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Current Diabetes Reviews


ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

Potential Biomarkers in Diabetic Retinopathy

Author(s): Kaveri M. Adki and Yogesh A. Kulkarni*

Volume 16, Issue 9, 2020

Page: [971 - 983] Pages: 13

DOI: 10.2174/1573399816666200217092022

Price: $65


Background: Diabetic retinopathy is one of the important complications of diabetes. In major cases, diabetic retinopathy is unnoticed until the irreversible damage to eye occurs and leads to blurred vision and, eventually, blindness.

Objective: The pathogenesis and diagnosis of diabetic retinopathy are very complex and not fully understood. Currently, well-established laser techniques and medications are available, but these treatment options have their own shortcomings on biological systems. Biomarkers can help to overcome this problem due to easy, fast and economical options for diagnosis of diabetic retinopathy.

Methods: The search terms used were “Diabetic retinopathy”, “Biomarkers in diabetic retinopathy”, “Novel biomarkers in diabetic retinopathy” and “Potential biomarkers of diabetic retinopathy” by using different scientific resources and databases like EBSCO, ProQuest, PubMed and Scopus. Eligibility criteria included biomarkers involved in diabetic retinopathy in the detectable range. Exclusion criteria included the repetition and duplication of the biomarker in diabetic retinopathy.

Results: Current review and literature study revealed that biomarkers of diabetic retinopathy can be categorized as inflammatory: tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor- β; antioxidant: nicotinamide adenine dinucleotide phosphate oxidase; nucleic acid: poly ADP ribose polymerase- α, Apelin, Oncofetal; enzyme: ceruloplasmin, protein kinase C; and miscellaneous: erythropoietin. These biomarkers have a great potential in the progression of diabetic retinopathy hence can be used in the diagnosis and management of this debilitating disease.

Conclusion: Above mentioned biomarkers play a key role in the pathogenesis of diabetic retinopathy; hence they can also be considered as potential targets for new drug development.

Keywords: Diabetic retinopathy, biomarkers, erythropoietin, MCP-1, TNF- α, TGF –β, NOX, PARP α.

Cunha-Vaz J, Ribeiro L, Lobo C. Phenotypes and biomarkers of diabetic retinopathy. Prog Retin Eye Res 2014; 41: 90-111.
Hammes H-P. Diabetic retinopathy: hyperglycaemia, oxidativestress and beyond 2018 [cited 2018 Dec 13].
Congdon NG, Friedman DS, Lietman T. Important causes of visual impairment in the world today. JAMA 2003; 290(15): 2057.
Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetesDiabetes Care 2004;27Suppl 1(suppl 1): S84-7.
Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35(3): 556-64.
Cavan D, Makaroff L, da Rocha Fernandes J, et al. The Diabetic Retinopathy Barometer Study: Global perspectives on access to and experiences of diabetic retinopathy screening and treatment. 2017 Jul. Diabetes Res Clin Pract 2019; 129: 16-24. Available from:
Chua J, Lim CXY, Wong TY, Sabanayagam C. Diabetic Retinopathy in the Asia-Pacific . Asia-Pacific J Ophthalmol 2018; 7(1): 3-16.Available from:
Forbes JM, Cooper ME. Mechanisms of Diabetic Complications. Physiol Rev 2013; 93: 137-88.
Dhoot DS, Baker K, Saroj N, et al. Baseline factors affecting changes in diabetic retinopathy severity scale score after intravitreal aflibercept or laser for diabetic macular edema: post hoc analyses from VISTA and VIVID. Ophthalmology 2018; 125(1): 51-6. Available from:
Henriques J, Vaz-Pereira S, Nascimento J, Rosa PC. [Diabetic eye disease]Acta Med Port 2015; 28(1): 107-3. Available from:
Joshi S, Karule PT. A review on exudates detection methods for diabetic retinopathy. Biomed Pharmacother 2018; 97: 1454-60. Available from: l
Kempen JH, O’Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United StatesArch Ophthalmol (Chicago, Ill 1960) 1960; 122(4): 552-63. Available from:
Das A. Diabetic retinopathy: Battling the global epidemic. Indian J Ophthalmol 2016; 64(1): 2. Available from:
Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O’Neal DN, Januszewski AS. Biomarkers in diabetic retinopathy. Rev Diabet Stud 2015; 12(1–2): 159-95. Available from:
Frank RN. Diabetic Retinopathy. N Engl J Med 2004; 350(1): 48-58. Available from:
Romeo G, Liu W-H, Asnaghi V, Kern TS, Lorenzi M. Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 2002; 51(7): 2241-8. Available from:
Bek T. Diameter changes of retinal vessels in diabetic retinopathy. Curr Diab Rep 2017; 17(10): 82. Available from:
Singh R, Barden A, Mori LBT. Advanced glycation end-products: a review Diabetol 2001; 44: 129-46. Available from:
Srinivasan K. Polyphenols in vision and eye health. Handb Nutr Diet Eye 2014; 413-21.
Steele C, Steel D, Waine C, Steele C, Steel D, Waine C. Pathophysiology of diabetic retinopathy. Diabetes Eye 2008; 59-70.
Ahsan H. Diabetic retinopathy – Biomolecules and multiple pathophysiology. Diabetes Metab SyndrClin Res Rev 2015; 9(1): 51-4.Available from:
Milne R, Brownstein S. Advanced glycation end products and diabetic retinopathy. Amino Acids 2013; 44(6): 1397-407.Available from:
Stillwell W, Stillwell W. Bioactive Lipids An Introd to Biol Membr 2016; 453-78.
Wan T-T, Li X-F, Sun Y-M, Li Y-B, Su Y. Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. Biomed Pharmacother 2015; 74: 145-7.
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.Available from:
Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003 Jun; 1 [cited 2019 Feb 14];; 9(6): 669-76.Available from:
Duffy AM, Bouchier Hayes DJ, Harmey JH. Vascular Endothelial Growth Factor (VEGF) and Its Role in Non-Endothelial Cells:Autocrine Signalling by VEGF McIntyre CL, editor Genome 2017; 60(3): 201-7.Available from:
Huang H, He J, Johnson D, et al. Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1α-VEGF pathway inhibition. Diabetes 2015; 64(1): 200-12.
Lupo G, Motta C, Giurdanella G, et al. Role of phospholipases A2 in diabetic retinopathy: In vitro and in vivo studies. Biochem Pharmacol 2013; 86(11): 1603-3.Available from:
Antonetti DA, Barber AJ, Hollinger LA, Wolpert EB, Gardner TW. Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors. J Biol Chem 1999; 274(33): 23463-7.Available from:
Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54(6): 1615-25.
ElTanboly A, Ghazaf M, Khalil A, et al. An integrated framework for automatic clinical assessment of diabetic retinopathy grade using spectral domain OCT images.In: 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018) IEEE 2018; 1431-5.
Jin J, Min H, Kim SJ, et al. Development of diagnostic biomarkers for detecting diabetic retinopathy at early stages using quantitative proteomics. J Diabetes Res 2016; 20166571976Available from:
Safi H, Safi S, Hafezi-Moghadam A, Ahmadieh H. Early detection of diabetic retinopathy. Surv Ophthalmol 2018; 63(5): 601-8.
Levine SZ, Rabinowitz J, Uher R, Kapur S. Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance. Eur Neuropsychopharmacol 2015; 25(10): 1578-85.Available from:
Lyons TJ, Basu A. Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers. Transl Res 2012; 159(4): 303-12.
Matheson A, Willcox MDP, Flanagan J, Walsh BJ. Urinary biomarkers involved in type 2 diabetes: a review. Diabetes Metab Res Rev 2010; 26(3): 150-71.
Fu Y, Li H. Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) levels in breast cancer patients: a meta-analysis. Med Sci Monit 2016; 22: 3154-62.Available from:
Nalini M, Raghavulu BV, Annapurna A, et al. Correlation of various serum biomarkers with the severity of diabetic retinopathy. Diabetes Metab Syndr Clin Res Rev. 2017; 11: S451-4.
Liew G, Lei Z, Tan G, et al. Metabolomics of diabetic retinopathy. Curr Diab Rep 2017; 17(11): 102.
Yao Y, Li R, Du J, et al. Tumor necrosis factor-α and diabetic retinopathy: Review and meta-analysis. Clin Chim Acta 2018; 485: 210-7.Available from:
Capitão M, Soares R. Angiogenesis and inflammation crosstalk in diabetic retinopathy. J Cell Biochem 2016; 117(11): 2443-53.Available from:
Gao X, Li Y, Wang H, Li C, Ding J. Inhibition of HIF-1 α decreases expression of pro-inflammatory IL-6 and TNF- α in diabetic retinopathy. Acta Ophthalmol 2017; 95(8): e746-50.Available from:
Hassan I, Luo Q, Majumdar S, Dominguez JM, Busik JV, Bhatwadekar AD. . Tumor Necrosis Factor Alpha (TNF-α) disrupts Kir4.1 channel expression resulting in müller cell dysfunction in the retina. Investig Opthalmology Vis Sci 2017; 58(5): 2473.Available from:
Behl T, Kaur I, Kotwani A. Role of leukotrienes in diabetic retinopathy. Prostaglandins Other Lipid Mediat 2016; 122: 1-9.Available from:
Naruse K, Ueno M, Satoh T, Nomiyama H, Tei H, Takeda M, et al. A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2. Genomics 1996; 34(2): 236-40.Available from:
Robinson EA, Yoshimura T, Leonard EJ, et al. Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions. Proc Natl Acad Sci USA 1989; 86(6): 1850-4.Available from:
Jiang Z, Hennein L, Xu Y, Bao N, Coh P, Tao L. Elevated serum monocyte chemoattractant protein-1 levels and its genetic polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Diabet Med 2016; 33(1): 84-90.Available from:
Yoshida S, Yoshida A, Ishibashi T. Induction of IL-8, MCP-1, and bFGF by TNF-α in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation. Graefe's Arch Clin Exp Ophthalmol 2004; 242(5): 409-13.Available from:
Sassa Y, Yoshida S, Ishikawa K, Asato R, Ishibashi T, Kono T. The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy. Eye 2016; 30(5): 746-53.Available from:
Huang H, Jing G, Wang JJ, Sheibani N, Zhang SX. ATF4 is a novel regulator of MCP-1 in microvascular endothelial cells. J Inflamm 2015; 12(1): 31.Available from:
Mitamura Y, Takeuchi S, Matsuda A, Tagawa Y, Mizue Y, Nishihira J. Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy. Ophthalmologica 2001; 215(6): 415-8.
Taghavi Y, Hassanshahi G, Kounis NG, Koniari I, Khorramdelazad H. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: latest evidence and clinical considerations. J Cell Commun Signal 2019.Available from:
Clark DA, Coker R. Transforming growth factor-beta (TGF-beta). Int J Biochem Cell Biol 1998; 30(3): 293-8.Available from:
Massagué J. How cells read TGF-β signals. Nat Rev Mol Cell Biol 2000; 1(3): 169-78.Available from:
Hirase K, Ikeda T, Sotozono C, Nishida K, Sawa H, Kinoshita S. Transforming growth factor beta2 in the vitreous in proliferative diabetic retinopathy. Arch Ophthalmol 1998; 116(6): 738-41.Available from:
Khuu L-A, Tayyari F, Sivak JM, et al. Aqueous humour concentrations of TGF-β, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy. Acta Ophthalmol 2017; 95(3): e206-11.Available from:
Garba ML, Frelinger JA. Intracellular cytokine staining for TGF-beta. J Immunol Methods 2001; 258(1–2): 193-8.Available from:
Kowluru A, Kowluru RA. Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes. Biochem Pharmacol 2014; 88(3): 275-83.Available from:
Filip-Ciubotaru F, Manciuc C, Stoleriu G, Foia L. NADPH Oxidase: Structure And Activation Mechanisms (Review). NOTE I Rev Med Chir Soc Med Nat Iasi 2016; 120(1): 29-33.Available from:
Wang H, Hartnett ME. Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase in angiogenesis: isoform-specific effects. Antioxidants 2017; 6(2): 40.Available from:
Brandes RP, Weissmann N, Schröder K. Nox family NADPH oxidases: Molecular mechanisms of activation. Free Radic Biol Med 2014; 76: 208-6.Available from:
Sedeek M, Montezano AC, Hébert RL. Oxidative Stress, Nox Isoforms and Complications of Diabetes—Potential Targets for Novel Therapies. Artic J Cardiovasc Transl Res 2012.Available from:
Deliyanti D, Wilkinson-Berka JL. Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate neuroglial cell inflammation in the retina. J Neuroinflammation 2015; 3012(1): 136.Available from:
Cai H, Griendling KK, Harrison DG. The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol Sci 2003; 24(9): 471-8.Available from:
Jha JC, Di Marco E, Gray SP, Jandeleit-Dahm KA. NAD(P)H oxidase isoforms as therapeutic targets for diabetic complications. Expert Rev Endocrinol MetabEarly online 2014; 1-12.Available from:
Al-Shabrawey M, Rojas M, Sanders T, Behzadian A, El-Remessy A, Bartoli M, et al. Role of NADPH Oxidase in Retinal Vascular Inflammation Investig Opthalmology Vis Sci 2008; 49(7): 3239.Available from:
Li Y, Pagano PJ. Microvascular NADPH oxidase in health and disease. Free Radic Biol Med 2017; 109: 33-47.
Jubin T, Kadam A, Jariwala M, et al. The PARP family: insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival. Cell Prolif 2016; 49(4): 421-37.Available from:
Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Ménissier-de Murcia J. Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication. Nucleic Acids Res 1998; 26(8): 1891.Available from:
Kun E, Kirsten E, Ordahl CP. Coenzymatic Activity of Randomly Broken or Intact Double-stranded DNAs in Auto and Histone H 1 Trans-poly(ADP-ribosylation), Catalyzed by Poly(ADP-ribose) Polymerase (PARP I)*. J Biol Chem 2002; 277(42): 39066-9.Available from:
Masutani M, Nakagama H, Sugimura T. Poly(ADP-ribose) and carcinogenesis Genes, Chromosom Cancer 2003; 38(4): 339-48.Available from:
Carney B, Kossatz S, Reiner T. Molecular Imaging of PARP. J Nucl Med 2017; 58(7): 1025-30.Available from:
Pacher P, Szabó C. Role of Poly(ADP-Ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal 2005; 7(11–12): 1568-80.Available from:
Zheng L, Kern TS. Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy Front Biosci (Landmark Ed 2009; 14: 3974-87.Available from: .
Hu H, He L, Li L, Chen L. Apelin/APJ system as a therapeutic target in diabetes and its complications. Mol Genet Metab 2016; 119(1–2): 20-7.Available from:
Zhong J-C, Zhang Z-Z, Wang W, McKinnie SMK, Vederas JC, Oudit GY. Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases. Biochim Biophys Acta Mol Basis Dis 1863; 1863(8): 1942-50.Available from:
Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005; 107(2): 198-211.Available from:
Luo X, Liu J, Zhou H, Chen L. Apelin/APJ system: A critical regulator of vascular smooth muscle cell. J Cell Physiol 2018; 233(7): 5180-8.Available from:
Alipour FG, Ashoori MR, Pilehvar-Soltanahmadi Y, Zarghami N. An overview on biological functions and emerging therapeutic roles of apelin in diabetes mellitus. Diabetes Metab SyndrClin Res Rev 2017; 11: S919-23.
Chaves-Almagro C, Castan-Laurell I, Dray C, Knauf C, Valet P, Masri B. Apelin receptors: From signaling to antidiabetic strategy. Eur J Pharmacol 2015; 763(Pt B): 149-59.Available from:
Pusparajah P, Lee L-H, Abdul Kadir K. Molecular markers of diabetic retinopathy: potential screening tool of the future? Front Physiol 2016; 7: 200.Available from:
Kasai A. Apelin-APJ system: from discovery to therapeutic target. Nihon Yakurigaku Zasshi 2012; 139(5): 198-202.Available from:
Gong Y, Woda BA, Jiang Z. Oncofetal Protein IMP3, a New Cancer Biomarker. Adv Anat Pathol 2014; 21(3): 191-200.
Khan ZA, Cukiernik M, Gonder JR, Chakrabarti S. Oncofetal Fibronectin in Diabetic Retinopathy. Investig Opthalmology Vis Sci 2004; 45(1): 287.
Chakrabarti S, Khan ZA, Cukiernik M, Zhang W, Sima AAF. C-peptide and Retinal Microangiopathy in Diabetes. Exp Diabesity Res 2004; 5(1): 91.Available from:
Khan ZA, Barbin YP, Farhangkhoee H, Beier N, Scholz W, Chakrabarti S. Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression. Biochem Biophys Res Commun 2005; 329(1): 275-80.Available from:
Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu Rev Nutr 2002; 22(1): 439-58.Available from:
Linder MC. Ceruloplasmin and other copper binding components of blood plasma and their functions: an update. Metallomics 2016; 8(9): 887-905.
Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Simic D, Radovanovic S, Simic T. Novel biomarkers of heart failure. Adv Clin Chem 2017; 79: 93-152.Available from:
Arnaud P, Gianazza E, Miribel L. Ceruloplasmin. Methods Enzymol 1988; 163: 441-52.Available from:
González-Jiménez E, Schmidt-Riovalle J, Sinausía L, Carmen Valenza M, Perona JS. Predictive value of ceruloplasmin for metabolic syndrome in adolescents. Biofactors 2016; (2): 163-70.Available from:
Huang Y, Chan P, Halliday G. Genetics of Parkinson’s Disease. Oxidative Stress and Neurodegenerative Disorders Internet.Elsevier 2007; 663-97.
Hoda K, Bowlus CL, Chu TW, Gruen JR. Iron metabolism and related disorders. Emery and Rimoin's Principles and Practice of Medical Genetics 2013; 1-41.
Nowak M, Wielkoszyński T, Marek B, et al. Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy. Clin Exp Med 2010; 10(3): 185-92.Available from:
Dong H, Li Q, Wang M, Wan G. Association Between IL-10 Gene Polymorphism and Diabetic Retinopathy. Med Sci Monit 2015; 21: 3203-8.Available from:
Lang GE, Kampmeier J. Die Bedeutung der Proteinkinase C in der Pathophysiologie der diabetischen Retinopathie. Klin Monbl Augenheilkd 2002; 219(11): 769.Available from:
Frank RN. Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol 2002; 133(5): 693-8.
Lang GE. Treatment of diabetic retinopathy with protein kinase C subtype Beta inhibitor. Dev Ophthalmol 2007; 39: 157-65.
Das Evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007; 55(6): 498-510.Available from:
Song HB, Jun H-O, Kim JH, Yu YS, Kim KW, Kim JH. Suppression of protein kinase C-ζ attenuates vascular leakage via prevention of tight junction protein decrease in diabetic retinopathy. Biochem Biophys Res Commun 2014; 444(1): 63-8.Available from:
Bieber E. Erythropoietin, the biology of erythropoiesis and epoetin alfa. J Reprod Med 2001; 46(5)(Suppl.): 521-30.Available from:
Cazzola M. Erythropoietin pathophysiology and erythropoietin deficiency anemia. Hematol J 2004; 5: S100-3.
Krantz SB. Erythropoietin. Blood 1991; 77(3): 419-34.Available from:
Maiese K. Erythropoietin and diabetes mellitus. World J Diabetes 2015 Oct; 25 [cited 2019 Jan 31]; 6(14): 1259.
Mocini D, Leone T, Tubaro M, Santini M, Penco M. Structure, production and function of erythropoietin: implications for therapeutical use in cardiovascular disease. Curr Med Chem 2007; (21): 2278-87.
Eckardt K-U. Erythropoietin and microvascular diabetic complications*. Nephrol Dial Transpl 2008; 1(3)Available from:
Monti G. The renal control of hemopoiesis: Erythropoietin. Policlinico [Med] 1963; 70: 307-23.Available from:
Tong Z, Yang Z, Patel S, et al. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications. Proc Natl Acad Sci 2008; 105(19): 6998-7003.
Thomas MC, Tsalamandris C, MacIsaac R, Jerums G. Functional erythropoietin deficiency in patients with Type 2 diabetes and anaemia. Diabet Med 2006; 23(5): 502-9.Available from:
Spivak JL. Erythropoietin. Blood Rev 1989; 3(2): 130-5.Available from:
Elliott S, Pham E, Macdougall IC. Erythropoietins: A common mechanism of action. Exp Hematol 2008; 36(12): 1573-84.Available from:
Rossert J, Eckardt K-U. Erythropoietin receptors: their role beyond erythropoiesis. Nephrol Dial Transplant 2005; 20(6): 1025-8.Available from:
Lange RD, Pavlovic-Kentera V. Erythropoietin. Prog Hematol 1964; 4: 72-96.Available from:
Mitchell P, Bandello F, Schmidt-Erfurth U, et al. The RESTORE Study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011; 118(4): 615-25.Available from:
Heier JS, Korobelnik J-F, Brown DM, et al. Intravitreal Aflibercept for Diabetic Macular Edema. Ophthalmology 2016; 123(11): 2376-85.
Sultan MB, Zhou D, Loftus J, Dombi T, Ice KS. Macugen 1013 Study Group. A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 2011; 118(6): 1107-8.Available from:
Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. Ophthalmology 2016; 123(6): 1351-9. Available from:
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(10): 1904-4. Available from:.
Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 2011; 118(4): 626-35.
Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010; 117(6): 1064-77.
Alam NM, Mills WC, Wong AA, Douglas RM, Szeto HH, Prusky GT. A mitochondrial therapeutic reverses visual decline in mouse models of diabetes. Dis Model Mech 2015; 8(7): 701-10.
Gębka A, Serkies-Minuth E, Raczyńska D. Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes. Mediators Inflamm 2014; 2014: 1-7.Available from:
Moschos MM, Dettoraki M, Tsatsos M, Kitsos G, Kalogeropoulos C. Effect of carotenoids dietary supplementation on macular function in diabetic patients. Eye Vis 2017; 4(1): 23.
Agbaje IM, Rogers DA, McVicar CM, et al. Insulin dependant diabetes mellitus: implications for male reproductive function. Hum Reprod 2007; 22(7): 1871-7.
Staurenghi G, Ye L, Magee MH, et al. Darapladib, a lipoprotein-associated phospholipase a2 inhibitor, in diabetic macular edema. Ophthalmology 2015; 122(5): 990-6.Available from:
van Dijk HW, Kok PHB, Garvin M, et al. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy Investig Opthalmology Vis Sci 2009; 50(7): 3404.Available from:
Patz A, Fine S, Finkelstein D, et al. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology 1978; 85(1): 82-106.Available from:
Blumenkranz MS, Leung L-S, Martin DF, Rosenfeld PJ, Zarbin MA. Pharmacotherapy of Age-Related Macular Degeneration. Retina 2013; 1213-55.
Vujosevic S, Martini F, Convento E, et al. Subthreshold laser therapy for diabetic macular edema: metabolic and safety issues. Curr Med Chem 2013; 2026: 3267-71.

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