530
Views
23
CrossRef citations to date
0
Altmetric
Review Article

Current treatment strategies and nanocarrier based approaches for the treatment and management of diabetic retinopathy

, , , , &
Pages 386-405 | Received 09 Sep 2016, Accepted 03 Jan 2017, Published online: 25 Jan 2017

References

  • World Health Organization, Diabetes. Fact sheet; 2015. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/.
  • International Diabetes Federation, Diabetes Atlas, 6th ed.; 2014. Available from: http://www.diabetesatlas.org [last accessed 2014].
  • Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA 2007;298:902–16.
  • National Institute for Health and Care Excellence (NICE CKS); 2015. Diabetes – type 2 (UK access only).
  • Kompella UB, Amrite AC, Pacha Ravi R, et al. Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 2013;36:172–98.
  • Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010;376:124–36.
  • Early Treatment Diabetic Retinopathy Study Research Group: Early photocoagulation for diabetic retinopathy. ETDRS Report No. 9. Ophthalmology 1991;98:766–85.
  • Diabetic Retinopathy Vitrectomy Study Research Group: Early vitrectomy for severe proliferative Diabetic retinopathy in eyes with useful vision: results of a randomized trial: Diabetic retinopathy Vitrectomy Study Report No. 3. Ophthalmology 1988;95:1307–20.
  • Sampat KM, Garg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol 2010;21:178–83.
  • Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review. Retina (Philadelphia, PA) 2004;24:676–98.
  • Kierston B. What is diabetic retinopathy? American Academy of Ophthalmology; 2013. Available from: http://www.aao.org/eye-health/diseases/what-is-diabetic-retinopathy.
  • Cunha-Vaz JG. Blood-retinal barriers in health and disease. Trans Ophthalmol Soc UK 1980;100:337–40.
  • Cunha-Vaz JG. The blood–retinal barriers. Doc Ophthalmol 1976;41:287–327.
  • Kim JH, Kim JH, Park JA, et al. Blood–neural barrier: intercellular communication at glio-vascular interface. J Biochem Mol Biol 2006;39:339–45.
  • Fujimoto K. Pericyte–endothelial gap junctions in developing rat cerebral capillaries: a fine structural study. Anat Rec 1995;242:562–5.
  • Neuman E, Reichenbach A. The Müller cell: a functional element of the retina. Trends Neurosci 1996;19:307–12.
  • Yang XL. Muller cells and retinal function. Shen Li Ke Xue Jin Zhan 1998;29:7–10.
  • Thomas WG, Antonetti DA, Barber AJ, et al. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol 2002;47:S253–62.
  • Hudson C. The clinical features and classification of diabetic retinopathy. Ophthalmic Physiol Opt 1996;16:S43–8.
  • Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615–25.
  • Merlak M, Kovacevic D, Balog T, et al. Expression of vascular endothelial growth factor in proliferative diabetic retinopathy. Coll Antropol 2008;32:39–43.
  • 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;331:1480–7.
  • Wilkinson-Berka JL, Wraight C, Werther G. The role of growth hormone, insulin like growth factor and somatostatin in diabetic retinopathy. Curr Med Chem 2006;13:3307–17.
  • Haurigot V, Villacampa P, Ribera A, et al. Increased intraocular insulin-like growth factor-I triggers blood–retinal barrier breakdown. E J Biol Chem 2009;284:22961–9.
  • Rangasamy S, Srinivasan R, Maestas J, et al. A potential role for angiopoietin 2 in the regulation of the blood–retinal barrier in diabetic retinopathy. Invest Ophthalmol Vis Sci 2011;52:3784–91.
  • Patel JI, Hykin PG, Gregor ZJ, et al. Angiopoietin concentrations in diabetic retinopathy. Br J Ophthalmol 2005;89:480–3.
  • Brooks Jr HL, Caballero S, Newell CK, et al. Vitreous levels of vascular endothelial growth factor and stromal-derived factor in patients with diabetic retinopathy and cystoid macular edema before and after intraocular injection of triamcinolone. Arch Ophthalmol 2004;122:1801–7.
  • Hueber A, Wiedemann P, Esser P, et al. Basic fibroblast growth factor mRNA, bFgF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders (PVR and PDR). Int Ophthalmol 1996;20:345–50.
  • Katsura Y, Okano T, Noritake M, et al. Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. Diabetes Care 1998;21:1759–63.
  • Joussen AM, Doehmen S, LML, et al. TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long term histopathological alterations. Mol Vis 2009;15:1418–28.
  • Zorena K, Mysliwska J, Mysliwiec M, et al. Serum TNF-alpha level predicts non-proliferative diabetic retinopathy. Mediat Inflamm 2007;2007:921–96.
  • Mocan C, Kadayifcilar S, Eldem B. Elevated intravitreal interleukin-6 levels in patients with proliferative diabetic retinopathy. Can J Ophthalmol 2006;41:747–52.
  • Wilkinson CP, Ferris 3rd FL, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110:1677–82.
  • NIH National Eye Institute. Facts about diabetic eye disease; 2015. Available from: https://nei.nih.gov/health/diabetic/retinopathy.
  • Susanne Althauser Diabetic eye disease-screening and treatment options; 2014. Available from: http://www.totalhealth.co.uk/clinical-experts/miss-susanne-althauser/diabetic-eye-disease-screening-and-treatment-options.
  • Blumenkraz MS. History of laser therapy for retinal disease; 2013. Available from: www.aao.org/munnerlyn-laser-surgery-center/history-of-laser-therapy-retinal-diseases.
  • Luttrull JK, Dorin G. Subthrehold diode micropulse laser photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema: a review. Curr Diabetes Rev 2012;8:274–84.
  • Pelosini L, Hamilton R, Mohamed M, et al. Retina rejuvenation therapy for diabetic macular edema: a pilot study. Retina (Philadelphia, PA) 2013;33:548–58.
  • Clinical trials.gov. Selective retinal therapy (SRT) for clinically significant diabetic macular edema; 2013. Available from: http://clinicaltrails.gov/ct2/show/NCT00994955 [last updated 15 Jan 2013].
  • Roider J, Liew SH, Klatt C, et al. Selective retinal therapy (SRT) for clinically significant diabetic macular edema. Grafes Arch Clin Exp Ophthalmol 2010;248:1263–72.
  • Williams GA. 25-, 23- or 20-gauge instrumentation for vitreous surgery? Eye 2008;22:1263–6.
  • Ferraz DA, Vasquez LM, Preti RC, et al. A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy. Retina (Philadelphia, PA) 2015;35:280–7.
  • Clinical trials Gov. Prospective, randomized, open label, phase II study to assess efficacy and safety of Macugen® (Pegaptanib 0.3 mg intravitreal injections) plus panretinal photocoagulation (PRP) and PRP (monotherapy) in the treatment with high risk proliferative diabetic retinopathy; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT01281098 [last updated 18 Mar 2015].
  • Clinical trials.Gov. Laser therapy combined with intravitreal aflibercept vs intravitreal aflibercept monotherapy (LADAMO); 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02432547 [last updated 2 Jun 2015].
  • Boyer DS, Yoon YH, Belfort R, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904–14.
  • Fluocinolone acetonide ophthalmic – Bausch and Lomb: fluocinolone actinide Envision TD implant. Drugs R D 2005;6:116–19.
  • Messenger BY, Beardsley RM, Flaxel C. Fluocinolone acetonide intravitreal implant for the treatment of diabetic macular edema. Drug Des Dev Ther 2013;7:425–34.
  • Li J, Guo X, Liu Z, et al. Preparation and evaluation of charged solid lipid nanoparticles of tetrandrine for ocular drug delivery system: pharmacokinetics, cytotoxicity and cellular uptake studies. Drug Dev Ind Pharm 2014;40:980–7.
  • Fangueiro JF, Andreani T, Fernandes L, et al. Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCGLNs) for ocular instillation. Colloids Surf B: Biointerfaces 2014;123:452–60.
  • Liu R, Liu Z, Zhang C, et al. Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability. J Pharm Sci 2012;101:3833–44.
  • Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical applications of diabetic retinopathy study findings, DRS report no. 8. Ophthalmology 1981;88:583–600.
  • Marilyn Haddrill. Treatment of diabetic retinopathy and macular edema; 2015. Available from: http://www.allaboutvision.com/conditions/diabetic-treatment.htm.
  • Russell PW, Sekuler R, Fetkenhour C. Visual function after pan-retinal photocoagulation: a survey. Diabetes Care 1985;8:57–63.
  • Birch J, Hamilton AM. Xenon arc and argon laser photocoagulation in the treatment of diabetic disc neovascularization: Part 2. Effect on colour vision. Trans Ophthalmol Soc UK 1981;101:93–9.
  • Khosla PK, Rao V, Tewari HK, Kumar A. Contrast sensitivity in diabetic retinopathy after panretinal photocoagulation. Ophthalmic Surg 1994;25:516–20.
  • McDonald HR, Schatz H. Visual loss following panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 1985;92:388–93.
  • Fong DS, Girach A, Boney A. Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: a literature review. Retina (Philadelphia, PA) 2007;27:816–24.
  • Henricsson M, Heijl A. The effect of pan retinal laser photocoagulation on visual acuity, visual fields and on subjective visual impairment in pre-proliferative and early proliferative diabetic retinopathy. Acta Ophthalmol (Copenh) 1994;72:570–5.
  • Kierstan B. Diabetic retinopathy treatment. American Academy of Ophthalmology; 2013. Available from: http://www.geteyesmart.org/eyesmart/diseases/diabeticretinopathy/treatment.cfm.
  • Ferreira N, Pessoa B, Macedo M, et al. Vitrectomy in DR. European Vitreo Retinal Society a certain philosophy; 2011. Available from: http://www.evrs.eu/vitrectomyindiabeticretinopathy/.
  • Luan J, Ando F, Hirose H, Yasui O. Vitectomy results in proliferative diabetic retinopathy. Int J Ophthalmol 2008;1:356–8.
  • Smiddy WE, Filymn JRHW. Vitrectomy in the management of diabetic retinopathy. Surv Ophthalmol 1999;43:491–507.
  • Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond) 2010;24:441–9.
  • Park DH, Shin JP, Kim SY. Comparison of clinical outcomes between 23-gauge and 20-gauge vitrectomy in patients with proliferative diabetic retinopathy. Retina (Philadelphia, PA) 2010;30:1662–70.
  • Doggrell SA. Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration. Expert Opin Pharmacother 2005;6:1421–3.
  • FDA news release. FDA approves Lucentis to treat diabetic macular edema; 2012. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315130.htm [last updated 13 Aug 2012].
  • FDA news release. FDA approves Lucentis to treat diabetic retinopathy in patients with diabetic macular edema; 2015. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm433392.htm [last updated 10 Feb 2015].
  • Day S, Acquah K, Mruthyunjaya P, et al. Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration. Am J Opthalmol 2011;152:266–72.
  • Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004;3:391–400.
  • Andreoli MT, Pinnolis M, Kieser T, et al. Feasibility and efficacy of a mass switch from ranibizumab (Lucentis) to bevacizumab (Avastin®) for treatment of neovascular age related macular degeneration. Digit J Ophthalmol 2015;21:1–8.
  • Clinicaltrials.Gov. Laser vs bevacizumab injection alone in treatment of diabetic macular edema; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02229175 [last updated Dec 2015].
  • Economides AN, Carpenter LR, Rudge JS, et al. Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med 2003;9:47–52.
  • Eylea approval history; 2016. Available from: www.drugs.com/history/eylea.html [last accessed 15 Jan 2016].
  • FDA News and Events. FDA approves new treatment for diabetic retinopathy in patients with diabetic macular edema; 2015. Available from: www.fda.gov/news/events/newsroom/pressannouncement/ucm439838.html [last updated 27 Mar 2015].
  • Matsuda S, Gomi F, Oshima Y, et al. Vascular endothelial growth factor reduced and connective tissue growth factor induced by triamcinolone in ARPE19 cells under oxidative stress. Invest Ophthalmol Vis Sci 2005;46:1062–8.
  • Ciulla TA, Walker JD, Fong DS, et al. Corticosteroids in posterior segment disease: an update on new delivery systems and new indications. Curr Opin Ophthalmol 2004;15:211–20.
  • Luo D, Zhu B, Zheng Z, et al. Subtenon vs intravitreal triamcinolone injection in diabetic macular edema: a prospective study in Chinese population. Pak J Med Sci 2014;30:749–54.
  • Jonas JB. Intravitreal triamcinolone acetonide for diabetic retinopathy. Dev Ophthalmol 2007;39:96–110.
  • Machemer R, Sugita G, Tano Y. Treatment of intraocular proliferations with intravitreal steroids. Trans Am Ophthalmol Soc 1979;77:171–80.
  • Hida T, Chandler D, Arena J, et al. Experimental and clinical observations of the intraocular toxicity of commercial corticosteroid preparations. Am J Ophthalmol 1986;101:190–5.
  • McCuen B, Bressler N, Tano Y, et al. The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol 1981;91:785–8.
  • Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920–7.
  • Bressler NM, Edwards AR, Beck RW, et al. Diabetic retinopathy clinical research network. Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation. Arch Ophthalmol 2009;127:1566–71.
  • Beck RW, Edwards AR, Aiello LP, et al. Diabetic retinopathy clinical research network. Three-year follow up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 2009;127:245–51.
  • Kuppermann BD. Sustained-release dexamethasone intravitreal implant for treatment of diabetic macular edema. Expert Rev Ophthalmol 2011;6:11–20.
  • Kurz PA, Suhler EB, Flaxel CJ, et al. Injectable intraocular corticosteroids. In: Becker MD, Davis J, eds. Surgical management of inflammatory eye disease. Berlin Heidelberg: Springer; 2008:5–16.
  • Thakur A, Kadam R, Kompella UB. Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts. Arch Ophthalmol 2011;129:914–20.
  • Haller JA, Bandello F, Belfort R, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 2011;118:2453–60.
  • Lowder C, Belfort R, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545–53.
  • Zucchiatti I, Lattanzio R, Querques G, et al. Intravitreal dexamethasone implant in patients with persistent diabetic macular edema. Ophthalmologica 2012;228:117–22.
  • Boyer DS, Faber D, Gupta S, et al. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina (Philadelphia, PA) 2011;31:915–23.
  • Kuppermann BD, Blumenkranz MS, Haller JA, et al. Dexamethasone DDS Phase II Study Group. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007;125:309–17.
  • Clinicaltials.Gov. A study of the safety and efficacy of a new treatment for diabetic macularedema; 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT00168389?term=Dexamethasone+%28posurdex%29&rank =4 [last updated 10 Jul 2014].
  • Taylor SR, Isa H, Joshi L, et al. New developments in corticosteroid therapy for uveitis. Ophthalmologica 2010;224:S46–S53.
  • Psivida Corp. Diabetic macular edema/ILUVIEN; 2015. Available from: http://www.psivida.com/products-iluvien.html [last accessed 2015].
  • Pearson PA, Comstock TL, Ip M, et al. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 2011;118:1580–7.
  • Campochiaro PA, Brown DM, Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 2012;119:2125–32.
  • Schwartz SG, Flynn HW. Jr. Fluocinolone acetonide implantable device for diabetic retinopathy. Curr Pharm Biotechnol 2011;12:347–51.
  • Sanford M. Fluocinolone acetonide intravitreal implant (Iluvien®): in diabetic macular oedema. Drugs 2013;73:187–93.
  • Duffy M. The FDA approves injectable implant ILUVIEN for treatment of diabetic macular edema; 2014. Available from: http://www.visionaware.org/blog/visionaware-blog/the-fda-approves-injectable-implant-iluvien-for-treatment-of-diabetic-macular-edema-1546/12.
  • The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.
  • UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.
  • The ACCORD Study Group; ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233–44.
  • Clinicaltrials.gov. Action to Control Cardiovascular Risk in Diabetes (ACCORD); 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT00000620 [last updated 21 Nov 2016].
  • UK prospective diabetes study group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703–13.
  • Beulens JW, Patel A, Vingerling JR, et al. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia 2009;52:2027–36.
  • Wilkinson-Berka JL. Angiotensin and diabetic retinopathy. Int J Biochem Cell Biol 2006;38:752–65.
  • The EUCLID Study Group. Randomised placebo controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet 1997;349:1787–92.
  • 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;351:28–31.
  • Sjølie AK. The Diabetic Retinopathy Candesartan Trials (DIRECT) Programme. JRAAS 2001;2:58.
  • Harindhanavudhi T, Mauer M, Klein R, et al. Benefits of renin-angiotensin blockade on retinopathy in type 1 diabetes vary with glycemic control. Diabetes Care 2011;34:1838–42.
  • Clinicaltrials.gov. Renin and angiotensin system study; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT00143949 [last updated 5 Nov 2008].
  • Klein BE, Moss SE, Klein R, Surawicz TS. The Wisconsin epidemiologic study of diabetic retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology 1991;98:1261–5.
  • 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;114:1079–84.
  • 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;370:1687–97.
  • Tomizawa A, Hattori Y, Inoue T, et al. Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation. Metab Clin Exp 2011;60:513–22.
  • Kim J, Ahn J-H, Kim J-H, et al. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp Eye Res 2007;84:886–93.
  • Cheung N, Wong TY. Fenofibrate and diabetic retinopathy. Lancet 2008;371:721–2.
  • Fischer N, Narayanan R, Loewenstein A, Kuppermann BD. Drug delivery to the posterior segment of the eye. Eur J Ophthalmol 2011;21:S20–S6.
  • The PKC-DRS Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe non-proliferative diabetic retinopathy: initial results of the protein kinase C beta inhibitor diabetic retinopathy study (PKC-DRS) multicenter randomized clinical trial. Diabetes 2005;54:2188–97.
  • The PKC-DRS Group. Effect of ruboxistaurin in patients with diabetic macular edema; thirty-month results of the randomized PKC-DMES clinical trial. Arch Ophthalmol 2007;113:2221–30.
  • Toyoda F, Tanaka Y, Ota A, et al. Effect of Ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats. J Diabet Res 2014;2014:1–7.
  • Kato N, Yashima S, Suzuki T, et al. Long-term treatment with fidarestat suppresses the development of diabetic retinopathy in STZ-induced diabetic rats. J Diabet Complic 2003;17:374–9.
  • Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 2002;16:438–40.
  • Tsilimbaris MK, Panagiotoglou TD, Charisis SK, et al. The use of intravitreal etanercept in diabetic macular oedema. Semin Ophthalmol 2007;22:75–9.
  • Sfikakis PP, Grigoropoulos V, Emfietzoglou I, et al. Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, cross-over, 32-week study. Diabetes Care 2010;33:1523–8.
  • Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991;40:405–12.
  • Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058–70.
  • Nardino RJ. Vitamin E for treatment of diabetic retinopathy. AHC Media 2001;4:100–3.
  • Clinicaltrials.gov. Efficacy of ubiquinone and combined antioxidant therapy in non-proliferative diabetic retinopathy; 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02062034 [last updated 11 Feb 2014].
  • Clinicaltrials.Gov. The use of alpha lipoic acid for the treatment and prevention of diabetic retinopathy (ALA-TPD); 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01880372 [last updated 18 May 2016].
  • Clinicaltrials.gov. Effect of doxium on high sensitivity C-reactive protein (CRP) and endothelin-1 serum levels in patients with diabetic retinopathy; 2011. Available from: https://clinicaltrials.gov/ct2/show/NCT01382498 [last updated 24 Jun 2011].
  • Tabatabaei-Malazy O, Larijani B, Abdollahi M. A novel management of diabetes by means of strong antioxidants’ combination. J Med Hypoth Ideas 2013;7:25–30.
  • Bagli E, Stefaniotou M, Morbidelli B, et al. Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3-kinase activity. Cancer Res 2004;64:7936–46.
  • Kim YH, Kim YS, Roh GS, et al. Resveratrol blocks diabetes induced early vascular lesions and vascular endothelial growth factor induction in mouse retinas. Acta Ophthalmol 2012;90:e31–7.
  • Wang D, Wang L, Jianqiu G, et al. Scutellarin inhibits high glucose-induced and hypoxia-mimetic agent-induced angiogenic effects in human retinal endothelial cells through reactive oxygen species/hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. J Cardiovasc Pharmacol 2014;64:218–27.
  • Perossini M, Guidi G, Chiellini S, Siravo D. Diabetic and hypertensive retinopathy therapy with vaccinum myrtillus anthocianosides (Tegens) double blind placebo-controlled clinical trial. Ann Di Ottalmol Clin Oculist 1987;12:1173–90.
  • Lee HS, Jun J, Jung E, et al. Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular permeability in human retinal pigment epithelial and human retinal microvascular endothelial cells via suppression of MMP-9 and VEGF activation. Molecules 2014;19:12150–72.
  • Chen D. Novel antioxidants for the treatment of diabetic retinopathy; 2009. SBIR.Gov. Available from: https://www.sbir.gov/sbirsearch/detail/124065 [last accessed 2 May 2016].
  • Henry RP. Multiple roles of carbonic anhydrase in cellular transport and metabolism. Annu Rev Physiol 1996;58:523–38.
  • Ryan SJ, Hinton DR, Sadda SR, et al. Retina. 5th ed. Canada: Elsevier Health Sciences; 2012:580–600.
  • Gao B, Chen X, Timothy N, et al. Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. J Proteome Res 2008;7:2516–25.
  • Clinicaltrials Gov. Pharmacological intervention in diabetic retinopathy (XAVOT); 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT00619034 [last updated 28 Dec 2011].
  • Clinical trials Gov. Efficacy of dorzolamide as an adjuvant after focal photocoagulation in clinically significant macular edema; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02227745 [last updated 18 Mar 2015].
  • Patents. Use of carboanhydrase inhibitors for the prevention of diabetic retinopathy in diabetics. EP 1307185 B1; 2005. Available from: http://www.google.com/patents/EP1307185B1?cl=en [last accessed 13 Apr 2005].
  • Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. Diabetes 1989;38:491–8.
  • Ticlopidine treatment reduces the progression of nonproliferative diabetic retinopathy. Arch Ophthalmol 1990;108:1577–83.
  • Liou GI, Ahmad S, Naime M, et al. Role of adenosine in diabetic retinopathy. J Ocul Biol Dis Infor 2011;4:19–24.
  • Thrimawithana TR, Young S, Bunt CR, et al. Drug delivery to the posterior segment of the eye. Drug Discov Today 2011;16:270–7.
  • Loftsson T, Hreinsdóttir D, Stefansson E. Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol 2007;59:629–35.
  • Williams KA, Brereton HM, Farrall A, et al. Topically applied antibody fragments penetrate into the back of the rabbit eye. Eye (Lond) 2005;19:910–13.
  • Lim JI, Maguire AM, John G, et al. Intraocular tissue plasminogen activator concentrations after subconjunctival delivery. Ophthalmology 1993;100:373–6.
  • Kern TS, Miller CM, Du Y, et al. Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. Diabetes 2007;56:373–9.
  • Hariprasad SM, Callanan D, Gainey S, et al. Cystoid and diabetic macular edema treated with nepafenac 0.1%. J Ocul Pharmacol Ther 2007;23:585–90.
  • Clinicaltrilas.gov. Topical nepafenac as supplement for diabetic macular edema; 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02443012 [last updated May 2015].
  • Lu B, Gao Y, Shen W, et al. Therapeutic potential of topical fenofibrate eyedrops in diabetic retinopathy and AMD rat models. J Clin Exp Ophthalmol 2014;5:347.
  • Ottiger M, Thiel MA, Feige U, et al. Efficient intraocular penetration of topical anti-TNF-alpha single chain antibody (ESBA105) to anterior and posterior segment without penetration enhancer. Invest Ophthalmol Vis Sci 2009;50:779–86.
  • Poulsen JE. Recovery from retinopathy in a case of diabetes with Simmonds' disease. Diabetes 1953;2:7–12.
  • Wilkinson-Berka JL, Wraight C, Werther G. The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. Curr Med Chem 2006;13:3307–17.
  • Boehm BO, Lang GK, Jehle PM, et al. Octreotide reduces vitreous hemorrhage and loss of visual acuity risk in patients with high risk proliferative diabetic retinopathy. Horm Metab Res 2001;33:300–6.
  • 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;23:504–49.
  • Hernandez C, García-Ramirez M, Corraliza L, et al. Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes. Diabetes 2013;62:2569–78.
  • De Smet Marc D, Valmaggia C, Zarranz-Ventura J, et al. Microplasmin: ex vivo characterization of its activity in porcine vitreous. Invest Ophthalmol Vis Sci 2009;50:814–19.
  • Takano A, Hirata A, Ogasawara K, et al. Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel enzyme for pharmacologic vitreolysis. Invest Ophthalmol Vis Sci 2006;47:2075–9.
  • Hageman GS, Russell SR. Chondroitinase-mediated disinsertion of the primate vitreous body. Invest Opthamol Vis Sci 1994;35:1260–4.
  • Bishop PN, Mcleod Reardon A. Effects of hyaluronan lyase, hyaluronidase, and chondroitin ABC lyase on mammalian vitreous gel. Invest Ophthalmol Vis Sci 1999;40:2173–8.
  • Diaz-Liopis M, Udaondo P, Millan JM, et al. Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema. World J Diabetes 2013;4:319–23.
  • Huang Y, Enzmann V, Ildstad ST. Stem cell-based therapeutic applications in retinal degenerative diseases. Stem Cell Rev 2011;7:434–45.
  • Rajashekhar G. Mesenchymal stem cells: new players in retinopathy therapy. Front Endocrinol (Lausanne) 2014;5:59.
  • Lu B, Morgans CW, Girman S, et al. Neural stem cells derived by small molecules preserve vision. Transl Vis Sci Technol 2013;2:1.
  • Cui L, Guan Y, Qu Z, et al. WNT signaling determines tumorigenicity and function of ESC-derived retinal progenitors. J Clin Invest 2013;123:1647–61.
  • Decembrini S, Koch U, Radtke F, et al. Derivation of traceable and transplantable photoreceptors from mouse embryonic stem cells. Stem Cell Rep 2014;2:853–65.
  • Gonzalez-Cordero A, West EL, Pearson RA, et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat Biotechnol 2013;31:741–7.
  • Diniz B, Thomas P, Thomas B, et al. Subretinal implantation of retinal pigment epithelial cells derived from human embryonic stem cells: improved survival when implanted as a monolayer. Invest Ophthalmol Vis Sci 2013;54:5087–96.
  • Kamao H, Mandai M, Okamoto S, et al. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep 2014;2:205–18.
  • Maeda T, Lee MJ, Palczewska G, et al. Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. J Biol Chem 2013;288:34484–93.
  • Zhou L, Wang W, Liu Y, et al. Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells 2011;29:972–80.
  • Satarian L, Javan M, Kiani S, et al. Engrafted human induced pluripotent stem cell derived anterior specified neural progenitors protect the rat crushed optic nerve. PLoS One 2013;8:e71855.
  • Haddad-Mashadrizeh A, Bahrami AR, Matin MM, et al. Human adipose-derived mesenchymal stem cells can survive and integrate into the adult rat eye following xenotransplantation. Xenotransplantation 2013;20:165–76.
  • Ezquer M, Urzua CA, Montecino S, et al. Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Res Ther 2016;7:42.
  • Rajashekhar G, Ramadan A, Abburi C, et al. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy. PLoS One 2014 9:e84671.
  • Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch Clin Exp Ophthalmol 2010;248:1415–22.
  • Ting JH, Martin DK. Basic and clinical aspects of gene therapy for retinopathy induced by diabetes. Curr Gene Ther 2006;6:193–214.
  • Ideno J, Mizukami H, Kakehashi A, et al. Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model. Int J Mol Med 2007;19:75–9.
  • Shyong M, Lee F, Kou P, et al. Reduction of experimental diabetic vascular leakage by delivery of angiostatin with a recombinant adeno-associated virus vector. Mol Vis 2007;13:133–41.
  • Auricchio A, Behling KC, Maguire AM, et al. Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents. Mol Ther 2002;6:490–4.
  • Le Gat L, Gogat K, Bouquet C, et al. In vivo adenovirus-mediated delivery of a uPA/uPAR antagonist reduces retinal neovascularization in a mouse model of retinopathy. Gene Ther 2003;10:2098–103.
  • Lamartina S, Cimino M, Rosilli G, et al. Helper-dependent adenovirus for the gene therapy of proliferative retinopathies: stable gene transfer, regulated gene expression and therapeutic efficacy. J Gene Med 2007;9:862–74.
  • Igarashi T, Miyake K, Kato K, et al. Lentivirus-mediated expression of angiostatin efficiently inhibits neovascularization in a murine proliferative retinopathy model. Gene Ther 2003;10:219–26.
  • Borras T. Recent developments in ocular gene therapy. Exp Eye Res 2003;76:643–52.
  • Ikuno Y, Kazlauskas A. An in vivo gene therapy approaches for experimental proliferative vitreoretinopathy using the truncated platelet-derived growth factor a receptor. Invest Ophthalmol Vis Sci 2002;43:2406–11.
  • Luz-Madrigal A, Clapp C, Aranda J, et al. In vivo transcriptional targeting into the retinal vasculature using recombinant baculovirus carrying the human flt-1 promoter. Viro J 2007;4:88.
  • Kawakami S, Harada A, Sakanaka K, et al. In vivo gene transfection via intravitreal injection of cationic liposome/plasmid DNA complexes in rabbits. Int J Pharm 2004;278:255–62.
  • Bochot A, Fattal E, Boutet V, et al. Intravitreal delivery of oligonucleotides by sterically stabilized liposomes. Invest Ophthalmol Vis Sci 2002;43:253–9.
  • Del Pozo-Rodriguez A, Delgado D, Solinis MA, et al. Solid lipid nanoparticles for retinal gene therapy, transfection and intracellular trafficking in RPE cells. Int J Pharm 2008;360:177–83.
  • Wimmer N, Marano RJ, Kearns PS, et al. Synthesis of polycationic dendrimers on lipophilic peptide core for complexation and transport of oligonucleotides. Bioorg Med Chem Lett 2002;12:2635–7.
  • Bejjani RA, BenEzra D, Cohen H, et al. Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis 2005;11:124–32.
  • Bourges JL, Gautier SE, Delie F, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci 2003;44:3562–9.
  • Rafat M, Cleroux CA, Fong WG, et al. PEG-PLA microparticles for encapsulation and delivery of Tat-EGFP to retinal cells. Biomaterials 2010;31:3414–21.
  • Diabetic retinopathy clinical research network (DRCRS). Laser-ranibizumab-triamcinolone for proliferative diabetic retinopathy; 2016. Available from: https://clinicaltrials.gov/show/NCT00445003 [last updated 1 Jun 2016].
  • Clinical trials.Gov. Combined triple therapy in diabetic retinopathy (DRP); 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT0080616 [last updated 26 Sep 2012].
  • Csaky K, Do DV. Safety implications of vascular endothelial growth factor blockade for subjects receiving intravitreal anti-vascular endothelial growth factor therapies. Am J Ophthalmol 2009;148:647–56.
  • Curtis LH, Hammill BG, Schulman KA, et al. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol 2010;128:1273–9.
  • Ng WY, Tan GS, Ong PG, et al. Incidence of myocardial infarction, stroke, and death in patients with age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor therapy. Am J Ophthalmol 2015;159:557–64.
  • Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov Today 2008;13:144–51.
  • Edelhauser HF, RoweRendleman CL, Robinson MR, et al. Ophthalmic drug delivery systems for the treatment of retinal diseases: basic research to clinical applications. Invest Ophthalmol Vis Sci 2010;51:5403–20.
  • Duvvuri S, Majumdar S, Mitra AK. Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther 2003;3:45–56.
  • Geroski DH, Edelhauser HF. Drug delivery for posterior segment eye disease. Invest Ophthalmol Vis Sci 2000;41:961–4.
  • Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv 2004;1:99–114.
  • Donald DJ. Intravitreal injection: maximizing the benefits and minimizing the risks. RetinalPhysician; 2005. Available from: http://www.retinalphysician.com/articleviewer.aspx?articleID =100101.
  • Shima C, Sakaguchi H, Gomi F, et al. Complications in patients after intravitreal injection of bevacizumab. Acta Ophthalmol 2008;86:372–6.
  • Hughes PM, Olejnik O, Chang-Lin JE, et al. Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev 2005;57:2010–32.
  • Doukas J, Mahesh S, Umeda N, et al. Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. J Cell Physiol 2008;216:29–37.
  • Campochiaro PA, Shah SM, Hafiz G, et al. Topical mecamylamine for diabetic macular edema. Am J Ophthalmol 2010;149:839–5.
  • Diebold Y, Calonge M. Applications of nanoparticles in ophthalmology. Prog Retin Eye Res 2010;29:596–609.
  • De Salamanca AE, Diebold Y, Calonge M, et al. Chitosan nanoparticles as a potential drug delivery system for the ocular surface: toxicity, uptake mechanism and in vivo tolerance. Invest Opthalmol Vis Sci 2006;47:1416–25.
  • Alonso MJ, Sanchenz A. The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 2003;55:1451–63.
  • Wadhwa SR, Paliwal SR, Vyas PSP. Chitosan and its role in ocular therapeutics. Mini Rev Med Chem 2009;9:1639–47.
  • Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 2005;57:1595–639.
  • Han HD, Nam DE, Seo DH, et al. Preparation and biodegradation of thermosensitive chitosan hydrogel as a function of pH and temperature. Macromol Res 2004;12:507–11.
  • Attia Shafie MA, Mohammed Fayek HH. Formulation and evaluation of betamethasone sodium phosphate loaded nanoparticles for ophthalmic delivery. J Clin Exp Opthalmol 2013;4:273.
  • Yan XL, Khor E, Lim LY. Chitosan–alginate films prepared with chitosans of different molecular weights. J Biomed Mater Res 2001;58:358–65.
  • Hirano S, Seino H, Akiyama Y, Nonaka I. Biocompatibility of chitosan by oral and intravenous administration. Polym Eng Sci 1989;59:897–901.
  • Deepa P, Prashant K, Gowthamarajan K, et al. Physicochemical characterization and toxicological evaluation of plant based anionic polymers and their nanoparticulated system for ocular delivery. Nanotoxicology 2014;8:843–55.
  • Tamboli V, Mishra GP, Mitra AK. Polymeric vectors for ocular gene delivery. Ther Deliv 2011;2:523–36.
  • Avachat AM, Dash RR, Shrotriya SN. Recent investigations of plant based natural gums, mucilages and resins in novel drug delivery systems. Ind J Pharm Educ Res 2011;45:86–99.
  • Gowthamarajan K, Jawahar N, Wake P, et al. Development of buccal tablets for curcumin using Anacardium occidentale gum. Carbohydr Polym 2012;88:1177–83.
  • Mehra GR, Mathur M, Saroot R, et al. Enhancement of miotic potential of pilocarpine by tamarind gum based in-situ gelling ocular dosage form. Acta Pharm Sci 2010;52:145–54.
  • Lu Y, Zhou N, Huang X, et al. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats. Int J Ophthalmol 2014;7:1–7.
  • Jonas JB, Spandau UH, Rensch F, et al. Infectious and noninfectious endophthalmitis after intravitreal bevacizumab. J Ocul Pharmacol Ther 2007;23:240–2.
  • Jonas JB, Spandau UH, Schlichtenbrede F. Short-term complications of intravitreal injections of triamcinolone and bevacizumab. Eye (Lond) 2008;22:590–1.
  • Gelisken F, Ziemssen F, Voelker M, et al. Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration. Eye (Lond) 2009;23:694–702.
  • Souto EB, Doktorovovoa S, Mira GE, et al. Feasibility of lipid nanoparticles for ocular delivery of anti-inflammatory drugs. Curr Eye Res 2010;35:537–52.
  • Gasco MR, Saettone MF, Zara GP. Pharmaceutical compositions suitable for the treatment of ophthalmic diseases. US2006/0024374; 2006.
  • Hirlekar R, Garse H, Kadam V. Solid lipid nanoparticles and nanostructured lipid carriers: a review. Curr Drug Ther 2011;6:240–50.
  • Guo L, Zhang X, Zhang S. An experimental study of inhibition of tetrandrine on posterior capsular opacification in rabbits. Zhonghua Yan Ke Za Zhi 2002;38:235–8.
  • Huang P, Xu Y, Wei R, et al. Efficacy of tetrandrine on lowering intraocular pressure in animal model with ocular hypertension. J Glaucoma 2011;20:183–8.
  • Liang XC, Hagino N, Guo SS, et al. Therapeutic efficacy of Stephania tetrandra S. Moore for treatment of neovascularization of retinal capillary (retinopathy) in diabetes – in vitro study. Phytomedicine 2002;9:377–84.
  • Fangueiro JF, Andreani T, Egea MA, et al. Experimental factorial design applied to mucoadhesive lipid nanoparticles via multiple emulsion process. Colloids Surf B Biointerfaces 2012;100:84–9.
  • Lallemand F, Daull P, Benita S, et al. Successfully improving ocular drug delivery using the cationic nanoemulsion, novasorb. J Drug Deliv 2012;2012:604204.
  • Fangueiro JF, Calpena AC, Clares B, et al. Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): in vivo, in vitro and ex vivo studies. Int J Pharm 2016;502:161–9.
  • Seyfoddin A, Al-Kassas R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 2012;39:508–19.
  • Shen J, Wang Y, Ping Q, et al. Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular drug delivery. J Control Release 2009;137:217–23.
  • Gan L, Wang J, Jiang M, et al. Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers. Drug Discov Today 2013;18:290–7.
  • Luo Q, Zhao J, Zhang XW, Pan W. Nanostructured lipid carrier (NLC) coated with chitosan oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm 2011;403:185–91.
  • Araújo J, Gonzalez-Mira E, Egea MA, et al. Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications. Int J Pharm 2010;393:167–75.
  • Jonas J. Intravitreal injection of triamcinolone acetonide. In: Spaide RF, ed. Medical retina. Ruprecht-Karls-University of Heidelberg, Germany: Springer; 2005:143–64.
  • Beebe DC, Holekamp NM, Shui YB. Oxidative damage and the prevention of age-related cataracts. Ophthalmic Res 2010;44:155–65.
  • Joubert E, Richards ES, Merwe JD, et al. Effect of species variation and processing on phenolic composition and in vitro antioxidant activity of aqueous extracts of Cyclopia spp. (Honeybush Tea). J Agric Food Chem 2008;56:954–63.
  • Engels C, Knodler M, Zhao YY, et al. Antimicrobial activity of gallotannins isolated from mango (Mangifera indica L.) kernels. J Agric Food Chem 2009;57:7712–8.
  • Sá-Nunes A, Rogerio AP, Medeiros AI, et al. Modulation of eosinophil generation and migration by Mangifera indica L. extract (VimangR). Int Immunopharmacol 2006;6:1515–23.
  • Niesman MR. The use of liposomes as drug carriers in ophthalmology. Crit Rev Ther Drug Carrier Syst 1992;9:1–38.
  • Agarwal R, Iezhitsa I, Agarwal P, et al. Liposomes in topical ophthalmic drug delivery: an update. Drug Deliv 2015;21:1–17.
  • Bochot A, Fattal E. Liposomes for intravitreal drug delivery: a state of the art. J Control Release 2012;161:628–34.
  • Abrishami M, Ganavati S, Soroush D, et al. Preparation, characterization, and in vivo evaluation of nanoliposomes-encapsulated bevacizumab (Avastin) for intravitreal administration. Retina 2009;29:699–703.
  • Kaiser JM, Imai H, Jeremy K, et al. Nanoliposomal minocycline for ocular drug delivery. Nanomedicine 2013;9:130–40.
  • Nanjwade BK, Bechraa HM, Derkar GK, et al. Dendrimers: emerging polymers for drug-delivery systems. Eur J Pharm Sci 2009;38:185–96.
  • Vandamme TF, Brobeck L. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 2005;102:23–38.
  • Yavuz B, Pehlivan SB, Vural I, Unlu N. In vitro/in vivo evaluation of dexamethasone-PAMAM dendrimer complexes for retinal drug delivery. J Pharm Sci 2015;104:3814–23.
  • Kambhampati SP, Clunies-Ross AJM, Bhutto I, et al. Systemic and intravitreal delivery of dendrimers to activated microglia/macrophage in ischemia/reperfusion mouse retina. Invest Ophthalmol Vis Sci 2015;56:4413–24.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.