Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial

被引:50
作者
Campochiaro, Peter A. [1 ]
Hafiz, Gulnar [1 ]
Mir, Tahreem A. [1 ]
Scott, Adrienne W. [1 ]
Zimmer-Galler, Ingrid [1 ]
Shah, Syed M. [1 ]
Wenick, Adam S. [1 ]
Brady, Christopher J. [1 ]
Han, Ian [1 ]
He, Lingmin [1 ]
Channa, Roomasa [1 ]
Poon, David [1 ]
Meyerle, Catherine [1 ]
Aronow, Mary Beth [1 ]
Sodhi, Akrit [1 ]
Handa, James T. [1 ]
Kherani, Saleema [1 ]
Han, Yong [1 ]
Sophie, Raafay [1 ]
Wang, Guohua [1 ]
Qian, Jiang [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA
关键词
ENDOTHELIAL GROWTH-FACTOR; RETINAL VASCULAR-PERMEABILITY; GLUCOCORTICOID-RECEPTOR; AQUEOUS CONCENTRATIONS; VEIN OCCLUSION; ACTIVATES TIE2; C-JUN; NEOVASCULARIZATION; RANIBIZUMAB; BEVACIZUMAB;
D O I
10.1016/j.ajo.2016.04.017
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE: The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. DESIGN: Prospective, randomized crossover clinical trial. METHODS: Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients. RESULTS: After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P < .001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant, suggesting their modulation is likely secondary to changes in edema rather than causative. CONCLUSIONS: Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME. (C) 2016 Elsevier Inc. All rights reserved.)
引用
收藏
页码:13 / 23
页数:11
相关论文
共 35 条
  • [1] Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy
    Babapoor-Farrokhran, Savalan
    Jee, Kathleen
    Puchner, Brooks
    Hassan, Syed Junaid
    Xin, Xiaoban
    Rodrigues, Murilo
    Kashiwabuchi, Fabiana
    Ma, Tao
    Hu, Ke
    Deshpande, Monika
    Daoud, Yassine
    Solomon, Sharon
    Wenick, Adam
    Lutty, Gerard A.
    Semenza, Gregg L.
    Montaner, Silvia
    Sodhi, Akrit
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (23) : E3030 - E3039
  • [2] Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema
    Boyer, David S.
    Yoon, Young Hee
    Belfort, Rubens, Jr.
    Bandello, Francesco
    Maturi, Raj K.
    Augustin, Albert J.
    Li, Xiao-Yan
    Cui, Harry
    Hashad, Yehia
    Whitcup, Scott M.
    [J]. OPHTHALMOLOGY, 2014, 121 (10) : 1904 - 1914
  • [3] Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study
    Campochiaro, Peter A.
    Hafiz, Gulnar
    Mir, Tahreem A.
    Scott, Adrienne W.
    Sophie, Raafay
    Shah, Syed M.
    Ying, Howard S.
    Lu, Lili
    Chen, Connie
    Campbell, J. Peter
    Kherani, Saleema
    Zimmer-Galler, Ingrid
    Wenick, Adam
    Han, Ian
    Paulus, Yannis
    Sodhi, Akrit
    Wang, Guohua
    Qian, Jiang
    [J]. AMERICAN JOURNAL OF OPHTHALMOLOGY, 2015, 160 (02) : 313 - 321
  • [4] Treatment of Diabetic Macular Edema with an Inhibitor of Vascular Endothelial-Protein Tyrosine Phosphatase That Activates Tie2
    Campochiaro, Peter A.
    Sophie, Raafay
    Tolentino, Michael
    Miller, Daniel M.
    Browning, David
    Boyer, David S.
    Heier, Jeffrey S.
    Gambino, Laura
    Withers, Barbara
    Brigell, Mitchell
    Peters, Kevin
    [J]. OPHTHALMOLOGY, 2015, 122 (03) : 545 - 554
  • [5] Factors affecting visual outcomes in patients with diabetic macular edema treated with ranibizumab
    Channa, R.
    Sophie, R.
    Khwaja, A. A.
    Do, D. V.
    Hafiz, G.
    Nguyen, Q. D.
    Campochiaro, P. A.
    [J]. EYE, 2014, 28 (03) : 269 - 278
  • [6] Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics
    Clermont, Allen C.
    Cahill, Mark
    Salti, Haytham
    Rook, Susan L.
    Rask-Madsen, Christian
    Goddard, Lucy
    Wong, Jun S.
    Bursell, Dahlia
    Bursell, Sven E.
    Aiello, Lloyd Paul
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (06) : 2701 - 2708
  • [7] Ranibizumab for Edema of the Macula in Diabetes Study 3-Year Outcomes and the Need for Prolonged Frequent Treatment
    Do, Diana V.
    Nguyen, Quan D.
    Khwaja, Afsheen A.
    Channa, Roomasa
    Sepah, Yasir J.
    Sophie, Raafay
    Hafiz, Gulnar
    Campochiaro, Peter A.
    [J]. JAMA OPHTHALMOLOGY, 2013, 131 (02) : 139 - 145
  • [8] Study of 27 Aqueous Humor Cytokines in Type 2 Diabetic Patients with or without Macular Edema
    Dong, Ning
    Xu, Bing
    Chu, Liqun
    Tang, Xin
    [J]. PLOS ONE, 2015, 10 (04):
  • [9] Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema
    Funatsu, H
    Yamashita, H
    Ikeda, T
    Mimura, T
    [J]. OPHTHALMOLOGY, 2003, 110 (09) : 1690 - 1696
  • [10] Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema
    Funatsu, H
    Yamashita, H
    Noma, H
    Mimura, T
    Yamashita, T
    Hori, S
    [J]. AMERICAN JOURNAL OF OPHTHALMOLOGY, 2002, 133 (01) : 70 - 77