Interdisciplinary approach to the management of diabetic retinopathy: The role of ophthalmologist and endocrinologist

Diabetic retinopathy (DR) and diabetic macular edema (DME) are common chronic complications of diabetes mellitus, the fight against which is an urgent problem of modern healthcare. DR is the fifth most common cause of blindness worldwide and the main cause of vision loss in patients with diabetes. An interdisciplinary approach plays a key role in the effective management of DR, in which the role of the endocrinologist is to achieve optimal indicators of glycemic control as the main pathogenetic factor, and regular referral to screening of patients from risk groups. In turn, ophthalmologists are faced with the task of directly diagnosing changes in the fundus and treating eye diseases at various stages. Modern ideas about the mechanisms of development of DR and the role of VEGF allow us to identify several main areas of therapy. Thus, the main method of treating DR is laser retinal coagulation (LRC), and the most effective method of treating DME is considered to be a combination of LRC and intravitreal administration of angiogenesis inhibitors. Currently, intravitreal administration of agents that prevent the neoangiogenesis is the first-line treatment for DME involving the center of the macula. This review provides information on the pathogenesis, modern classification and current approaches to the management of patients with DR in the framework of the interaction of an ophthalmologist and an endocrinologist.

1. Sun H, Saeedi P, Karuranga S et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022; 183: 109119. doi: 10.1016/j.diabres.2021.109119.

2. GBD 2019 Blindness and Visual Impairment Collaborators. Causes of blindness and visual impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to vision 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob Healthю 2021; 9(2): e144–60. doi: 10.1016/S2214-109X(20)30489-7.

3. Teo ZL, Tham YC, Yu M et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis. Ophthalmology. 2021; 128(11): 1580–91. doi: 10.1016/j.ophtha.2021.04.027.

4. Дедов И.И., Шестакова М.В., Викулова О.К. с соавт. Сахарный диабет в Российской Федерации: динамика эпидемиологических показателей по данным Федерального регистра сахарного диабета за период 2010–2022 гг. Сахарный диабет. 2023; 26(2): 104–123. doi: 10.14341/DM13035.

5. Yang J, Liu Z. Mechanistic pathogenesis of endothelial dysfunction in diabetic nephropathy and retinopathy. Front Endocrinol (Lausanne). 2022; 13: 816400. doi: 10.3389/fendo.2022.816400.

6. Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol. 2020; 37: 101799. doi: 10.1016/j.redox.2020.101799.

7. Клинические рекомендации. Сахарный диабет: диабетическая ретинопатия, диабетический макулярный отек. Общероссийская общественная организация «Ассоциация врачей-офтальмологов», Российская ассоциация эндокринологов. Рубрикатор клинических рекомендаций Минздрава России. 2023. ID: 115. Доступ: https://cr.minzdrav.gov.ru/schema/115_2 (дата обращения – 01.11.2024).

8. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991; 98 (5 Suppl): 823–33.

9. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017; 237(4): 185–222. doi: 10.1159/000458539.

10. Massin P, Bandello F, Garweg JG et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care. 2010; 33(11): 2399–405. doi: 10.2337/dc10-0493.

11. Mitchell P, Bandello F, Schmidt-Erfurth U et al.; RESTORE Study Group. The RESTORE study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011; 118(4): 615–25. doi: 10.1016/j.ophtha.2011.01.031.

12. Do DV, Schmidt-Erfurth U, Gonzalez VH et al. The DA VINCI study: Phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011; 118(9): 1819–26. doi: 10.1016/j.ophtha.2011.02.018.

13. Brown DM, Emanuelli A, Bandello F et al. KESTREL and KITE: 52-week results from two phase III pivotal trials of brolucizumab for diabetic macular edema. Am J Ophthalmol. 2022; 238: 157–72. doi: 10.1016/j.ajo.2022.01.004.

14. Wong TY, Haskova Z, Asik K et al. Faricimab treat-and-extend for diabetic macular edema: Two-year results from the randomized phase 3 YOSEMITE and RHINE Trials. Ophthalmology. 2024; 131(6): 708–23. doi: 10.1016/j.ophtha.2023.12.026.

15. Boyer DS, Yoon YH, Belfort R Jr et al.; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014; 121(10): 1904–14. doi: 10.1016/j.ophtha.2014.04.024.

16. Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J et al. The effect of intensive treatment of diabetes on the development and prevention of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med 1993; 329(14): 977–86. doi: 10.1056/NEJM199309303291401.

17. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia. 1991; 34(12): 877–90.

18. Thangarajah H, Yao D, Chang EI et al. The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc Natl Acad Sci U S A 2009; 106(32): 13505–10. doi: 10.1073/pnas.0906670106.

19. Kohner EM, Patel V, Rassam SM. Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy. Diabetes. 1995; 44(6): 603–7. doi: 10.2337/diab.44.6.603.

20. Zinman B, Wanner C, Lachin JM et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373(22): 2117–28. doi: 10.1056/NEJMoa1504720.

21. Wiviott SD, Raz I, Bonaca MP et al.; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380(4): 347–57. doi: 10.1056/NEJMoa1812389.

22. Neal B, Perkovic V, Mahaffey KW et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(7): 644–57. doi: 10.1056/NEJMoa1611925.

23. Malyszczak A, Przezdziecka-Dolyk J, Szydelko-Pasko U, Misiuk-Hojlo M. Novel antidiabetic drugs and the risk of diabetic retinopathy: A systematic review and meta-analysis of randomized controlled trials. J Clin Med. 2024; 13(6): 1797. doi: 10.3390/jcm13061797.

24. Zhou HR, Ma XF, Lin WJ et al. Neuroprotective role of GLP-1 analog for retinal ganglion cells via PINK1/Parkin-mediated mitophagy in diabetic retinopathy. Front Pharmacol. 2021; 11: 589114. doi: 10.3389/fphar.2020.589114.

25. Hebsgaard JB, Pyke C, Yildirim E et al. Glucagon-like peptide-1 receptor expression in the human eye. Diabetes Obes Metab. 2018; 20(9): 2304–8. doi: 10.1111/dom.13339.

26. Marso SP, Bain SC, Consoli A et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834–44. doi: 10.1056/NEJMoa1607141.

27. Vilsboll T, Bain SC, Leiter LA et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018; 20(4): 889–97. doi: 10.1111/dom.13172.

28. Gerstein HC, Colhoun HM, Dagenais GR et al.; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet. 2019; 394(10193): 121–30. doi: 10.1016/S0140-6736(19)31149-3.

29. Marso SP, Daniels GH, Brown-Frandsen K et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311–22. doi: 10.1056/NEJMoa1603827.

30. Jung E, Kim J, Kim CS et al. Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy. Biochim Biophys Acta. 2015; 1852(12): 2618–29. doi: 10.1016/j.bbadis.2015.09.010.

31. Jackle A, Ziemssen F, Kuhn EM et al. Sitagliptin and the blood-retina barrier: Effects on retinal endothelial cells manifested only after prolonged exposure. J Diabetes Res. 2020; 2020: 2450781. doi: 10.1155/2020/2450781.