LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS.

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.

In vivo exploration of retinal nerve fiber layer morphology in Parkinson's disease patients.

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.

Attenuation coefficient estimation in Fourier-domain OCT of multi-layered phantoms.

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.

Analysis of attenuation coefficient estimation in Fourier-domain OCT of semi-infinite media.

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.

Predictive modeling of cardiac fiber orientation using the Knutsson mapping.

The construction of realistic subject-specific models of the myocardial fiber architecture is relevant to the understanding and simulation of the electromechanical behavior of the heart. This paper presents a statistical approach for the prediction of fiber orientation from myocardial morphology based on the Knutsson mapping. In this space, the orientation of each fiber is represented in a continuous and distance preserving manner, thus allowing for consistent statistical analysis of the data. Furthermore, the directions in the shape space which correlate most with the myocardial fiber orientations are extracted and used for subsequent prediction. With this approach and unlike existing models, all shape information is taken into account in the analysis and the obtained latent variables are statistically optimal to predict fiber orientation in new datasets. The proposed technique is validated based on a sample of canine Diffusion Tensor Imaging (DTI) datasets and the results demonstrate marked improvement in cardiac fiber orientation modeling and prediction.