Search

Your search keyword '"Ritch R"' showing total 983 results
Start Over Author "Ritch R"
983 results on '"Ritch R"'

1. Exfoliation syndrome in Northern Nigeria

Author

Idakwo U, Olawoye O, Ajayi BGK, and Ritch R

Subjects
Exfoliation syndrome, glaucoma, cataract, Northern Nigeria, Ophthalmology, RE1-994
Abstract

Ugbede Idakwo,1 Olusola Olawoye,2 Benedictus GK Ajayi,1 Robert Ritch3 1Eleta Eye Institute, Ibadan, Nigeria; 2Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria; 3Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA Purpose: To estimate the frequency of exfoliation syndrome (XFS) and its association with ocular diseases in Northern Nigeria.Materials and methods: Consecutive patients who presented to the outpatient department of ECWA Eye Hospital Kano from February 2015 to May 2015 were included in the study. Each patient had a complete ophthalmic examination. The anterior segment examination included tonometry, gonioscopy, and detailed slit-lamp examination to assess for the presence or absence of exfoliation material, inflammatory cells, and other abnormal findings. Patients with exfoliation material on the anterior lens surface and/or pupillary margin in either or both eyes were considered to have XFS. Statistical analysis was performed using the Statistical Package for the Social Sciences version 16.0.Results: A total of 620 patients living in Northern Nigeria from the 6 geopolitical zones were examined. The majority of them (34.5%) were indigenous Hausas. There was a male preponderance of 56.6%, while the mean age at presentation for examination in all age groups was 55.7±13.7 years. There were 9 patients with XFS; the frequency was 1.5%, with most of the patients being 70–80 years old. In patients who were ≥50 years, the frequency was 2.5%. Patients with XFS had a higher mean age of 68±4.9 years. The frequency of XFS among glaucoma patients was 4.4%, while among cataract patients it was 3.7%. No other associated ocular disease was found in the patients with XFS.Conclusion: This study shows that XFS does exist in Northern Nigeria, as was found in the South. The prevalence of XFS was, however, not reported in the Nigerian National Blindness and Visual Impairment Survey. Therefore, a population-based study is still needed to determine the true prevalence of XFS in Northern Nigeria. Keywords: exfoliation syndrome, glaucoma, cataract, Northern Nigeria, intra-ocular pressure

Published
2018

2. Evaluation of community eye outreach programs for early glaucoma detection in Nigeria

Author

Olawoye O, Fawole OI, Teng CC, and Ritch R

Subjects
Ophthalmology, RE1-994
Abstract

Olusola Olawoye,1 Olufunmilayo I Fawole,2 Christopher C Teng,3–5 Robert Ritch4,5 1Department of Ophthalmology, University College Hospital Ibadan, Nigeria and College of Medicine University of Ibadan, Ibadan, Nigeria; 2Department of Epidemiology, Medical Statistics and Environmental Health, College of Medicine, University of Ibadan, Nigeria; 3Department of Ophthalmology, New York University Langone Medical Center, New York, NY, USA; 4Einhorn Clinical Research Center, The New York Eye and Ear Infirmary, New York, NY, USA; 5New York Medical College, Valhalla, NY, USA Purpose: To evaluate the relevance of community eye outreach programs in the early detection of glaucoma patients in southwest Nigeria. Methods: This was a retrospective, cross-sectional study that was conducted among glaucoma patients referred to the eye clinic of the University College Hospital (UCH), Ibadan, Nigeria, between January 2009 and December 2010 from different sources, including community eye outreach programs. The source of referral, stage of glaucoma, and visual field were recorded. Results: Six hundred and fifty-three patients were studied during this period. The mean age was 56.3 years ± 16.6 years, with a median age of 60 years. Patients referred from eye outreach programs were more likely to have mild to moderate disease than patients referred from other sources, who were more likely to have severe disease according to both the optic nerve head assessment (P < 0.01, Pearson's Chi-square = 10.67, odds ratio = 1.7 [confidence interval = 1.23–2.31]) and visual field assessment (24-2) (P < 0.01, Pearson's Chi-square = 6.07, odds ratio = 1.5 [confidence interval = 1.08–2.03]). Conclusion: Community eye outreach programs appear highly useful in the earlier detection of glaucoma in sub-Saharan Africa. Keywords: community eye outreach, early glaucoma detection, Nigeria glaucoma detection, glaucoma awareness, sub-Saharan Africa.

Published
2013

4. The Glaucoma Symptom Scale: A Brief Index of Glaucoma-Specific Symptoms

Author

Lee, BL, Gutierrez, P, Gordon, M, Wilson, MR, Cioffi, GA, Ritch, R, Sherwood, M, and Mangione, CM

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Neurodegenerative, Clinical Research, Neurosciences, Aging, Clinical Trials and Supportive Activities, Eye Disease and Disorders of Vision, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Eye, Cross-Sectional Studies, Female, Glaucoma, Health Status Indicators, Humans, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Severity of Illness Index, Surveys and Questionnaires, Visual Fields, Opthalmology and Optometry, Ophthalmology & Optometry
Abstract

ObjectiveTo develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS).DesignCross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma.PatientsA sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers.Main outcome measuresParticipants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing.ResultsThe GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between persons with and without glaucoma. Additionally, tests of association with clinical markers of glaucoma severity support the clinical validity of the measure and tests of association with established vision-targeted measures provide evidence of construct validity.ConclusionThe simplicity, brevity, and psychometric properties of the GSS support its use in clinical practice and research to quantify symptoms in patients with glaucoma and to assist in investigations concerning the effect of glaucoma and treatments.

Published
1998

5. Influence of Glaucomatous Visual Field Loss on Health-Related Quality of Life

Author

Gutierrez, P, Wilson, MR, Johnson, C, Gordon, M, Cioffi, GA, Ritch, R, Sherwood, M, Meng, K, and Mangione, CM

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Aging, Prevention, Neurosciences, Clinical Trials and Supportive Activities, Eye Disease and Disorders of Vision, Clinical Research, Neurodegenerative, Eye, Adult, Aged, Aged, 80 and over, Glaucoma, Health Status, Humans, Middle Aged, Models, Theoretical, Multivariate Analysis, Prospective Studies, Quality of Life, Sensitivity and Specificity, Surveys and Questionnaires, Visual Fields, Ophthalmology and optometry
Abstract

We examined the influence of glaucomatous visual field defects on vision-targeted and generic health-related quality of life. Vision-targeted and generic health status were assessed across 5 glaucoma treatment categories and a normal reference group from 5 tertiary care ophthalmology practices during regularly scheduled eye care visits. The sample consisted of 147 patients who were members of specific glaucoma treatment categories and 44 reference group patients. For patients with glaucoma, eligibility included a diagnosis of glaucoma at least 1 year prior to enrollment and no evidence of other eye disease. Participants completed 2 vision-targeted surveys, the National Eye Institute Visual Functioning Questionnaire and the VF-14, and a generic health-related quality of life measure, the Medical Outcomes Study 36-Item Short Form. Data from automated perimetry (Humphrey Field Analyzer 24-2, Humphrey Instruments, San Leandro, Calif) were used to generate Advanced Glaucoma Intervention Study scores for all participants. The Medical Outcomes Study 36-Item Short Form scores from glaucoma and reference group participants collected on a random half of the sample were similar. However, comparisons of the vision-targeted surveys demonstrated significant mean differences on 7 of 11 National Eye Institute Visual Functioning Questionnaire scales, and a trend toward significant differences for the VF-14 (P < .07 by linear regression). Greater visual field defects in the better eye were significantly associated with poorer National Eye Institute Visual Functioning Questionnaire scores (P < .05), as well as with worse VF-14 scores. These findings were most dramatic for patients with the most severe field loss in the better eye. Vision-targeted questionnaires were more sensitive than a generic health-related quality of life measure to differences between glaucoma and normal reference participants. Our findings indicate that self-reports of vision-targeted health-related quality of life are sensitive to visual field loss and may be useful in tandem with the clinical examination to fully understand outcomes of treatment for glaucoma.

Published
1997

8. Exome-based investigation of the genetic basis of human pigmentary glaucoma

Author

van der Heide, C, Goar, W, Meyer, KJ, Alward, WLM, Boese, EA, Sears, NC, Roos, BR, Kwon, YH, DeLuca, AP, Siggs, OM, Gonzaga-Jauregui, C, Sheffield, VC, Wang, K, Stone, EM, Mullins, RF, Anderson, MG, Fan, BJ, Ritch, R, Craig, JE, Wiggs, JL, Scheetz, TE, Fingert, JH, van der Heide, C, Goar, W, Meyer, KJ, Alward, WLM, Boese, EA, Sears, NC, Roos, BR, Kwon, YH, DeLuca, AP, Siggs, OM, Gonzaga-Jauregui, C, Sheffield, VC, Wang, K, Stone, EM, Mullins, RF, Anderson, MG, Fan, BJ, Ritch, R, Craig, JE, Wiggs, JL, Scheetz, TE, and Fingert, JH

Abstract

BACKGROUND: Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. RESULTS: Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. CONCLUSIONS: We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

Published
2021

15. 8-Isoprostaglandin [F.sub.2a] and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome. (Laboratory Science)

Author

Koliakos, G.G., Konstas, A.G.P., Schlotzer-Schrehardt, U., Hollo, G., Katsimbris, I.E., Georgiadis, N., and Ritch, R.

Subjects
Cataract -- Surgery, Vitamin C -- Research, Surgery -- Research, Health, Research
Abstract

Background/aim: The authors investigated the concentrations of 8-isoprostaglandin [F.sub.2a], a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients [...]

Published
2003

23. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), Duijn, C.M. (Cornelia) van, Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), and Duijn, C.M. (Cornelia) van

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019
Full Text
View/download PDF

24. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, PWM, van Leeuwen, EM, Iglesias, AI, Gharahkhani, P, Vitart, V, Khawaja, AP, Simcoe, M, Hoehn, R, Cree, AJ, Igo, RP, Burdon, KP, Craig, JE, Hewitt, AW, Jonas, J, Khor, C-C, Pasutto, F, Mackey, DA, Mitchell, P, Mishra, A, Pang, C, Pasquale, LR, Springelkamp, H, Thorleifsson, G, Thorsteinsdottir, U, Viswanathan, AC, Wojciechowski, R, Wong, T, Young, TL, Zeller, T, Atan, D, Aslam, T, Barman, SA, Barrett, JH, Bishop, P, Blows, P, Bunce, C, Carare, RO, Chakravarthy, U, Chan, M, Chua, SYL, Crabb, DP, Cumberland, PM, Day, A, Desai, P, Dhillon, B, Dick, AD, Egan, C, Ennis, S, Foster, P, Fruttiger, M, Gallacher, JEJ, Garway, DF, Gibson, J, Gore, D, Guggenheim, JA, Hardcastle, A, Harding, SP, Hogg, RE, Keane, PA, Khaw, PT, Lascaratos, G, Macgillivray, T, Mackie, S, Martin, K, McGaughey, M, McGuinness, B, Mckay, GJ, McKibbin, M, Mitry, D, Moore, T, Morgan, JE, Muthy, ZA, O'Sullivan, E, Owen, CG, Patel, P, Paterson, E, Peto, T, Petzold, A, Rahi, JS, Rudnikca, AR, Self, J, Sivaprasad, S, Steel, D, Stratton, I, Strouthidis, N, Sudlow, C, Thomas, D, Trucco, E, Tufail, A, Vernon, SA, Williams, C, Williams, K, Woodside, JV, Yates, MM, Yip, J, Zheng, Y, Allingham, R, Budenz, D, Bailey, JC, Fingert, J, Gaasterland, D, Gaasterland, T, Haines, JL, Hark, L, Hauser, M, Kang, JH, Kraft, P, Lee, R, Lichter, P, Liu, Y, Moroi, S, Pericak, M, Realini, A, Rhee, D, Richards, JR, Ritch, R, Scott, WK, Singh, K, Sit, A, Vollrath, D, Weinreb, R, Wollstein, G, Wilmer, DZ, Gerhold-Ay, A, Nickels, S, Wilson, JF, Hayward, C, Boutin, TS, Polasek, O, Aung, T, Khor, CC, Amin, N, Lotery, AJ, Wiggs, JL, Cheng, C-Y, Hysi, PG, Hammond, CJ, Thiadens, AAHJ, MacGregor, S, Klaver, CCW, van Duijn, CM, Bonnemaijer, PWM, van Leeuwen, EM, Iglesias, AI, Gharahkhani, P, Vitart, V, Khawaja, AP, Simcoe, M, Hoehn, R, Cree, AJ, Igo, RP, Burdon, KP, Craig, JE, Hewitt, AW, Jonas, J, Khor, C-C, Pasutto, F, Mackey, DA, Mitchell, P, Mishra, A, Pang, C, Pasquale, LR, Springelkamp, H, Thorleifsson, G, Thorsteinsdottir, U, Viswanathan, AC, Wojciechowski, R, Wong, T, Young, TL, Zeller, T, Atan, D, Aslam, T, Barman, SA, Barrett, JH, Bishop, P, Blows, P, Bunce, C, Carare, RO, Chakravarthy, U, Chan, M, Chua, SYL, Crabb, DP, Cumberland, PM, Day, A, Desai, P, Dhillon, B, Dick, AD, Egan, C, Ennis, S, Foster, P, Fruttiger, M, Gallacher, JEJ, Garway, DF, Gibson, J, Gore, D, Guggenheim, JA, Hardcastle, A, Harding, SP, Hogg, RE, Keane, PA, Khaw, PT, Lascaratos, G, Macgillivray, T, Mackie, S, Martin, K, McGaughey, M, McGuinness, B, Mckay, GJ, McKibbin, M, Mitry, D, Moore, T, Morgan, JE, Muthy, ZA, O'Sullivan, E, Owen, CG, Patel, P, Paterson, E, Peto, T, Petzold, A, Rahi, JS, Rudnikca, AR, Self, J, Sivaprasad, S, Steel, D, Stratton, I, Strouthidis, N, Sudlow, C, Thomas, D, Trucco, E, Tufail, A, Vernon, SA, Williams, C, Williams, K, Woodside, JV, Yates, MM, Yip, J, Zheng, Y, Allingham, R, Budenz, D, Bailey, JC, Fingert, J, Gaasterland, D, Gaasterland, T, Haines, JL, Hark, L, Hauser, M, Kang, JH, Kraft, P, Lee, R, Lichter, P, Liu, Y, Moroi, S, Pericak, M, Realini, A, Rhee, D, Richards, JR, Ritch, R, Scott, WK, Singh, K, Sit, A, Vollrath, D, Weinreb, R, Wollstein, G, Wilmer, DZ, Gerhold-Ay, A, Nickels, S, Wilson, JF, Hayward, C, Boutin, TS, Polasek, O, Aung, T, Khor, CC, Amin, N, Lotery, AJ, Wiggs, JL, Cheng, C-Y, Hysi, PG, Hammond, CJ, Thiadens, AAHJ, MacGregor, S, Klaver, CCW, and van Duijn, CM

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019

28. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma

Author

King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), Zeller, T. (Tanja), King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), and Zeller, T. (Tanja)

Abstract

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60–100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP rs7631

Published
2018
Full Text
View/download PDF

29. Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: analysis in Two Large Datasets

Author

Bailey, JNC, Gharahkhani, P, Kang, JH, Butkiewicz, M, Sullivan, DA, Weinreb, RN, Aschard, H, Allingham, RR, Ashley-Koch, A, Lee, RK, Moroi, SE, Brilliant, MH, Wollstein, G, Schuman, JS, Fingert, JH, Budenz, DL, Realini, T, Gaasterland, T, Scott, WK, Singh, K, Sit, AJ, Igo, RP, Song, YE, Hark, L, Ritch, R, Rhee, DJ, Vollrath, D, Zack, DJ, Medeiros, F, Vajaranant, TS, Chasman, DI, Christen, WG, Pericak-Vance, MA, Liu, Y, Kraft, P, Richards, JE, Rosner, BA, Hauser, MA, Craig, JE, Burdon, KP, Hewitt, AW, Mackey, DA, Haines, JL, MacGregor, S, Wiggs, JL, Pasquale, LR, Bailey, JNC, Gharahkhani, P, Kang, JH, Butkiewicz, M, Sullivan, DA, Weinreb, RN, Aschard, H, Allingham, RR, Ashley-Koch, A, Lee, RK, Moroi, SE, Brilliant, MH, Wollstein, G, Schuman, JS, Fingert, JH, Budenz, DL, Realini, T, Gaasterland, T, Scott, WK, Singh, K, Sit, AJ, Igo, RP, Song, YE, Hark, L, Ritch, R, Rhee, DJ, Vollrath, D, Zack, DJ, Medeiros, F, Vajaranant, TS, Chasman, DI, Christen, WG, Pericak-Vance, MA, Liu, Y, Kraft, P, Richards, JE, Rosner, BA, Hauser, MA, Craig, JE, Burdon, KP, Hewitt, AW, Mackey, DA, Haines, JL, MacGregor, S, Wiggs, JL, and Pasquale, LR

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.

Published
2018

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

Author

Aschard, H., Kang, J.H., Iglesias, A.I., Hysi, P., Bailey, J.N., Khawaja, A.P., Allingham, R.R., Ashley-Koch, A., Lee, R.K., Moroi, S.E., Brilliant, M.H., Wollstein, G., Schuman, J.S., Fingert, J.H., Budenz, D.L., Realini, T., Gaasterland, T., Scott, W.K., Singh, K., Sit, A.J., Igo, R.P., Jr., Song, Y.E., Hark, L., Ritch, R., Rhee, D.J., Gulati, V., Haven, S., Vollrath, D., Zack, D.J., Medeiros, F., Weinreb, R.N., Cheng, C.Y., Chasman, D.I., Christen, W.G., Pericak-Vance, M.A., Liu, Y., Kraft, P., Richards, J.E., Rosner, B.A., Hauser, M.A., Klaver, C.C.W., vanDuijn, C.M., Haines, J., Wiggs, J.L., Pasquale, L.R., Aschard, H., Kang, J.H., Iglesias, A.I., Hysi, P., Bailey, J.N., Khawaja, A.P., Allingham, R.R., Ashley-Koch, A., Lee, R.K., Moroi, S.E., Brilliant, M.H., Wollstein, G., Schuman, J.S., Fingert, J.H., Budenz, D.L., Realini, T., Gaasterland, T., Scott, W.K., Singh, K., Sit, A.J., Igo, R.P., Jr., Song, Y.E., Hark, L., Ritch, R., Rhee, D.J., Gulati, V., Haven, S., Vollrath, D., Zack, D.J., Medeiros, F., Weinreb, R.N., Cheng, C.Y., Chasman, D.I., Christen, W.G., Pericak-Vance, M.A., Liu, Y., Kraft, P., Richards, J.E., Rosner, B.A., Hauser, M.A., Klaver, C.C.W., vanDuijn, C.M., Haines, J., Wiggs, J.L., and Pasquale, L.R.

Abstract

Item does not contain fulltext, 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 x 10(-27)) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 x 10(-5)); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

Published
2017

32. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Author

Chintalapudi, S.R. (Sumana R.), Maria, D. (Doaa), Di Wang, X. (Xiang), Bailey, J.N.C. (Jessica N. Cooke), Allingham, R. (Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Igo Jr., R.P. (Robert), Hee Kang, J. (Jae), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Wollstein, G. (Gadi), Zack, D.J. (Donald), Aung, T. (Tin), Bonnemaijer, P. (Peter), Cheng, C.-Y. (Cheng-Yu), Craig, J.E. (Jamie), Duijn, C.M. (Cornelia) van, Gharahkhani, P. (Puya), Iglesias Gonzalez, A. (Adriana), Hammond, C.J. (Christopher J.), Hewitt, A. (Alex), Hoehn, R. (Rene), Jonansson, F. (Fridbert), Khawaja, A.P. (Anthony), Chuen Khor, C. (Chiea), Klaver, C.C.W. (Caroline), Lotery, A.J. (Andrew), Mackey, D.A. (David), MacGregor, S. (Stuart), Pang, C. (Calvin), Pasutto, F. (Francesca), Zwart, J-A. (John-Anker), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnar), Vitart, V. (Veronique), Vithana, E.N. (Eranga), Young, T.L. (Terri L.), Zeller, T. (Tanja), Hysi, P.G. (Pirro), Wiggs, J.L. (Janey L.), Williams, R.W. (Robert W.), Jablonski, M.M. (Monica M.), Chintalapudi, S.R. (Sumana R.), Maria, D. (Doaa), Di Wang, X. (Xiang), Bailey, J.N.C. (Jessica N. Cooke), Allingham, R. (Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Igo Jr., R.P. (Robert), Hee Kang, J. (Jae), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Wollstein, G. (Gadi), Zack, D.J. (Donald), Aung, T. (Tin), Bonnemaijer, P. (Peter), Cheng, C.-Y. (Cheng-Yu), Craig, J.E. (Jamie), Duijn, C.M. (Cornelia) van, Gharahkhani, P. (Puya), Iglesias Gonzalez, A. (Adriana), Hammond, C.J. (Christopher J.), Hewitt, A. (Alex), Hoehn, R. (Rene), Jonansson, F. (Fridbert), Khawaja, A.P. (Anthony), Chuen Khor, C. (Chiea), Klaver, C.C.W. (Caroline), Lotery, A.J. (Andrew), Mackey, D.A. (David), MacGregor, S. (Stuart), Pang, C. (Calvin), Pasutto, F. (Francesca), Zwart, J-A. (John-Anker), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnar), Vitart, V. (Veronique), Vithana, E.N. (Eranga), Young, T.L. (Terri L.), Zeller, T. (Tanja), Hysi, P.G. (Pirro), Wiggs, J.L. (Janey L.), Williams, R.W. (Robert W.), and Jablonski, M.M. (Monica M.)

Abstract

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with know

Published
2017
Full Text
View/download PDF

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

Author

Bailey, JNC, Loomis, SJ, Kang, JH, Allingham, RR, Gharahkhani, P, Khor, CC, Burdon, KP, Aschard, H, Chasman, DI, Igo, RP, Hysi, PG, Glastonbury, CA, Ashley-Koch, A, Brilliant, M, Brown, AA, Budenz, DL, Buil, A, Cheng, CY, Choi, H, Christen, WG, Curhan, G, De Vivo, I, Fingert, JH, Foster, PJ, Fuchs, C, Gaasterland, D, Gaasterland, T, Hewitt, AW, Hu, F, Hunter, DJ, Khawaja, AP, Lee, RK, Li, Z, Lichter, PR, Mackey, DA, McGuffin, P, Mitchell, P, Moroi, SE, Perera, SA, Pepper, KW, Qi, Q, Realini, T, Richards, JE, Ridker, PM, Rimm, E, Ritch, R, Ritchie, M, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Song, YE, Tamimi, RM, Topouzis, F, Viswanathan, AC, Verma, SS, Vollrath, D, Wang, JJ, Weisschuh, N, Wissinger, B, Wollstein, G, Wong, TY, Yaspan, BL, Zack, DJ, Zhang, K, Weinreb, RN, Pericak-Vance, MA, Small, K, Hammond, CJ, Aung, T, Liu, Y, Vithana, EN, MacGregor, S, Craig, JE, Kraft, P, Howell, G, Hauser, MA, and Pasquale, LR

Subjects
ANZRAG Consortium
Abstract

© 2016 Nature America, Inc. 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.

Published
2016

34. Evaluation of LOXL1 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Author

Aragon-Martin, JA, Ritch, R, Liebmann, J, O'Brien, C, Blaaow, K, Mercieca, F, Spiteri, A, Cobb, CJ, Damji, KF, Tarkkanen, A, Rezaie, T, Child, AH, and Sarfarazi, M

Subjects
Polymorphism, Genetic, Chromosome Mapping, Exfoliation Syndrome, Polymorphism, Single Nucleotide, eye diseases, Cohort Studies, Europe, Haplotypes, Case-Control Studies, North America, Humans, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Research Article
Abstract

Purpose: To evaluate genetic susceptibility of lysyl oxidase-like 1 (LOXL1) gene polymorphisms to exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in a case-control cohort of American and European patients.\ud \ud Methods: DNA from a total of 620 individuals including 287 exfoliation patients and 333 healthy control subjects were\ud extracted by standard methods. Three single nucleotide polymorphisms (SNPs) of rs1048661 (R141L), rs3825942\ud (G153D), and rs2165241 were genotyped in these individuals by SNaPshot Assay. The seven coding exons of the LOXL1 gene and their immediate flanking regions were directly sequenced in 95 affected patients. Data management and\ud case-control association studies were performed with SNP-STAT and PLINK programs. The obtained DNA sequences\ud were evaluated with the STADEN package.\ud \ud Results: The 287 unrelated exfoliation cases comprised of 171 American patients (mostly of European background) and\ud 116 patients from 12 European countries. This phenotype was further divided into patients with exfoliation only and no\ud glaucoma (XFO; n=95), exfoliation with glaucoma (XFG; n=133), and exfoliation unclassified (XFU; n=59). Genotypic\ud data were analyzed separately for XFO, XFG, XFU, and XFS (all exfoliations; n=287) and for Americans and Europeans.\ud The observed genotypic frequencies for each exfoliation phenotype or population were tabulated separately and tested for deviation from the Hardy–Weinberg equilibrium (HWE) using a standard Χ2 test. There were no HWE deviations and no significant genotypic differences between these subcategories for the three studied SNPs. For the combined exfoliation cohort, homozygote genotypes of G/G (rs1048661), G/G (rs3825942), and T/T (rs2165241) were significantly overrepresented. Likewise, case-control allelic association for rs1048661 (p=7.74x10−9), rs3825942 (p=3.10x10−17), and rs2165241 (p=4.85x10−24) were highly significant. The corresponding two-locus haplotype frequencies of GG for rs1048661-rs3825942 (p=1.47x10−27), GT for rs1048661-rs2165241 (p=1.29x10−24), and GT for rs3825942-rs2165241 (p=2.02x10−24) were highly associated with exfoliation phenotypes. The combined effect of these three SNPs revealed that the GGT haplotype is overrepresented by 66% in exfoliation cases, and this deviation from controls is highly significant\ud (p=1.93x10−24). This haplotype constituted a major risk factor for development of exfoliation in both XFS and XFG. By contrast, the GAC haplotype was significantly underrepresented (p=4.99x10−18) in exfoliation cases by 83% and may potentially have a protective effect for this condition with an estimated attributable risk percent reduction of 457%. The only other haplotype that was significantly different between cases and controls was TGC (p=5.82x10−9). No observation was made for the GAT haplotype. The combined three haplotypes of GGT, GAC, and TGC were associated with 91% of the exfoliation syndrome cases in the studied populations. Seven coding exons of LOXL1 were also sequenced in 95 affected cases. In addition to the three above-mentioned SNPs, 12 other variations were also observed in these patients(G240G, D292D, A320A, V385V, rs2304719, IVS3+23C>T, IVS3–155G>A, IVS3–101G>A, IVS4+49G>A,\ud rs2304721, IVS5–121C>T, and rs2304722). None were considered a disease-causing mutation.\ud \ud Conclusions: We confirmed a strong association with LOXL1 variants in our patients. For the LOXL1 gene, individual\ud alleles of rs1048661 (G), rs3825942 (G), and rs2165241 (T) are highly associated with XFS and XFG in American and\ud European populations. The GGT haplotype constitutes a major risk haplotype for exfoliation, and GAC may have a\ud protective role. DNA sequencing of 95 affected patients did not show any mutations in this gene. The LOXL1 SNPs are\ud located in the 15q24.1 band and within a genetic locus (GLC1N) that is associated with primary open-angle glaucoma\ud (POAG). However, the LOXL1 genetic predisposition is only limited to exfoliation with or without glaucoma and does\ud not include the POAG phenotype.

Published
2008

35. Nailfold capillary morphology in exfoliation syndrome

Author

Cousins, C C, primary, Kang, J H, additional, Bovee, C, additional, Wang, J, additional, Greenstein, S H, additional, Turalba, A, additional, Shen, L Q, additional, Brauner, S, additional, Boumenna, T, additional, Blum, S, additional, Levkovitch-Verbin, H, additional, Ritch, R, additional, Wiggs, J L, additional, Knepper, P A, additional, and Pasquale, L R, additional

Published
2017
Full Text
View/download PDF

36. Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure

Author

Girkin, CA, Nievergelt, CM, Kuo, JZ, Maihofer, AX, Huisingh, C, Liebmann, JM, Ayyagari, R, Weinreb, RN, Ritch, R, Zangwill, LM, and Grp, ADAGESS

Subjects
Retinal Ganglion Cells, Male, Aging, genetic structures, Optic Disk, Black People, Eye, Ophthalmology & Optometry, optic disc, Medical and Health Sciences, Cornea, Cohort Studies, Nerve Fibers, biogeographic ancestry, Genetics, Humans, race, Eye Disease and Disorders of Vision, African Continental Ancestry Group, Aged, Neurosciences, retinal nerve fiber layer, Glaucoma, Middle Aged, Blacks, Biological Sciences, corneal thickness, eye diseases, Open-Angle, Regression Analysis, Female, sense organs, ADAGES Study Group
Abstract

PurposeWe determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness.MethodsData were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the current substudy. A total of 31 ancestry informative markers (AIMs) with large allele frequencies differences between populations was used to calculate admixture proportion (implemented in STRUCTURE). Correlations with BGA adjusted for diagnosis, age, and sex for CCT and optic disc area using the whole group and RNFL thickness adjusted for age and sex for the normal study participants were determined.ResultsThe mean percentage of African admixture was 79.6% in the self-described African Descent (AD) group and 3.5% in the European Descent (ED) group. Percent African ancestry was significantly correlated with CCT (ρ = -0.27, P < 0.0001) and disc area (ρ = 0.15, P < 0.0001), but only marginally associated with RNFL thickness (ρ = 0.20, P = 0.092) in adjusted models.ConclusionsThe BGA correlates with variation in ocular features that significantly differ across racial groups and that have been associated with the development of glaucoma. While BGA can provide an objective measurement of the biologic component of self-described race for ocular research, for most nongenetic epidemiologic studies, self-described race may adequately describe the associations with these ocular characteristics. (ClinicalTrials.gov number, NCT00221923.).

Published
2015

37. A New Provocative Test for Glaucoma

Author

Ritch, R, primary, Kanadani, Fabio N, additional, Moreira, TCA, additional, Campos, LF, additional, Vianello, MP, additional, Corradi, J, additional, Dorairaj, SK, additional, and Freitas, ALA, additional

Published
2016
Full Text
View/download PDF

38. A common variant near TGFBR3 is associated with primary open angle glaucoma

Author

Li, Z, Allingham, RR, Nakano, M, Jia, L, Chen, Y, Ikeda, Y, Mani, B, Chen, L-J, Kee, C, Garway-Heath, DF, Sripriya, S, Fuse, N, Abu-Amero, KK, Huang, C, Namburi, P, Burdon, K, Perera, SA, Gharahkhani, P, Lin, Y, Ueno, M, Ozaki, M, Mizoguchi, T, Krishnadas, SR, Osman, EA, Lee, MC, Chan, ASY, Tajudin, L-SA, Do, T, Goncalves, A, Reynier, P, Zhang, H, Bourne, R, Goh, D, Broadway, D, Husain, R, Negi, AK, Su, DH, Ho, C-L, Blanco, AA, Leung, CKS, Wong, TT, Yakub, A, Liu, Y, Nongpiur, ME, Han, JC, Hon, DN, Shantha, B, Zhao, B, Sang, J, Zhang, N, Sato, R, Yoshii, K, Panda-Jonas, S, Koch, AEA, Herndon, LW, Moroi, SE, Challa, P, Foo, JN, Bei, J-X, Zeng, Y-X, Simmons, CP, Tran, NBC, Sharmila, PF, Chew, M, Lim, B, Tam, POS, Chua, E, Ng, XY, Yong, VHK, Chong, YF, Meah, WY, Vijayan, S, Seongsoo, S, Xu, W, Teo, YY, Bailey, JNC, Kang, JH, Haines, JL, Cheng, CY, Saw, S-M, Tai, E-S, Richards, JE, Ritch, R, Gaasterland, DE, Pasquale, LR, Liu, J, Jonas, JB, Milea, D, George, R, Al-Obeidan, SA, Mori, K, Macgregor, S, Hewitt, AW, Girkin, CA, Zhang, M, Sundaresan, P, Vijaya, L, Mackey, DA, Wong, TY, Craig, JE, Sun, X, Kinoshita, S, Wiggs, JL, Khor, C-C, Yang, Z, Pang, CP, Wang, N, Hauser, MA, Tashiro, K, Aung, T, Vithana, EN, Li, Z, Allingham, RR, Nakano, M, Jia, L, Chen, Y, Ikeda, Y, Mani, B, Chen, L-J, Kee, C, Garway-Heath, DF, Sripriya, S, Fuse, N, Abu-Amero, KK, Huang, C, Namburi, P, Burdon, K, Perera, SA, Gharahkhani, P, Lin, Y, Ueno, M, Ozaki, M, Mizoguchi, T, Krishnadas, SR, Osman, EA, Lee, MC, Chan, ASY, Tajudin, L-SA, Do, T, Goncalves, A, Reynier, P, Zhang, H, Bourne, R, Goh, D, Broadway, D, Husain, R, Negi, AK, Su, DH, Ho, C-L, Blanco, AA, Leung, CKS, Wong, TT, Yakub, A, Liu, Y, Nongpiur, ME, Han, JC, Hon, DN, Shantha, B, Zhao, B, Sang, J, Zhang, N, Sato, R, Yoshii, K, Panda-Jonas, S, Koch, AEA, Herndon, LW, Moroi, SE, Challa, P, Foo, JN, Bei, J-X, Zeng, Y-X, Simmons, CP, Tran, NBC, Sharmila, PF, Chew, M, Lim, B, Tam, POS, Chua, E, Ng, XY, Yong, VHK, Chong, YF, Meah, WY, Vijayan, S, Seongsoo, S, Xu, W, Teo, YY, Bailey, JNC, Kang, JH, Haines, JL, Cheng, CY, Saw, S-M, Tai, E-S, Richards, JE, Ritch, R, Gaasterland, DE, Pasquale, LR, Liu, J, Jonas, JB, Milea, D, George, R, Al-Obeidan, SA, Mori, K, Macgregor, S, Hewitt, AW, Girkin, CA, Zhang, M, Sundaresan, P, Vijaya, L, Mackey, DA, Wong, TY, Craig, JE, Sun, X, Kinoshita, S, Wiggs, JL, Khor, C-C, Yang, Z, Pang, CP, Wang, N, Hauser, MA, Tashiro, K, Aung, T, and Vithana, EN

Abstract

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

Published
2015

39. Molecular biomarkers in glaucoma

Author

Bhattacharya, S. K., Lee, R. K., Grus, F. H., Bhattacharya, S, Grus, F, Lee, R, Beuerman, R, Burlingame, A, Coutinho, A, Crabb, J. W., Crowston, J, Dodel, R, Fingert, J, Hauser, M. A., John, S, Kaur, I, Martin, K, Miller, S, Pandey, A, Pasquale, L. R., Pericak-Vance, M, Petricoin, E, Pfeiffer, N, Ritch, R, Schmetterer, L, Tezel, G, Topouzis, F, Viswanathan, A, Weinreb, R, Wiggs, J. L., Zack, D, Zhou, Y, Asai, N, Bell, K, Bitoun, P, Boatright, J, Boehm, N, Bonakdar, M, Borras, T, Cao, J, Carper, D, Chin, H, Coca-Prados, M, Dong C., -J, Faunce, D, Fautsch, M, Flanagan, J, Gong, H, Gonzalez, H, Grishanin, R, Grosskreutz, C, Grunden, J, Hong, S, Hood, D, Ju W., -K, Junk, A, Kang, K. D., Karl, M, Kaufman, H, Kaufman, P, Khaw, P, Kim I., -B, Kirihara, T, Komaromy, A, Kramann, C, Liebmann, J, Lindsey, J, Lorenz, K, Mackey, D, Markabi, S, Mest, M, Miller, R, Moroi, S, O’Brien, J, O’Brien, C, Parikh, T, Park, S. C., Pe’Er, J, Petrash, J. M., Qu, J, Rittenhouse, K, Roberds, S, Sharif, N, Shepard, A, Sui, R, Toris, C, Traverso, C, Valorie, T, Weinmann, R, Wheeler, L, Whitlock, A, and Wirostko, B.

Subjects
Genetic Markers, Proteomics, medicine.medical_specialty, genetic structures, Glaucoma, Human health, Cellular and Molecular Neuroscience, Ophthalmology, Medicine, Humans, Biomarkers, Genomics, Metabolome, Sensory Systems, Medicine (all), Biomarker discovery, Blindness, business.industry, Articles, medicine.disease, Molecular biomarkers, eye diseases, Bench to bedside, Optometry, sense organs, business
Abstract

The seventh annual ARVO/Pfizer Ophthalmic Research Institute conference was held Friday and Saturday, April 29 and 30, 2011, at the Fort Lauderdale Hyatt Regency Pier 66, Fort Lauderdale, Florida. The conference, funded by The ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to determine the state of knowledge pertaining to molecular biomarkers associated with glaucoma, as well as the methods to identify and validate them to predict (a) those who would be susceptible to development of glaucoma; (b) markers that will enable prediction of glaucoma progression; and (c) markers that will predict efficacy of treatment of glaucoma. Identification of such biomarkers will aid in prevention of glaucoma-related vision loss and blindness. The conference focused on an evaluation of glaucoma molecular biomarkers and progress needed for future validation of glaucoma biomarkers. A working group of 21 glaucoma researchers, 7 scientists focused on diseases other than glaucoma and with expertise in areas such as proteomic biomarkers or molecular mechanisms for neurodegeneration, and 60 observers from ARVO, Pfizer, and clinical and basic ophthalmic research convened to evaluate current understanding of the molecular biomarkers of glaucoma. The meeting format emphasized discussion and concentrated on questions within areas of glaucoma molecular biomarker research: Session I: How to define a biomarker in medicine? Current knowledge about biomarkers in human health and in glaucoma Session II: Genetic biomarkers in glaucoma Session III: Proteomic biomarkers in glaucoma Session IV: Pre-immune and immune events: Immunoproteomics and its possible applications in glaucoma Session V: From bench to bedside: How can a translational approach be successful? Each session began with a 10-minute overview by a glaucoma researcher followed by a 30-minute presentation by an outside expert, with parallels between their fields of expertise and the eye included. Invited outside experts covered several areas of research, including proteomic biomarker discovery in cancer (Emanuel Petricoin, PhD, George Mason University, Maryland; and Akhilesh Pandey, MD, PhD, Johns Hopkins University, Maryland) and astroglial cells in neurodegeneration (Stephen D. Miller, PhD, Northwestern University, Illinois).

Published
2013

41. Preliminary testing of a new ice impact panel

Author

Gagnon, R., Bugden, A., and Ritch, R.

Subjects
Ice impact
Abstract

A modular ice impact panel, intended for future ship / bergy bit collision tests, has been designed that incorporates new pressure-sensing technology. A single module of the panel, with sensing area of 1 m2, has been fabricated and tested in the lab by dropping heavy masses of freshwater ice on it from heights up to 1.8 m. The central component of the Impact Module is a large cast acrylic block, 1 m x 1 m x 0.5 m, housed in a strong steel frame. The Impact Module design is made possible by the strength and transparency characteristics of the acrylic. The Module utilizes two types of pressure sensors, one consisting of strain-gauged acrylic cylinders (2.5 cm diameter) that are imbedded in the face of the acrylic block at 9 locations. The other technology is an optomechanical system consisting of many thin narrow strips (13 mm x 0.9 m x 4 mm) of acrylic that cover the impacting face of the acrylic block. Elastic flattening of the slightly convex bottom surface of the strips occurs when pressed against the face of the block during impacts. A highspeed video camera, positioned behind the transparent block, records the deformation of the strips from which the corresponding pressure is determined from calibrations. The effective squareshaped unit sensing area for this technology is 13 mm x 13 mm, implying that the Impact Module has the equivalent of about 4500 symmetric-shaped pressure sensors on its surface. The acrylic block is supported on four large flat-jack load cells that measure the impact loads. The tests demonstrated that the Impact Module is very robust and the pressure-sensing technologies yield consistent results. The large capacity load sensors were also shown to be functional., 20th International Conference on Port and Ocean Engineering under Arctic Conditions, 9-12 June 2009, Luleå, Sweden

Published
2009

42. Overview of bergy bit impact trials

Author

Gagnon, R. E., Cumming, D., Ritch, R., Browne, R. P., Johnston, M., Frederking, R., McKenna, R. F., and Ralph, F.

Abstract

This paper presents and overview of bergy bit impact trials carried out on the CCGS Terry Fox off the northern tip of the island of Newfoundland in June 18-23, 2001. The trial consisted of impacting target iceberg ice masses ranging from roughly 30 t (growlers) to 22,000 t (bergy bits) on an instrumented bow area of the 'Terry Fox' at various forward speeds. Parameters measured included impact forces, pressure and contact areas, ship motions with six degrees of freedom, ship forward speed, and ambient environmental factors. In addition, extensive video and photographic records were compiled, including stereo photographs of the bergy bits. Furthermore, a multi-beam sonar was used to determine underwater profiles of some of the targeted ice massed. Temperature profiles were obtained for a number of bergy bits and some ice samples were collected from undamaged and impacted ice. This paper includes a description of the 'Terry Fox', instrumentation/set-up used, ice characterization and some sample results., 16th International Symposium on Ice, 2-6 December 2002, Dunedin, New Zealand

Published
2002

44. Combined exfoliation and pigment dispersion: an overlap syndrome

Author

Mudumbai, R, Liebmann, J M, and Ritch, R

Subjects
Male, food and beverages, Iris, Middle Aged, Exfoliation Syndrome, Prognosis, eye diseases, Risk Factors, Humans, Female, Pigment Epithelium of Eye, Glaucoma, Open-Angle, Intraocular Pressure, Research Article, Retrospective Studies
Abstract

PURPOSE: To describe a series of patients with combined pigment dispersion syndrome (PDS) and exfoliation syndrome (XFS) and to introduce a concept, the overlap syndrome, to aid in assessing multiple risk factors for glaucomatous damage. METHODS: A retrospective review of the records of all patients on our database who carried a diagnosis of both PDS/pigmentary glaucoma (PG) and XFS/exfoliative glaucoma (XFG). RESULTS: We identified 26 patients as having both XFS/XFG and PDS/PG. The average age was 64.3 +/- 9.8 years and 19 of 26 were men. All patients had bilateral PDS/PG. Bilateral XFS/XFG was present in 9 of 26 patients, and of the 17 patients with unilateral involvement, the left eye was affected in 13. CONCLUSION: Both XFS and PDS are common. Middle-aged patients with known PDS/PG should be suspected of having the onset of XFS if 1 eye escapes intraocular pressure control. Patients presenting with unilateral XFG may also have signs of PDS/PG, often remitted. We define an overlap syndrome as the appearance of a new co-morbidity for glaucomatous damage in a patient with a pre-existing risk factor, which then changes the course, and prognosis of the disease. This concept should be particularly useful in dealing with secondary and normal-tension glaucoma.

Published
1999

46. A unification hypothesis of pigment dispersion syndrome

Author

Ritch, R

Subjects
Male, Philosophy, Animals, Humans, Iris, Eye Diseases, Hereditary, Female, sense organs, Exfoliation Syndrome, Research Article, Ultrasonography
Abstract

PURPOSE: To synthesize recent findings regarding pigment dispersion syndrome in order to arrive at a hypothesis concerning the nature of an underlying genetic predisposition. METHODS: The literature on the subject was reviewed and analyzed. RESULTS: Eyes with pigment dispersion syndrome differ from normal in that they have a larger iris, a midperipheral posterior iris concavity that increases with accommodation, a more posterior iris insertion, increased iridolenticular contact that is reversed by inhibition of blinking, possibly an inherent weakness of the iris pigment epithelium, and an increased incidence of lattice degeneration of the retina. CONCLUSION: A gene affecting some aspect of the development of the middle third of the eye early in the third trimester appears at the present time to be the most likely cause.

Published
1996

Catalog

Books, media, physical & digital resources
See catalog results