42 results on '"Isaacs, Timothy"'
Search Results
2. The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma
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O'Day, Roderick F., Conway, R. Max, Lim, Li-Anne, Giblin, Michael, Cherepanoff, Svetlana, Joshua, Anthony, McKay, Daniel, McKenzie, John D., Fog, Lotte S., Holly, Peta, Shackleton, Mark, Kee, Damien, Philips, Claire, McKelvie, Penny, Bhikoo, Riyaz, Hadden, Peter, Negretti, Guy S., Sagoo, Mandeep S., Damato, Bertil E., Sia, David, McGrath, Lindsay, Glasson, William, Isaacs, Timothy, Gillies, Mark, and Barthelmes, Daniel
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- 2024
- Full Text
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3. Future perspectives of uveal melanoma blood based biomarkers
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Beasley, Aaron B., Chen, Fred K., Isaacs, Timothy W., and Gray, Elin S.
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- 2022
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4. The Visual Outcomes of Macular Hole Surgery: A Registry-Based Study by the Australian and New Zealand Society of Retinal Specialists
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Allen, Penelope, Ambler, John, Bourke, Robert, Branley, Michael, Buttery, Robert, Campbell, William, Chang, Andrew, Chauhan, Devinder, Chen, Fred, Chen, Simon, Clark, Ben, Donaldson, Mark, Downie, John, Essex, Rohan, Evans, Kay, Fabinyi, David, Fleming, Ben, Fung, Adrian, Gilhotra, J.S., Gorbatov, Mark, Groenveld, Erwin, Guest, Stephen, Hadden, Peter, Hall, Anthony B., Heriot, Wilson, Ho, I-Van, Hunyor, Alex, Isaacs, Timothy, Jones, Andrew, Kwan, Tony, Kang, Hyong Kwon, Lake, Stewart, Lee, Lawrence, Luckie, Alan, McAllister, Ian, McCombe, Mark, McKay, David, O’Rourke, Mike, Park, Joseph, Phillips, Russell, Reddie, Ian, Roufail, Ed, Saha, Niladri, Subramaniam, Devaraj, Tsanaktsidis, Gina, Vandeleur, Kevin, Vilacorta-Sandez, Welch, Sarah, Wong, H.C., Yellachich, Dimitri, Essex, Rohan W., Hunyor, Alex P., Moreno-Betancur, Margarita, Yek, John T.O., Kingston, Zabrina S., Campbell, William G., Connell, Paul P., and McAllister, Ian L.
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- 2018
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5. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours
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Johansson, Peter A., Brooks, Kelly, Newell, Felicity, Palmer, Jane M., Wilmott, James S., Pritchard, Antonia L., Broit, Natasa, Wood, Scott, Carlino, Matteo S., Leonard, Conrad, Koufariotis, Lambros T., Nathan, Vaishnavi, Beasley, Aaron B., Howlie, Madeleine, Dawson, Rebecca, Rizos, Helen, Schmidt, Chris W., Long, Georgina V., Hamilton, Hayley, Kiilgaard, Jens F., Isaacs, Timothy, Gray, Elin S., Rolfe, Olivia J., Park, John J., Stark, Andrew, Mann, Graham J., Scolyer, Richard A., Pearson, John V., van Baren, Nicolas, Waddell, Nicola, Wadt, Karin W., McGrath, Lindsay A., Warrier, Sunil K., Glasson, William, and Hayward, Nicholas K.
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- 2020
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6. Capturing uveal melanoma (UM) global practice patterns and clinical outcomes in the collaborative ocular melanoma natural history (OMNi) study (NCT04588662).
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Sacco, Joseph J., primary, Orloff, Marlana M., additional, Patel, Sapna Pradyuman, additional, Conway, Max, additional, Lim, Li-Anne, additional, Fog, Lotte S., additional, Sia, David, additional, McKenzie, John, additional, McKay, Daniel, additional, O'day, Roderick, additional, Isaacs, Timothy, additional, Shoushtari, Alexander Noor, additional, Sullivan, Ryan J., additional, Kin, Sarah, additional, Gwadry-Sridhar, Femida Hussein, additional, Joshua, Anthony M., additional, and Carvajal, Richard D., additional
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- 2022
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7. Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
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Beasley, Aaron B., primary, Isaacs, Timothy W., additional, Vermeulen, Tersia, additional, Freeman, James, additional, DeSousa, Jean-Louis, additional, Bhikoo, Riyaz, additional, Hennessy, Doireann, additional, Reid, Anna, additional, Chen, Fred K., additional, Bentel, Jacqueline, additional, McKay, Daniel, additional, Conway, R. Max, additional, Pereira, Michelle R., additional, Mirzai, Bob, additional, Calapre, Leslie, additional, Erber, Wendy N., additional, Ziman, Melanie R., additional, and Gray, Elin S., additional
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- 2021
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8. Survival from uveal melanoma in Western Australia 1981–2005
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Chew, Avenell L, Spilsbury, Katrina, and Isaacs, Timothy W
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- 2015
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9. Complement Factor H Y402H and C-Reactive Protein Polymorphism and Photodynamic Therapy Response in Age-Related Macular Degeneration
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Feng, Xuefeng, Xiao, Jing, Longville, Brooke, Tan, Alexander X.J., Wu, Xia Ni, Cooper, Matthew N., McAllister, Ian L., Isaacs, Timothy, Palmer, Lyle J., and Constable, Ian J.
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- 2009
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10. Rosai–Dorfman disease presenting as choroidal melanoma: a case report and review of the literature
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Vermeulen, Tersia L., Isaacs, Timothy W., Spagnolo, Dominic, and Amanuel, Benhur
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- 2013
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11. Analysis of circulating tumour cells in early-stage uveal melanoma: Evaluation of tumour marker expression to increase capture
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Beasley, Aaron B., Isaacs, Timothy W., Vermeulen, Tersia, Freeman, James, De Sousa, Jean-Louis, Bhikoo, Riyaz, Hennessy, Doireann, Reid, Anna, Chen, Fred K., Bentel, Jacqueline, McKay, Daniel, Max Conway, R., Pereira, Michelle R., Mirzai, Bob, Calapre, Leslie, Erber, Wendy N., Ziman, Melanie R., Gray, Elin S., Beasley, Aaron B., Isaacs, Timothy W., Vermeulen, Tersia, Freeman, James, De Sousa, Jean-Louis, Bhikoo, Riyaz, Hennessy, Doireann, Reid, Anna, Chen, Fred K., Bentel, Jacqueline, McKay, Daniel, Max Conway, R., Pereira, Michelle R., Mirzai, Bob, Calapre, Leslie, Erber, Wendy N., Ziman, Melanie R., and Gray, Elin S.
- Abstract
Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.
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- 2021
12. Low-pass whole-genome sequencing as a method of determining copy number variations in uveal melanoma tissue samples
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Beasley, Aaron B., Bentel, Jacqueline, Allcock, Richard J.N., Vermeulen, Tersia, Calapre, Leslie, Isaacs, Timothy, Ziman, Melanie R., Chen, Fred K., Gray, Elin S., Beasley, Aaron B., Bentel, Jacqueline, Allcock, Richard J.N., Vermeulen, Tersia, Calapre, Leslie, Isaacs, Timothy, Ziman, Melanie R., Chen, Fred K., and Gray, Elin S.
- Abstract
Analysis of specific somatic copy number alterations (SCNAs) using multiplex ligation-dependent probe amplification (MLPA) is used routinely as a prognostic test for uveal melanoma (UM). This technique requires relatively large amounts of input DNA, unattainable from many small fine-needle aspirate biopsy specimens. Herein, we compared the use of MLPA with whole-genome amplification (WGA) combined with low-pass whole-genome sequencing (LP-WGS) for detection of SCNA profiles in UM biopsy specimens. DNA was extracted from 21 formalin-fixed, paraffin-embedded UM samples and SCNAs were assessed using MLPA and WGA followed by LP-WGS. Cohen's κ was used to assess the concordance of copy number calls of each individual chromosome arm for each patient. MLPA and WGA/LP-WGS detection of SCNAs in chromosomes 1p, 3, 6, and 8 were compared and found to be highly concordant with a Cohen's κ of 0.856 (bias-corrected and accelerated 95% CI, 0.770–0.934). Only 13 of 147 (8.8%) chromosomal arms investigated resulted in discordant calls, predominantly SCNAs detected by WGA/LP-WGS but not MLPA. These results indicate that LP-WGS might be a suitable alternative or adjunct to MLPA for the detection of SCNAs associated with prognosis of UM, for cases with limiting tissue or DNA yields. © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology
- Published
- 2020
13. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours
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Johansson, Peter A, Brooks, Kelly, Newell, Felicity, Palmer, Jane M, Wilmott, James S, Pritchard, Antonia L, Broit, Natasa, Wood, Scott, Carlino, Matteo S, Leonard, Conrad, Koufariotis, Lambros T, Nathan, Vaishnavi, Beasley, Aaron B, Howlie, Madeleine, Dawson, Rebecca, Rizos, Helen, Schmidt, Chris W, Long, Georgina V, Hamilton, Hayley, Kiilgaard, Jens F, Isaacs, Timothy, Gray, Elin S, Rolfe, Olivia J, Park, John J, Stark, Andrew, Mann, Graham J, Scolyer, Richard A, Pearson, John V, van Baren, Nicolas, Waddell, Nicola, Wadt, Karin W, McGrath, Lindsay A, Warrier, Sunil K, Glasson, William, Hayward, Nicholas K, Johansson, Peter A, Brooks, Kelly, Newell, Felicity, Palmer, Jane M, Wilmott, James S, Pritchard, Antonia L, Broit, Natasa, Wood, Scott, Carlino, Matteo S, Leonard, Conrad, Koufariotis, Lambros T, Nathan, Vaishnavi, Beasley, Aaron B, Howlie, Madeleine, Dawson, Rebecca, Rizos, Helen, Schmidt, Chris W, Long, Georgina V, Hamilton, Hayley, Kiilgaard, Jens F, Isaacs, Timothy, Gray, Elin S, Rolfe, Olivia J, Park, John J, Stark, Andrew, Mann, Graham J, Scolyer, Richard A, Pearson, John V, van Baren, Nicolas, Waddell, Nicola, Wadt, Karin W, McGrath, Lindsay A, Warrier, Sunil K, Glasson, William, and Hayward, Nicholas K
- Abstract
Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).
- Published
- 2020
14. 16. AUSTRALIAN AND NEW ZEALAND STUDY OF PDT IN CHOROIDAL AMELANOTIC MELANOMA (ANZSOPICAM) - THREE YEAR RESULTS: 2416
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Campbell, William, Glasson, William, Finnigan, Sid, Giblin, Michael, Hadden, Peter, Isaacs, Timothy, McKenzie, John, Muecke, James, and Pejnovic, Tanya
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- 2012
15. 10. CLINICAL IMPLICATIONS OF CHROMOSOMAL ABERRATIONS IN CHOROIDAL MELANOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS: 1610
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Franchina, Maria, Isaacs, Timothy, Mackey, David, and Hewitt, Alex
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- 2012
16. Low-Pass Whole-Genome Sequencing as a Method of Determining Copy Number Variations in Uveal Melanoma Tissue Samples
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Beasley, Aaron B., primary, Bentel, Jacqueline, additional, Allcock, Richard J.N., additional, Vermeulen, Tersia, additional, Calapre, Leslie, additional, Isaacs, Timothy, additional, Ziman, Melanie R., additional, Chen, Fred K., additional, and Gray, Elin S., additional
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- 2020
- Full Text
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17. SURVIVAL FROM UVEAL MELANOMA IN WESTERN AUSTRALIA 1981-2005: 11.
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Chew, Avenell, Spilsbury, Katrina, and Isaacs, Timothy
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- 2010
18. Choroidal involvement in Rosai-Dorfman syndrome may be depicted and followed using enhanced depth imaging optical coherence tomography (EDI-OCT)
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Isaacs, Timothy William, Vermeulen, Tersia L., Spagnolo, Dominic, and Amanuel, Ben
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- 2015
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19. A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision
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Stark, Mitchell S., primary, Gray, Elin S., additional, Isaacs, Timothy, additional, Chen, Fred K., additional, Millward, Michael, additional, McEvoy, Ashleigh, additional, Zaenker, Pauline, additional, Ziman, Melanie, additional, Soyer, H. Peter, additional, Glasson, William J., additional, Warrier, Sunil K., additional, Stark, Andrew L., additional, Rolfe, Olivia J., additional, Palmer, Jane M., additional, and Hayward, Nicholas K., additional
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- 2019
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20. Rapid resolution of severe disc new vessels in proliferative diabetic retinopathy following a single intravitreal injection of bevacizumab (Avastin)
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Isaacs, Timothy W and Barry, Chris
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- 2006
21. A panel of circulating MicroRNAs detects uveal melanoma with high precision
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Stark, Mitchell S., Gray, Elin S., Isaacs, Timothy, Chen, Fred K., Millward, Michael, McEvoy, Ashleigh, Zaenker, Pauline, Ziman, Melanie, Soyer, H. Peter, Glasson, William J., Warrier, Sunil K., Stark, Andrew L., Rolfe, Olivia J., Palmer, Jane M., Hayward, Nicholas K., Stark, Mitchell S., Gray, Elin S., Isaacs, Timothy, Chen, Fred K., Millward, Michael, McEvoy, Ashleigh, Zaenker, Pauline, Ziman, Melanie, Soyer, H. Peter, Glasson, William J., Warrier, Sunil K., Stark, Andrew L., Rolfe, Olivia J., Palmer, Jane M., and Hayward, Nicholas K.
- Abstract
Purpose: To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi. Methods: We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system. Results: A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point. Conclusions: This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel’s high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features. Translational Relevance: Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.
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- 2019
22. Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration
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Waksmunski, Andrea R., Grunin, Michelle, Kinzy, Tyler G., Igo, Robert P., Jr., Haines, Jonathan L., Bailey, Jessica N. Cooke, Fritsche, Lars G., Igl, Wilmar, Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L., Burdon, Kathryn P., Hebbring, Scott J., Wen, Cindy, Gorski, Mathias, Kim, Ivana K., Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P. N., Bala, Elisa, Lee, Kristine E., Hunter, David J., Sardell, Rebecca J., Mitchell, Paul, Merriam, Joanna E., Cipriani, Valentina, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T. E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabrielle H. S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad, I, Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L., Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A., Constable, Ian J., Craig, Jamie E., Kitchner, Terrie E., Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Ouyang, Hong, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Stark, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J., Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Said, Saddek, Sahel, Jose-Alain, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas, V, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frederic, Blanche, Helene, Deleuze, Jean-Francois, Truitt, Barbara, Peachey, Neal S., Meuer, Stacy M., Myers, Chelsea E., Moore, Emily L., Klein, Ronald, Hauser, Michael A., Postel, Eric A., Courtenay, Monique D., Schwartz, Stephen G., Kovach, Jaclyn L., Scott, William K., Liew, Gerald, Tan, Ava G., Gopinath, Bamini, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Renee, Brantley, Milam A., Jr., Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T. M., de Jong, Eiko K., Hoyng, Carel B., Cain, Melinda S., Richardson, Andrea J., Martin, Tammy M., Blangero, John, Weeks, Daniel E., Dhillon, Bal, van Duijn, Cornelia M., Doheny, Kimberly F., Romm, Jane, Klaver, Caroline C. W., Hayward, Caroline, Gorin, Michael B., Klein, Michael L., Baird, Paul N., den Hollander, Anneke, I, Fauser, Sascha, Yates, John R. W., Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A., Klein, Barbara E. K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Leveillard, Thierry, Zhang, Kang, Brilliant, Murray H., Hewitt, Alex W., Swaroop, Anand, Chew, Emily Y., Pericak-Vance, Margaret A., DeAngelis, Margaret, Stambolian, Dwight, Iyengar, Sudha K., Weber, Bernhard H. F., Abecasis, Goncalo R., Heid, Iris M., Waksmunski, Andrea R., Grunin, Michelle, Kinzy, Tyler G., Igo, Robert P., Jr., Haines, Jonathan L., Bailey, Jessica N. Cooke, Fritsche, Lars G., Igl, Wilmar, Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L., Burdon, Kathryn P., Hebbring, Scott J., Wen, Cindy, Gorski, Mathias, Kim, Ivana K., Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P. N., Bala, Elisa, Lee, Kristine E., Hunter, David J., Sardell, Rebecca J., Mitchell, Paul, Merriam, Joanna E., Cipriani, Valentina, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T. E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabrielle H. S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad, I, Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L., Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A., Constable, Ian J., Craig, Jamie E., Kitchner, Terrie E., Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Ouyang, Hong, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Stark, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J., Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Said, Saddek, Sahel, Jose-Alain, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas, V, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frederic, Blanche, Helene, Deleuze, Jean-Francois, Truitt, Barbara, Peachey, Neal S., Meuer, Stacy M., Myers, Chelsea E., Moore, Emily L., Klein, Ronald, Hauser, Michael A., Postel, Eric A., Courtenay, Monique D., Schwartz, Stephen G., Kovach, Jaclyn L., Scott, William K., Liew, Gerald, Tan, Ava G., Gopinath, Bamini, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Renee, Brantley, Milam A., Jr., Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T. M., de Jong, Eiko K., Hoyng, Carel B., Cain, Melinda S., Richardson, Andrea J., Martin, Tammy M., Blangero, John, Weeks, Daniel E., Dhillon, Bal, van Duijn, Cornelia M., Doheny, Kimberly F., Romm, Jane, Klaver, Caroline C. W., Hayward, Caroline, Gorin, Michael B., Klein, Michael L., Baird, Paul N., den Hollander, Anneke, I, Fauser, Sascha, Yates, John R. W., Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A., Klein, Barbara E. K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Leveillard, Thierry, Zhang, Kang, Brilliant, Murray H., Hewitt, Alex W., Swaroop, Anand, Chew, Emily Y., Pericak-Vance, Margaret A., DeAngelis, Margaret, Stambolian, Dwight, Iyengar, Sudha K., Weber, Bernhard H. F., Abecasis, Goncalo R., and Heid, Iris M.
- Abstract
PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) drive'' the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD.
- Published
- 2019
23. Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma
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Beasley, Aaron, primary, Isaacs, Timothy, additional, Khattak, Muhammad A., additional, Freeman, James B., additional, Allcock, Richard, additional, Chen, Fred K., additional, Pereira, Michelle R., additional, Yau, Kyle, additional, Bentel, Jaqueline, additional, Vermeulen, Tersia, additional, Calapre, Leslie, additional, Millward, Michael, additional, Ziman, Melanie R., additional, and Gray, Elin S., additional
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- 2018
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24. Postmortem Identification by Means of a Recovered Intraocular Lens
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Isaacs, Timothy W., Margolius, Karin A., and Chester, Graeme H.
- Published
- 1997
25. Benign fleck retina
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ISAACS, TIMOTHY W, McALLISTER, IAN L, and WADE, MATTHEW S
- Published
- 1996
26. Low-Pass Whole-Genome Sequencing as a Method of Determining Copy Number Variations in Uveal Melanoma Tissue Samples
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Beasley, Aaron B., Bentel, Jacqueline, Allcock, Richard J.N., Vermeulen, Tersia, Calapre, Leslie, Isaacs, Timothy, Ziman, Melanie R., Chen, Fred K., and Gray, Elin S.
- Abstract
Analysis of specific somatic copy number alterations (SCNAs) using multiplex ligation-dependent probe amplification (MLPA) is used routinely as a prognostic test for uveal melanoma (UM). This technique requires relatively large amounts of input DNA, unattainable from many small fine-needle aspirate biopsy specimens. Herein, we compared the use of MLPA with whole-genome amplification (WGA) combined with low-pass whole-genome sequencing (LP-WGS) for detection of SCNA profiles in UM biopsy specimens. DNA was extracted from 21 formalin-fixed, paraffin-embedded UM samples and SCNAs were assessed using MLPA and WGA followed by LP-WGS. Cohen's κ was used to assess the concordance of copy number calls of each individual chromosome arm for each patient. MLPA and WGA/LP-WGS detection of SCNAs in chromosomes 1p, 3, 6, and 8 were compared and found to be highly concordant with a Cohen's κ of 0.856 (bias-corrected and accelerated 95% CI, 0.770–0.934). Only 13 of 147 (8.8%) chromosomal arms investigated resulted in discordant calls, predominantly SCNAs detected by WGA/LP-WGS but not MLPA. These results indicate that LP-WGS might be a suitable alternative or adjunct to MLPA for the detection of SCNAs associated with prognosis of UM, for cases with limiting tissue or DNA yields.
- Published
- 2024
- Full Text
- View/download PDF
27. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
- Author
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Fritsche, Lars G., Igl, Wilmar, Bailey, Jessica N. Cooke, Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L., Burdon, Kathryn P., Hebbring, Scott J., Wen, Cindy, Gorski, Mathias, Kim, Ivana K., Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P. N., Bala, Elisa, Lee, Kristine E., Hunter, David J., Sardell, Rebecca J., Mitchell, Paul, Merriam, Joanna E., Cipriani, Valentina, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T. E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabrielle H. S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad I., Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L., Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A., Constable, Ian J., Craig, Jamie E., Kitchner, Terrie E., Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Starke, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J., Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Said, Saddek, Sahel, Jose-Main, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas V., Grunin, Michelle, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frederic, Blanche, Helene, Deleuze, Jean-Francois, Igo, Robert P., Jr., Truitt, Barbara, Peachey, Neal S., Meuer, Stacy M., Myers, Chelsea E., Moore, Emily L., Klein, Ronald, Hauser, Michael A., Postel, Eric A., Courtenay, Monique D., Schwartz, Stephen G., Kovach, Jaclyn L., Scott, William K., Liew, Gerald, Tan, Ava G., Gopinath, Bamini, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Renee, Brantley, Milam A., Jr., Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T. M., de Jong, Eiko K., Hoyng, Carel B., Cain, Melinda S., Richardson, Andrea J., Martin, Tammy M., Blangero, John, Weeks, Daniel E., Dhillon, Bal, van Duijn, Cornelia M., Doheny, Kimberly F., Romm, Jane, Klaver, Caroline C. W., Hayward, Caroline, Gorin, Michael B., Klein, Michael L., Baird, Paul N., den Hollander, Anneke I., Fauser, Sascha, Yates, John R. W., Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A., Klein, Barbara E. K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Leveillard, Thierry, Zhang, Kang, Brilliant, Murray H., Hewitt, Alex W., Swaroop, Anand, Chew, Emily Y., Pericak-Vance, Margaret A., DeAngelis, Margaret, Stambolian, Dwight, Haines, Jonathan L., Iyengar, Sudha K., Weber, Bernhard H. F., Abecasis, Goncalo R., Heid, Iris M., Fritsche, Lars G., Igl, Wilmar, Bailey, Jessica N. Cooke, Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L., Burdon, Kathryn P., Hebbring, Scott J., Wen, Cindy, Gorski, Mathias, Kim, Ivana K., Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P. N., Bala, Elisa, Lee, Kristine E., Hunter, David J., Sardell, Rebecca J., Mitchell, Paul, Merriam, Joanna E., Cipriani, Valentina, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T. E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabrielle H. S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad I., Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L., Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A., Constable, Ian J., Craig, Jamie E., Kitchner, Terrie E., Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Starke, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J., Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Said, Saddek, Sahel, Jose-Main, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas V., Grunin, Michelle, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frederic, Blanche, Helene, Deleuze, Jean-Francois, Igo, Robert P., Jr., Truitt, Barbara, Peachey, Neal S., Meuer, Stacy M., Myers, Chelsea E., Moore, Emily L., Klein, Ronald, Hauser, Michael A., Postel, Eric A., Courtenay, Monique D., Schwartz, Stephen G., Kovach, Jaclyn L., Scott, William K., Liew, Gerald, Tan, Ava G., Gopinath, Bamini, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Renee, Brantley, Milam A., Jr., Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T. M., de Jong, Eiko K., Hoyng, Carel B., Cain, Melinda S., Richardson, Andrea J., Martin, Tammy M., Blangero, John, Weeks, Daniel E., Dhillon, Bal, van Duijn, Cornelia M., Doheny, Kimberly F., Romm, Jane, Klaver, Caroline C. W., Hayward, Caroline, Gorin, Michael B., Klein, Michael L., Baird, Paul N., den Hollander, Anneke I., Fauser, Sascha, Yates, John R. W., Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A., Klein, Barbara E. K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Leveillard, Thierry, Zhang, Kang, Brilliant, Murray H., Hewitt, Alex W., Swaroop, Anand, Chew, Emily Y., Pericak-Vance, Margaret A., DeAngelis, Margaret, Stambolian, Dwight, Haines, Jonathan L., Iyengar, Sudha K., Weber, Bernhard H. F., Abecasis, Goncalo R., and Heid, Iris M.
- Abstract
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 x 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 x 10(-10)). Very rare coding variants (frequency <0.1 %) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
- Published
- 2016
28. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration
- Author
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Cuellar-Partida, Gabriel, primary, Craig, Jamie E., additional, Burdon, Kathryn P., additional, Wang, Jie Jin, additional, Vote, Brendan J., additional, Souzeau, Emmanuelle, additional, McAllister, Ian L., additional, Isaacs, Timothy, additional, Lake, Stewart, additional, Mackey, David A., additional, Constable, Ian J., additional, Mitchell, Paul, additional, Hewitt, Alex W., additional, and MacGregor, Stuart, additional
- Published
- 2016
- Full Text
- View/download PDF
29. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
- Author
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Fritsche, Lars G, primary, Igl, Wilmar, additional, Bailey, Jessica N Cooke, additional, Grassmann, Felix, additional, Sengupta, Sebanti, additional, Bragg-Gresham, Jennifer L, additional, Burdon, Kathryn P, additional, Hebbring, Scott J, additional, Wen, Cindy, additional, Gorski, Mathias, additional, Kim, Ivana K, additional, Cho, David, additional, Zack, Donald, additional, Souied, Eric, additional, Scholl, Hendrik P N, additional, Bala, Elisa, additional, Lee, Kristine E, additional, Hunter, David J, additional, Sardell, Rebecca J, additional, Mitchell, Paul, additional, Merriam, Joanna E, additional, Cipriani, Valentina, additional, Hoffman, Joshua D, additional, Schick, Tina, additional, Lechanteur, Yara T E, additional, Guymer, Robyn H, additional, Johnson, Matthew P, additional, Jiang, Yingda, additional, Stanton, Chloe M, additional, Buitendijk, Gabriëlle H S, additional, Zhan, Xiaowei, additional, Kwong, Alan M, additional, Boleda, Alexis, additional, Brooks, Matthew, additional, Gieser, Linn, additional, Ratnapriya, Rinki, additional, Branham, Kari E, additional, Foerster, Johanna R, additional, Heckenlively, John R, additional, Othman, Mohammad I, additional, Vote, Brendan J, additional, Liang, Helena Hai, additional, Souzeau, Emmanuelle, additional, McAllister, Ian L, additional, Isaacs, Timothy, additional, Hall, Janette, additional, Lake, Stewart, additional, Mackey, David A, additional, Constable, Ian J, additional, Craig, Jamie E, additional, Kitchner, Terrie E, additional, Yang, Zhenglin, additional, Su, Zhiguang, additional, Luo, Hongrong, additional, Chen, Daniel, additional, Ouyang, Hong, additional, Flagg, Ken, additional, Lin, Danni, additional, Mao, Guanping, additional, Ferreyra, Henry, additional, Stark, Klaus, additional, von Strachwitz, Claudia N, additional, Wolf, Armin, additional, Brandl, Caroline, additional, Rudolph, Guenther, additional, Olden, Matthias, additional, Morrison, Margaux A, additional, Morgan, Denise J, additional, Schu, Matthew, additional, Ahn, Jeeyun, additional, Silvestri, Giuliana, additional, Tsironi, Evangelia E, additional, Park, Kyu Hyung, additional, Farrer, Lindsay A, additional, Orlin, Anton, additional, Brucker, Alexander, additional, Li, Mingyao, additional, Curcio, Christine A, additional, Mohand-Saïd, Saddek, additional, Sahel, José-Alain, additional, Audo, Isabelle, additional, Benchaboune, Mustapha, additional, Cree, Angela J, additional, Rennie, Christina A, additional, Goverdhan, Srinivas V, additional, Grunin, Michelle, additional, Hagbi-Levi, Shira, additional, Campochiaro, Peter, additional, Katsanis, Nicholas, additional, Holz, Frank G, additional, Blond, Frédéric, additional, Blanché, Hélène, additional, Deleuze, Jean-François, additional, Igo, Robert P, additional, Truitt, Barbara, additional, Peachey, Neal S, additional, Meuer, Stacy M, additional, Myers, Chelsea E, additional, Moore, Emily L, additional, Klein, Ronald, additional, Hauser, Michael A, additional, Postel, Eric A, additional, Courtenay, Monique D, additional, Schwartz, Stephen G, additional, Kovach, Jaclyn L, additional, Scott, William K, additional, Liew, Gerald, additional, Tan, Ava G, additional, Gopinath, Bamini, additional, Merriam, John C, additional, Smith, R Theodore, additional, Khan, Jane C, additional, Shahid, Humma, additional, Moore, Anthony T, additional, McGrath, J Allie, additional, Laux, Reneé, additional, Brantley, Milam A, additional, Agarwal, Anita, additional, Ersoy, Lebriz, additional, Caramoy, Albert, additional, Langmann, Thomas, additional, Saksens, Nicole T M, additional, de Jong, Eiko K, additional, Hoyng, Carel B, additional, Cain, Melinda S, additional, Richardson, Andrea J, additional, Martin, Tammy M, additional, Blangero, John, additional, Weeks, Daniel E, additional, Dhillon, Bal, additional, van Duijn, Cornelia M, additional, Doheny, Kimberly F, additional, Romm, Jane, additional, Klaver, Caroline C W, additional, Hayward, Caroline, additional, Gorin, Michael B, additional, Klein, Michael L, additional, Baird, Paul N, additional, den Hollander, Anneke I, additional, Fauser, Sascha, additional, Yates, John R W, additional, Allikmets, Rando, additional, Wang, Jie Jin, additional, Schaumberg, Debra A, additional, Klein, Barbara E K, additional, Hagstrom, Stephanie A, additional, Chowers, Itay, additional, Lotery, Andrew J, additional, Léveillard, Thierry, additional, Zhang, Kang, additional, Brilliant, Murray H, additional, Hewitt, Alex W, additional, Swaroop, Anand, additional, Chew, Emily Y, additional, Pericak-Vance, Margaret A, additional, DeAngelis, Margaret, additional, Stambolian, Dwight, additional, Haines, Jonathan L, additional, Iyengar, Sudha K, additional, Weber, Bernhard H F, additional, Abecasis, Gonçalo R, additional, and Heid, Iris M, additional
- Published
- 2015
- Full Text
- View/download PDF
30. Rosai–Dorfman disease presenting as choroidal melanoma: a case report and review of the literature
- Author
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Vermeulen, Tersia L., primary, Isaacs, Timothy W., additional, Spagnolo, Dominic, additional, and Amanuel, Benhur, additional
- Published
- 2012
- Full Text
- View/download PDF
31. Biallelic Mutations in PLA2G5, Encoding Group V Phospholipase A2, Cause Benign Fleck Retina
- Author
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Sergouniotis, Panagiotis I., primary, Davidson, Alice E., additional, Mackay, Donna S., additional, Lenassi, Eva, additional, Li, Zheng, additional, Robson, Anthony G., additional, Yang, Xu, additional, Kam, Jaimie Hoh, additional, Isaacs, Timothy W., additional, Holder, Graham E., additional, Jeffery, Glen, additional, Beck, Jonathan A., additional, Moore, Anthony T., additional, Plagnol, Vincent, additional, and Webster, Andrew R., additional
- Published
- 2011
- Full Text
- View/download PDF
32. Management and Outcomes of Postoperative Endophthalmitis since the Endophthalmitis Vitrectomy Study
- Author
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Ng, Jonathon Q., primary, Morlet, Nigel, additional, Pearman, John W., additional, Constable, Ian J., additional, McAllister, Ian L., additional, Kennedy, Christopher J., additional, Isaacs, Timothy, additional, and Semmens, James B., additional
- Published
- 2005
- Full Text
- View/download PDF
33. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
- Author
-
Fritsche, Lars G, Igl, Wilmar, Bailey, Jessica N Cooke, Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L, Burdon, Kathryn P, Hebbring, Scott J, Wen, Cindy, Gorski, Mathias, Kim, Ivana K, Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P N, Bala, Elisa, Lee, Kristine E, Hunter, David J, Sardell, Rebecca J, Mitchell, Paul, Merriam, Joanna E, Cipriani, Valentina, Hoffman, Joshua D, Schick, Tina, Lechanteur, Yara T E, Guymer, Robyn H, Johnson, Matthew P, Jiang, Yingda, Stanton, Chloe M, Buitendijk, Gabriëlle H S, Zhan, Xiaowei, Kwong, Alan M, Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E, Foerster, Johanna R, Heckenlively, John R, Othman, Mohammad I, Vote, Brendan J, Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L, Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A, Constable, Ian J, Craig, Jamie E, Kitchner, Terrie E, Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Ouyang, Hong, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Stark, Klaus, von Strachwitz, Claudia N, Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A, Morgan, Denise J, Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E, Park, Kyu Hyung, Farrer, Lindsay A, Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A, Mohand-Saïd, Saddek, Sahel, José-Alain, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J, Rennie, Christina A, Goverdhan, Srinivas V, Grunin, Michelle, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G, Blond, Frédéric, Blanché, Hélène, Deleuze, Jean-François, Igo, Robert P, Truitt, Barbara, Peachey, Neal S, Meuer, Stacy M, Myers, Chelsea E, Moore, Emily L, Klein, Ronald, Hauser, Michael A, Postel, Eric A, Courtenay, Monique D, Schwartz, Stephen G, Kovach, Jaclyn L, Scott, William K, Liew, Gerald, Tan, Ava G, Gopinath, Bamini, Merriam, John C, Smith, R Theodore, Khan, Jane C, Shahid, Humma, Moore, Anthony T, McGrath, J Allie, Laux, Reneé, Brantley, Milam A, Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T M, de Jong, Eiko K, Hoyng, Carel B, Cain, Melinda S, Richardson, Andrea J, Martin, Tammy M, Blangero, John, Weeks, Daniel E, Dhillon, Bal, van Duijn, Cornelia M, Doheny, Kimberly F, Romm, Jane, Klaver, Caroline C W, Hayward, Caroline, Gorin, Michael B, Klein, Michael L, Baird, Paul N, den Hollander, Anneke I, Fauser, Sascha, Yates, John R W, Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A, Klein, Barbara E K, Hagstrom, Stephanie A, Chowers, Itay, Lotery, Andrew J, Léveillard, Thierry, Zhang, Kang, Brilliant, Murray H, Hewitt, Alex W, Swaroop, Anand, Chew, Emily Y, Pericak-Vance, Margaret A, DeAngelis, Margaret, Stambolian, Dwight, Haines, Jonathan L, Iyengar, Sudha K, Weber, Bernhard H F, Abecasis, Gonçalo R, and Heid, Iris M
- Abstract
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10−8) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10−10). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
- Published
- 2016
- Full Text
- View/download PDF
34. Early resolution of premacular haemorrhage following Nd:YAG laser photodisruption of posterior hyaloid
- Author
-
Isaacs, Timothy W., primary, Barry, Chris, additional, and McAllister, Ian L., additional
- Published
- 1996
- Full Text
- View/download PDF
35. Familial idiopathic juxtafoveolar retinal telangiectasis
- Author
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Isaacs, Timothy W, primary and McAllister, Ian L, additional
- Published
- 1996
- Full Text
- View/download PDF
36. Adenocarcinoma metastatic to the choroid: Diagnosis by trans-scleral biopsy
- Author
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Isaacs, Timothy W, primary and McAllister, Ian L, additional
- Published
- 1995
- Full Text
- View/download PDF
37. Clinical application of circulating tumor cells and circulating tumor DNA in uveal melanoma
- Author
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Beasley, Aaron, Isaacs, Timothy, Khattak, Muhammad K., Freeman, James B., Allcock, Richard, Chen, Fred K., Pereira, Michelle R., Yau, Kyle, Bentel, Jaqueline, Vermeulen, Tersia, Calapre, Leslie, Millward, Michael, Ziman, Melanie R., Gray, Elin S., Beasley, Aaron, Isaacs, Timothy, Khattak, Muhammad K., Freeman, James B., Allcock, Richard, Chen, Fred K., Pereira, Michelle R., Yau, Kyle, Bentel, Jaqueline, Vermeulen, Tersia, Calapre, Leslie, Millward, Michael, Ziman, Melanie R., and Gray, Elin S.
- Abstract
Beasley, A., Isaacs, T., Khattak, M. A., Freeman, J. B., Allcock, R., Chen, F. K., ... & Calapre, L. (2018). Clinical application of circulating tumor cells and circulating tumor DNA in uveal melanoma. JCO Precision Oncology, 2, 1-12. Available here.
38. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours
- Author
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<p>Funding information available at https://doi.org/10.1007/s00429-020-02071-1</p>, Johansson, Peter A., Brooks, Kelly, Newell, Felicity, Palmer, Jane M., Wilmott, James S., Pritchard, Antonia L., Broit, Natasa, Wood, Scott, Carlino, Matteo S., Leonard, Conrad, Koufariotis, Labros T., Nathan, Vaishnavi, Beasley, Aaron B., Howlie, Madeleine, Dawson, Rebecca, Rizos, Helen, Schmidt, Chris W., Long, Georgina V., Hamilton, Hayley, Kiilgaard, Jens F., Isaacs, Timothy, Gray, Elin S., Rolfe, Olivia J., Park, John J., Stark, Andrew, Mann, Graham J., Scolyer, Richard A., Pearson, John V., van Baren, Nicolas, Waddell, Nicola, Wadt, Karin W., McGrath, Lindsay A., Warrier, Sunil K., Glasson, William, Hayward, Nicholas K., <p>Funding information available at https://doi.org/10.1007/s00429-020-02071-1</p>, Johansson, Peter A., Brooks, Kelly, Newell, Felicity, Palmer, Jane M., Wilmott, James S., Pritchard, Antonia L., Broit, Natasa, Wood, Scott, Carlino, Matteo S., Leonard, Conrad, Koufariotis, Labros T., Nathan, Vaishnavi, Beasley, Aaron B., Howlie, Madeleine, Dawson, Rebecca, Rizos, Helen, Schmidt, Chris W., Long, Georgina V., Hamilton, Hayley, Kiilgaard, Jens F., Isaacs, Timothy, Gray, Elin S., Rolfe, Olivia J., Park, John J., Stark, Andrew, Mann, Graham J., Scolyer, Richard A., Pearson, John V., van Baren, Nicolas, Waddell, Nicola, Wadt, Karin W., McGrath, Lindsay A., Warrier, Sunil K., Glasson, William, and Hayward, Nicholas K.
- Abstract
Johansson, P. A., Brooks, K., Newell, F., Palmer, J. M., Wilmott, J. S., Pritchard, A. L., ... & Koufariotis, L. T. (2020). Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours. Nature communications, 11(1), Article number: 2408. https://doi.org/10.1038/s41467-020-16276-8
39. A panel of circulating MicroRNAs detects uveal melanoma with high precision
- Author
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Stark, Mitchell S., Gray, Elin S., Isaacs, Timothy, Chen, Fred K., Millward, Michael, McEvoy, Ashleigh, Zaenker, Pauline, Ziman, Melanie, Soyer, H. Peter, Glasson, William J., Warrier, Sunil K., Stark, Andrew L., Rolfe, Olivia J., Palmer, Jane M., Hayward, Nicholas K., Stark, Mitchell S., Gray, Elin S., Isaacs, Timothy, Chen, Fred K., Millward, Michael, McEvoy, Ashleigh, Zaenker, Pauline, Ziman, Melanie, Soyer, H. Peter, Glasson, William J., Warrier, Sunil K., Stark, Andrew L., Rolfe, Olivia J., Palmer, Jane M., and Hayward, Nicholas K.
- Abstract
Stark, M. S., Gray, E. S., Isaacs, T., Chen, F. K., Millward, M., McEvoy, A., ... Hayward, N. K. (2019). A panel of circulating microRNAs detects uveal melanoma with high precision. Translational Vision Science and Technology, 8(6), Article 12. Available here
40. Analysis of circulating tumour cells in early-stage uveal melanoma: Evaluation of tumour marker expression to increase capture
- Author
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<p>Edith Cowan University</p> <p>Cancer Council of Western Australia</p> <p>National Health and Medical Research Council</p> <p>Raine Medical Research Foundation</p> <p>Ophthalmic Research Institute of Australia</p>, Beasley, Aaron B., Isaacs, Timothy W., Vermeulen, Tersia, Freeman, James, De Sousa, Jean-Louis, Bhikoo, Riyaz, Hennessy, Doireann, Reid, Anna, Chen, Fred K., Bentel, Jacqueline, McKay, Daniel, Max Conway, R., Pereira, Michelle R., Mirzai, Bob, Calapre, Leslie, Erber, Wendy N., Ziman, Melanie R., Gray, Elin S., <p>Edith Cowan University</p> <p>Cancer Council of Western Australia</p> <p>National Health and Medical Research Council</p> <p>Raine Medical Research Foundation</p> <p>Ophthalmic Research Institute of Australia</p>, Beasley, Aaron B., Isaacs, Timothy W., Vermeulen, Tersia, Freeman, James, De Sousa, Jean-Louis, Bhikoo, Riyaz, Hennessy, Doireann, Reid, Anna, Chen, Fred K., Bentel, Jacqueline, McKay, Daniel, Max Conway, R., Pereira, Michelle R., Mirzai, Bob, Calapre, Leslie, Erber, Wendy N., Ziman, Melanie R., and Gray, Elin S.
- Abstract
Beasley, A. B., Isaacs, T. W., Vermeulen, T., Freeman, J., DeSousa, J. L., Bhikoo, R., . . . Gray, E. S. (2021). Analysis of circulating tumour cells in early-stage uveal melanoma: Evaluation of tumour marker expression to increase capture. Cancers, 13(23), article 5990. https://doi.org/10.3390/cancers13235990
41. Biallelic Mutations in PLA2G5, Encoding Group V Phospholipase A2, Cause Benign Fleck Retina
- Author
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Sergouniotis, Panagiotis I., Davidson, Alice E., Mackay, Donna S., Lenassi, Eva, Li, Zheng, Robson, Anthony G., Yang, Xu, Kam, Jaimie Hoh, Isaacs, Timothy W., Holder, Graham E., Jeffery, Glen, Beck, Jonathan A., Moore, Anthony T., Plagnol, Vincent, and Webster, Andrew R.
- Subjects
- *
RETINAL diseases , *PHOSPHOLIPASE A2 , *GENETIC disorders , *GENETIC mutation , *NEURODEGENERATION , *IMMUNOHISTOCHEMISTRY , *GENETICS - Abstract
Flecked-retina syndromes, including fundus flavimaculatus, fundus albipunctatus, and benign fleck retina, comprise a group of disorders with widespread or limited distribution of yellow-white retinal lesions of various sizes and configurations. Three siblings who have benign fleck retina and were born to consanguineous parents are the basis of this report. A combination of homozygosity mapping and exome sequencing helped to identify a homozygous missense mutation, c.133G>T (p.Gly45Cys), in PLA2G5, a gene encoding a secreted phospholipase (group V phospholipase A2). A screen of a further four unrelated individuals with benign fleck retina detected biallelic variants in the same gene in three patients. In contrast, no loss of function or common (minor-allele frequency>0.05%) nonsynonymous PLA2G5 variants have been previously reported (EVS, dbSNP, 1000 Genomes Project) or were detected in an internal database of 224 exomes (from subjects with adult onset neurodegenerative disease and without a diagnosis of ophthalmic disease). All seven affected individuals had fundoscopic features compatible with those previously described in benign fleck retina and no visual or electrophysiological deficits. No medical history of major illness was reported. Levels of low-density lipoprotein were mildly elevated in two patients. Optical coherence tomography and fundus autofluorescence findings suggest that group V phospholipase A2 plays a role in the phagocytosis of photoreceptor outer-segment discs by the retinal pigment epithelium. Surprisingly, immunohistochemical staining of human retinal tissue revealed localization of the protein predominantly in the inner and outer plexiform layers. [Copyright &y& Elsevier]
- Published
- 2011
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42. Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration.
- Author
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Feng XF, Constable IJ, McAllister IL, and Isaacs T
- Abstract
Aim: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD)., Methods: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA., Results: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patients from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained ≥15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857)., Conclusion: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.
- Published
- 2011
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