New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage

PURPOSE: The aim of the present study was to investigate whether bone marrow-derived cells (BMCs) can be induced to express retinal pigment epithelial (RPE) cell markers in vitro and can home to the site of RPE damage after mobilization and express markers of RPE lineage in vivo. METHODS: Adult RPE cells were cocultured with green fluorescence protein (GFP)-labeled stem cell antigen-1 positive (Sca-1(+)) BMCs for 1, 2, and 3 weeks. Cell morphology and expression of RPE-specific markers and markers for other retinal cell types were studied. Using an animal model of sodium iodate (NaIO(3))-induced RPE degeneration, BMCs were mobilized into the peripheral circulation by granulocyte-colony stimulating factor, flt3 ligand, or both. Immunocytochemistry was used to identify and characterize BMCs in the subretinal space in C57BL/6 wild-type (wt) mice and GFP chimeric mice. RESULTS: In vitro, BMCs changed from round to flattened, polygonal cells and expressed cytokeratin, RPE65, and microphthalmia transcription factor (MITF) when cocultured in direct cell-cell contact with RPE. In vivo, BMCs were identified in the subretinal space as Sca-1(+) or c-kit(+) cells. They were also double labeled for GFP and RPE65 or MITF. These cells formed a monolayer on the Bruch membrane in focal areas of RPE damage. CONCLUSIONS: Thus, it appears that BMCs, when mobilized into the peripheral circulation, can home to focal areas of RPE damage and express cell markers of RPE lineage. The use of endogenous BMCs to replace damaged retinal tissue opens new possibilities for cell replacement therapy in ophthalmology.

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.

Multimodal Registration Procedure for the Initial Spatial Alignment of a Retinal Video Sequence to a Retinal Composite Image

Accurate placement of lesions is crucial for the effectiveness and safety of a retinal laser photocoagulation treatment. Computer assistance provides the capability for improvements to treatment accuracy and execution time. The idea is to use video frames acquired from a scanning digital ophthalmoscope (SDO) to compensate for retinal motion during laser treatment. This paper presents a method for the multimodal registration of the initial frame from an SDO retinal video sequence to a retinal composite image, which may contain a treatment plan. The retinal registration procedure comprises the following steps: 1) detection of vessel centerline points and identification of the optic disc; 2) prealignment of the video frame and the composite image based on optic disc parameters; and 3) iterative matching of the detected vessel centerline points in expanding matching regions. This registration algorithm was designed for the initialization of a real-time registration procedure that registers the subsequent video frames to the composite image. The algorithm demonstrated its capability to register various pairs of SDO video frames and composite images acquired from patients.

Reproducibility of retinal thickness measurements in patients with age-related macular degeneration using 3D Fourier-domain optical coherence tomography (OCT) (Topcon 3D-OCT 1000)

Conventional time-domain optical coherence tomography (OCT) has become an important tool for following dry or exudative age-related macular degeneration (AMD). Fourier-domain three-dimensional (3D) OCT was recently introduced. This study tested the reproducibility of 3D-OCT retinal thickness measurements in patients with dry and exudative AMD.

Posterior versus anterior circulation strokes: comparison of clinical, radiological and outcome characteristics

Physicians treating patients with posterior circulation strokes (PCS) tended to debate more on whether or not to introduce anticoagulation rather than performing investigations to identify stroke aetiology, as in patients with anterior circulation strokes (ACS). Recent findings suggest that stroke aetiologies of PCS and ACS are more alike than dissimilar, suggesting that PCS deserve the same investigations as ACS. The characteristics and current diagnostic evaluation between patients with PCS and ACS were compared.

Autotransfusion system or integrated automatic suction device in minimized extracorporeal circulation: influence on coagulation and inflammatory response

To measure surrogate markers of coagulation activation as well as of the systemic inflammatory response in patients undergoing primary elective coronary artery bypass grafting (CABG) using either the so-called Smart suction device or a continuous autotransfusion system (C.A.T.S.®).

The human coronary collateral circulation

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts and improve survival.

Urinary proteomics before and after extracorporeal circulation in patients with and without acute kidney injury

Acute kidney injury is a well-known complication with high morbidity and mortality after cardiopulmonary bypass. Cardiopulmonary bypass-associated acute kidney injury is still poorly understood.

Predictors of Short-Term Visual Outcome after Anti-VEGF Therapy of Macular Edema due to Central Retinal Vein Occlusion

The purpose of this study was to analyze predictive factors for best-corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Stem cell-based therapeutic applications in retinal degenerative diseases

Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus on stem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease.

Real-Time Multimodal Retinal Image Registration for a Computer Assisted Laser Photocoagulation System

An algorithm for the real-time registration of a retinal video sequence captured with a scanning digital ophthalmoscope (SDO) to a retinal composite image is presented. This method is designed for a computer-assisted retinal laser photocoagulation system to compensate for retinal motion and hence enhance the accuracy, speed, and patient safety of retinal laser treatments. The procedure combines intensity and feature-based registration techniques. For the registration of an individual frame, the translational frame-to-frame motion between preceding and current frame is detected by normalized cross correlation. Next, vessel points on the current video frame are identified and an initial transformation estimate is constructed from the calculated translation vector and the quadratic registration matrix of the previous frame. The vessel points are then iteratively matched to the segmented vessel centerline of the composite image to refine the initial transformation and register the video frame to the composite image. Criteria for image quality and algorithm convergence are introduced, which assess the exclusion of single frames from the registration process and enable a loss of tracking signal if necessary. The algorithm was successfully applied to ten different video sequences recorded from patients. It revealed an average accuracy of 2.47 ± 2.0 pixels (∼23.2 ± 18.8 μm) for 2764 evaluated video frames and demonstrated that it meets the clinical requirements.

Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke

Intravenous thrombolysis is an approved treatment for anterior (ACS) and posterior (PCS) circulation stroke. However, no randomized controlled trial has investigated safety and efficacy of intravenous thrombolysis according to stroke territory, although PCS is assumed to differ from ACS in many ways. We aimed to compare the safety and clinical outcome of intravenous thrombolysis applied to patients with PCS and ACS.

Retinal Complications after Damaging the Vitreolenticular Barrier

This article gives an overview of the vitreal anatomy and its changes in ageing, which have a significant impact on the two main retinal complications after damage of the vitreolenticular barrier, namely retinal detachment and cystoid macular edema. The possible reasons and pathomechanisms for this entity of retinal diseases in the context of anterior segment interaction are highlighted, and a summary of references is provided showing the epidemiology and consequences of such interventions.