Thesis (Ph. D.)--University of Florida, 2003. / Title from title page of source document. Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Florida, 2003. / Title from title page of source document. Includes vita. Includes bibliographical references.

Licentiatavhandling (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 2 uppsatser.

Introduction: Inherited retinal diseases (IRDs) are one of the most common causes of incurable blindness in children and young adults. In the Czech Republic, prior to the start of our work, these disorders had not been the subject of a systematic research. The aim of the study was to identify, clinically characterize and molecular genetically analyse Czech patients with monogenic IRDs and based on the knowledge gained subsequently implement preventive and therapeutic measures to clinical practice. Material and methods: We have performed a comprehensive clinical examination, genealogical analysis and molecular genetic investigation in patients with IRDs and their family members. Detailed ocular examination included spectral domain optical coherence tomography, high-resolution fundus photography and autofluorescence imaging. DNA was isolated from venous blood samples or buccal cells. Causal variants were searched for using Sanger and massively parallel sequencing, and their pathogenicity was evaluated in the context of previously published data, bioinformatical analysis and segregation in available family members. Results: In total, 103 individuals from 76 Czech families diagnosed with IRDs were characterized and their data published. Specifically, we have described clinical and molecular genetic...

No description available.

Yes / Fundus-controlled perimetry (FCP, also called 'microperimetry') allows for spatially-resolved mapping of visual sensitivity and measurement of fixation stability, both in clinical practice as well as research. The accurate spatial characterization of visual function enabled by FCP can provide insightful information about disease severity and progression not reflected by best-corrected visual acuity in a large range of disorders. This is especially important for monitoring of retinal diseases that initially spare the central retina in earlier disease stages. Improved intra- and inter-session retest-variability through fundus-tracking and precise point-wise follow-up examinations even in patients with unstable fixation represent key advantages of these technique. The design of disease-specific test patterns and protocols reduces the burden of extensive and time-consuming FCP testing, permitting a more meaningful and focused application. Recent developments also allow for photoreceptor-specific testing through implementation of dark-adapted chromatic and photopic testing. A detailed understanding of the variety of available devices and test settings is a key prerequisite for the design and optimization of FCP protocols in future natural history studies and clinical trials. Accordingly, this review describes the theoretical and technical background of FCP, its prior application in clinical and research settings, data that qualify the application of FCP as an outcome measure in clinical trials as well as ongoing and future developments.

The retina is a thin layer of tissue lining the back of the eye and is primarily responsible for sight in vertebrates. The neural retina has a distinct layered structure with three dense nuclear layers, separated by plexiform layers comprising of axons and dendrites, and a layer of photoreceptor segments. The retinal and choroidal vasculatures nourish the retina from either side, with an avascular layer comprised largely of photoreceptor cells. Diseases that directly affect the neural retina like retinal degeneration as well as those of vascular origin like diabetic retinopathy can lead to partial or total blindness. Early detection of these diseases can potentially pave the way for a timely intervention and improve patient prognosis. Current techniques of retinal imaging rely mainly on optical techniques, which have limited depth resolution and depend mainly on the clarity of visual pathway. Magnetic resonance imaging is a versatile tool that has long been used for anatomical and functional imaging in humans and animals, and can potentially be used for retinal imaging without the limitations of optical methods. The work reported in this thesis involves the development of high resolution magnetic resonance imaging techniques for anatomical and functional imaging of the retina in rats. The rats were anesthetized using isoflurane, mechanically ventilated and paralyzed using pancuronium bromide to reduce eye motion during retinal MRI. The retina was imaged using a small, single-turn surface coil placed directly over the eye. The several physiological parameters, like rectal temperature, fraction of inspired oxygen, end-tidal CO2, were continuously monitored in all rats. MRI parameters like T1, T2, and the apparent diffusion coefficient of water molecules were determined from the rat retina at high spatial resolution and found to be similar to those obtained from the brain at the same field strength. High-resolution MRI of the retina detected the three layers in wild-type rats, which were identified as the retinal vasculature, the avascular layer and the choroidal vasculature. Anatomical MRI performed 24 hours post intravitreal injection of MnCl2, an MRI contrast agent, revealed seven distinct layers within the retina. These layers were identified as the various nuclear and plexiform layers, the photoreceptor segment layer and the choroidal vasculature using Mn54Cl2emulsion autoradiography. Blood-oxygenlevel dependent (BOLD) functional MRI (fMRI) revealed layer-specific vascular responses to hyperoxic and hypercapnic challenges. Relative blood volume of the retina calculated by using microcrystalline iron oxide nano-colloid, an intravascular contrast agent, revealed a superfluous choroidal vasculature. Fractional changes to blood volume during systemic challenges revealed a higher degree of autoregulation in the retinal vasculature compared to the choroidal vasculature, corroborating the BOLD fMRI data. Finally, the retinal MRI techniques developed were applied to detect structural and vascular changes in a rat model of retinal dystrophy. We conclude that retinal MRI is a powerful investigative tool to resolve layerspecific structure and function in the retina and to probe for changes in retinal diseases. We expect the anatomical and functional retinal MRI techniques developed herein to contribute towards the early detection of diseases and longitudinal evaluation of treatment options without interference from overlying tissue or opacity of the visual pathway.

Retinal degenerative disease are the leading cause of vision loss in adult patients. Important role in the development of these types of disease play gradual death of retinal cells and an inflammatory reaction that leads to the production of cytokines, formation of inflamasome, increased angiogenesis and scar formation. These pathologies result in irreversible degeneration of retinal cells. Retinal pigmenetd epithelium cells, photoreceptors and ganglion cells are the most frequently damaged cell types in this conditions. The available treatments are currently very limited and effective only at the early stages of the disease. Therefore, the use of stem cell- based therapy could be a promising option. For therapeutic purposes it would be possible to use mesenchymal stem cells (MSCs) which may be isolated for example from bone marrow or adipose tissue. MSCs are capable of production of neuroprotective factors, differentiation into the variety of cells types and regulation of immune response. In this study we tested the therapeutic potential of MSC administered locally to the damaged retina in an experimental model of retinal degeneration. We focused on the protective effect of MSCs on photoreceptor cells, regulation of the local immune response and expression of genes for cytokines involved in...

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No / PURPOSE: To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS: Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS: A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 x 6-mm area with a resolution of 256 x 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES: Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS: Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 mum; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 mum; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS: Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.