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Glaucoma: HELP
Articles by Gadi Wollstein
Based on 63 articles published since 2008
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Between 2008 and 2019, G. Wollstein wrote the following 63 articles about Glaucoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review The Future of Imaging in Detecting Glaucoma Progression. 2017

Lavinsky, Fabio / Wollstein, Gadi / Tauber, Jenna / Schuman, Joel S. ·NYU Langone Eye Center, New York University School of Medicine, New York, New York. · NYU Langone Eye Center, New York University School of Medicine, New York, New York. Electronic address: Joel.Schuman@med.nyu.edu. ·Ophthalmology · Pubmed #29157365.

ABSTRACT: Ocular imaging has been heavily incorporated into glaucoma management and provides important information that aids in the detection of disease progression. Longitudinal studies have shown that the circumpapillary retinal nerve fiber layer is an important parameter for glaucoma progression detection, whereas other studies have demonstrated that macular parameters, such as the ganglion cell inner plexiform layer and optic nerve head parameters, also are useful for progression detection. The introduction of novel technologies with faster scan speeds, wider scanning fields, higher resolution, and improved tissue penetration has enabled the precise quantification of additional key ocular structures, such as the individual retinal layers, optic nerve head, choroid, and lamina cribrosa. Furthermore, extracting functional information from scans such as blood flow rate and oxygen consumption provides new perspectives on the disease and its progression. These novel methods promise improved detection of glaucoma progression and better insight into the mechanisms of progression that will lead to better targeted treatment options to prevent visual damage and blindness.

2 Review Adaptive optics optical coherence tomography in glaucoma. 2017

Dong, Zachary M / Wollstein, Gadi / Wang, Bo / Schuman, Joel S. ·University of Pittsburgh Medical Center (UPMC) Eye Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Ophthalmology and Visual Science Research Center, Pittsburgh, PA, United States. Electronic address: dongzm@upmc.edu. · New York University (NYU) Langone Eye Center, NYU Langone Medical Center, Department of Ophthalmology, NYU School of Medicine, New York, NY, United States. Electronic address: gadi.wollstein@nyumc.org. · University of Pittsburgh Medical Center (UPMC) Eye Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Ophthalmology and Visual Science Research Center, Pittsburgh, PA, United States. Electronic address: wangb4@upmc.edu. · New York University (NYU) Langone Eye Center, NYU Langone Medical Center, Department of Ophthalmology, NYU School of Medicine, New York, NY, United States; Department of Electrical and Computer Engineering, New York University Tandon School of Engineering, Brooklyn, NY, United States. Electronic address: joel.schuman@nyu.edu. ·Prog Retin Eye Res · Pubmed #27916682.

ABSTRACT: Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15-20 μm and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3 μm

3 Review Clinical Utility of Optical Coherence Tomography in Glaucoma. 2016

Dong, Zachary M / Wollstein, Gadi / Schuman, Joel S. ·University of Pittsburgh Medical Center (UPMC) Eye Center Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States. · University of Pittsburgh Medical Center (UPMC) Eye Center Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States 2Departmen. ·Invest Ophthalmol Vis Sci · Pubmed #27537415.

ABSTRACT: Optical coherence tomography (OCT) has established itself as the dominant imaging modality in the management of glaucoma and retinal diseases, providing high-resolution visualization of ocular microstructures and objective quantification of tissue thickness and change. This article reviews the history of OCT imaging with a specific focus on glaucoma. We examine the clinical utility of OCT with respect to diagnosis and progression monitoring, with additional emphasis on advances in OCT technology that continue to facilitate glaucoma research and inform clinical management strategies.

4 Review New developments in optical coherence tomography. 2015

Kostanyan, Tigran / Wollstein, Gadi / Schuman, Joel S. ·aDepartment of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine bDepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ·Curr Opin Ophthalmol · Pubmed #25594766.

ABSTRACT: PURPOSE OF REVIEW: Optical coherence tomography (OCT) has become the cornerstone technology for clinical ocular imaging in the past few years. The technology is still rapidly evolving with newly developed applications. This manuscript reviews recent innovative OCT applications for glaucoma diagnosis and management. RECENT FINDINGS: The improvements made in the technology have resulted in increased scanning speed, axial and transverse resolution, and more effective use of the OCT technology as a component of multimodal imaging tools. At the same time, the parallel evolution in novel algorithms makes it possible to efficiently analyze the increased volume of acquired data. SUMMARY: The innovative iterations of OCT technology have the potential to further improve the performance of the technology in evaluating ocular structural and functional characteristics and longitudinal changes in glaucoma.

5 Review OCT for glaucoma diagnosis, screening and detection of glaucoma progression. 2014

Bussel, Igor I / Wollstein, Gadi / Schuman, Joel S. ·Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ·Br J Ophthalmol · Pubmed #24357497.

ABSTRACT: Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening.

6 Review Imaging of the lamina cribrosa in glaucoma: perspectives of pathogenesis and clinical applications. 2013

Kim, Tae-Woo / Kagemann, Larry / Girard, Michaël J A / Strouthidis, Nicholas G / Sung, Kyung Rim / Leung, Christopher K / Schuman, Joel S / Wollstein, Gadi. ·Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. ·Curr Eye Res · Pubmed #23768229.

ABSTRACT: The lamina cribrosa (LC) is a sieve-like structure in the sclera where retinal ganglion cell axons exit from the eye. The LC has been known to play a critical role in the pathogenesis of glaucoma. With the advent of imaging technologies, such as enhanced depth imaging, spectral-domain optical coherence tomography (OCT) enables us to unveil the LC in vivo features. The application of adaptive optics technology and a compensatory image-processing algorithm has further improved the visualization of the beams and pores and neural pathways of the LC and the scleral insertion sites. Monitoring the changes of these structures in relation to acute and chronic elevation of intraocular pressure would be germane to decipher the relationship between the stress and strain response of the LC and optic nerve damage and improve our understanding of glaucoma pathophysiology. While the impact of investigating the integrity of LC is substantive, considerable challenges remain for imaging the LC. Nevertheless, with the rapid development of the OCT technology, it is expected that some of these limitations can be overcome and the potentials of LC imaging will be unraveled.

7 Review Macular assessment using optical coherence tomography for glaucoma diagnosis. 2012

Sung, Kyung Rim / Wollstein, Gadi / Kim, Na Rae / Na, Jung Hwa / Nevins, Jessica E / Kim, Chan Yun / Schuman, Joel S. ·Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Korea. sungeye@gmail.com ·Br J Ophthalmol · Pubmed #23018425.

ABSTRACT: Optical coherence tomography (OCT) is an interferometry-based imaging modality that generates high-resolution cross-sectional images of the retina. Circumpapillary retinal nerve fibre layer (cpRNFL) and optic disc assessments are the mainstay of glaucomatous structural measurements. However, because these measurements are not always available or precise, it would be useful to have another reliable indicator. The macula has been suggested as an alternative scanning location for glaucoma diagnosis. Using time-domain (TD) OCT, macular measurements have been shown to provide good glaucoma diagnostic capabilities. Performance of cpRNFL measurement was generally superior to macular assessment. However, macular measurement showed better glaucoma diagnostic performance and progression detection capability in some specific cases, which suggests that these two measurements may be combined to produce a better diagnostic strategy. With the adoption of spectral-domain OCT, which allows a higher image resolution than TD-OCT, segmentation of inner macular layers becomes possible. The role of macular measurements for detection of glaucoma progression is still under investigation. Improvement of image quality would allow better visualisation, development of various scanning modes would optimise macular measurements, and further refining of the analytical algorithm would provide more accurate segmentation. With these achievements, macular measurement can be an important surrogate for glaucomatous structural assessment.

8 Review Optical coherence tomography: future trends for imaging in glaucoma. 2012

Folio, Lindsey S / Wollstein, Gadi / Schuman, Joel S. ·Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ·Optom Vis Sci · Pubmed #22488265.

ABSTRACT: Optical coherence tomography captures a major role in clinical assessment in eye care. Innovative hardware and software improvements in the technology would further enhance its usefulness. In this review, we present several promising initiatives currently in development or early phase of assessment that we expect to have a future impact on optical coherence tomography.

9 Review Clinical use of OCT in assessing glaucoma progression. 2011

Kotowski, Jacek / Wollstein, Gadi / Folio, Lindsey S / Ishikawa, Hiroshi / Schuman, Joel S. ·Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ·Ophthalmic Surg Lasers Imaging · Pubmed #21790113.

ABSTRACT: Detection of disease progression is an important and challenging component of glaucoma management. Optical coherence tomography (OCT) has proved to be valuable in the detection of glaucomatous damage. With its high resolution and proven measurement reproducibility, OCT has the potential to become an important tool for glaucoma progression detection. This manuscript presents the capabilities of the OCT technology pertinent for detection of progressive glaucomatous damage and provides a review of the current knowledge on the device's clinical performance.

10 Review Imaging of the retinal nerve fibre layer with spectral domain optical coherence tomography for glaucoma diagnosis. 2011

Sung, Kyung Rim / Kim, Jong S / Wollstein, Gadi / Folio, Lindsey / Kook, Michael S / Schuman, Joel S. ·Department of Ophthalmology, University of Ulsan, College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea. sungeye@gmail.com ·Br J Ophthalmol · Pubmed #21030413.

ABSTRACT: Optical coherence tomography (OCT) techniques have been applied to develop a new generation of the technology, called spectral domain (SD) or Fourier domain (FD) OCT. The commercially available SD-OCT technology offers benefits over the conventional time domain (TD) OCT such as a scanning speed up to 200 times faster and higher axial resolution (3 to 6 μm). Overall, SD-OCT offers improved performance in terms of reproducibility. SD-OCT has a level of discriminating capability, between healthy and perimetric glaucoma eyes similar to that obtained with TD-OCT. Furthermore, the capabilities and features of SD-OCT are rapidly evolving, mainly due to three-dimensional imaging and image rendering. More sophisticated approaches for macular and optic disc assessment are expected to be employed in clinical practice. Analysis software should be further refined for interpretation of SD-OCT images in order to enhance the sensitivity and specificity of glaucoma diagnostics. Most importantly for SD-OCT is determination of its ability to diagnostic structural glaucomatous progression. Considering the recent launch time of the commercially available SD-OCT and slow progressing characteristic of glaucoma, we must wait for longitudinal SD-OCT data, with a long enough follow-up, to become available.

11 Review Imaging of the retinal nerve fibre layer for glaucoma. 2009

Townsend, K A / Wollstein, G / Schuman, J S. ·UPMC Eye Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Pittsburgh, PA 15213, USA. ·Br J Ophthalmol · Pubmed #19028735.

ABSTRACT: BACKGROUND: Glaucoma is a group of diseases characterised by retinal ganglion cell dysfunction and death. Detection of glaucoma and its progression are based on identification of abnormalities or changes in the optic nerve head (ONH) or the retinal nerve fibre layer (RNFL), either functional or structural. This review will focus on the identification of structural abnormalities in the RNFL associated with glaucoma. DISCUSSION: A variety of new techniques have been created and developed to move beyond photography, which generally requires subjective interpretation, to quantitative retinal imaging to measure RNFL loss. Scanning laser polarimetry uses polarised light to measure the RNFL birefringence to estimate tissue thickness. Optical coherence tomography (OCT) uses low-coherence light to create high-resolution tomographic images of the retina from backscattered light in order to measure the tissue thickness of the retinal layers and intraretinal structures. Segmentation algorithms are used to measure the thickness of the retinal nerve fibre layer directly from the OCT images. In addition to these clinically available technologies, new techniques are in the research stages. Polarisation-sensitive OCT has been developed that combines the strengths of scanning laser polarimetry with those of OCT. Ultra-fast techniques for OCT have been created for research devices. The continued utilisation of imaging devices into the clinic is refining glaucoma assessment. In the past 20 years glaucoma has gone from a disease diagnosed and followed using highly subjective techniques to one measured quantitatively and increasingly objectively.

12 Article Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. 2018

Bailey, Jessica N Cooke / Gharahkhani, Puya / Kang, Jae H / Butkiewicz, Mariusz / Sullivan, David A / Weinreb, Robert N / Aschard, Hugues / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John H / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Vajaranant, Thasarat S / Chasman, Daniel I / Christen, William G / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Craig, Jamie E / Burdon, Kathryn P / Hewitt, Alex W / Mackey, David A / Haines, Jonathan L / MacGregor, Stuart / Wiggs, Janey L / Pasquale, Louis R / Anonymous8431162. ·Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States. · Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, University of California at San Diego, La Jolla, California, United States. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States. · Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, Wisconsin, United States. · Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States. · Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, Iowa, United States. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States. · Department of Ophthalmology, WVU Eye Institute, Morgantown, West Virginia, United States. · Scripps Genome Center, University of California at San Diego, San Diego, California, United States. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology, Stanford University, Palo Alto, California, United States. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States. · Wills Eye Hospital, Glaucoma Research Center, Philadelphia, Pennsylvania, United States. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, United States. · Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States. · Department of Genetics, Stanford University, Palo Alto, California, United States. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States. · Department of Ophthalmology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, United States. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States. · Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. · School of Medicine, Menzies Research Institute of Tasmania, Hobart, Australia. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia. · Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #29392307.

ABSTRACT: Purpose: Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

13 Article In-vivo effects of intraocular and intracranial pressures on the lamina cribrosa microstructure. 2017

Wang, Bo / Tran, Huong / Smith, Matthew A / Kostanyan, Tigran / Schmitt, Samantha E / Bilonick, Richard A / Jan, Ning-Jiun / Kagemann, Larry / Tyler-Kabara, Elizabeth C / Ishikawa, Hiroshi / Schuman, Joel S / Sigal, Ian A / Wollstein, Gadi. ·Department of Ophthalmology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States of America. · Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. · New York University Langone Eye Center, New York University School of Medicine, New York, New York, United States of America. · Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America. ·PLoS One · Pubmed #29161320.

ABSTRACT: There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health.

14 Article Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis. 2017

Aschard, Hugues / Kang, Jae H / Iglesias, Adriana I / Hysi, Pirro / Cooke Bailey, Jessica N / Khawaja, Anthony P / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John H / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Gulati, Vikas / Haven, Shane / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Weinreb, Robert N / Cheng, Ching-Yu / Chasman, Daniel I / Christen, William G / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Anonymous6180917 / Klaver, Caroline C W / vanDuijn, Cornelia M / Haines, Jonathan / Wiggs, Janey L / Pasquale, Louis R. ·Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Department of Epidemiology, Genetic Epidemiology Unit, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA. · Department of Medicine, Duke University Medical Center, Durham, NC, USA. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. · Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, NY, USA. · Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO, USA. · Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA. · Department of Ophthalmology, WVU Eye Institute, Morgantown, WV, USA. · Scripps Genome Center, University of California at San Diego, San Diego, CA, USA. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Ophthalmology, Stanford University, Palo Alto, CA, USA. · Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA. · Wills Eye Hospital, Glaucoma Research Center, Philadelphia, PA, USA. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA. · Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Department of Ophthalmology &Visual Sciences, University of Nebraska Medical Center, Omaha, NE, USA. · Department of Genetics, Stanford University, Palo Alto, CA, USA. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD, USA. · Department of Ophthalmology, Hamilton Eye Center, University of California at San Diego, San Diego, CA, USA. · Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore. · Ophthalmology &Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Cellular Biology &Anatomy, Augusta University, Augusta, GA, USA. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA. · Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. ·Eur J Hum Genet · Pubmed #28853718.

ABSTRACT: Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10

15 Article Thick Prelaminar Tissue Decreases Lamina Cribrosa Visibility. 2017

Lucy, Katie A / Wang, Bo / Schuman, Joel S / Bilonick, Richard A / Ling, Yun / Kagemann, Larry / Sigal, Ian A / Grulkowski, Ireneusz / Liu, Jonathan J / Fujimoto, James G / Ishikawa, Hiroshi / Wollstein, Gadi. ·Langone Medical Center, Department of Ophthalmology, New York University School of Medicine, New York, New York, United States. · UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 3Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. · UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 4Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. · UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 5Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. · Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, United States. · Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #28324116.

ABSTRACT: Purpose: Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). Methods: The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. Results: A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05). The average prelaminar tissue thickness in regions of scans where the LC was analyzable (214 μm) was significantly thinner than in regions where the LC was not analyzable (569 μm; P < 0.001). Healthy eyes had significantly thicker average prelaminar tissue measurements than glaucoma or glaucoma suspect eyes (both P < 0.001), and glaucoma suspect eyes had significantly thicker average prelaminar tissue measurements than glaucoma eyes (P = 0.008). Significantly more of the ALC boundary was visible in glaucoma eyes (63% of ONH) than in healthy eyes (41%; P = 0.005). Conclusions: Thick prelaminar tissue was associated with impaired visualization of the LC. Healthy subjects generally had thicker prelaminar tissue, which potentially could create a selection bias against healthy eyes when comparing LC structures.

16 Article Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample. 2017

Pasquale, Louis R / Aschard, Hugues / Kang, Jae H / Bailey, Jessica N Cooke / Lindström, Sara / Chasman, Daniel I / Christen, William G / Allingham, R Rand / Ashley-Koch, Allison / Lee, Richard K / Moroi, Sayoko E / Brilliant, Murray H / Wollstein, Gadi / Schuman, Joel S / Fingert, John / Budenz, Donald L / Realini, Tony / Gaasterland, Terry / Gaasterland, Douglas / Scott, William K / Singh, Kuldev / Sit, Arthur J / Igo, Robert P / Song, Yeunjoo E / Hark, Lisa / Ritch, Robert / Rhee, Douglas J / Gulati, Vikas / Havens, Shane / Vollrath, Douglas / Zack, Donald J / Medeiros, Felipe / Weinreb, Robert N / Pericak-Vance, Margaret A / Liu, Yutao / Kraft, Peter / Richards, Julia E / Rosner, Bernard A / Hauser, Michael A / Haines, Jonathan L / Wiggs, Janey L. ·1 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA · 2 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA · 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA · 4 Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH · 5 Institute of Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH · 6 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA · 7 Department of Ophthalmogy, Duke University, Duke University Medical Center, Durham, NC · 8 Department of Medicine, Duke University, Duke University Medical Center, Durham, NC · 9 Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL · 10 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI · 11 Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI · 12 Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA · 13 Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO · 14 Department of Ophthalmology, University of North Carolina, Chapel Hill, NC · 15 Department of Ophthalmology, WVU Eye Institute, Morgantown, WV · 16 Scripps Genome Center, University of California at San Diego, San Diego, CA · 17 Emmes Corporation, Chevy Chase, MD · 18 Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL · 19 Department of Ophthalmology, Stanford University, Palo Alto, CA · 20 Department of Ophthalmology, Mayo Clinic, Rochester, MN · 21 Wills Eye Institute, Philadelphia, PA · 22 Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY · 23 Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH · 24 Department of Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, NE · 25 Department of Genetics; Stanford University, Palo Alto, CA · 26 Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD · 27 Department of Ophthalmology, Hamilton Eye Center; University of California at San Diego, San Diego, CA · 28 Department of Cellular Biology & Anatomy, Augusta University, Augusta, GA. ·Menopause · Pubmed #27760082.

ABSTRACT: OBJECTIVE: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. METHODS: Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. RESULTS: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). CONCLUSIONS: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

17 Article Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation. 2016

Ho, Leon C / Sigal, Ian A / Jan, Ning-Jiun / Yang, Xiaoling / van der Merwe, Yolandi / Yu, Yu / Chau, Ying / Leung, Christopher K / Conner, Ian P / Jin, Tao / Wu, Ed X / Kim, Seong-Gi / Wollstein, Gadi / Schuman, Joel S / Chan, Kevin C. ·NeuroImaging Laboratory , University of Pittsburgh, Pittsburgh, PA, USA. · UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China. · McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, China. · Division of Biomedical Engineering, Hong Kong University of Science and Technology, Hong Kong, China. · University Eye Center, Hong Kong Eye Hospital, Hong Kong, China. · Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. · Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA. · Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea. · Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea. · Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA. ·Sci Rep · Pubmed #27561353.

ABSTRACT: The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0-40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

18 Article A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium. 2016

Liu, Yutao / Bailey, Jessica Cooke / Helwa, Inas / Dismuke, W Michael / Cai, Jingwen / Drewry, Michelle / Brilliant, Murray H / Budenz, Donald L / Christen, William G / Chasman, Daniel I / Fingert, John H / Gaasterland, Douglas / Gaasterland, Terry / Gordon, Mae O / Igo, Robert P / Kang, Jae H / Kass, Michael A / Kraft, Peter / Lee, Richard K / Lichter, Paul / Moroi, Sayoko E / Realini, Anthony / Richards, Julia E / Ritch, Robert / Schuman, Joel S / Scott, William K / Singh, Kuldev / Sit, Arthur J / Song, Yeunjoo E / Vollrath, Douglas / Weinreb, Robert / Medeiros, Felipe / Wollstein, Gadi / Zack, Donald J / Zhang, Kang / Pericak-Vance, Margaret A / Gonzalez, Pedro / Stamer, W Daniel / Kuchtey, John / Kuchtey, Rachel W / Allingham, R Rand / Hauser, Michael A / Pasquale, Louis R / Haines, Jonathan L / Wiggs, Janey L. ·Department of Cellular Biology and Anatomy Augusta University, Augusta, Georgia, United States 2James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States 3Center for Biotechnology and Genomic Medicine, Augusta Uni. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States. · Department of Cellular Biology and Anatomy Augusta University, Augusta, Georgia, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States. · Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States. · The Emmes Corporation, Rockville, Maryland, United States. · Scripps Genome Center, University of California at San Diego, San Diego, California, United States. · Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States. · School of Public Health, Harvard University, Boston, Massachusetts, United States. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States. · Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, United States. · Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. · Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States. · Department of Ophthalmology, Stanford University, Palo Alto, California, United States. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States. · Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, California, United States. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States. · Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States 26Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States 27Department of Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States. · Department of Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #27537254.

ABSTRACT: PURPOSE: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG). METHODS: Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls. RESULTS: Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment. CONCLUSIONS: Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

19 Article Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma. 2016

Murphy, Matthew C / Conner, Ian P / Teng, Cindy Y / Lawrence, Jesse D / Safiullah, Zaid / Wang, Bo / Bilonick, Richard A / Kim, Seong-Gi / Wollstein, Gadi / Schuman, Joel S / Chan, Kevin C. ·NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, PA, USA. · UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · Louis J. Fox Center for Vision Restoration, University of Pittsburgh, PA, USA. · Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, PA, USA. · Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, PA, USA. · McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA. · Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea. · Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea. · Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA. · Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA. ·Sci Rep · Pubmed #27510406.

ABSTRACT: Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

20 Article Optic Nerve Head Measurements With Optical Coherence Tomography: A Phantom-Based Study Reveals Differences Among Clinical Devices. 2016

Agrawal, Anant / Baxi, Jigesh / Calhoun, William / Chen, Chieh-Li / Ishikawa, Hiroshi / Schuman, Joel S / Wollstein, Gadi / Hammer, Daniel X. ·Division of Biomedical Physics Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, United States. · Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States 3Department of Bioengineering, Swanson School of En. ·Invest Ophthalmol Vis Sci · Pubmed #27409500.

ABSTRACT: PURPOSE: Optical coherence tomography (OCT) can monitor for glaucoma by measuring dimensions of the optic nerve head (ONH) cup and disc. Multiple clinical studies have shown that different OCT devices yield different estimates of retinal dimensions. We developed phantoms mimicking ONH morphology as a new way to compare ONH measurements from different clinical OCT devices. METHODS: Three phantoms were fabricated to model the ONH: One normal and two with glaucomatous anatomies. Phantoms were scanned with Stratus, RTVue, and Cirrus clinical devices, and with a laboratory OCT system as a reference. We analyzed device-reported ONH measurements of cup-to-disc ratio (CDR) and cup volume and compared them with offline measurements done manually and with a custom software algorithm, respectively. RESULTS: The mean absolute difference between clinical devices with device-reported measurements versus offline measurements was 0.082 vs. 0.013 for CDR and 0.044 mm3 vs. 0.019 mm3 for cup volume. Statistically significant differences between devices were present for 16 of 18 comparisons of device-reported measurements from the phantoms. Offline Cirrus measurements tended to be significantly different from those from Stratus and RTVue. CONCLUSIONS: The interdevice differences in CDR and cup volume are primarily caused by the devices' proprietary ONH analysis algorithms. The three devices yield more similar ONH measurements when a consistent offline analysis technique is applied. Scan pattern on the ONH also may be a factor in the measurement differences. This phantom-based study has provided unique insights into characteristics of OCT measurements of the ONH.

21 Article What is a typical optic nerve head? 2016

Voorhees, A P / Grimm, J L / Bilonick, R A / Kagemann, L / Ishikawa, H / Schuman, J S / Wollstein, G / Sigal, I A. ·Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: Ian@ocularbiomechanics.com. ·Exp Eye Res · Pubmed #27339747.

ABSTRACT: Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

22 Article Decreased Lamina Cribrosa Beam Thickness and Pore Diameter Relative to Distance From the Central Retinal Vessel Trunk. 2016

Wang, Bo / Lucy, Katie A / Schuman, Joel S / Sigal, Ian A / Bilonick, Richard A / Kagemann, Larry / Kostanyan, Tigran / Lu, Chen / Liu, Jonathan / Grulkowski, Ireneusz / Fujimoto, James G / Ishikawa, Hiroshi / Wollstein, Gadi. ·Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States 2Department of Bioengineering, Swanson School of En. · Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States. · Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Pittsburgh, Pennsylvania, United States 4Department of Biostatistics, University of Pittsbu. · Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States. ·Invest Ophthalmol Vis Sci · Pubmed #27286366.

ABSTRACT: PURPOSE: To investigate how the lamina cribrosa (LC) microstructure changes with distance from the central retinal vessel trunk (CRVT), and to determine how this change differs in glaucoma. METHODS: One hundred nineteen eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) of 105 subjects were imaged using swept-source optical coherence tomography (OCT). The CRVT was manually delineated at the level of the anterior LC surface. A line was fit to the distribution of LC microstructural parameters and distance from CRVT to measure the gradient (change in LC microstructure per distance from the CRVT) and intercept (LC microstructure near the CRVT). A linear mixed-effects model was used to determine the effect of diagnosis on the gradient and intercept of the LC microstructure with distance from the CRVT. A Kolmogorov-Smirnov test was applied to determine the difference in distribution between the diagnostic categories. RESULTS: The percent of visible LC in all scans was 26 ± 7%. Beam thickness and pore diameter decreased with distance from the CRVT. Glaucoma eyes had a larger decrease in beam thickness (-1.132 ± 0.503 μm, P = 0.028) and pore diameter (-0.913 ± 0.259 μm, P = 0.001) compared with healthy controls per 100 μm from the CRVT. Glaucoma eyes showed increased variability in both beam thickness and pore diameter relative to the distance from the CRVT compared with healthy eyes (P < 0.05). CONCLUSIONS: These findings results demonstrate the importance of considering the anatomical location of CRVT in the assessment of the LC, as there is a relationship between the distance from the CRVT and the LC microstructure, which differs between healthy and glaucoma eyes.

23 Article Glaucoma Structural and Functional Progression in American and Korean Cohorts. 2016

Kostanyan, Tigran / Sung, Kyung Rim / Schuman, Joel S / Ling, Yun / Lucy, Katie A / Bilonick, Richard A / Ishikawa, Hiroshi / Kagemann, Larry / Lee, Jin Y / Wollstein, Gadi. ·UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. · Asan Medical Center, Department of Ophthalmology, University of Ulsan College of Medicine, Seoul, Republic of Korea. · Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: schumanjs@upmc.edu. · UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. · UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania. ·Ophthalmology · Pubmed #26778345.

ABSTRACT: PURPOSE: To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months. METHODS: All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits. MAIN OUTCOME MEASUREMENTS: The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. RESULTS: The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 μm/year vs. -0.24 μm/year; P < 0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. CONCLUSIONS: Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.

24 Article Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. 2016

Bailey, Jessica N Cooke / Loomis, Stephanie J / Kang, Jae H / Allingham, R Rand / Gharahkhani, Puya / Khor, Chiea Chuen / Burdon, Kathryn P / Aschard, Hugues / Chasman, Daniel I / Igo, Robert P / Hysi, Pirro G / Glastonbury, Craig A / Ashley-Koch, Allison / Brilliant, Murray / Brown, Andrew A / Budenz, Donald L / Buil, Alfonso / Cheng, Ching-Yu / Choi, Hyon / Christen, William G / Curhan, Gary / De Vivo, Immaculata / Fingert, John H / Foster, Paul J / Fuchs, Charles / Gaasterland, Douglas / Gaasterland, Terry / Hewitt, Alex W / Hu, Frank / Hunter, David J / Khawaja, Anthony P / Lee, Richard K / Li, Zheng / Lichter, Paul R / Mackey, David A / McGuffin, Peter / Mitchell, Paul / Moroi, Sayoko E / Perera, Shamira A / Pepper, Keating W / Qi, Qibin / Realini, Tony / Richards, Julia E / Ridker, Paul M / Rimm, Eric / Ritch, Robert / Ritchie, Marylyn / Schuman, Joel S / Scott, William K / Singh, Kuldev / Sit, Arthur J / Song, Yeunjoo E / Tamimi, Rulla M / Topouzis, Fotis / Viswanathan, Ananth C / Verma, Shefali Setia / Vollrath, Douglas / Wang, Jie Jin / Weisschuh, Nicole / Wissinger, Bernd / Wollstein, Gadi / Wong, Tien Y / Yaspan, Brian L / Zack, Donald J / Zhang, Kang / Study, Epic-Norfolk Eye / Anonymous3990854 / Weinreb, Robert N / Pericak-Vance, Margaret A / Small, Kerrin / Hammond, Christopher J / Aung, Tin / Liu, Yutao / Vithana, Eranga N / MacGregor, Stuart / Craig, Jamie E / Kraft, Peter / Howell, Gareth / Hauser, Michael A / Pasquale, Louis R / Haines, Jonathan L / Wiggs, Janey L. ·Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Division of Human Genetics, Genome Institute of Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. · Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA. · Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Eye Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore. · Section of Rheumatology and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA. · Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa, USA. · Department of Anatomy and Cell Biology, University of Iowa, College of Medicine, Iowa City, Iowa, USA. · National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK. · Department of Ophthalmology, University College London, London, UK. · Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. · Eye Doctors of Washington, Chevy Chase, Maryland, USA. · Scripps Genome Center, University of California at San Diego, San Diego, California, USA. · Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia. · Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia. · Medical Research Council Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK. · Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia. · Duke-National University of Singapore Graduate Medical School, Singapore. · The Jackson Laboratory, Bar Harbor, Maine, USA. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. · Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, USA. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA. · Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA. · Center for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA. · Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA. · Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. · Department of Genetics, Stanford University School of Medicine, Palo Alto, California, USA. · Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. · Genentech, San Francisco, California, USA. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, USA. · Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, USA. · Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA. · James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, USA. ·Nat Genet · Pubmed #26752265.

ABSTRACT: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

25 Article Agreement among graders on Heidelberg retina tomograph (HRT) topographic change analysis (TCA) glaucoma progression interpretation. 2015

Iester, Michele M / Wollstein, Gadi / Bilonick, Richard A / Xu, Juan / Ishikawa, Hiroshi / Kagemann, Larry / Schuman, Joel S. ·Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Eye Clinic, DiNOGMI, University of Genoa, Genoa, Italy. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ·Br J Ophthalmol · Pubmed #25336573.

ABSTRACT: PURPOSE: To evaluate agreement among experts of Heidelberg retina tomography's (HRT) topographic change analysis (TCA) printout interpretations of glaucoma progression and explore methods for improving agreement. METHODS: 109 eyes of glaucoma, glaucoma suspect and healthy subjects with ≥5 visits and 2 good quality HRT scans acquired at each visit were enrolled. TCA printouts were graded as progression or non-progression. Each grader was presented with 2 sets of tests: a randomly selected single test from each visit and both tests from each visit. Furthermore, the TCA printouts were classified with grader's individual criteria and with predefined criteria (reproducible changes within the optic nerve head, disregarding changes along blood vessels or at steep rim locations and signs of image distortion). Agreement among graders was modelled using common latent factor measurement error structural equation models for ordinal data. RESULTS: Assessment of two scans per visit without using the predefined criteria reduced overall agreement, as indicated by a reduction in the slope, reflecting the correlation with the common factor, for all graders with no effect on reducing the range of the intercepts between the graders. Using the predefined criteria improved grader agreement, as indicated by the narrower range of intercepts among the graders compared with assessment using individual grader's criteria. CONCLUSIONS: A simple set of predefined common criteria improves agreement between graders in assessing TCA progression. The inclusion of additional scans from each visit does not improve the agreement. We, therefore, recommend setting standardised criteria for TCA progression evaluation.

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