Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy

被引：172

作者：

Abraham, Prema ^{[1
]}

Adelman, Ron A. ^{[1
]}

Alfaro, Daniel Virgil, III ^{[1
]}

Anand, Rajiv ^{[1
]}

Antoszyk, Andrew ^{[1
]}

Bergsma, Donald ^{[1
]}

Hartnett, Mary Elizabeth ^{[1
]}

Brucker, Alexander J. ^{[1
]}

Carr, Tyree ^{[1
]}

Casey, Raynor C. ^{[1
]}

Rubino, John ^{[1
]}

Chandler, Thomas W. ^{[1
]}

Charles, Steven ^{[1
]}

Chaudhry, Nauman ^{[1
]}

Combs, James ^{[1
]}

Doft, Bernard ^{[1
]}

Young, Lucy H. Y. ^{[1
]}

Drouilhet, John H. ^{[1
]}

Dugel, Pravin U. ^{[1
]}

Feman, Stephen S. ^{[1
]}

Finkelstein, Daniel ^{[1
]}

Foster, Robert E. ^{[1
]}

Petersen, Michael R. ^{[1
]}

Fox, Gregory ^{[1
]}

Garretson, Bruce ^{[1
]}

Gieser, Jon P. ^{[1
]}

Gentile, Ronald C. ^{[1
]}

Giovinazzo, Vincent ^{[1
]}

Glazer, Louis ^{[1
]}

Goodart, Roy A. ^{[1
]}

Gottlieb, Justin ^{[1
]}

Greven, Craig ^{[1
]}

Grizzard, William S. ^{[1
]}

Hainsworth, Dean P. ^{[1
]}

Halperin, Lawrence ^{[1
]}

Heier, Jeffrey S. ^{[1
]}

Jackson, William ^{[1
]}

Kubacki, Joseph J. ^{[1
]}

Kanter, Eric D. ^{[1
]}

Keyser, Bruce ^{[1
]}

Kingsley, Ronald ^{[1
]}

Ko, Paula ^{[1
]}

Kokame, Gregg T. ^{[1
]}

Kuppermann, Baruch ^{[1
]}

Lambert, H. Michael ^{[1
]}

Lewis, Hilel ^{[1
]}

Lewis, Richard Alan ^{[1
]}

Marcus, Dennis ^{[1
]}

Nussbaum, Julian ^{[1
]}

Maturi, Raj K. ^{[1
]}

机构：

[1] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA

来源：

OPHTHALMOLOGY | 2006年 / 113卷 / 12期

关键词：

D O I：

10.1016/j.ophtha.2006.07.032

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Objective: To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes. Design: Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial. Participants: Six hundred eighty-five patients randomized at 70 clinical sites. Methods: Ophthalmologic examination was performed at screening and at each 3-month visit. Retinopathy status was assessed every 6 months with Early Treatment Diabetic Retinopathy Study (ETDRS) standard 7-field 30 color stereoscopic fundus photography. Levels of diabetic retinopathy and diabetic macular edema were determined by 2 independent graders masked to site and treatment assignment, with additional independent adjudication as required. Eligible patients had a best-corrected visual acuity (VA) score of >= 45 letters, retinopathy level >= 47A and <= 53E, and no prior panretinal photocoagulation in at least one eye. Main Outcome Measure: Effect of oral ruboxistaurin (32 mg/day) on reduction of sustained moderate visual loss (>= 15-letter decrease in ETDRS VA score maintained >= 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy. Results: Sustained moderate visual loss occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin-treated patients after 12 months. Baseline-to-end point visual improvement of >= 15 letters was more frequent (4.9% vs. 2.4%) and >= 15-letter worsening was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to placebo (P = 0.005). When clinically significant macular edema was > 100 p,m from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 mu m (68% vs. 50%, P = 0.003). Initial laser treatment for macular edema was 26% less frequent in eyes of ruboxistaurin-treated patients (P = 0.008). Conclusion: Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with non proliferative retinopathy.

引用

页码：2221 / 2230

页数：10

共 43 条

[1] Inhibition of PKC β by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients
Aiello, LP
Clermont, A
Arora, V
Davis, MD
Sheetz, MJ
Bursell, SE
[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (01) : 86 - 92
[2] Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor
Aiello, LP
Bursell, SE
Clermont, A
Duh, E
Ishii, H
Takagi, C
Mori, F
Ciulla, TA
Ways, K
Jirousek, M
Smith, LEH
King, GL
[J]. DIABETES, 1997, 46 (09) : 1473 - 1480
[3] Aiello LP, 2005, DIABETES, V54, P2188
[4] [Anonymous], 1991, OPHTHALMOLOGY, V98, P741
[5] [Anonymous], 1991, Ophthalmology, V98, P823
[6] [Anonymous], 1991, Ophthalmology, V98, P786
[7] [Anonymous], 1985, ARCH OPHTHALMOL-CHIC, V103, P1796, DOI [DOI 10.1001/ARCHOPHT.1985.01050120030015, 10.1001/archopht.1985.01050120030015]
[8] Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content - Vascular endothelial growth factor decreases occludin in retinal endothelial cells
Antonetti, DA
Barber, AJ
Khin, S
Lieth, E
Tarbell, JM
Gardner, TW
[J]. DIABETES, 1998, 47 (12) : 1953 - 1959
[9] Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412
Campochiaro, PA
[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (03) : 922 - 931
[10] Centers for Disease Control and Prevention, 1996, MMWR-MORBID MORTAL W, V45, P937

← 1 2 3 4 5 →