Serum Amyloid A, C-reactive Protein and Retinal Microvascular Changes in Hypertensive Diabetic and Non-diabetic Individuals: An ASCOT Substudy

To study the association of the inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) with retinal microvascular parameters in hypertensive individuals with and without type 2 diabetes.

Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia

Our previous data suggested that angiopoietin-2 (Ang-2) is linked to pericyte loss, thereby playing an important role in diabetic retinopathy. In this study, we investigated the effect of retinal overexpression of human Ang-2 (mOpsinhAng2 mouse) on vascular morphology in non-diabetic and streptozotozin-induced diabetic animals. Pericyte (PC) coverage and acellular capillary (AC) formation were quantitated in retinal digest preparations after 3 and 6 months of diabetes duration. The degree of retinopathy in non-diabetic mOpsinhAng2 mice at 3 months (-21% PC, +49% AC) was comparable to age-matched diabetic wild type mice. Diabetic mOpsinhAng2 mice exhibited significantly worse vascular pathology than wild type counterparts at 6 months. Quantitative PCR revealed that human Ang-2 mRNA was highly overexpressed in retinas of transgenic mice. Our data demonstrate that overexpression of Ang-2 in the retina enhances vascular pathology, indicating that Ang-2 plays an essential role in diabetic vasoregression via destabilization of pericytes.

Retinal thickness in Parkinson's disease

BACKGROUND: Visual symptoms are common in Parkinson's disease with studies consistently demonstrating reductions in visual acuity, contrast sensitivity, colour and motion perception as well as alterations in electroretinogram latencies and amplitudes. Optical coherence tomography can examine retinal structure non-invasively and retinal thinning has been suggested as a potential biomarker for neurodegeneration in Parkinson's disease. Our aim was to examine the retinal thickness of a cohort of Parkinson's disease subjects (and age-matched controls) to establish the practical utility of optical coherence tomography in a representative older Parkinson's disease group. METHODS: Fifty-one established Parkinson's disease subjects and 25 healthy controls were subjected to ophthalmological assessment and optical coherence tomography (Zeiss Stratus 3000™) of macular thickness and volume and retinal nerve fibre thickness around the optic nerve head. Twenty four percent of control and 20% of Parkinson's disease subjects were excluded from final analysis due to co-morbid ocular pathology. Further data was excluded either due to poor tolerability of optical coherence tomography or poor quality scans. RESULTS: Despite a reduction in both visual acuity and contrast sensitivity in the residual evaluable Parkinson's disease cohort, we did not detect any differences between the two study groups for any measures of retinal thickness, in contrast to previously published work. CONCLUSIONS: In addition to technical problems inherent in the evaluation, the lack of difference between Parkinson's disease and healthy control subjects suggests longitudinal studies, employing newer techniques, will be required to define the role of optical coherence tomography as a potential diagnostic biomarker.

X-ray phase contrast imaging of metallized and non-metallized biological samples

Imaging of biological samples has been performed with a variety of techniques for example electromagnetic waves, electrons, neutrons, ultrasound and X-rays. Also conventional X-ray imaging represents the basis of medical diagnostic imaging, it remains of limited use in this application because it is based solely on the differential absorption of X-rays by tissues. Coherent and bright photon beams, such as those produced by third-generation synchrotron X-ray sources, provide further information on subtle X-ray phase changes at matter interfaces. This complements conventional X-ray absorption by edge enhancement phenomena. Thus, phase contrast imaging has the potential to improve the detection of structures on images by detecting those structures that are invisible with X-ray absorption imaging. Images of a weakly absorbing nylon fibre were recorded in in-line holography geometry using a high resolution low-noise CCD camera at the ESRF in Grenoble. The method was also applied to improve image contrast for images of biological tissues. This paper presents phase contrast microradiographs of vascular tree casts and images of a housefly. These reveal very fine structures, that remain invisible with conventional absorption contrast only.

Rare retinal haemorrhages in translational accidental head trauma in children

PURPOSE: The characteristic findings in accidental head injury consist of linear skull fracture, epidural haematoma, localized subdural haematoma, or cortical contusion because of a linear or translational impact force. Retinal haemorrhages have been found, although uncommon, in accidental head trauma. METHODS: We performed a retrospective study of 24 consecutive cases of children with severe head injuries caused by falls. Inclusion criteria were skull fractures and/or intracranial haemorrhages documented by computerized tomography. All patients underwent a careful ophthalmic examination including dilated indirect fundoscopy within the first 48 h following admission. RESULTS: No retinal haemorrhages could be found in patients whose accidents were plausible and physical and imaging findings were compatible with reported histories. Excessive bilateral retinal haemorrhages were found in only three children with the typical signs of shaken baby syndrome. In eight children, trauma had led to orbital roof fractures. CONCLUSIONS: Retinal haemorrhages were not found in any of the patients with accidental trauma despite the severity of their head injuries. Hence, we add more evidence that there are strong differences between the ocular involvement in accidental translational trauma and those in victims of non-accidental trauma. Fall-related injuries carry a very low risk of retinal haemorrhages.

Methylnitrosourea (MNU)-induced retinal degeneration and regeneration in the zebrafish: histological and functional characteristics.

Retinal degenerative diseases, e.g. retinitis pigmentosa, with resulting photoreceptor damage account for the majority of vision loss in the industrial world. Animal models are of pivotal importance to study such diseases. In this regard the photoreceptor-specific toxin N-methyl-N-nitrosourea (MNU) has been widely used in rodents to pharmacologically induce retinal degeneration. Previously, we have established a MNU-induced retinal degeneration model in the zebrafish, another popular model system in visual research. A fascinating difference to mammals is the persistent neurogenesis in the adult zebrafish retina and its regeneration after damage. To quantify this observation we have employed visual acuity measurements in the adult zebrafish. Thereby, the optokinetic reflex was used to follow functional changes in non-anesthetized fish. This was supplemented with histology as well as immunohistochemical staining for apoptosis (TUNEL) and proliferation (PCNA) to correlate the developing morphological changes. In summary, apoptosis of photoreceptors occurs three days after MNU treatment, which is followed by a marked reduction of cells in the outer nuclear layer (ONL). Thereafter, proliferation of cells in the inner nuclear layer (INL) and ONL is observed. Herein, we reveal that not only a complete histological but also a functional regeneration occurs over a time course of 30 days. Now we illustrate the methods to quantify and follow up zebrafish retinal de- and regeneration using MNU in a video-format.

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

Improved star camera attitude data and their effect on the gravity field

Efforts are ongoing to decrease the noise of the GRACE gravity field models and hence to arrive closer to the GRACE baseline. The most significant error sources belong the untreated errors in the observation data and the imperfections in the background models. The recent study (Bandikova&Flury,2014) revealed that the current release of the star camera attitude data (SCA1B RL02) contain noise systematically higher than expected by about a factor 3-4. This is due to an incorrect implementation of the algorithms for quaternion combination in the JPL processing routines. Generating improved SCA data requires that valid data from both star camera heads are available which is not always the case because the Sun and Moon at times blind one camera. In the gravity field modeling, the attitude data are needed for the KBR antenna offset correction and to orient the non-gravitational linear accelerations sensed by the accelerometer. Hence any improvement in the SCA data is expected to be reflected in the gravity field models. In order to quantify the effect on the gravity field, we processed one month of observation data using two different approaches: the celestial mechanics approach (AIUB) and the variational equations approach (ITSG). We show that the noise in the KBR observations and the linear accelerations has effectively decreased. However, the effect on the gravity field on a global scale is hardly evident. We conclude that, at the current level of accuracy, the errors seen in the temporal gravity fields are dominated by errors coming from sources other than the attitude data.

Retinal slit lamp video mosaicking

Purpose To this day, the slit lamp remains the first tool used by an ophthalmologist to examine patient eyes. Imaging of the retina poses, however, a variety of problems, namely a shallow depth of focus, reflections from the optical system, a small field of view and non-uniform illumination. For ophthalmologists, the use of slit lamp images for documentation and analysis purposes, however, remains extremely challenging due to large image artifacts. For this reason, we propose an automatic retinal slit lamp video mosaicking, which enlarges the field of view and reduces amount of noise and reflections, thus enhancing image quality. Methods Our method is composed of three parts: (i) viable content segmentation, (ii) global registration and (iii) image blending. Frame content is segmented using gradient boosting with custom pixel-wise features. Speeded-up robust features are used for finding pair-wise translations between frames with robust random sample consensus estimation and graph-based simultaneous localization and mapping for global bundle adjustment. Foreground-aware blending based on feathering merges video frames into comprehensive mosaics. Results Foreground is segmented successfully with an area under the curve of the receiver operating characteristic curve of 0.9557. Mosaicking results and state-of-the-art methods were compared and rated by ophthalmologists showing a strong preference for a large field of view provided by our method. Conclusions The proposed method for global registration of retinal slit lamp images of the retina into comprehensive mosaics improves over state-of-the-art methods and is preferred qualitatively.

Retinal ganglion cell layer change in patients treated with anti-VEGF for neovascular age related macular degeneration.

PURPOSE To evaluate macular retinal ganglion cell thickness in patients with neovascular age-related macular degeneration (AMD) and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. DESIGN Retrospective case series with fellow-eye comparison METHODS: Patients with continuous unilateral anti-VEGF treatment for sub- and juxtafoveal neovascular AMD and a minimum follow-up of 24 months were included. The retinal nerve fiber (RNFL) and retinal ganglion cell layer (RGCL) in the macula were segmented using an ETDRS grid. RNFL and RGCL thickness of the outer ring of the ETDRS grid were quantified at baseline and after repeated anti-VEGF injections, and compared to the patients' untreated fellow eye. Furthermore, best-corrected visual acuity (BCVA), age, and retinal pigment epithelium (RPE) atrophy were recorded and correlated with RNFL and RGCL. RESULTS Sixty eight eyes of 34 patients (23 female and 11 male; mean age 76.7 (SD±8.2) with a mean number of 31.5 (SD ±9.8) anti-VEGF injections and a mean follow-up period of 45.3 months (SD±10.5) were included. Whereas the RGCL thickness decreased significantly compared to the non-injected fellow eye (p=0.01) the decrease of the RNFL was not significant. Visual acuity gain was significantly correlated with RGCL thickness (r=0.52, p<0.05) at follow-up and negatively correlated (r=-0.41, p<0.05) with age. Presence of RPE atrophy correlated negatively with the RGCL thickness at follow-up (r= -0.37, p=0.03). CONCLUSION During the course of long term anti-VEGF therapy there is a significant decrease of the RGCL in patients with neovascular AMD to the fellow (untreated) eye.