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Review

Emerging drugs for diabetic retinopathy

, MD BSc (Hons) FRCOphth & , MD PhD
Pages 675-694 | Published online: 02 Dec 2008

Bibliography

  • Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetes. Diabetes Care 2004;27(Suppl 1):S84-7
  • Fong DS, Aiello L, Gardner TW, et al. Diabetic retinopathy. Diabetes Care 2003;26(1):226-9
  • Diabetes Atlas. Available from: http://www.eatlas.idf.org
  • Narayan KM, Boyle JP, Geiss LS, et al. Impact of recent increase in incidence on future diabetes burden: US, 2005-2050. Diabetes Care 2006;29(9):2114-6
  • The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329(14):977-86
  • Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837-53
  • Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 1993;341(8856):1306-19
  • Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):703-13
  • ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358(24):2560-72
  • Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008;371(9614):736-43
  • Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology 1978;85(1):82-106
  • Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88(7):583-600
  • Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98(5 Suppl):766-85
  • Aiello LM. Perspectives on diabetic retinopathy. Am J Ophthalmol 2003;136(1):122-35
  • Pahor D. Visual field loss after argon laser panretinal photocoagulation in diabetic retinopathy: full- versus mild-scatter coagulation. Int Ophthalmol 1998;22(5):313-9
  • Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol 1995;113(9):1144-55
  • Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA 2007;298(8):902-16
  • CDC national estimates on diabetes. Available from: http://www.diabetes.org/diabetes-statistics.jsp
  • Sherris D. Ocular drug development: future directions. Angiogenesis 2007;10(2):71-6
  • Lorenzi M. The Polyol Pathway as a Mechanism for Diabetic Retinopathy: Attractive, Elusive, and Resilient. Experimental Diabetes Research. 2007; Article ID 61038, 1-10
  • Miwa K, Nakamura J, Hamada Y, et al. The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes. Diabetes Res Clin Pract 2003;60(1):1-9
  • Chung SS, Chung SK. Aldose reductase in diabetic microvascular complications. Curr Drug Targets 2005;6(4):475-86
  • King GL, Kunisaki M, Nishio Y, et al. Biochemical and molecular mechanisms in the development of diabetic vascular complications. Diabetes 1996;45(Suppl 3):S105-8
  • Demaine AG. Polymorphisms of the aldose reductase gene and susceptibility to diabetic microvascular complications. Curr Med Chem 2003;10(15):1389-98
  • Dagher Z, Park YS, Asnaghi V, et al. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes 2004;53(9):2404-11
  • Drel VR, Pacher P, Ali TK, et al. Aldose reductase inhibitor fidarestat counteracts diabetes-associated cataract formation, retinal oxidative-nitrosative stress, glial activation, and apoptosis. Int J Mol Med 2008;21(6):667-76
  • Naruse K, Nakamura J, Hamada Y, et al. Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. Exp Eye Res 2000;71(3):309-15
  • Obrosova IG, Minchenko AG, Vasupuram R, et al. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Diabetes 2003;52(3):864-71
  • A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Sorbinil Retinopathy Trial Research Group. Arch Ophthalmol 1990;108(9):1234-44
  • Foppiano M, Lombardo G. Worldwide pharmacovigilance systems and tolrestat withdrawal. Lancet 1997;349(9049):399-400
  • Sundkvist G, Armstrong FM, Bradbury JE, et al. Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat Trial. J Diabetes Complications 1992;6(2):123-30
  • Hotta N, Akanuma Y, Kawamori R, et al. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial. Diabetes Care 2006;29(7):1538-44
  • Sun W, Oates PJ, Coutcher JB, et al. A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy. Diabetes 2006;55(10):2757-62
  • Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin Investig Drugs 2002;11(9):1205-23
  • Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813-20
  • Chibber R, Molinatti PA, Rosatto N, et al. Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: relevance to diabetic retinopathy. Diabetologia 1997;40(2):156-64
  • Genuth S, Sun W, Cleary P, et al. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes 2005;54(11):3103-11
  • Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial. Diabetes 1999;48(4):870-80
  • Uribarri J, Cai W, Sandu O, et al. Diet-derived advanced glycation end products are major contributors to the body's AGE pool and induce inflammation in healthy subjects. Ann NY Acad Sci 2005;1043:461-6
  • Yamagishi S, Nakamura K, Matsui T, et al. Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders. Med Hypotheses 2007;69(3):666-8
  • Yamagishi S, Ueda S, Okuda S. Food-derived advanced glycation end products (AGEs): a novel therapeutic target for various disorders. Curr Pharm Des 2007;13(27):2832-6
  • Bolton WK, Cattran DC, Williams ME, et al. Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am J Nephrol 2004;24(1):32-40
  • Jain SK, Lim G. Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na+ + K+)-ATPase activity reduction in high glucose-treated human erythrocytes. Free Radic Biol Med 2001;30(3):232-7
  • Metz TO, Alderson NL, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications. Arch Biochem Biophys 2003;419(1):41-9
  • Stitt A, Gardiner TA, Alderson NL, et al. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 2002;51(9):2826-32
  • Williams ME, Bolton WK, Khalifah RG, et al. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 2007;27(6):605-14
  • Bhatwadekar A, Glenn JV, Figarola JL, et al. A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats. Br J Ophthalmol 2008;92(4):545-7
  • Liu J, Masurekar MR, Vatner DE, et al. Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am J Physiol Heart Circ Physiol 2003;285(6):2587-91
  • Forbes JM, Thorpe SR, Thallas-Bonke V, et al. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol 2005;16(8):2363-72
  • Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003;9:(3):294-9
  • Cuccurullo C, Iezzi A, Fazia ML, et al. Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006;26:(12):2716-23
  • Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998;47(6):859-66
  • Xia P, Inoguchi T, Kern TS, et al. Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes 1994;43:(9):1122-9
  • Aiello LP. The potential role of PKC beta in diabetic retinopathy and macular edema. Surv Ophthalmol 2002;47(Suppl 2):S263-9
  • Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 1995;92:23:10457-61
  • Williams B, Gallacher B, Patel H, Orme C. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 1997;46(9):1497-503
  • Donnelly R, Idris I, Forrester JV. Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research. Br J Ophthalmol 2004;88(1):145-51
  • Campochiaro PA, C99-PKC412-003 Study Group. Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412. Invest Ophthalmol Vis Sci 2004;45(3):922-31
  • The PKC-DRS Study Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes 2005;54(7):2188-97
  • Ruboxistaurin: LY 333531. Drugs R D 2007;8(3):193-9
  • Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54(6):1615-25
  • Kunisaki M, Bursell SE, Umeda F, et al. Prevention of diabetes-induced abnormal retinal blood flow by treatment with d-alpha-tocopherol. Biofactors 1998;7(1-2):55-67
  • Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 1999;22(8):1245-51
  • Lonn E, Yusuf S, Hoogwerf B, et al. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care 2002;25(11):1919-27
  • Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med 2004;21(2):114-21
  • Berkowitz BA, Roberts R, Stemmler A, et al. Impaired apparent ion demand in experimental diabetic retinopathy: correction by lipoic acid. Invest Ophthalmol Vis Sci 2007;48(10):4753-8
  • Kowluru RA, Odenbach S. Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 2004;53(12):3233-8
  • Stirban A, Negrean M, Stratmann B, et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care 2006;29(9):2064-71
  • Benfotiamine Study. Available from: http://clinicaltrials.gov/show/NCT00117026
  • Du X, Edelstein D, Brownlee M. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia 2008;51(10):1930-2
  • Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 2002;16(3):438-40
  • Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group. Diabetes 1989;38(4):491-8
  • Ticlopidine treatment reduces the progression of nonproliferative diabetic retinopathy. The TIMAD Study Group. Arch Ophthalmol 1990;108(11):1577-83
  • Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98(5 Suppl):757-65
  • Chew EY, Klein ML, Murphy RP, et al. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report no. 20. Arch Ophthalmol 1995;113(1):52-5
  • Ayalasomayajula SP, Amrite AC, Kompella UB. Inhibition of cyclooxygenase-2, but not cyclooxygenase-1, reduces prostaglandin E2 secretion from diabetic rat retinas. Eur J Pharmacol 2004;498(1-3):275-8
  • Ayalasomayajula SP, Kompella UB. Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 2003;458(3):283-9
  • A phase III study evaluating celecoxib in patients with DR. Available from: http://clinicaltrials.gov/show/NCT00050479
  • Kearney PM, Baigent C, Godwin J, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006;332(7553):1302-8
  • Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol 2005;511(2-3):191-8
  • Hardy J, Ciric IS. Selective anterior hypophysectomy in the treatment of diabetic retinopathy. A transsphenoidal microsurgical technique. JAMA 1968;203(2):73-8
  • Ray BS, Pazianos AG, Greenberg E, et al. Pituitary ablation for diabetic retinopathy. I. Results of hypophysectomy. (A ten-year evaluation). JAMA 1968;203(2):79-84
  • Sönksen PH, Russell-Jones D, Jones RH. Growth hormone and diabetes mellitus. A review of sixty-three years of medical research and a glimpse into the future? Horm Res 1993;40(1-3):68-79
  • Grant MB, Mames RN, Fitzgerald C, et al. The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care 2000;23(4):504-9
  • Kirkegaard C, Nørgaard K, Snorgaard O, et al. Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus. Acta Endocrinol(Copenh) 1990;122(6):766-72
  • Octreotide long release study. Available from: http://clinicaltrials.gov/ct/show/NCT00248157
  • Octreotide LAR. Available from: http://clinicaltrials.gov/ct/show/NCT00248131
  • Grant MB. Treating diabetic retinopathy with IGF-1 antagonists. Diabetic retinopathy: diagnostic and treatment novelties. Program and abstracts of the American Diabetes Association 66th Scientific Sessions; June 9 – 13, 2006; Washington, DC
  • Growth Hormone Antagonist for Proliferative Diabetic Retinopathy Study Group. The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology 2001;108(12):2266-72
  • Aiello LP. Angiogenic pathways in diabetic retinopathy. N Engl J Med 2005;353(8):839-41
  • Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004;25(4):581-611
  • Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331(22):1480-7
  • Funatsu H, Yamashita H, Nakamura S, et al. Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 2006;113(2):294-301
  • Xia P, Aiello LP, Ishii H, et al. Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 1996;98(9):2018-26
  • Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 2005;333(2):328-35
  • Cobleigh MA, Langmuir VK, Sledge GW, et al. A Phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 2003;30(5 Suppl 16):117-24
  • Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature 2005;438(7070):937-45
  • Food and Drug Administration. MedWatch safety alert. Available from: www.fda.gov/medwatch/SAFETY/2004/safety04.htm#avastin
  • Cunningham ET, Adamis AP, Altaweel M, et al. A Phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 2005;112(10):1747-57
  • Adamis AP, Altaweel M, Bressler NM, et al. Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 2006;113(1):23-8
  • A multi-center trial to evaluate the safety and efficacy of pegaptanib sodium (Macugen®) injected into the eye every 6 weeks for up to 2 years for macular swelling associated with diabetes. Available from: http://clinicaltrials.gov/ct2/show/NCT00605280
  • Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1432-44
  • Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1419-31
  • Chun DW, Heier JS, Topping TM, et al. A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema. Ophthalmology 2006;113(10):1706-12
  • RESOLVE: safety and efficacy of ranibizumab in diabetic macular edema with center involvement. Available from: http://clinicaltrials.gov/ct2/show/NCT00284050
  • The READ-2 (ranibizumab for edema of the macula in diabetes) study. Available from: http://clinicaltrials.gov/ct2/show/NCT00407381
  • A study of ranibizumab injection in subjects with clinically significant macular edema with center involvement secondary to diabetes mellitus (RISE). Available from: http://clinicaltrials.gov/ct2/show/NCT00473330
  • Efficacy and safety of ranibizumab (intravitreal injections) in patients with visual impairment due to diabetic macular edema (RESTORE). Available from: http://clinicaltrials.gov/show/NCT00687804
  • Study of rnibizumab injection in subjects with clinically significant macular edema with center involvement secondary to diabetes mellitus (RIDE). Available from: http://clinicaltrials.gov/ct2/show/NCT00473382
  • Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113(10):1695,e1-15
  • Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina 2006;26(3):352-4
  • Bakri SJ, Donaldson MJ, Link TP. Rapid regression of disc neovascularization in a patient with proliferative diabetic retinopathy following adjunctive intravitreal bevacizumab. Eye 2006;20(12):1474-5
  • Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina 2006;26(3):275-8
  • Gillies MC. What we don't know about avastin might hurt us. Arch Ophthalmol 2006;124(10):1478-9
  • Wickremasinghe SS, Michalova K, Gilhotra J, et al. Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration. Ophthalmology 2008; In press
  • Scott IU, Edwards AR, et al. Diabetic Retinopathy Clinical Research Network. A Phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114(10):1860-7
  • Saishin Y, Saishin Y, Takahashi K, et al. VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol 2003;195(2):241-8
  • Benz MS, Nguyen QD, Chu K, et al. CLEAR-IT-2: interim results of the Phase II, randomized, controlled dose-and interval-ranging study of repeated intravitreal VEGF trap administration in patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2007;48(5):4549
  • Regeneron and Bayer HealthCare announce VEGF trap-eye achieved durable improvement in vision over 52 weeks in a Phase 2 study in patients with age-related macular degeneration. Available from: http://investor.regeneron.com/phoenix.zhtml?c=119576&p=irol-newsArticle&ID=1188658&highlight=
  • Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF trap. Br J Ophthalmol 2008;92(5):667-8
  • Do DV, Nguyen QD, Browning DJ, et al. Results of a Phase I study of intravitreal VEGF trap in subjects with diabetic macular edema: the CLEAR-IT DME study. Invest Ophthalmol Vis Sci 2007;48(5):1430
  • Kalluri R, Kanasaki K. RNA interference: generic block on angiogenesis. Nature 2008;452(7187):543-5
  • Prenner JL, RACE Study Group. The RACE study: bevasiranib for the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci 2007;48(5):5045
  • PF-4523655 (RTP801i-14) is another siRNA drug candidate. Available from: http://www.quarkpharma.com/qbi-en/products/rtp801i-14/
  • PF-4523655 for DME. Available from: http://www.quarkpharma.com/qbi-en/newslist/firstDMEpatient/
  • Tanaka M, Nyce JW. Respirable antisense oligonucleotides: a new drug class for respiratory disease. Respir Res 2001;2(1):5-9
  • Hnik P, Clement JG, Ono SJ, Henry SP. iCo-007, a VEGF ‘+’ agent for the potential treatment of diabetic macular edema and diabetic retinopathy. Invest Ophthalmol Vis Sci 2008;49(5):3503
  • Nauck M, Karakiulakis G, Perruchoud AP, et al. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 1998;341(2-3):309-15
  • Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007;2007:95103
  • Ciulla TA, Walker JD, Fong DS, Criswell MH. Corticosteroids in posterior segment disease: an update on new delivery systems and new indications. Curr Opin Ophthalmol 2004;15(3):211-20
  • Cunningham MA, Edelman JL, Kaushal S. Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol 2008;53(2):139-49
  • Sobrin L, D'Amico DJ. Controversies in intravitreal triamcinolone acetonide use. Int Ophthalmol Clin 2005;45(4):133-41
  • Audren F, Erginay A, Haouchine B, et al. Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial. Acta Ophthalmol Scand 2006;84(5):624-30
  • Audren F, Lecleire-Collet A, Erginay A, et al. Intravitreal triamcinolone acetonide for diffuse diabetic macular edema: phase 2 trial comparing 4 mg vs 2 mg. Am J Ophthalmol 2006;142(5):794-9
  • Avitabile T, Longo A, Reibaldi A. Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema. Am J Ophthalmol 2005;140(4):695-702
  • Jonas JB, Kreissig I, Söfker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121(1):57-61
  • Jonas JB, Kamppeter BA, Harder B, et al. Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective, randomized study. J Ocul Pharmacol Ther 2006;22(3):200-7
  • Kang SW, Sa HS, Cho HY, Kim JI. Macular grid photocoagulation after intravitreal triamcinolone acetonide for diffuse diabetic macular edema. Arch Ophthalmol 2006;124(5):653-8
  • Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 2004;111(2):218-24; discussion 224-5
  • Gillies MC, Sutter FK, Simpson JM, et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology 2006;113(9):1533-1538
  • Ockrim ZK, Sivaprasad S, Falk S, et al. Intravitreal triamcinolone versus laser photocoagulation for persistent diabetic macular oedema. Br J Ophthalmol 2008;92(6):795-9
  • Grover D, Li TJ, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 2008;1:CD005656
  • Chew E, Strauber S, Beck R, et al. Diabetic Retinopathy Clinical Research Network, Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study. Ophthalmology 2007;114(6):1190-6
  • Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 2008;115(9):1447-9,1449,e1-10
  • Maia M, Farah ME, Belfort RN, et al. Effects of intravitreal triamcinolone acetonide injection with and without preservative. Br J Ophthalmol 2007;91(9):1122-4
  • Jonisch J, Lai JC, Deramo VA, et al. Increased incidence of sterile endophthalmitis following intravitreal preserved triamcinolone acetonide. Br J Ophthalmol 2008;92(8):1051-4
  • Jaffe G, Fluocinolone Acetonide Uveitis Study Group. Fluocinolone acetonide intravitreal implant for uveitis affecting the posterior segment of the eye. Invest Ophthalmol Vis Sci 2004;45(5):3369
  • Pearson P, Baker CW, Eliott D, et al. Fluocinolone acetonide intravitreal implant in patients with diabetic macular edema: 12 month results. Invest Ophthalmol Vis Sci 2003;44(5):4288
  • Pearson P, Levy B, Fluconolone Acetonide Implant Study Group. Fluocinolone acetonide intravitreal implant to treat diabetic macular edema: 2-year results of a multi-center clinical trial. Invest Ophthalmol Vis Sci 2005;46(5):4673
  • Pearson P, Levy B, Comstock T, Fluocinolone Acetonide Implant Study Group. Fluocinolone acetonide intravitreal implant to treat diabetic macular edema: 3-year results of a multi-center clinical trial. Invest Ophthalmol Vis Sci 2006;47(5):5442
  • Kuppermann BD, Blumenkranz MS, Haller JA, et al. An intravitreous dexamethasone bioerodible drug delivery system for the treatment of persistent diabetic macular edema. Invest Ophthalmol Vis Sci 2003;44(5):4289
  • Safety and Tolerability of NOVA63035 ‘corticosteroid’ in Patients With Diabetic Macular Edema Secondary to Diabetic Retinopathy Phase 1 study. Available from: http://clinicaltrials.gov/ct2/show/NCT00665106
  • Novagali Pharma. A new paradigm in the management of retinopathies. Available from: http://www.novagali.com/en/eye-therapy/retinopathies
  • Chacko M, Weinberg JM. Efalizumab. Dermatol Ther 2007;20(4):265-9
  • Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol 2002;86(4):363-5
  • Combined aPproach to Treatment Using Ranibizumab and Efalizumab for Diabetic Macular Edema Study: The CAPTURE DME Study. Available from: http://clinicaltrials.gov/ct2/show/NCT00676559
  • Giansanti F, Barbera ML, Virgili G, et al. Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease. Eur J Ophthalmol 2004;14(5):445-8
  • Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005;123(7):903-12
  • Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 2007;27(4):399-413
  • Treatment of Refractory Diabetic Macular Edema With Infliximab. Available from: http://clinicaltrials.gov/ct2/show/NCT00505947
  • Giansanti F, Ramazzotti M, Vannozzi L, et al. A pilot study on ocular safety of intravitreal infliximab in a rabbit model. Invest Ophthalmol Vis Sci 2008;49(3):1151-6
  • Intravitreal Infliximab for Diabetic Macular Edema (DME) and Choroidal Neovascularization (CNV) (ITVR). Available from: http://clinicaltrials.gov/ct2/show/NCT00695682
  • Webster AC, Lee VW, Chapman JR, Craig JC. Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients: a systematic review and meta-analysis of randomized trials. Transplantation 2006;81(9):1234-48
  • Blumenkranz MS, Dugel PU, Solley WA, et al. A Randomized Dose-Escalation Trial of Locally-Administered Sirolimus to Treat Diabetic Macular Edema. Invest Ophthalmol Vis Sci 2008;49(5):1567
  • Sirolimus to Treat Diabetic Macular Edema. Available from: http://clinicaltrials.gov/ct2/show/NCT00711490
  • Dose Ranging Study of an Ocular Sirolimus (Rapamycin) Formulation in Patients With Diabetic Macular Edema. Available from: http://clinicaltrials.gov/ct2/show/NCT00656643
  • Otani A, Takagi H, Suzuma K, Honda Y. Angiotensin II potentiates vascular endothelial growth factor-induced angiogenic activity in retinal microcapillary endothelial cells. Circ Res 1998;82(5):619-28
  • Chaturvedi N, Sjolie AK, Stephenson JM, et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus. Lancet 1998;351(9095):28-31
  • Larsen M, Hommel E, Parving HH, Lund-Andersen H. Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. Graefes Arch Clin Exp Ophthalmol 1990;228(6):505-9
  • Matthews DR, Stratton IM, Aldington SJ, et al. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol 2004;122(11):1631-40
  • Estacio RO, Jeffers BW, Gifford N, Schrier RW. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 2000;23(Suppl 2):B54-64
  • Schrier RW, Estacio RO, Jeffers B. Appropriate Blood Pressure Control in NIDDM (ABCD) Trial. Diabetologia 1996;39(12):1646-54
  • Stubanus M, Endemann D, Fischereder M, et al. The HOPE study and diabetes. Heart Outcomes Prevention Evaluation. Lancet 2000;355(9210):1183-4; author reply
  • Gilbert RE, Kelly DJ, Cox AJ, et al. Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes. Diabetologia 2000;43(11):1360-7
  • Knudsen ST, Bek T, Poulsen PL, et al. Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized, double-masked study. J Intern Med 2003;254(2):147-58
  • ADVANCE Collaborative Group. ADVANCE-Action in Diabetes and Vascular Disease: patient recruitment and characteristics of the study population at baseline. Diabet Med 2005;22(7):882-8
  • Sjølie AK, Porta M, Parving HH, et al. The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline characteristics. J Renin Angiotensin Aldosterone Syst 2005;6(1):25-32
  • Klein R, Sharrett AR, Klein BE, et al. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes : the atherosclerosis risk in communities study. Ophthalmology 2002;109(7):1225-34
  • van Leiden HA, Dekker JM, Moll AC, et al. Blood pressure, lipids, and obesity are associated with retinopathy: The Hoorn study. Diabetes Care 2002;25(8):1320-5
  • Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 1996;114(9):1079-84
  • Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996;348(9034):1079-82
  • Vaughan CJ, Gotto AM. Update on statins: 2003. Circulation 2004;110(7):886-92
  • Sen K, Misra A, Kumar A, Pandey RM. Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. Diabetes Res Clin Pract 2002;56(1):1-11
  • Colhoun HM, Thomason MJ, Mackness MI, et al. Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. Diabet Med 2002;19(3):201-11
  • Thomason MJ, Colhoun HM, Livingstone SJ, et al. Baseline characteristics in the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with Type 2 diabetes. Diabet Med 2004;21(8):901-5
  • Knopp RH, d'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29(7):1478-85
  • Cullen JF, Town SM, Campbell CJ. Double-blind trial of Atromid-S in exudative diabetic retinopathy. Trans Ophthalmol Soc UK 1974;94(2):554-62
  • Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007;370(9600):1687-97
  • Evaluating How the Treatments in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Affect Diabetic Retinopathy (The ACCORD Eye Study). Available from: http://clinicaltrials.gov/ct2/show/NCT00542178
  • Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997;74(2):111-22
  • Evaluation of Doxycyline for the Treatment of Nonproliferative and Early Proliferative Diabetic Retinopathy (POC1). Available from: http://clinicaltrials.gov/ct2/show/NCT00511875
  • Ozerdem U, Mach-Hofacre B, Cheng L, et al. The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinases, on a subacute model of proliferative vitreoretinopathy. Curr Eye Res 2000;20(6):447-53
  • Garcia C, Bartsch DU, Rivero ME, et al. Efficacy of Prinomastat) (AG3340), a matrix metalloprotease inhibitor, in treatment of retinal neovascularization. Curr Eye Res 2002;24(1):33-8
  • Hayreh SS, Jonas JB. Posterior vitreous detachment: clinical correlations. Ophthalmologica 2004;218:5:333-43
  • Gandorfer A. Pharmacologic vitreolysis. Dev Ophthalmol 2007;39:149-56
  • Zhu D, Chen H, Xu X. Effects of intravitreal dispase on vitreoretinal interface in rabbits. Curr Eye Res 2006;31(11):935-46
  • Azzolini C, D'Angelo A, Maestranzi G, et al. Intrasurgical plasmin enzyme in diabetic macular edema. Am J Ophthalmol 2004;138(4):560-6
  • Kuppermann BD, Thomas EL, De Smet MD, et al. Pooled Efficacy Results From Two Multinational Randomized Controlled Clinical Trials of a Single Intravitreous Injection of Highly Purified Ovine Hyaluronidase (Vitrase®) for the Management of Vitreous Hemorrhage. Am J of Ophthalmol 2005;140(4):573-84
  • A Safety and Efficacy Study of Vitreosolve® for Non-Proliferative Diabetic Retinopathy Subjects. Available from: http://clinicaltrials.gov/show/NCT00664183
  • Gandorfer A. Experimental evaluation of microplasmin: an alternative to vital dyes. Dev Ophthalmol 2008;42:153-9
  • A Multicenter Study to Compare Multiple Doses of Intravitreal Microplasmin vs Sham Injection for Treatment of Patients With DME (MIVI-II). Available from: http://clinicaltrials.gov/ct2/show/NCT00412451

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