Multimodal Retinal Vessel Analysis in CADASIL Patients

Purpose To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging. Methods 28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD- OCT. Results Mean age of patients was 56.2±11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77±0.46 mm3 and 8.83±2.24 mm3. RNFL measurements showed a global increase of 105.2 µm (Control group: 98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients. Conclusions The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases

Criteria for Blood Vessel Discrimination

Introduction The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist. Objective This study reviewed labeling criteria originally developed for color fundus photography (CFP) images. Methods The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree. Results and Conclusion They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations

Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo®) Injection

This case report describes a 78-year-old patient who developed a tear of the retinal pigment epithelium (RPE) during faricimab (Vabysmo®) therapy. After three consecutive intravitreal aflibercept (Eylea®) injections with persistent disease activity, therapy was switched to faricimab. The patient experienced a tear in the RPE 4 weeks postinjection. We report the first published case of RPE tear development after intravitreal faricimab injection in neovascular age-related macular degeneration. Faricimab has a new target structure in the angiopoietin-2 receptor in addition to VEGF. Patients at risk for RPE rupture were excluded from pivotal studies. Further investigation is needed to understand the effect of faricimab not only on visual acuity and intraretinal and subretinal fluid but also on mechanical stress on the RPE monolayer

RELEASE AND VELOCITY OF MICRONIZED DEXAMETHASONE IMPLANTS WITH AN INTRAVITREAL DRUG DELIVERY SYSTEM Kinematic Analysis With a High-Speed Camera

10.1097/IAE.0b013e31825699e5RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES32102133-214

Correlation analysis of physical fitness and retinal microvasculature by OCT angiography in healthy adults

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (β = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies

OCT-Angiography reveals reduced vessel density in the deep retinal plexus of CADASIL patients

Optical coherence tomography angiography (OCT-A) represents the most recent tool in ophthalmic imaging. It allows for a non-invasive, depth-selective and quantitative visualization of blood flow in central retinal vessels and it has an enormous diagnostic potential not only in ophthalmology but also with regards to neurologic and systemic diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular small-vessel disease caused by Notch3 mutations and represents the most common form of hereditary stroke disorder. In this study, CADASIL patients prospectively underwent OCT-A imaging to evaluate retinal and choriocapillaris blood flow as well as blood flow at the optic nerve head. The vessel density of the macular region and the size of the foveal avascular zone in the superficial and deep retinal plexus were determined as well as the vessel density at the optic nerve head and in the choriocapillaris. Additionally, cerebral magnetic resonance images were evaluated. The main finding was that vessel density of the deep retinal plexus was significantly decreased in CADASIL patients compared to healthy controls which may reflect pericyte dysfunction in retinal capillaries

Semi-automated vessel measurements based on confocal scanning laser ophthalmoscopy (cSLO): healthy controls compared to CADASIL patients.

<p>(n) number of total eyes; (v) number of total vessels; (n/a) too few vessels in the respective sector to calculate p-value.</p><p>Semi-automated vessel measurements based on confocal scanning laser ophthalmoscopy (cSLO): healthy controls compared to CADASIL patients.</p

Mechanism of Chemical and Electrochemical N₂ Splitting by a Rhenium Pincer Complex

A comprehensive mechanistic study of N₂ activation and splitting into terminal nitride ligands upon reduction of the rhenium dichloride complex [ReCl₂(PNP)] is presented (PNP^– = N­(CH₂CH₂P<i>t</i>Bu₂)₂^–). Low-temperature studies using chemical reductants enabled full characterization of the N₂-bridged intermediate [{(PNP)­ClRe}₂(N₂)] and kinetic analysis of the N–N bond scission process. Controlled potential electrolysis at room temperature also resulted in formation of the nitride product [Re­(N)­Cl­(PNP)]. This first example of molecular electrochemical N₂ splitting into nitride complexes enabled the use of cyclic voltammetry (CV) methods to establish the mechanism of reductive N₂ activation to form the N₂-bridged intermediate. CV data was acquired under Ar and N₂, and with varying chloride concentration, rhenium concentration, and N₂ pressure. A series of kinetic models was vetted against the CV data using digital simulations, leading to the assignment of an ECCEC mechanism (where “E” is an electrochemical step and “C” is a chemical step) for N₂ activation that proceeds via initial reduction to Re^II, N₂ binding, chloride dissociation, and further reduction to Re^I before formation of the N₂-bridged, dinuclear intermediate by comproportionation with the Re^III precursor. Experimental kinetic data for all individual steps could be obtained. The mechanism is supported by density functional theory computations, which provide further insight into the electronic structure requirements for N₂ splitting in the tetragonal frameworks enforced by rigid pincer ligands

A–D Combined simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT).

<p><b>A–B</b> Infrared cSLO image centered on the optic disc of a healthy control subject (A) and a CADASIL patient (B). Green circle indicates the position of corresponding SD-OCT scan. Light green section inferiorly on the circle marks the localization of corresponding SD-OCT scan shown aside. <b>C–D</b> Magnified SD-OCT scans of healthy control subject (C) and CADASIL patient (D) show sections of major retinal vessels appearing as a group of heterogeneous reflectivities in a round-shaped configuration. Asterisks mark the inner and outer reflections of arterial vessel walls and diamonds indicate inner and outer reflections of venous vessel walls. Hyperreflectivities representing the vessel walls seem thicker and more accentuated in the CADASIL patient. Particularly in veins, demarcation of the inferior vessel wall (towards the retinal pigment epithelium) often remains challenging due to absorption effects also seen as acoustical shadow underneath the vessel (towards the retinal pigment epithelium). Note the typical hour-glass shaped configuration within the vessel lumen in both subjects. Lateral vessel walls cannot be visualized as OCT laser beam is not projected perpendicularly to them.</p

Retinal nerve fiber layer thickness (RNFL) measured by spectral-domain optical coherence tomography: healthy controls compared to CADASIL patients.

<p>(n) number of eyes.</p><p>*superior and inferior measurements were calculated based on data from nasal superior and temporal superior quadrants and from nasal inferior and temporal inferior quadrants respectively.</p><p>Retinal nerve fiber layer thickness (RNFL) measured by spectral-domain optical coherence tomography: healthy controls compared to CADASIL patients.</p