Yes / Purpose: We have developed customized maps that relate visual field and optic nerve head (ONH) regions according to individual anatomy. In this study, we aimed to determine feasible map resolution for research use, and to make a principled recommendation of sector size for clinical applications. Methods: Measurement variability in fovea–ONH distance and angle was estimated from 10 repeat OCT scans of 10 healthy people. Errors in estimating axial length from refractive error were determined from published data. Structure–function maps were generated, and customized to varied clinically-plausible anatomical parameters. For each parameter set (n = 210), 200 maps were generated by sampling from measurement/estimation error distributions. Mapped 1° sectors at each visual field location from each parameter set were normalized to difference from their mean. Variation (90% ranges) in normalized mapped sectors represents the precision of individualized maps. Results: Standard deviations of repeated measures of fovea–ONH distance and angle were 61 μm and 0.97° (coefficients of variation 1.3% and 12.0%, respectively). Neither measure varied systematically with mean (Spearmans's ρ = 0.26, P = 0.47 for distance, ρ = −0.31, P = 0.39 for angle). Variation (90% ranges) in normalized mapped sectors varied across the visual field and ranged from 3° to 18° when axial length was measured accurately, and from 6° to 32° when axial length was estimated from refractive error. Conclusions: The 90% ranges represent the minimum feasible ONH sector size at each visual field location. For clinical use an easily interpretable scheme of 30° sectors is suggested.

No / Purpose To determine whether the structure–function relationship in glaucoma can be strengthened by using more precise structural and functional measurements combined with individualized structure–function maps and custom sector selection on the optic nerve head (ONH). Design Cross-sectional study. Participants One eye of each of 23 participants with glaucoma. Methods Participants were tested twice. Visual fields were collected on a high-resolution 3° × 3° grid (164 locations) using a Zippy Estimation by Sequential Testing test procedure with uniform prior probability to improve the accuracy and precision of scotoma characterization relative to standard methods. Retinal nerve fiber layer (RNFL) thickness was measured using spectral-domain optical coherence tomography (OCT; 4 scans, 2 per visit) with manual removal of blood vessels. Individualized maps, based on biometric data, were used. To customize the areas of the ONH and visual field to correlate, we chose a 30° sector centered on the largest defect shown by OCT and chose visual field locations using the individualized maps. Baseline structure–function correlations were calculated between 24-2 locations (n = 52) of the first tested visual field and RNFL thickness from 1 OCT scan, using the sectors of the Garway-Heath map. We added additional data (averaged visual field and OCT, additional 106 visual field locations and OCT without blood vessels, individualized map, and customized sector) and recomputed the correlations. Main Outcome Measures Spearman correlation between structure and function. Results The highest baseline correlation was 0.52 (95% confidence interval [CI], 0.13–0.78) in the superior temporal ONH sector. Improved measurements increased the correlation marginally to 0.58 (95% CI, 0.21–0.81). Applying the individualized map to the large, predefined ONH sectors did not improve the correlation; however, using the individualized map with the single 30° ONH sector resulted in a large increase in correlation to 0.77 (95% CI, 0.47–0.92). Conclusions Using more precise visual field and OCT measurements did not improve structure–function correlation in our cohort, but customizing the ONH sector and its associated visual field points substantially improved correlation. We suggest using customized ONH sectors mapped to individually relevant visual field locations to unmask localized structural and functional loss.

Glaucoma is the second leading cause of blindness worldwide. The clinical standard for monitoring the functional deficits in the retina that are caused by glaucoma is the visual field test. In addition to monitoring the functional loss, evaluating the disease-related structural changes in the human retina also helps with diagnosis and management of this progressive disease. The characteristic changes of retinal structures such as the optic nerve head (ONH) are monitored utilizing imaging modalities such as color (stereo) fundus photography and, more recently, spectral-domain optical coherence tomography (SD-OCT). With the inherent subjectivity and time required for manually segmenting retinal structures, there has been a great interest in automated approaches. Since both fundus and SD-OCT images are often acquired for the assessment of glaucoma, the automated segmentation approaches can benefit from combining the multimodal complementary information from both sources. The goal of the current work is to automatically segment the retinal structures and extract the proper parameters of the optic nerve head related to the diagnosis and management of glaucoma. The structural parameters include the cup-to-disc ratio (CDR) which is a 2D parameter and is obtainable from both fundus and SD-OCT modalities. Bruch's membrane opening-minimum rim width (BMO-MRW) is a recent 3D structural parameter that is obtainable from the SD-OCT modality only. We propose to use the complementary information from both fundus and SD-OCT modalities in order to enhance the segmentation of structures of interest. In order to enable combining information from different modalities, a feature-based registration method is proposed for aligning the fundus and OCT images. In addition, our goal is to incorporate the machine-learning techniques into the graph-theoretic approach that is used for segmenting the structures of interest. Thus, the major contributions of this work include: 1) use of complementary information from SD-OCT and fundus images for segmenting the optic disc and cup boundaries in both modalities, 2) identifying the extent that accounting for the presence of externally oblique border tissue and retinal vessels in rim-width-based parameters affects structure-structure correlations, 3) designing a feature-based registration approach for registering multimodal images of the retina, and 4) developing a multimodal graph-based approach to segment the optic nerve head (ONH) structures such as Internal Limiting Membrane (ILM) surface and Bruch's membrane surface's opening.

Glaucoma is a leading cause of irreversible blindness worldwide. Primary Open Angle Glaucoma is the most common form of the disease and can be characterized by the slow and irreversible apoptotic death of retinal ganglion cells, a unique optic nerve neuropathy resulting in loss of vision. Increased intra-ocular pressure is known to be a leading risk-factor for glaucoma, and lowering IOP is currently the only evidence based method for the clinical management of the disease. However the exact mechanism by which an elevated IOP leads to the death of the retinal ganglion cells is still poorly understood. By using previous finite element models of glaucoma to quantify the biomechanical environment within the optic nerve head we have built human primary cell culture models in an attempt to replicate aspects of early glaucomatous optic neuropathy. In these models we mimic the in vivo biomechanical environment in the lamina cribrosa by growing human optic nerve head astrocytes and lamina cribrosa cells on compliant substrates and subjecting the cells to deformation. Specifically, a global protein scan using isobaric tags for relative and absolute quantitation (iTRAQ) was performed on all the experiments to identify potential biomarkers for glaucoma. A secondary analysis using enzyme-linked immunosorbent assay (ELISA) identified extracellular proteins of interest. Over 520 proteins were identified in response to biomechnical strain from both cell types. Many of these proteins centred on TGF-, p53 and TNF, which have previously been shown to play a role in the pathogenesis of glaucoma. Proteins found in astrocytes were astrocytic phosphoprotein (PEA15), UDP-glucose dehydrogenase (UGDH), and annexin A4 (ANXA4). LC proteins were bcl-2-associated athanogene 5 (BAG5), nucleolar protein 66 (NO66) and Eukaryotic translation initiation factor 5A (eIF-5A). These proteomic results will enable a series of functional studies looking into the role select markers play in ONH glial cell activation, a process still not well understood. Candidates for this work will be prioritized based on novelty and relevance to mechanisms of cellular stress and death. We hypothesize that study of these molecular pathways will provide insight into this process, as well as improve our understanding of how glial activation contributes to the development of glaucomatous optic neuropathy.

Glaucoma is a leading cause of irreversible blindness worldwide. Primary Open Angle Glaucoma is the most common form of the disease and can be characterized by the slow and irreversible apoptotic death of retinal ganglion cells, a unique optic nerve neuropathy resulting in loss of vision. Increased intra-ocular pressure is known to be a leading risk-factor for glaucoma, and lowering IOP is currently the only evidence based method for the clinical management of the disease. However the exact mechanism by which an elevated IOP leads to the death of the retinal ganglion cells is still poorly understood. By using previous finite element models of glaucoma to quantify the biomechanical environment within the optic nerve head we have built human primary cell culture models in an attempt to replicate aspects of early glaucomatous optic neuropathy. In these models we mimic the in vivo biomechanical environment in the lamina cribrosa by growing human optic nerve head astrocytes and lamina cribrosa cells on compliant substrates and subjecting the cells to deformation. Specifically, a global protein scan using isobaric tags for relative and absolute quantitation (iTRAQ) was performed on all the experiments to identify potential biomarkers for glaucoma. A secondary analysis using enzyme-linked immunosorbent assay (ELISA) identified extracellular proteins of interest. Over 520 proteins were identified in response to biomechnical strain from both cell types. Many of these proteins centred on TGF-, p53 and TNF, which have previously been shown to play a role in the pathogenesis of glaucoma. Proteins found in astrocytes were astrocytic phosphoprotein (PEA15), UDP-glucose dehydrogenase (UGDH), and annexin A4 (ANXA4). LC proteins were bcl-2-associated athanogene 5 (BAG5), nucleolar protein 66 (NO66) and Eukaryotic translation initiation factor 5A (eIF-5A). These proteomic results will enable a series of functional studies looking into the role select markers play in ONH glial cell activation, a process still not well understood. Candidates for this work will be prioritized based on novelty and relevance to mechanisms of cellular stress and death. We hypothesize that study of these molecular pathways will provide insight into this process, as well as improve our understanding of how glial activation contributes to the development of glaucomatous optic neuropathy.

Abstract Glaucoma is a progressive neuropathy of the optic nerve. It causes degeneration of ganglion cell axons resulting in defects in the retinal nerve fibre layer (RNFL) and characteristic changes in the optic nerve head (ONH). The Heidelberg Retina Tomograph (HRT) is a confocal scanning laser imaging device, which measures the topography of the ONH and the adjacent RNFL. To quantify the measurements of the ONH topography, various stereometric parameters are calculated. The change in the stereometric parameters of the HRT was studied in 34 eyes with glaucomatous progression in RNFL photographs and 34 eyes without progression. The change in only one stereometric parameter, the cup shape measure, showed a statistically significant correlation with the progression of the RNFL defect. An optimised change in the best three-parameter combination had 77% sensitivity and 79% specificity for progression. The change in the stereometric parameters was compared in 51 eyes with glaucomatous progression in stereoscopic ONH photographs and 425 eyes without progression. The parameters having the best correlation with progression include cup:disc area ratio, vertical cup:disc ratio, cup volume and rim area. The parameter with the largest area under the receiver operating characteristics curve (0.726) was the vertical cup:disc ratio. A change of 0.007 in the vertical cup:disc ratio had a sensitivity of 80% and a specificity of 65% for progression. The factors having the most significant effect on the sensitivity and specificity of the stereometric parameters for progression were the reference height difference and the mean topography standard deviation, indicating image quality. The change in image quality and age also showed a consistent, but variably significant influence on all parameters tested. Exercise was associated with an increase in variance in 17 of the 18 stereometric parameters. In conclusion, the change in the stereometric parameters provides useful information on ONH topography, especially when image quality is excellent. However, the evaluation of glaucomatous progression should not rely solely on the stereometric parameters of the HRT.

Visual field tests are routinely used for the detection and management of glaucoma. This thesis focuses on monitoring the vigilance during perimetry with pupil dynamics (pupillary movements, blinks) in glaucoma patients and the performance of using subsets of standard test patterns at detecting glaucomatous field loss. It describes the spatial pattern of visual field changes in diabetic retinopathy patients after treatment and the usage of multispectral imaging of the optic nerve head in glaucoma patients.The first investigation evaluated the use of pupillary parameters (pupil size and amplitude of pupillary oscillations) to monitor vigilance during perimetry in comparison to electroencephalography. A significant correlation was observed between the decreased pupil size and increased slow brain activities (theta and alpha). The inter-test threshold variability correlated with the pupil miosis.Another investigation explored blinks during a perimetric test and their relationship to the variability of threshold sensitivity in glaucoma patients. A wide range of blink frequencies was observed in glaucoma patients during perimetry and the timing of blinks was correlated with the stimuli presentations when they were supra-threshold. No significant relationship was observed between the threshold sensitivity variability and blink parameters (frequency, duration and microsleep numbers).The third investigation evaluated the use of subset of the 24-2 visual field test pattern at detecting glaucomatous field loss. A high sensitivity and specificity was observed when using subsets of the 24-2 pattern and test locations optimized by the positive predictive values showed a better performance than the test locations in random sequences.With the usage of a self-organized mapping method, nine spatial patterns of visual field loss in untreated diabetic retinopathy patients were classified. After laser treatment, a significant improvement on the spatial patterns of field loss and global indices was found.In the multispectral imaging study, the haemoglobin dependent differential light absorption (DLA) properties of the glaucomatous optic nerve head was evaluated with multispectral imaging. Change of DLA after medical hypotensive treatment was graded by five experts and no difference was observed in most of the patients.

The aim of this thesis was to design and implement the interactive Java applet used for topography 3D optic nerve head visualization. Primary purpose of the 3D vizualization is ophthalmology, especially for diagnosis of glaucoma. More over should serve as a training material, which enables to study the transformation of 2D figures to 3D model and to test the effects of adjustments and regulations to imaging of the model in 3D space. Two program versions were designed in this work using the development system NetBeans version 5.5. Their final realization is implemented as .html application working in web browser window. First version of the designed applet is simple intuitive application with several default settings, so that the figure is opened automatically to 3D model. Subsequently, the applet enables to set the size of the image, 3D depth of the image, smoothing of the surface and selection of monochrome or coloured image. The second version is the extension of the first version of the designed applet, and provides the possibility to display x, y, z axis, depiction of the 3D model surface by dots, curves or grid, and illumination of the surface. Software was tested on available topographic data acquired by HRT equipment and in different web browsers. Technical documentation and user’s manual are also involved in this thesis.

This work is focused on detection of loss in nerve fibre layer on colour pictures of retina, witch are makes by fundus camera. It describe every simple objects of retina, optic nerve head, macula lutea and vascular bed. It detect optic nerve head and his near area, witch is general for detection of breakdownds. It use several metodes of picture adjusting for picture elaboration and objects detection (segmentation, thresholding, enhancement, hough transformation ). The detection of loss in nerve fibre layer is based on comparing of statistic parameters ( average, standart deviation, skewness coefficient and kurtosis coefficient histogram, entropy ) in choosed areas with and withou destruction of nerve layers. Vascular bed have badwatsh on results, cause of this we using hand choosing of essay.

Yes / Purpose: Inter-individual variance in optic nerve head (ONH) position, axial length and location of the temporal raphe suggest that customizing mapping between visual field locations and optic nerve head sectors for individuals may be clinically useful. Here we quantify the proportion of the population predicted to have structure-function mappings that markedly deviate from “average”, and thus would benefit from customized mapping. Design: Database study and case report Participants: Population database of 2836 eyes from the Beijing Eye Study; single case report of an individual with primary open angle glaucoma Methods: Using the morphometric fundus data of the Beijing Eye Study on 2836 eyes and applying a recently developed model based on axial length and ONH position relative to the fovea, we determined for each measurement location in the 24-2 Humphrey visual field the proportion of eyes for which, in the customized approach as compared to the generalized approach, the mapped ONH sector was shifted into a different sector. We determined the proportion of eyes for which the mapped ONH location was shifted by 15°, 30° or 60°. Main outcome measures: Mapping correspondence between locations in visual field space to localized sectors on the optic nerve head Results: The largest inter-individual differences in mapping are in the nasal step region where the same visual field location can map to either the superior or inferior ONH depending on other anatomical features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. Conclusions: Anatomically customised mapping shifts the map markedly in approximately 12% of the general population in the nasal step region where visual field locations can map to the opposite pole of the ONH than conventionally considered. Early glaucomatous damage commonly affects this region, hence individually matching structure to function may prove clinically useful for the diagnosis and monitoring of progression within individuals. / Australian Research Council Linkage Project 130100055 (industry partner, Heidelberg Engineering, GmBH, Germany).