Preview

Diabetes mellitus

Advanced search

Biomarkers for diabetic retinopathy

https://doi.org/10.14341/DM10045

Abstract

A data analysis on the actual direction of biomedicine, the study of biomarkers in diabetic retinopathy (DR), was done. Biomarkers identification is important for screening, diagnosis, monitoring, prevention and prediction of the clinical response of the patient to the treatment. In addition, studying the biomarkers allows increase of the effectiveness and safety of using various treatment options. The review examines two main groups of biomarkers, molecular and visualised, which shows the current state of the problem and the prospects for studying biomarkers in the context of the DR treatment. Nowadays, searching for and finding new biomarkers is important and will allow us to develop individual treatment regimens for DR and personalised medicine in an interdisciplinary aspect: ophthalmology and endocrinology.

About the Authors

Maria V. Budzinskaya
Research institute of eye diseases
Russian Federation

MD, PhD



Dmitry V. Lipatov
Endocrinology research centre
Russian Federation

MD, PhD, Professor



Vladislav G. Pavlov
Research institute of eye diseases
Russian Federation

MD



Denis V. Petrachkov
Research institute of eye diseases
Russian Federation

MD, PhD



References

1. Aronson JK. Biomarkers and surrogate endpoints. Br J Clin Pharm. 2005;59(5):491–494. doi: https://doi.org/10.1111/J.1365-2125.2005.02435.X

2. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharm Ther. 2001;69(3):89–95. doi: https://doi.org/10.1067/Mcp.2001.113989

3. Мирошниченко И.И., Птицина С.Н. Биомаркеры в современной медико-биологической практике // Биомедицинская химия. — 2009. — Т. 55. — №4. — С. 425−440. [Miroshnichenko II, Ptitsyna SN. Biomarkers in the modern medical and biologic practice. Biomed khim. 2009;55(4):425−440. (In Russ.)]

4. Waldman S, Terzic A. Targeted diagnostics and therapeutics for individualized patient management. Biomark Med. 2007;1(1):3–8. doi: https://doi.org/10.2217/17520363.1.1.3

5. Ginsburg GS, Willard HF. Genomic and personalized medicine: foundations and applications. Transl Res. 2009;154(6):277–287. doi: https://doi.org/10.1016/J.Trsl.2009.09.005

6. Дедов И.И., Шестакова М.В., Викулова О.К. Эпидемиология сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета // Сахарный диабет. — 2017. — T. 20. — №1. — C.13–41. [Dedov II, Shestakova MV, Vikulova OK. Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the Federal diabetes registry. Diabetes mellitus. 2017;20(1):13–41. (In Russ.)] doi: https://doi.org/10.14341/Dm8664

7. Федеральные клинические рекомендации: диагностика и лечение диабетической ретинопатии и диабетического макулярного отека. — М., 2013. [Federal clinical guidelines: diagnosis and treatment of diabetic retinopathy and diabetic macular edema. Moscow; 2013. (In Russ.)] Доступно по: https://zodorov.ru/federalenie-klinicheskie-rekomendacii-diagnostika-i-lechenie-d.html. Ссылка активна на 12.11.2019.

8. Липатов Д.В., Викулова О.К., Железнякова А.В., и др. Эпидемиология диабетической ретинопатии в Российской Федерации по данным Федерального регистра больных сахарным диабетом (2013–2016 гг.) // Сахарный диабет. — 2018. — Т. 21. — №4. — С. 230–240. [Lipatov DV, Vikulova OK, Zheleznyakova AV, et al. Trends in the epidemiology of diabetic retinopathy in Russian Federation according to the Federal diabetes register (2013–2016). Diabetes mellitus. 2018;21(4):230–240. (In Russ.)] doi: https://doi.org/10.14341/Dm9797

9. Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 9-й вып // Сахарный диабет. — 2019. — Т. 22. — №1S1. — C. 1–144. [Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Ed. by Dedov II, Shestakova MV, Mayorov AYu. 9th edition. Diabetes mellitus. 2019;22(1S1):1-144. (In Russ.)] doi: https://doi.org/10.14341/DM221S1

10. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors ofdiabetic retinopathy. Diabetes care. 2012;35(3):556–564. doi: https://doi.org/10.2337/Dc11-1909

11. Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world outcomes of anti–vascular endothelial growth factor therapy in diabetic macular edema in the United States. Ophthalmol Retina. 2018;2(12):1179–1187. doi: https://doi.org/10.1016/J.Oret.2018.06.004

12. Iglicki M, Lavaque A, Ozimek M, et al. Biomarkers and predictors for functional and anatomic outcomes for small gauge pars plana vitrectomy and peeling of the internal limiting membrane in naïve diabetic macular edema: the vital study. Plos One 2018;13(7):e0200365. doi: https://doi.org/10.1371/Journal.Pone.0200365

13. Borsey DQ, Prowse CV, Gray RS, et al. Platelet and coagulation factors in proliferative diabetic retinopathy. J Clin Pathol. 1984;37(6):659–664. doi: https://doi.org/10.1136/jcp.37.6.659

14. Madan R, Gupt B, Saluja S, et al. Coagulation profile in diabetes and its association with diabetic microvascular complications. J Assoc Physicians India. 2010;58:481–484.

15. Das R, Kerr R, Chakravarthy U, Hogg RE. Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis. Ophthalmol. 2015;122(9):1820–1827. doi: https://doi.org/10.1016/J.Ophtha.2015.05.011

16. Singh RP, Habbu K, Ehlers JP, et al. The impact of systemic factors on clinical response to ranibizumab for diabetic macular edema. Ophthalmol. 2016;123(7):1581–1587. doi: https://doi.org/10.1016/J.Ophtha.2016.03.038

17. Астахов Ю.С., Залевская А.Г., Карпова И.А., и др. Факторы, влияющие на прогрессирование диабетической ретинопатии у больных сахарным диабетом 2-го типа после перевода на инсулинотерапию // РМЖ. Клиническая офтальмология. — 2005. — Т. 6. — №3. — С. 110–114. [Astakhov YuS, Zalevskaya AG, Karpova IA, et al. Factors, influencing diabetic retinopathy progression in type 2 diabetic patients after switching to insulin therapy. RMJ. Klinicheskaya oftal’mologiya. 2005;6(3):110–114. (In Russ.)]

18. Funatsu H, Yamashita H, Ikeda T, et al. Angiotensin and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol. 2002;133(4):537–543. doi: https://doi.org/10.1016/s0002-9394(02)01323-5

19. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358(19):2039–2049. doi: https://doi.org/10.1056/nejmra0706596

20. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280(6):1358–1366. doi: https://doi.org/10.1152/ajpcell.2001.280.6.c1358

21. Борзилова Ю.А., Болдырева Л.А., Валеева Р.Р., и др. Уровень VEGF-а в слезной жидкости у пациентов с различными стадиями диабетической ретинопатии // Современные технологии в офтальмологии. — 2016. — №1. — С. 43–47. [Borzilova YuA, Boldyreva LA, Valeyeva RR, i dr. Uroven’ VEGF-a v sleznoy zhidkosti u patsiyentov s razlichnymi stadiyami diabeticheskoy retinopatii. Sovremennyye tekhnologii v oftal’mologii. 2016;(1):43–47. (In Russ.)]

22. Homme RP, Singh M, Majumder A, et al. Remodeling of retinal architecture in diabetic retinopathy: disruption of ocular physiology and visual functions by inflammatory gene products and pyroptosis. Front Physiol. 2018;9:1268. doi: https://doi.org/10.3389/Fphys.2018.01268

23. Кузьмин А.Г., Липатов Д.В., Смирнова О.М., Шестакова М.В. Анти-VEGF препараты для лечения диабетической ретинопатии // Офтальмохирургия. — 2009. — №3. — С. 53–57. [Kuz’min AG, Lipatov DV, Smirnova OM, Shestakova MV. Anti-VEGF preparaty dlya lecheniya diabeticheskoy retinopatii. Ophthalmosurgery. 2009;(3):53–57. (In Russ.)]

24. Dugel PU, Layton A, Varma R. Diabetic macular edema diagnosis and treatment in the real world: an analysis of medicare claims data (2008 to 2010). Ophthalmic Surg Lasers Imaging Retina. 2016;47(3):258–267. doi: https://doi.org/10.3928/23258160-20160229-09

25. Funatsu H, Noma H, Mimura T, et al. Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmol. 2009;116(1):73–79. doi: https://doi.org/10.1016/J.Ophtha.2008.09.037

26. Kwon SH, Shin JP, Kim IT, Park DH. Aqueous levels of angiopoietin-like 4 and semaphorin 3e correlate with nonperfusion area and macular volume in diabetic retinopathy. Ophthalmol. 2015;122(5):968–975. doi: https://doi.org/10.1016/J.Ophtha.2015.01.007

27. Rübsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy. Int J Mol Sci. 2018;19(4). pii: E942. doi: https://doi.org/10.3390/ijms19040942

28. Shu DY, Lovicu FJ. Myofibroblast transdifferentiation: the dark force in ocular wound healing and fibrosis. Prog Retin Eye Res. 2017;60:44–65. doi: https://doi.org/10.1016/j.preteyeres.2017.08.001

29. Di Carlo SE, Peduto L. The perivascular origin of pathological fibroblasts. J Clin Invest. 2018;128(1):54–63. doi: https://doi.org/10.1172/JCI93558

30. Arevalo JF, Maia M, Flynn HW, et al. Tractional retinal detachment following intravitreal bevacizumab (avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol. 2008;92(2):213–216. doi: https://doi.org/10.1136/bjo.2007.127142

31. Pang JP, Son G, Yoon YH, et al. Combined vitrectomy with intravitreal dexamethasone implant for refractory macular edema secondary to diabetic retinopathy, retinal vein occlusion, and noninfectious posterior uveitis. Retina. 2020;40(1):56–65. doi: https://doi.org/10.1097/Iae.0000000000002358

32. Choi JA, Ko SH, Park YR, et al. Retinal nerve fiber layer loss is associated with urinary albumin excretion in patients with type 2 diabetes. Ophthalmol. 2015;122(5):976–981. doi: https://doi.org/10.1016/J.Ophtha.2015.01.001

33. Wang H, Chhablani J, Freeman WR, et al. Characterization of diabetic microaneurysms by simultaneous fluorescein angiography and spectral-domain optical coherence tomography. Am J Ophthalmol. 2012;153(5):861–867.e1. doi: https://doi.org/10.1016/j.ajo.2011.10.005

34. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmol. 1991;98(5 Suppl):766–785. doi: https://doi.org/10.1016/s0161-6420(13)38011-7

35. Silva PS, Cavallerano JD, Haddad NM, et al. Peripheral lesions identified on ultrawide field imaging predict increased risk of diabetic retinopathy progression over 4 years. Ophthalmol. 2015;122(5):949–956. doi: https://doi.org/10.1016/J.Ophtha.2015.01.008

36. Witmer MT, Kiss S. The clinical utility of ultra-wide-field imaging [Internet]. Rev Ophthalmol. [cited 2012 March 8] Available from: https://www.reviewofophthalmology.com/article/the-clinical-utility-of-ultra-wide-field-imaging

37. Silva PS, El-Rami H, Barham R, et al. Hemorrhage and/or microaneurysm severity and count in ultrawide field images and early treatment diabetic retinopathy study photography. Ophthalmol 2017;124(7):970–976. doi: https://doi.org/10.1016/J.Ophtha.2017.02.012

38. Shah VP, Shah SA, Mrejen S, Freund KB. Subretinal hyperreflective exudation associated with neovascular age-related macular degeneration. Retina. 2014;34(7):1281–12888. doi: https://doi.org/10.1097/IAE.0000000000000166

39. Dugel PU, Campbell JH, Kiss S, et al. Association between early anatomic response to anti-vascular endothelial growth factor therapy and long-term outcome in diabetic macular edema. Retina. 2019;39(1):88–97. doi: https://doi.org/10.1097/Iae.0000000000002110

40. Santos A, Costa M, Schwartz C, et al. Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema. Retina. 2018;38(6):1110–1119. doi: https://doi.org/10.1097/IAE.0000000000001687

41. Sun JK, Lin MM, Lammer J, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132(11):1309–1316. doi: https://doi.org/10.1001/Jamaophthalmol.2014.2350

42. Sophie R, Lu N, Campochiaro PA. Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab. Ophthalmol. 2015;122(7):1395–1401. doi: https://doi.org/10.1016/J.Ophtha.2015.02.036

43. Santos AR, Alves D, Santos T, et al. Measurements of retinal fluid by optical coherence tomography leakage in diabetic macular edema. Retina. 2019;39(1):52–60. doi: https://doi.org/10.1097/Iae.0000000000001905

44. Moein HR, Novais EA, Rebhun CB, et al. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic macular edema. Retina. 2018;38(12):2277–2284. doi: https://doi.org/10.1097/Iae.0000000000001902

45. Regatieri CV, Branchini L, Carmody J, et al. Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina. 2012;32(3):563–568. doi: https://doi.org/10.1097/Iae.0b013e31822f5678

46. Niestrata-Ortiz M, Fichna P, Stankiewicz W, Stopa M. Determining the effect of diabetes duration on retinal and choroidal thicknesses in children with type 1 diabetes mellitus. Retina. 2020;40(3):421–427. doi: https://doi.org/10.1097/Iae.0000000000002420

47. Kang HM, Lee NE, Choi JH, et al. Significant reduction of both peripapillary and subfoveal choroidal thickness after panretinal photocoagulationin patients with type 2 diabetes. Retina. 2018;38(10):1905–1912. doi: https://doi.org/10.1097/Iae.0000000000001804

48. Coscas G, De Benedetto U, Coscas F, et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration. Ophthalmologica. 2013;229(1):32–37. doi: https://doi.org/10.1159/000342159

49. Vujosevic S, Bini S, Torresin T, et al. Hyperreflective retinal spots innormal and diabetic eyes: b-scan and en face spectral domain optical coherence tomography evaluation. Retina. 2017;37(6):1092–1103. doi: https://doi.org/10.1097/Iae.0000000000001304

50. Chen KC, Jung JJ, Curcio CA, el al. Intraretinal hyperreflective foci in acquired vilelliform lesions of the macula: clinical and histologic study. Am J Ophthalmol. 2016;164:89–98. doi: https://doi.org/10.1016/j.ajo.2016.02.002

51. Zanzottera EC, Messinger JD, Ach T, et al. The project macula retinal pigment epithelium grading system for histology and optical coherence tomography in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015;56(5):3253–3268. doi: https://doi.org/10.1167/iovs.15-16431

52. Pang CE, Messinger JD, Zanzottera EC, et al. The onion sign in neovascular age-related macular degeneration represents cholesterol crystals. Ophthalmol. 2015;122(11):2316–2326. doi: https://doi.org/10.1016/j.ophtha.2015.07.008

53. Sadiq MA, Soliman MK, Sarwar S, et al. Effect of vitreomacular adhesion on treatment outcomes in the ranibizumab for edema of the macula in diabetes (read-3) study. Ophthalmol. 2016;123(2):324–329. doi: https://doi.org/10.1016/J.Ophtha.2015.09.032

54. Ip MS, Domalpally A, Sun JK, Ehrlich JS. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmol. 2015;122(2):367–374. doi: https://doi.org/10.1016/J.Ophtha.2014.08.048

55. Zur D, Iglicki M, Busch C, et al. Optical coherence tomography biomarkers as functional outcome predictors in diabetic macular edema treated with dexamethasone implant. Ophthalmol. 2018;125(2):267–275. doi: https://doi.org/10.1016/J.Ophtha.2017.08.031

56. Kim JH, Lee MW, Byeon SH, et al. Associations between individual retinal layer thicknesses and diabetic peripheral neuropathy using retinal layer segmentation analysis. Retina. 2018;38(11):2190–2196. doi: https://doi.org/10.1097/Iae.0000000000001835

57. Ho J, Dans K, You Q, et al. Comparison of 3 mm × 3 mm versus 6 mm × 6 mm optical coherence tomography angiography scan sizes in the evaluation of non-proliferative diabetic retinopathy. Retina. 2019;39(2):259–264. doi: https://doi.org/10.1097/Iae.0000000000001951

58. Alibhai AY, De Pretto LR, Moult EM, et al. Quantification of retinal capillary nonperfusion in diabetics using wide-field optical coherence tomography angiography. Retina. 2020;40(3):412–420. doi: https://doi.org/10.1097/Iae.0000000000002403

59. Alam M, Zhang Y, Lim JI, et al. Quantitative optical coherence tomography angiography features for objective classification and staging of diabetic retinopathy. Retina. 2018. doi: https://doi.org/10.1097/Iae.0000000000002373

60. Lee J, Moon BG, Cho AR, et al. Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology. 2016;123(11):2368–2375. doi: https://doi.org/10.1016/j.ophtha.2016.07.010


Supplementary files

Review

For citations:


Budzinskaya M.V., Lipatov D.V., Pavlov V.G., Petrachkov D.V. Biomarkers for diabetic retinopathy. Diabetes mellitus. 2020;23(1):88-94. (In Russ.) https://doi.org/10.14341/DM10045

Views: 1498


ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)