Citations 2
SEGMENTAL DIFFUSE VASCULAR LEAKAGE: A FLUORESCEIN ANGIOGRAPHIC FINDING IN PATIENTS WITH VON HIPPEL–LINDAU DISEASE
Deák, Gábor , Pulido, José S. , Jampol, Lee M. , Deák, Gabor Gy
RETINAL Cases & Brief Reports | April 8, 2019 | Volume: 15 | Issue: 5 | Pages: 628-631
Purpose: To describe a novel fluorescein angiographic finding in patients with von Hippel–Lindau disease. Methods: Retrospective case series of patients diagnosed with retinal capillary hemangioblastoma (RCH) in the setting of von Hippel–Lindau. Results: We identified six eyes of three patients with von Hippel–Lindau and leaky retinal vessels. All eyes showed segmental diffuse vascular leakage (SDVL) that was seen in the late phase of the angiogram and that originated from third order and more peripheral retinal veins and adjacent capillaries. These vessels did not drain from the RCHs. Segmental diffuse vascular leakage was mainly seen in the mid and far periphery. In some cases, it was located near the RCHs, while in other cases, it was remote. Segmental diffuse vascular leakage was also seen in one eye without RCHs. On follow-up, the extent and intensity of segmental diffuse vascular leakage did not change after the RCHs were treated with laser or cryotherapy. Conclusion: Diffuse vascular leakage from retinal venules around and away from RCHs in patients with von Hippel–Lindau disease is seen, but the clinical and prognostic importance of this finding is uncertain.
Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration
Stambolian, Dwight, Edwards, Albert O., Branham, Kari , Othman, Mohammad , Jakobsdóttir, Jóhanna , Tosakulwong, Nirubol , Pericak‐Vance, Margaret A. , Klein, Michael L. , Tan, Perciliz L. , Kanda, Atsuhiro , Kopplin, Laura J. , Li, Yanming , Augustaitis, Katherine J., Karoukis, Athanasios J., Scott, William K. , Agarwal, Anita , Kovach, Jaclyn L. , Postel, Eric A. , Brooks, Matthew, Baratz, Keith H. , Brown, William L. , Brucker, Alexander J., Orlin, Anton, Brown, Gary C. , Ho, Allen C. , Regillo, Carl D. , Donoso, Larry A., Tian, Lifeng , Kaderli, Brian, Hadley, Dexter , Hagstrom, Stephanie A. , Peachey, Neal S. , Klein, Ronald , Klein, Barbara E.K. , Gotoh, Norimoto, Yamashiro, Kenji , Ferris, Frederick L. , Fagerness, Jesen, Reynolds, Robyn, Farrer, Lindsay A. , Kim, Ivana K. , Miller, Joan W. , Cortón, Marta , Carracedo, Ãngel , Sánchez‐Salorio, Manuel, Pugh, Elizabeth, Doheny, Kimberly F. , Brión, Marı́a , Weeks, Daniel E. , Zack, Donald J. , Heckenlively, John R., Yoshimura, Nagahisa , Iyengar, Sudha K. , Francis, Peter J. , Katsanis, Nicholas , Seddon, Johanna M. , Haines, Jonathan L. , Abecasis, Gonçalo R. , Swaroop, Anand , Johnson, Robert N., Ai, Everett, McDonald, H. Richard , Stolarczuk, Margaret, Pavan, Peter R., Billiris, Karina K., Iyer, Mohan , Menosky, Matthew M., Pautler, Scott E. , Millard, Sharon M., Hubbard, G. Baker , Aaberg, Thomas , DuBois, Lindy, Lyon, Alice T., Anderson-Nelson, Susan, Jampol, Lee M. , Muñana, Annie, Rozenbajgier, Zuzanna, Orth, David H., Cohen, Jack, MacCumber, Matthew, Figliulo, Celeste, Porcz, Liz, Folk, James C. , Boldt, H. Culver , Russell, Stephen R. , Ivins, Rachel, Hinz, Connie J., Bloom, Steve, Jaegers, Ken, Kritchman, Brian, Whittington, Greg K., Frederick, Albert R., Morley, Michael G., Topping, Trexler M., Davis, Heather L., Bressler, Susan B., Bressler, Neil M. , Doll, W T Jr, Trese, Michael T. , Garretson, Bruce R., Ruby, Alan, Osentoski, Tammy, Ruszczyk, Margaret, Grand, G., Joseph, Daniel P., Shah, Gaurav K. , Nobel, Ginny, Antoszyk, Andrew N., Stallings, Alison H, Singerman, Lawrence J. , Miller, David T. , Novák, Michael, Pendergast, Scott, Zegarra, Hernando, Schura, Stephanie A., Smith-Brewer, Sheila, Davidorf, Frederick H., Chorich, Louis J., Salerno, Jill, Dreyer, Richard F., Ma, Colin, Kopfer, Marcia, Wilson, David J. , Nolte, Susan K., Grunwald, Juan E. , Dunaief, Josh, Fine, Stuart L., Maguire, Albert M. , Stoltz, Robert A., McRay, Monique, Fish, Gary E., Anand, Rajiv, Spencer, Rand , Arnwine, Jean, Chandra, Suresh R., Blodi, Barbara, Gottlieb, Justin L., Ip, Michael S. , Nork, T. Michael , Perry-Raymond, Jennie, Brightwell-Arnold, Mary, Harkins, Sandra, Peskin, Ellen, Ying, Gui‐Shuang , Kurinij, Natalie, Chen, Wei , Campochiaro, Peter A. , Conley, Yvette P. , Schwartz, Stephen G. , DeAngelis, Margaret M. , Chew, Emily Y. , Gorin, Michael B. , Menosky, Matthew M., Weinberg, David V. , Barr, Charles C. , Heier, Jeffrey S. , Capone, A. , Hassan, T. , McCannel, Colin A. , Blinder, Kevin J. , Holekamp, Nancy M. , Browning, David J. , Chambers, Robert , Altaweel, Michael M. , Maguire, Maureen G. , Weeks, Daniel E , Brion, María , Abecasis, Gonçalo
Proceedings of the National Academy of Sciences | April 12, 2010 | Volume: 107 | Issue: 16 | Pages: 7401-7406
We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.