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Introduction: Glaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE--Aß axis plays a role in RGC loss in experimental glaucoma. Methods: Retinal ischemia was induced by an acute elevation of intraocular pressure in RAGE [ABSTRACT FROM AUTHOR]

Purpose: The amplitude of spontaneous retinal venous pulsations (SRVP) is known to be affected by intraocular pressure (IOP), retinal venous pressure, and intracranial pressure (ICP). This study characterized SRVPs adjacent to the disc and quantified changes in the amplitude of these pulsations during IOP manipulation in normal subjects. Methods: The study included 12 subjects (40 ± 15, 4 females, 8 males). Baseline IOP (range 10-25 mmHg) was measured and SRVP recorded using the dynamic retinal vessel analyzer (DVA). IOP was lowered using aproclonidine 0.5% and measured every 15 min, followed by dynamic recording of SRVP. Two subjects were also tested with timolol 0.5%, and three were treated with a placebo drop. Mean amplitude of SRVP was determined within each sample at the same site. Blood pressure and heart rate were tracked continuously. Results: Amplitude of SRVP decreased in all subjects with reduction of IOP with aproclonidine and timolol. Mean SRVP amplitude was 8.5 ± 6 μm at baseline and reduced to 2.5 ± 1.8 μm after 45 min ( p < 0.0001). IOP fell from 14.4 ± 2.6 mmHg to 10.2 ± 2.9 mmHg over the same period ( p < 0.001). Venous diameter, blood pressure, and heart rate did not change significantly from the baseline. Analysis of waveforms showed a slight phase shift only (150 ± 78.5 ms, p = 0.93) between disc veins and adjacent retinal vein. Conclusion: SRVPs in the peripapillary retina have similar waveform characteristics to those at the disc. SRVP amplitudes are reduced by manipulation of IOP downwards with pharmacological intervention. The relationship was consistent in all individuals tested for two classes of drugs and was independent of BP or heart rate changes. [ABSTRACT FROM AUTHOR]

Spontaneous retinal Venous Pulsations (SVP) are rhythmic changes in the caliber of the central retinal vein and are observed in the optic disc region (ODR) of the retina. Its absence is a critical indicator of various ocular or neurological abnormalities. Recent advances in imaging technology have enabled the development of portable smartphone-based devices for observing the retina and assessment of SVPs. However, the quality of smartphone-based retinal videos is often poor due to noise and image jitting, which in return, can severely obstruct the observation of SVPs. In this work, we developed a fully automated retinal video stabilization method that enables the examination of SVPs captured by various mobile devices. Specifically, we first propose an ODR Spatio-Temporal Localization (ODR-STL) module to localize visible ODR and remove noisy and jittering frames. Then, we introduce a Noise-Aware Template Matching (NATM) module to stabilize high-quality video segments at a fixed position in the field of view. After the processing, the SVPs can be easily observed in the stabilized videos, significantly facilitating user observations. Furthermore, our method is cost-effective and has been tested in both subjective and objective evaluations. Both of the evaluations support its effectiveness in facilitating the observation of SVPs. This can improve the timely diagnosis and treatment of associated diseases, making it a valuable tool for eye health professionals.

Studying dynamic characteristics of retinal vessels, as opposed to static measures, may provide additional insight into pathophysiological changes associated with local and systemic abnormalities such as glaucoma and hypertension. Various approaches have been developed to derive static biomarkers from retinal still images, but not many for dynamic analysis of video sequences. This study presents a novel method for the assessment of time-dependent diameter changes in high-speed videos (125 fps) from the rat retina. The proposed method is composed of a vessel segmentation and a diameter measurement module. The specificity and sensitivity of the segmentation method over 25 images were 95.1% and 97.3% respectively. The mean and standard deviation of the diameter measurement errors were -0.147±0.41 pixels over 100 measurements.

Background: Retinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer's disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort., Methods: We studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD. Following a complete dilated ocular examination, the amplitude of retinal vascular pulsations and dynamic response, retinal nerve fibre layer thickness and retinal ganglion cell layer (RGCL) thickness were determined in all patients. Systemic blood pressure and carotid-to-femoral pulse wave velocity were measured. The elderly cohort also underwent magnetic resonance imaging and 18 F-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical Aβ standardised uptake value ratio (SUVR), and this was used to characterise a 'preclinical' group (SUVR >1.4)., Results: The mean FBB neocortical SUVR was 1.35 ± 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical Aβ scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical Aβ scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05)., Conclusions: The correlation between retinal vascular changes and Aβ plaque load supports the possibility of a vascular component to AD. Dynamic retinal vascular parameters may provide an additional inexpensive tool to aid in the preclinical assessment of AD.

The eye is the only organ through which microcirculation can be visualized non-invasively. This unique feature makes the eye and specifically retinal vasculature an excellent target area to monitor and study micro-vascular damage in systemic diseases. Dynamic (real-time) changes of retinal vessels have been shown to be more specific to the disease in comparison with static measurements. In this study we utilize high speed imaging (i.e. 125 fps) to study and derive dynamic changes of retinal vessels in a rat model of hypertension. A Eulerian video magnification algorithm was used to extract retinal arterial and venous pulse amplitude from five Spontaneously Hypertensive Rats (SHR) and five Wister Kyoto (WKY) rats were used as the control group. Results showed that retinal arterial diameter and pulse amplitude are significantly lower in the SHRs compared with WKYs. Dynamic biomarkers of retinal micro-vasculature may be used as a diagnostic tool for systemic diseases.

Magnetic Resonance Imaging (MRI) is a high resolution medical imaging technique to image internal anatomical structures. Phase contrast MRI (pcMRI) technique is an add-on specification of MRI devices in order to quantify flow. Although different attempts have been introduced to measure orbital flows, a relationship between different ophthalmic physiological structures including superior ophthalmic vein, ophthalmic artery and optic nerve sheath (containing cerebrospinal fluid) using phase contrast MRI has not been established. In this study we investigate orbital flow in 5 normal subjects using a 3 tesla MRI device. pcMRI technique has been applied to extract flow in the superior ophthalmic vein and optic nerve sheath. Electrocardiogram of each subject was monitored and gated to the MRI in order to extract flow waveforms. Results show multiple peaks when assessing orbital flow waveforms, suggesting possible reflection of flow from back of the eye. These peaks have been characterized and a possible explanation to this phenomenon has been provided. This study enhances understanding of interaction between physiological structures at the retrolaminar portion of the eye which may be responsible for different ophthalmic abnormalities.

Cerebrospinal fluid pressure (CSFp) provides vital information in various neurological abnormalities including hydrocephalus, intracranial hypertension and brain tumors. Currently, CSFp is measured invasively through implanted catheters within the brain (ventricles and parenchyma) which is associated with a risk of infection and morbidity. In humans, the cerebrospinal fluid communicates indirectly with the ocular circulation across the lamina cribrosa via the optic nerve subarachnoid space. It has been shown that a relationship between retinal venous pulsation, intraocular pressure (IOP) and CSFp exists with the amplitude of retinal venous pulsation being associated with the trans-laminar pressure gradient (i.e. IOP-CSFp). In this study we use this characteristic to develop a non-invasive approach to estimate CSFp. 15 subjects were included in this study. Dynamic retinal venous diameter changes and IOP were measured and fitted into our model. Artificial neural networks (ANN) were applied to construct a relationship between retinal venous pulsation amplitude, IOP (input) and CSFp (output) and develop an algorithm to estimate CSFp based on these parameters. Results show a mean square error of 2.4 mmHg and 1.27 mmHg for train and test data respectively. There was no significant difference between experimental and ANN estimated CSFp values (p>0.01).This study suggests measurement of retinal venous pulsatility in conjunction with IOP may provide a novel approach to estimate CSFp non-invasively.