scholarly journals Automated AI labelling of optic nerve head enables new insights into cross-ancestry glaucoma risk and genetic discovery in over 280,000 images from the UK Biobank and Canadian Longitudinal Study on Aging

2020 ◽  
Author(s):  
Xikun Han ◽  
Kaiah Steven ◽  
Ayub Qassim ◽  
Henry N Marshall ◽  
Cameron Bean ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Optic Nerve ◽  
Optic Nerve Head ◽  
Genome Wide Association Study ◽  
Normal Tension Glaucoma ◽  
Independent Study ◽  
Glaucomatous Optic Neuropathy ◽  
Uk Biobank ◽  
Neural Network Models ◽  
Genetic Discovery

AbstractCupping of the optic nerve head, a highly heritable trait, is a hallmark of glaucomatous optic neuropathy. Two key parameters are vertical cup-to-disc ratio (VCDR) and vertical disc diameter (VDD). However, manual assessment often suffers from poor accuracy and is time-intensive. Here, we show convolutional neural network models can accurately estimate VCDR and VDD for 282,100 images from both UK Biobank and an independent study (Canadian Longitudinal Study on Aging), enabling cross-ancestry epidemiological studies and new genetic discovery for these optic nerve head parameters. Using the AI approach we perform a systematic comparison of the distribution of VCDR and VDD, and compare these with intraocular pressure and glaucoma diagnoses across various genetically determined ancestries, which provides an explanation for the high rates of normal tension glaucoma in East Asia. We then used the large number of AI gradings to conduct a more powerful genome-wide association study (GWAS) of optic nerve head parameters. Using the AI based gradings increased estimates of heritability by ~50% for VCDR and VDD. Our GWAS identified more than 200 loci for both VCDR and VDD (double the number of loci from previous studies), uncovers dozens of novel biological pathways, with many of the novel loci also conferring risk for glaucoma.

Parapapillary atrophy in optic neuropathies: Histology and clinical relevance

2021 ◽  
pp. 112067212110606
Author(s):  
Ana Banc ◽  
Stefania Bianchi Marzoli
Keyword(s):  
Optic Nerve ◽  
Optic Neuropathy ◽  
Optic Nerve Head ◽  
Clinical Findings ◽  
Age Related Macular Degeneration ◽  
Glaucomatous Optic Neuropathy ◽  
Age Related ◽  
High Resolution Images ◽  
Parapapillary Atrophy ◽  
Optic Nerve Disorders

Parapapillary atrophy is one of the parameters of the optic nerve head area which are assessed during the ophthalmoscopic examination particularly useful to characterize glaucomatous optic neuropathy. Optical coherence tomography evaluation provides high-resolution images of the optic nerve head and surrounding area, and can be used to study parapapillary atrophy. Different parapapillary atrophy zones were described depending on their histological features and research has been conducted to investigate the possible association between the presence and/ or size of parapapillary atrophy zones and several optic nerve disorders. In this review we discuss the histology and the clinical findings related to parapapillary atrophy in patients with glaucomatous optic neuropathy, non-glaucomatous optic neuropathies (e.g. arteritic and non-arteritic anterior ischemic optic neuropathies; suprasellar and parasellar tumors), and other ocular conditions (e.g. high myopia; age-related macular degeneration). Two different histologic classifications were identified. Parapapillary atrophy was demonstrated in glaucoma and glaucoma-like neuropathies, but not in other types of optic nerve disorders.

scholarly journals Clinical Usefulness of the Measurement of Optic Nerve Head Blood Flow in Myopic Normal-Tension Glaucoma

2015 ◽  
Vol 1 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Tetsuya Sugiyama ◽  
◽  
Hajime Nakamura ◽  
Emiko Shimizu ◽  
Kazuaki Miyamoto ◽  
...  
Keyword(s):  
Blood Flow ◽  
Optic Nerve ◽  
Optic Nerve Head ◽  
Normal Tension Glaucoma ◽  
Clinical Usefulness

Association of Scleral Deformation Around the Optic Nerve Head With Central Visual Function in Normal-Tension Glaucoma and Myopia

2020 ◽  
Vol 217 ◽  
pp. 287-296
Author(s):  
Soo Ji Jeon ◽  
Hae-Young Lopilly Park ◽  
Yong Chan Kim ◽  
Eun Kyoung Kim ◽  
Chan Kee Park
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Visual Function ◽  
Normal Tension Glaucoma

scholarly journals Differential Activation of Glioprotective Intracellular Signaling Pathways in Primary Optic Nerve Head Astrocytes after Treatment with Different Classes of Antioxidants

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 324 ◽  
Author(s):  
Anita K. Ghosh ◽  
Vidhya R. Rao ◽  
Victoria J. Wisniewski ◽  
Alexandra D. Zigrossi ◽  
Jamie Floss ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Cell Viability ◽  
Optic Nerve Head ◽  
Intracellular Signaling ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glaucomatous Optic Neuropathy ◽  
Related Factor ◽  
Expression Levels ◽  
Reactive Astrocytosis

Optic nerve head astrocytes are the specialized glia cells that provide structural and trophic support to the optic nerve head. In response to cellular injury, optic nerve head astrocytes undergo reactive astrocytosis, the process of cellular activation associated with cytoskeletal remodeling, increases in the rate of proliferation and motility, and the generation of Reactive Oxygen Species. Antioxidant intervention has previously been proposed as a therapeutic approach for glaucomatous optic neuropathy, however, little is known regarding the response of optic nerve head astrocytes to antioxidants under physiological versus pathological conditions. The goal of this study was to determine the effects of three different antioxidants, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), resveratrol and xanthohumol in primary optic nerve head astrocytes. Effects on the expression of the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2), the antioxidant enzyme, manganese-dependent superoxide dismutase 2 (SOD2), and the pro-oxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), were determined by quantitative immunoblotting. Furthermore, efficacy in preventing chemically and reactive astrocytosis-induced increases in cellular oxidative stress was quantified using cell viability assays. The results were compared to the effects of the prototypic antioxidant, Trolox. Antioxidants elicited highly differential changes in the expression levels of Nrf2, SOD2, and NOX4. Notably, Mn-TM-2-PyP increased SOD2 expression eight-fold, while resveratrol increased Nrf2 expression three-fold. In contrast, xanthohumol exerted no statistically significant changes in expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake and lactate dehydrogenase (LDH) release assays were performed to assess cell viability after chemically and reactive astrocytosis-induced oxidative stress. Mn-TM-2-PyP exerted the most potent glioprotection by fully preventing the loss of cell viability, whereas resveratrol and xanthohumol partially restored cell viability. Our data provide the first evidence for a well-developed antioxidant defense system in optic nerve head astrocytes, which can be pharmacologically targeted by different classes of antioxidants.

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