Early diagnosis of retinal diseases such as glaucoma will benefit from unbiased an precise estimation of both optical and structural properties of the RNFL as they provide a better understanding of the tissue characteristics. The main objective of this thesis was first to improve the estimation of the attenuation coefficients of layered samples and, second, to estimate the structural properties of RNFL. Unbiased estimation of optical tissue properties such as the attenuation coefficient require a model of the recorded OCT signal. To study the characteristics of the OCT signal, in Chapter 2, two simulation methods were presented for homogeneous samples. In both methods single-scattering of the OCT light was assumed and the effect of the shape of OCT beam was taken into account. The more complex simulation also takes into account the interference of the electrical fields in the sample and reference arms and several post processing steps. Later in this thesis the simpler model was used to model the OCT signal since both simulation methods generated similar results. In Chapter 3, we improved an existing depth-resolved method to estimate the attenuation coefficients. The existing method does not handle noise at the larger depths, where the OCT light is fully attenuated, which results in a variation of the estimated attenuation coefficient values. We introduced a technique to detect and exclude the noise regions from the OCT scans to improve the accuracy and reduce the Aline-by-Aline variation of the estimated attenuation coefficients. The results show a better accuracy of the estimated attenuation coefficient, especially in sub-RPE regions and a better quality of the attenuation coefficient images. In Chapter 4, a method was presented to estimate the attenuation coefficients of a homogeneous medium accounting for the shape of the focused light beam. For this, the model presented in Chapter 2 was fitted to the measured OCT signal of a homogeneous sample to estimate the model parameters. The presented method was first implemented for the semi-infinite samples and was tested for different concentrations of TiO2 in silicone for different locations of focus. In addition, a statistical and numerical analysis was performed to evaluate the presented method under various experimental conditions. The estimation result shows a reasonable correlation between the TiO2 weight-concentration and the estimated attenuation coefficient. While the method could estimate the attenuation coefficients of a uniform samples, most biological tissues such as the retina are layered, hence the method was extended in Chapter 5 to estimate the attenuation coefficients of the multi-layer samples. This method was tested on the simulation and measurements of a multi-layer phantom with different concentration of TiO2 in silicone with two systems: one with a small (40 μm) and one with a larger (300 μm) Rayleigh length. The numerical results show an acceptable estimation of the attenuation coefficients for the Rayleigh lengths less than 0.5 mm in air and acceptable for clinical application using clinical OCT systems. For both single- and multi-layer samples, a linear relation between the estimated attenuation coefficients and the particle concentration of the perspective layer was observed while using single and multiple B-scans. In Chapter 6, an automatic technique was developed to estimate the orientation of RNFBs from volumetric OCT scans. The RNFB orientations of six macular scans from three subjects were used to evaluate the results. We observed a good correlation between the manual tracing and the estimated orientations of the RNFLs. RNFBs orientation in combination with other techniques such as VF and SAP can assist the ophthalmologists to have a more reliable measurement for an early diagnosis of retinal diseases such as glaucoma.@en

Optical properties, such as the attenuation coefficients of multi-layer tissue samples, could be used as a biomarker for diagnosis and disease progression in clinical practice. In this paper, we present a method to estimate the attenuation coefficients in a multi-layer sample by fitting a single scattering model for the OCT signal to the recorded OCT signal. In addition, we employ numerical simulations to obtain the theoretically achievable precision and accuracy of the estimated parameters under various experimental conditions. Finally, the method is applied to two sets of measurements obtained from a multi-layer phantom by two experimental OCT systems: One with a large and one with a small Rayleigh length. Numerical and experimental results show an accurate estimation of the attenuation coefficients when using multiple B-scans.

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The attenuation coefficient (AC) is an optical property of tissue that can be estimated from optical coherence tomography (OCT) data. In this paper, we aim to estimate the AC accurately by compensating for the shape of the focused beam. For this, we propose a method to estimate the axial PSF model parameters and AC by fitting a model for an OCT signal in a homogenous sample to the recorded OCT signal. In addition, we employ numerical analysis to obtain the theoretical optimal precision of the estimated parameters for different experimental setups. Finally, the method is applied to OCT B-scans obtained from homogeneous samples. The numerical and experimental results show accurate estimations of the AC and the focus location when the focus is located inside the sample.

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PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes.

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The attenuation coefficient (AC) is a property related to the microstructure of tissue on a wavelength scale that can be estimated from optical coherence tomography (OCT) data. Since the OCT signal sensitivity is affected by the finite spectrometer/detector resolution called roll-off and the shape of the focused beam in the sample arm, ignoring these effects leads to severely biased estimates of AC. Previously, the signal intensity dependence on these factors has been modeled. In this paper, we study the dependence of the estimated AC on the beam-shape and focus depth experimentally. A method is presented to estimate the axial point spread function model parameters by fitting the OCT signal model for single scattered light to the averaged A-lines of multiple B-scans obtained from a homogeneous single-layer phantom. The estimated model parameters were used to compensate the signal for the axial point spread function and roll-off in order to obtain an accurate estimate of AC. The result shows a significant improvement in the accuracy of the estimation of AC after correcting for the shape of the OCT beam.@en

Thinning of the retinal nerve fiber layer (RNFL) is a recently discovered feature of Parkinson’s disease (PD). Its exact pathological mechanism is yet unknown. We aimed to determine whether morphological changes of the RNFL are limited to RNFL thinning or also comprise an altered internal structure of this layer. Therefore, we investigated RNFL thickness and applied the RNFL attenuation coefficient (RNFL-AC), a novel method derived from optical coherence tomography, in PD patients and healthy controls (HCs). In this pilot study, we included 20 PD patients and 20 HCs matched for age, sex, and ethnicity. An ophthalmologist investigated all participants thoroughly, and we acquired retinal images from both eyes of each participant with a Spectralis optical coherence tomography system. We obtained both the RNFL-AC and RNFL thickness from peripapillary RNFL scans for the entire RNFL, as well as for each quadrant separately. We found no significant differences in the average RNFL-AC or the RNFL-AC of the separate retinal quadrants between PD patients and the HC group. However, compared to the HC group, PD patients had a significantly thinner RNFL in the temporal retinal quadrant. RNFL thinning was found in the temporal quadrant in PD patients without a corresponding change in the RNFL-AC. These findings suggest a reduction in the number of RNFL axons (atrophy) without other major changes in the structural integrity of the remaining RNFL.

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Optical coherence tomography (OCT) yields high-resolution, three-dimensional images of the retina. A better understanding of retinal nerve fiber bundle (RNFB) trajectories in combination with visual field data may be used for future diagnosis and monitoring of glaucoma. However, manual tracing of these bundles is a tedious task. In this work, we present an automatic technique to estimate the orientation of RNFBs from volumetric OCT scans. Our method consists of several steps, starting from automatic segmentation of the RNFL. Then, a stack of en face images around the posterior nerve fiber layer interface was extracted. The image showing the best visibility of RNFB trajectories was selected for further processing. After denoising the selected en face image, a semblance structure-oriented filter was applied to probe the strength of local linear structure in a discrete set of orientations creating an orientation space. Gaussian filtering along the orientation axis in this space is used to find the dominant orientation. Next, a confidence map was created to supplement the estimated orientation. This confidence map was used as pixel weight in normalized convolution to regularize the semblance filter response after which a new orientation estimate can be obtained. Finally, after several iterations an orientation field corresponding to the strongest local orientation was obtained. The RNFB orientations of six macular scans from three subjects were estimated. For all scans, visual inspection shows a good agreement between the estimated orientation fields and the RNFB trajectories in the en face images. Additionally, a good correlation between the orientation fields of two scans of the same subject was observed. Our method was also applied to a larger field of view around the macula. Manual tracing of the RNFB trajectories shows a good agreement with the automatically obtained streamlines obtained by fiber tracking.@en

The attenuation coefficient (AC) is a tissue property that can be estimated from optical coherence tomography (OCT) data. We observed that excessive noise below the retina might cause both an underestimation and a significant variation of the estimated AC values by a state-of-the-art algorithm. Two methods were proposed to reduce these effects: I) by removing the average noise signal from the OCT data; II) by excluding the detected noise region below the retina. The methods were applied to four circular peripapillary retinal scans of a healthy subject. We evaluated all methods quantitatively using metrics for the inter- and intra-A-lines variation of the estimated ACs. Both methods resulted in higher ACs thereby reducing the bias. However, only method II succeeded in reducing the amount of variation by both metrics; method I made things worse. In conclusion, method II yields a more robust and more precise estimate of the AC, in particular for the choroid and sclera, compared to the baseline method.@en