Prognostic Relevance of Relative Ellipsoid Zone Reflectivity for Ellipsoid Zone Loss in Macular Telangiectasia Type 2.

Purpose: The relative ellipsoid zone reflectivity (rEZR) is an innovative biomarker for photoreceptor alterations and showed association with disease staging in macular telangiectasia type 2 (MacTel). However, its prognostic relevance for the ellipsoid zone (EZ) loss is unclear.

Methods: Longitudinal spectral-domain optical coherence tomography (SD-OCT) imaging of patients with MacTel from an observational natural history study was used for en face determination of manifest EZ loss.

Retinal pigment epithelial cells reduce vascular leak and proliferation in retinal neovessels.

In multiple neurodegenerative diseases, including age-related macular degeneration, retinitis pigmentosa, and macular telangiectasia type 2 (MacTel), retinal pigment epithelial (RPE)-cells proliferate and migrate into the neuroretina, forming intraretinal pigment plaques. Though these pigmentary changes are hallmarks of disease progression, it is unknown if their presence is protective or detrimental.Here, we first evaluated the impact of pigment plaques on vascular changes and disease progression in MacTel.

Developing a 10-Layer Retinal Segmentation for MacTel Using Semi-Supervised Learning.

Purpose: Automated segmentation software in optical coherence tomography (OCT) devices is usually developed for and primarily tested on common diseases. Therefore segmentation accuracy of automated software can be limited in eyes with rare pathologies.

Methods: We sought to develop a semisupervised deep learning segmentation model that segments 10 retinal layers and four retinal features in eyes with Macular Telangiectasia Type II (MacTel) using a small labeled dataset by leveraging unlabeled images.

Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration.

Objective: Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models.

Self-Supervised Learning for Improved Optical Coherence Tomography Detection of Macular Telangiectasia Type 2.

Importance: Deep learning image analysis often depends on large, labeled datasets, which are difficult to obtain for rare diseases.

Objective: To develop a self-supervised approach for automated classification of macular telangiectasia type 2 (MacTel) on optical coherence tomography (OCT) with limited labeled data.

Design, Setting, And Participants: This was a retrospective comparative study.

Relative Ellipsoid Zone Reflectivity in Macular Telangiectasia Type 2.

Purpose: The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages.

Methods: The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls.

Integrating human iPSC-derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche.

In the retina, microglia are resident immune cells that are essential for development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age-related neurodegeneration, ischemic retinopathy, and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers.

iPSC-derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function.

Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases.

Macular Telangiectasia Type 2: A Classification System Using MultiModal Imaging MacTel Project Report Number 10.

Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging.

Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development.

Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel.

Tamoxifen Retinopathy and Macular Telangiectasia Type 2: Similarities and Differences on Multimodal Retinal Imaging.

Purpose: Tamoxifen-induced retinopathy (TR) and macular telangiectasia type 2 (MacTel) share a highly similar retinal phenotype. In this study, we aimed to evaluate differences and similarities that may point toward underlying mechanisms linking both disease entities.

Design: Retrospective, cross sectional study.

Deletion of Tgfβ signal in activated microglia prolongs hypoxia-induced retinal neovascularization enhancing Igf1 expression and retinal leukostasis.

Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-β (Tgfβ) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfβ signaling in activated microglia during retinal NV.

Morphological characteristics preceding exudative neovascularisation secondary to macular telangiectasia type 2.

Aims: To identify morphological characteristics preceding the development of exudative neovascularisation secondary to Macular Telangiectasia type 2 (MacTel) using multimodal retinal imaging.

Methods: In this retrospective study, eyes with a minimum observation period of 6 months prior to the de novo diagnosis of an exudative neovascularisation secondary to MacTel were analysed. Morphological changes preceding the formation of neovascularisation were evaluated using colour fundus photography, infrared imaging, fluorescein angiography, macular pigment measurement and optical coherence tomography (OCT).

Functional Relevance of Hyper-Reflectivity in Macular Telangiectasia Type 2.

Purpose: The purpose of this study was to quantify hyper-reflective lesions on en face optical coherence tomography (OCT) and study its functional relevance in macular telangiectasia type 2 (MacTel).

Design: This was a retrospective, cross-sectional cohort study.

Methods: Baseline image and functional data from participants of a phase II clinical trial (NCT01949324) that studied the effect of Ciliary Neurotrophic Factor in patients with MacTel were analyzed.

Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder.

Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed a genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel genome-wide significant loci (p < 5 × 10), and confirmed all three previously reported loci. Using MAGMA, eQTL and transcriptome-wide association analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, and retinal vasculature and thickness.

HYPERREFLECTIVITY ON OPTICAL COHERENCE TOMOGRAPHY IN MACULAR TELANGIECTASIA TYPE 2.

Purpose: To define, characterize, and classify hyperreflectivity on optical coherence tomography and report its prevalence in macular telangiectasia Type 2.

Methods: In a primary cross-sectional analysis, multimodal imaging data were retrospectively analyzed. The definition of hyperreflectivity and neovascularization on optical coherence tomography followed optical coherence tomography angiography-based criteria.

WITHDRAWN: Hyper-reflectivity on optical coherence tomography in macular telangiectasia type 2.

Ahead of Print article withdrawn by publisher.

Deep learning-based classification and segmentation of retinal cavitations on optical coherence tomography images of macular telangiectasia type 2.

Aim: To develop a fully automatic algorithm to segment retinal cavitations on optical coherence tomography (OCT) images of macular telangiectasia type 2 (MacTel2).

Methods: The dataset consisted of 99 eyes from 67 participants enrolled in an international, multicentre, phase 2 MacTel2 clinical trial (NCT01949324). Each eye was imaged with spectral-domain OCT at three time points over 2 years.

CNTF Prevents Development of Outer Retinal Neovascularization Through Upregulation of CxCl10.

Purpose: Ciliary neurotrophic factor (CNTF) is a well-characterized neurotrophic factor currently in clinical trials for the treatment of macular telangiectasia type II. Our previous work showed that CNTF-induced STAT3 signaling is a potent inhibitor of pathologic preretinal neovascular tuft formation in the mouse model of oxygen-induced retinopathy. In this study, we investigated the effect of CNTF on outer retinal and choroidal angiogenesis and the mechanisms that underpin the observed decrease in outer retinal neovascularization following CNTF treatment.

Optical coherence tomography-angiography for monitoring neovascularisations in macular telangiectasia type 2.

Purpose: To evaluate the utility of optical coherence tomography-angiography (OCT-A) for monitoring activity, progression and response to therapy of neovascularisations (NVs) secondary to macular telangiectasia type 2 (MacTel).

Methods: In a retrospective analysis, eyes with NVs secondary to MacTel were reviewed over a period of ≥8 months. Examinations at monthly intervals included visual acuity testing, dilated funduscopy, spectral domain-OCT and OCT-A.

Beyond Performance Metrics: Automatic Deep Learning Retinal OCT Analysis Reproduces Clinical Trial Outcome.

Purpose: To validate the efficacy of a fully automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2).

Design: Evaluation of diagnostic test or technology.

Participants: A total of 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to 1 of 2 treatment groups METHODS: The ellipsoid zone (EZ) defect areas were measured on spectral domain OCT images of each eye at 2 time points (baseline and month 24) by a fully automatic, deep learning-based segmentation algorithm.

Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy.

Background: Identifying mechanisms of diseases with complex inheritance patterns, such as macular telangiectasia type 2, is challenging. A link between macular telangiectasia type 2 and altered serine metabolism has been established previously.

Methods: Through exome sequence analysis of a patient with macular telangiectasia type 2 and his family members, we identified a variant in encoding a subunit of serine palmitoyltransferase (SPT).

miR-30a-5p inhibition promotes interaction of Fas endothelial cells and FasL microglia to decrease pathological neovascularization and promote physiological angiogenesis.

Ischemia-induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti-VEGF agents but are not successful in all cases. In this study we determined that miR-30a-5p is another important mediator of retinal angiogenesis.