT) No. of bitstreams: 2 Dissertação - Luizmar Adriano Júnior - 2011.pdf: 4167499 bytes, checksum: 4e36a5a1dc0e88a79a75b9cc835c5185 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-10T16:31:04Z (GMT). No. of bitstreams: 2 Dissertação - Luizmar Adriano Júnior - 2011.pdf: 4167499 bytes, checksum: 4e36a5a1dc0e88a79a75b9cc835c5185 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2011-03-03 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In this work we study the dipole moment, linear polarizability and first hiperpolarizability of 09cis, 11cis, 13cis and all-trans retinal derivatives in the gaseous phase and in different solvents. The solvent effects were modelled using the sequential Quantum Mechanics/Molecular Mechanics – S-QM/MM – methodology and the electric properties were calculated numerically with the finite field method. We use an average solvent electrostatic configuration – ASEC – to obtain the same statistical average with just one quantum mechanics calculation, instead of performing several quantum mechanics calculations for each one of the configurations of liquid. The second-order Møller–Plesset perturbation theory – MP2 – were used to describe the electronic structure. Our results show that the presence of the solvent increases the first hyperpolarizability of molecules of retinal [retinoic acid] by 17%-120% [5%-65%] when compared with corresponding gas phase results. It is found, in addition, that the dipole moment and the first hyperpolarizability are particularly affected by changes in the polarity and nature of solvent. A comparative analysis between cis and trans retinal derivatives shows that the isomerization effects have a marked influence on both the dipole moment and the average first hyperpolarizability. / Neste trabalho estudamos o momento de dipolo, a polarizabilidade linear, e a primeira hiperpolarizabilidade de derivados de retinal 09cis, 11cis, 13cis e todo-trans em fase gasosa e diferentes solventes. Os efeitos de solvente foram modelados usando a metodologia seqüencial Mecânica Quântica/Mecânica Molecular - S-QM/MM - e as propriedades elétricas foram calculadas numericamente com o método de campo finito. Usamos uma configuração eletrostática média de solvente – ASEC – para obter a mesma média estatística com apenas um cálculo de mecânica quântica, ao invés de realizar diversos cálculos de mecânica quântica para cada uma das configurações de líquido. A teoria de perturbação de Møller–Plesset de segunda ordem - MP2 - foi usada para descrever a estrutura eletrônica. Nossos resultados mostram que a presença do solvente aumenta a primeira hiperpolarizabilidade de moléculas de retinal [ácido retinóico] em 17%-120% [5%-65%] quando comparados com os correspondentes resultados de fase gasosa. É encontrado, além disso, que o momento de dipolo e a primeira hiperpolarizabilidade são particularmente afetados pela mudança na polaridade e natureza do solvente. Uma análise comparativa entre derivados de retinal cis e trans mostra que os efeitos de isomerização têm uma influência marcante sobre ambos, o momento de dipolo e a primeira hiperpolarizabilidade média.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22119号 / 医博第4532号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 Shohab YOUSSEFIAN, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Yes / Recent developments in optical coherence tomography (OCT) technology enable direct enface visualisation of retinal nerve fibre bundle (RNFB) loss in glaucoma. However, the optimum depth at which to visualise RNFBs across the retina is unknown. We aimed to evaluate the range of depths and optimum depth at which RNFBs can be visualised across the retina in healthy eyes. The central ± 25° retina of 10 healthy eyes from 10 people aged 57–75 years (median 68.5 years) were imaged with spectral domain OCT. Slab images of maximum axial resolution (4 μm) containing depth‐resolved attenuation coefficients were extracted from 0 to 193.5 μm below the inner limiting membrane (ILM). Bundle visibility within 10 regions of a superimposed grid was assessed subjectively by trained optometrists (n = 8), according to written instructions. Anterior and posterior limits of RNFB visibility and depth of best visibility were identified for each grid sector. Effects of retinal location and individual eye on RNFB visibility were explored using linear mixed modelling with likelihood ratio tests. Intraclass correlation coefficient (ICC) was used to measure overall agreement and repeatability of grading. Spearman’s correlation was used to measure correlation between depth range of visible RNFBs and retinal nerve fibre layer thickness (RNFLT). Retinal location and individual eye affected anterior limit of visibility (χ2(9) = 58.6 and 60.5, both p < 0.0001), but none of the differences exceeded instrument resolution, making anterior limit consistent across the retina and different eyes. Greater differences were observed in the posterior limit of visibility across retinal areas (χ2(9) = 1671.1, p < 0.0001) and different eyes (χ2(9) = 88.7, p < 0.0001). Optimal depth for visualisation of RNFBs was around 20 µm below the ILM in most regions. It varied slightly with retinal location (χ2(9) = 58.8, p < 0.0001), but it was not affected by individual eye (χ2(9) = 10.7, p = 0.29). RNFB visibility showed good agreement between graders (ICC 0.89, 95%CI 0.87–0.91), and excellent repeatability (ICC 0.96–0.99). Depth range of visible RNFBs was highly correlated with RNFLT (ρ = 0.9, 95%CI: 0.86–0.95). The range of depths with visible RNFBs varies markedly across the healthy retina, consistently with RNFLT. To extract all RNFB information consistently across the retina, slab properties should account for differences across retinal locations and between individual eyes. / This work was supported by a College of Optometrists Research Fellowship (JD).