New Drugs for the Treatment of DME and the Role of Biomarkers in Predicting Their Effectiveness

Today, between 230 and 347 million people on the planet suffer from diabetes, which is approximately 6 % of the all adult population. Diabetic macular edema (DME) can occur at any stage of diabetic retinopathy (DR), and remains the most common cause of moderate vision loss in patients with DR, due to increased retinal vascular permeability leading to accumulation of extracellular/intracellular fluid and blood plasma components in the neurosensory retina. The use of objective, quantifiable medical signs, called biomarkers, has become more relevant in clinical practice and clinical research. They allow the identification of a normal biological or pathological process, becoming clinical and diagnostic tools in routine clinical practice. Over the past decade, there has been significant progress in the treatment of macular edema, but the search for a more effective method does not stop. Modern research is being carried out in the direction of creating new drugs and increasing the intervals between injections. New molecules target previously studied as well as new targets. The pharmaceuticals used are investigating at higher doses and different delivery methods. Viral vectors and new phototherapeutic agents are currently being tested. This wide range of research studies, with several therapeutics currently in phase 3, could lead to impressive results in the treatment of diabetic retinopathy in the not too distant future.

1. Diabetes mellitus in numbers: reality and predictions. Federal Service for Supervision of Consumer Rights Protection and Human Welfare in the Tambov Region, 2022 (In Russ.) URL: http://68.rospotrebnadzor.ru/content/545/21700/

2. Okonkwo O.N., Akanbi T., Agweye C.T. Current Management of Diabetic Macular Edema. In (Ed.), Diabetic Eye Disease — From Therapeutic Pipeline to the Real World. IntechOpen. 2022. DOI: 10.5772/intechopen.100157

3. Deák G.G., Bolz M., Ritter M., Prager S., Benesch T., Schmidt Erfurth U.; Diabetic Retinopathy Research Group Vienna. A systematic correlation between morphology and functional alterations in diabetic macular edema. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6710–6714. DOI: 10.1167/iovs.09-5064

4. Yoshitake T., Murakami T., Suzuma K. Hyperreflective Foci in the Outer Retinal Layers as a Predictor of the Functional Efficacy of Ranibizumab for Diabetic Macular Edema. Sci Rep. 2020;10:873. DOI: 10.1038/s41598-020-57646-y

5. Ehlers J.P., Uchida A., Hu M., Figueiredo N., Kaiser P.K., Heier J.S., Brown D.M., Boyer D.S., Do D.V., Gibson A., Saroj N., Srivastava S.K. Higher Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index. Ophthalmol Retina. 2019 Dec;3(12):1056–1066. DOI: 10.1016/j.oret.2019.06.010

6. Sheremet N.L., Shmelkova M.S., Andreeva N.A., Zhorzholadze N.V., Fomin A.V., Krylova T.D., Tsygankova P.G. Features of microvascular changes in the retina and optic nerve in patients with hereditary optic neuropathy according to optical coherence tomography angiography. Annals of Ophthalmology = Vestnik oftal’mologii 2020;136(4 2):171–182 (In Russ.). DOI: 10.17116/oftalma2020136042171

7. Arzhukhanov D.D., Petrachkov D.V., Matyushchenko A.G. Influence of thickness and vascular density of the retina on its photosensitivity in diabetic macular edema. Point of view. East — West. 2021;2:37–40 (In Russ.). DOI: 10.25276/2410-1257-2021-2-37-40

8. Sophie R., Lu N., Campochiaro P.A. Predictors of Functional and Anatomic Outcomes in Patients with Diabetic Macular Edema Treated with Ranibizumab. Ophthalmology. 2015 Jul;122(7):1395–1401. DOI: 10.1016/j.ophtha.2015.02.036

9. Roberts P.K. Quantification of fluid resolution and visual acuity gain in patients with diabetic macular edema using deep learning: A post hoc analysis of a randomized clinical trial. JAMA ophthalmology. 2020;138.9:945–953. DOI: 10.1001/jamaophthalmol.2020.2457

10. Daruich A. Mechanisms of macular edema: beyond the surface. Progress in retinal and eye research. 2018;63:20–68. DOI: 10.1016/j.preteyeres.2017.10.006

11. Durzhinskaya M.Kh. Microaneurysms as a marker of diabetic retinopathy. Annals of Ophthalmology = Vestnik oftal’mologii. 2021;137(5 2):300–305 (In Russ.). DOI: 10.17116/oftalma2021137052300

12. Campochiaro P.A., Choy D.F., Do D.V., Hafiz G., Shah S.M., Nguyen Q.D., Rubio R., Arron J.R. Monitoring ocular drug therapy by analysis of aqueous samples. Ophthalmology. 2009 Nov;116(11):2158–2164. DOI: 10.1016/j.ophtha.2009.04.038

13. Hinkle O., HSU J. The Future Looks Bright: The Therapeutics Pipeline for Diabetic Retinopathy. Retina today. 2020. Nov/Dec:38–40.

14. Brown D.M.., Emanuelli A, Bandello F., Barranco J.J.E., Figueira J, Souied E., Wolf S., Gupta V., Ngah N.F., Liew G.., Tuli R., Tadayoni R., Dhoot D., Wang L., Bouillaud E., Wang Y., Kovacic L., Guerard N., Garweg J.G.. KESTREL and KITE: 52 Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema. Am J Ophthalmol. 2022 Jun;238:157–172. DOI: 10.1016/j.ajo.2022.01.004