Patient Preferences with Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Multinational Discrete Choice Experiment Study.

Introduction: New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options.

Methods: This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the USA, Canada, France, Italy, Spain, and the UK.

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials.

Purpose: To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion.

Design: Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192).

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale.

Purpose: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).

Design: Two identically designed global, randomized, double-masked, active comparator-controlled studies.

The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease.

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data.

The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation.

THE ANGIOPOIETIN/TIE PATHWAY IN RETINAL VASCULAR DISEASES: A Review.

Purpose: To provide a concise overview for ophthalmologists and practicing retina specialists of available clinical evidence of manipulating the angiopoietin/tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains (Tie) pathway and its potential as a therapeutic target in retinal vascular diseases.

Methods: A literature search for articles on the angiopoietin/Tie pathway and molecules targeting this pathway that have reached Phase 2 or 3 trials was undertaken on PubMed, Association for Research in Vision and Ophthalmology meeting abstracts (2014-2019), and ClinicalTrials.gov databases.

Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice.

Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein.

Long-term efficacy of fractionated conformal radiotherapy for the management of primary optic nerve sheath meningioma.

Background/aim: Fractionated conformal radiotherapy (FCRT) is now used to treat vision-threatening optic nerve sheath meningioma (ONSM), but long-term efficacy and safety data are lacking; the purpose of this study was to assess these key data.

Methods: This is a retrospective chart review with prospective follow-up of adult patients treated with FCRT for primary ONSM at four academic medical centres between 1995 and 2007 with ≥10 years of follow-up after treatment.

Results: 16 patients were identified with a mean post-treatment follow-up of 14.

Ganglion Cell Complex in Early and Intermediate Age-Related Macular Degeneration: Evidence by SD-OCT Manual Segmentation.

Purpose: To evaluate ganglion cell layer (GCL) and ganglion cell complex (GCC) thickness manually by spectral-domain optical coherence tomography in subjects with early and intermediate age-related macular degeneration (AMD) in 12 locations on the horizontal meridian.

Methods: A total of 450 eyes (specifically, 246 eyes classified as having early/intermediate AMD plus 204 control eyes) were studied. Mann-Whitney U and Kruskal-Wallis tests were used to compare values between the healthy controls and the AMD group and also between the subgroups under study.

Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration.

Photoreceptors are the most numerous and metabolically demanding cells in the retina. Their primary nutrient source is the choriocapillaris, and both the choriocapillaris and photoreceptors require trophic and functional support from retinal pigment epithelium (RPE) cells. Defects in RPE, photoreceptors, and the choriocapillaris are characteristic of age-related macular degeneration (AMD), a common vision-threatening disease.

iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study.

Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells.

A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant.

Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities.

Global metabolomics reveals metabolic dysregulation in ischemic retinopathy.

Proliferative diabetic retinopathy (PDR) is the most severe form of diabetic retinopathy and, along with diabetic macular edema, is responsible for the majority of blindness in adults below the age of 65. Therapeutic strategies for PDR are ineffective at curtailing disease progression in all cases; however a deeper understanding of the ocular metabolic landscape in PDR through metabolomic analysis may offer new therapeutic targets. Here, global and targeted mass spectrometry-based metabolomics were used to investigate metabolism.

Angiogenesis and Eye Disease.

The retina consists of organized layers of photoreceptors, interneurons, glia, epithelial cells, and endothelial cells. The economic model of supply and demand used to appropriately determine cost is highly applicable to the retina, in which the extreme metabolic demands of phototransduction are met by precisely localized and designed vascular networks. Proper development and maintenance of these networks is critical to normal visual function; dysregulation is characteristic of several devastating human diseases, including but not limited to age-related macular degeneration and diabetic retinopathy.

Neurovascular crosstalk between interneurons and capillaries is required for vision.

Functional interactions between neurons, vasculature, and glia within neurovascular units are critical for maintenance of the retina and other CNS tissues. For example, the architecture of the neurosensory retina is a highly organized structure with alternating layers of neurons and blood vessels that match the metabolic demand of neuronal activity with an appropriate supply of oxygen within perfused blood. Here, using murine genetic models and cell ablation strategies, we have demonstrated that a subset of retinal interneurons, the amacrine and horizontal cells, form neurovascular units with capillaries in 2 of the 3 retinal vascular plexuses.

Parinaud's syndrome due to an unilateral vascular ischemic lesion.

A 59-year-old man who complained of binocular vertical diplopia after an exploratory laparotomy, complicated by cardiorespiratory arrest during anesthetic induction, was found to have Collier's sign, anisocoria, complete paralysis of upward vertical gaze associated with convergence-retraction nystagmus on attempted upgaze and skew deviation with hypertropia in the left eye without ptosis, and an absent Bielschowsky sign. Magnetic resonance imaging of the brain showed a small lesion in the left paramedian midbrain compatible with microvascular ischemic sequelae. This patient was diagnosed with Parinaud's syndrome (dorsal midbrain syndrome) associated with a vertical strabismus from an unilateral vascular ischemic paramedian midbrain lesion.

Comprehensive bioimaging with fluorinated nanoparticles using breathable liquids.

Fluorocarbons are lipophobic and non-polar molecules that exhibit remarkable biocompatibility, with applications in liquid ventilation and synthetic blood. The unique properties of these compounds have also enabled mass spectrometry imaging of tissues where the fluorocarbons act as a Teflon-like coating for nanostructured surfaces to assist in desorption/ionization. Here we report fluorinated gold nanoparticles (f-AuNPs) designed to facilitate nanostructure imaging mass spectrometry.