The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Zaytseva O.V.

Helmholtz National Medical Research Center of Eye Diseases;
A.I. Evdokimov Moscow State University of Medicine and Dentistry

Neroeva N.V.

Helmholtz National Medical Research Center of Eye Diseases

Okhotsimskaya T.D.

Helmholtz National Medical Research Center of Eye Diseases

Bobykin E.V.

Ural State Medical University

Current view on the issue of insufficient effectiveness of anti-VEGF therapy for age-related macular degeneration

Authors:

Zaytseva O.V., Neroeva N.V., Okhotsimskaya T.D., Bobykin E.V.

More about the authors

Journal: Russian Annals of Ophthalmology. 2022;138(1): 90‑99

DOI: 10.17116/oftalma202213801190

Read: 1572 times

Download PDF (RU)
Contact the author
Table of contents

CURRENT VIEW ON THE ISSUE OF INSUFFICIENT EFFECTIVENESS OF ANTI-VEGF THERAPY FOR AGE-RELATED MACULAR DEGENERATION
CURRENT VIEW ON THE ISSUE OF INSUFFICIENT EFFECTIVENESS OF ANTI-VEGF THERAPY FOR AGE-RELATED MACULAR DEGENERATION

To cite this article:

Zaytseva OV, Neroeva NV, Okhotsimskaya TD, Bobykin EV. Current view on the issue of insufficient effectiveness of anti-VEGF therapy for age-related macular degeneration. Russian Annals of Ophthalmology. 2022;138(1):90‑99. (In Russ.)
https://doi.org/10.17116/oftalma202213801190

Подписка 2026 Вестник офтальмологии (Russian Annals of Ophthalmology)
 
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Recommended articles:
Effi­cacy of brolucizumab in the treatment of reti­nal pathologies: a review of post-marketing studies. Russian Annals of Ophthalmology. 2024;(5):154-161
Analysis of the effe­ctiveness of cata­ract surgery in neovascular age-related macu­lar dege­neration. Russian Annals of Ophthalmology. 2024;(6):7-14
Mana­gement of patients with treatment-resistant neovascular age-related macu­lar dege­neration. Russian Annals of Ophthalmology. 2024;(6):63-68
Neuroprotective therapy for age-related macu­lar dege­neration. Russian Annals of Ophthalmology. 2024;(6):152-158
Choroidal neovascularization asso­ciated with choroidal nevi. Russian Annals of Ophthalmology. 2025;(1):104-112
Arti­ficial inte­lligence in asse­ssment of indi­vidual risks of age-related macu­lar dege­neration progression. Russian Annals of Ophthalmology. 2025;(2):123-128
Pote­ntial and prospects of the astragaloside IV use for age-associated diseases prevention. Russian Journal of Preventive Medi­cine. 2025;(7):94-99
Abstract:

Due to the significant medical and social importance of neovascular (wet) age-related macular degeneration (wAMD), increasing the effectiveness of anti-VEGF therapy used to treat this disease is one of the high-priority problems in modern retinology. This article focuses on pathobiological aspects and clinical manifestations of incomplete responses to anti-VEGF therapy of wAMD, considers the proposed ways to improve the terminology and classification of responses to therapy, as well as the assessment of its correctness and effectiveness of the treatment. It also discusses the available ways to optimize anti-VEGF therapy and define the criteria of its termination in cases when the treatment proves to be futile.

Keywords:

age-related macular degeneration
anti-VEGF therapy
neovascularization phenotypes
response to therapy
treatment futility

Authors:

Zaytseva O.V.

Helmholtz National Medical Research Center of Eye Diseases;
A.I. Evdokimov Moscow State University of Medicine and Dentistry

Neroeva N.V.

Helmholtz National Medical Research Center of Eye Diseases

Okhotsimskaya T.D.

Helmholtz National Medical Research Center of Eye Diseases

Bobykin E.V.

Ural State Medical University

Received:

27.10.2021

Accepted:

25.01.2022

Close metadata

References:

  1. Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther. 2016;10:1857-1867. https://doi.org/10.2147/DDDT.S976531
  2. Budzinskaya MV, Plyukhova AA, Andreeva IV, Kuznetsov AV, Shelankova AV, Sorokin PA. Pharmacological Analysis of Resistance to Anti-VEGF Therapy. Ophthalmology in Russia = Oftal’mologiya. 2018;15(4):382-387. (In Russ.). https://doi.org/10.18008/1816-5095-2018-4-382-387
  3. Zaytseva OV, Neroeva NV, Okhotsimskaya TD, Bobykin EV. Anti-VEGF therapy for neovascular age-related macular degeneration: causes of incomplete response. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2021;137(5):152-159. (In Russ.). https://doi.org/10.17116/oftalma2021137051152
  4. Stone TW, ed. ASRS 2018 Preferences and Trends Membership Survey. Chicago, IL. American Society of Retina Specialists; 2018. Accessed August 29, 2018. https://www.asrs.org/content/documents/_2018-pat-survey-results-for-website.pdf
  5. Zaytseva O, Neroev V, Zhulev Y, Petrakovskaya V, Paleeva A, Trifonova M, Efimenko I. Semantic analysis of patient voice in wet AMD and diabetic retinal disease: Patients’ journey and healthcare experience. Euretina 2021 Virtual Abstracts. Type Free Paper, No. 38. 
  6. Bobykin EV, Korotkih SA, Krokhalev VYa, Buslaev RV, Beresneva NS, Morozova OV. Anti-VEGF therapy of wet age-related macular degeneration: analysis of patients lost to follow-up. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2021;137(2):66-74. (In Russ.). https://doi.org/10.17116/oftalma202113702166
  7. Mettu PS, Allingham MJ, Cousins SW. Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities. Prog Retin Eye Res. 2021;82:100906. https://doi.org/10.1016/j.preteyeres.2020.100906
  8. Lad EM, Grunwald L, Mettu PS, Serrano NP, Crowell S, Cousins SW. Lesion Morphology on Indocyanine Green Angiography in Age-Related Macular Degeneration with Classic Choroidal Neovascular Membrane: Implications for Response to anti-VEGF Treatment. Invest Ophthalmol Vis Sci. 2012;53(14):5161.
  9. Mettu PS, Crowell S, Shaw J, Grunwald L, Lad EM, Serrano N, Cousins SW. Neovascular Morphology on ICG Angiography Predicts Response to Anti-VEGF Therapy in Eyes with Serous Pigment Epithelial Detachments and Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2012; 53(14):2654.
  10. Serrano NP, Shaw J, Mettu PS, Lad EM, Crowell S, Cousins SW. High-speed Indocyanine Green Angiography In Age Related Macular Degeneration With Fibrovascular Pigment Epithelial Detachments. Invest Ophthalmol Vis Sci. 2012;53(14):1151.
  11. Mettu PS, Allingham MJ, Nicholas PC, Cousins SW. Neovascular Morphology by ICG Angiography and Response to Loading-Dose Anti-VEGF Therapy in Patients with Neovascular AMD. Invest Ophthalmol Vis Sci. 2016; 57(12):No Pagination Specified.
  12. Ersoz MG, Karacorlu M, Arf S, Sayman Muslubas I, Hocaoglu M. Retinal pigment epithelium tears: Classification, pathogenesis, predictors, and management. Surv Ophthalmol. 2017;62(4):493-505.  https://doi.org/10.1016/j.survophthal.2017.03.004
  13. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Maguire MG, Martin DF, Ying GS, Jaffe GJ, Daniel E, Grunwald JE, Toth CA, Ferris FL 3rd, Fine SL. Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2016;123(8):1751-1761. https://doi.org/10.1016/j.ophtha.2016.03.045
  14. Pauleikhoff D, Löffert D, Spital G, Radermacher M, Dohrmann J, Lommatzsch A, Bird AC. Pigment epithelial detachment in the elderly. Clinical differentiation, natural course and pathogenetic implications. Graefes Arch Clin Exp Ophthalmol. 2002;240(7):533-538.  https://doi.org/10.1007/s00417-002-0505-8
  15. Guber J, Praveen A, Saeed MU. Higher incidence of retinal pigment epithelium tears after ranibizumab in neovascular age-related macular degeneration with increasing pigment epithelium detachment height. Br J Ophthalmol. 2013;97(11):1486-1487. https://doi.org/10.1136/bjophthalmol-2013-303978
  16. He X, Hahn P, Iacovelli J, Wong R, King C, Bhisitkul R, Massaro-Giordano M, Dunaief JL. Iron homeostasis and toxicity in retinal degeneration. Prog Retin Eye Res. 2007;26(6):649-673.  https://doi.org/10.1016/j.preteyeres.2007.07.004
  17. Avery RL, Fekrat S, Hawkins BS, Bressler NM. Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina. 1996; 16(3):183-189.  https://doi.org/10.1097/00006982-199616030-00001
  18. Altaweel MM, Daniel E, Martin DF, Mittra RA, Grunwald JE, Lai MM, Melamud A, Morse LS, Huang J, Ferris FL 3rd, Fine SL, Maguire MG; Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group; Comparison of Age-related Macular Degeneration Treatments Trials CATT Research Group. Outcomes of eyes with lesions composed of >50% blood in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Ophthalmology. 2015;122(2):391-398.e5.  https://doi.org/10.1016/j.ophtha.2014.08.020
  19. Daniel E, Toth CA, Grunwald JE, Jaffe GJ, Martin DF, Fine SL, Huang J, Ying GS, Hagstrom SA, Winter K, Maguire MG; Comparison of Age-related Macular Degeneration Treatments Trials Research Group. Risk of scar in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014;121(3):656-666.  https://doi.org/10.1016/j.ophtha.2013.10.019
  20. Cousins SW, Bearelly S, Reinoso MA, Chi SL, Espinosa-Heidmann DG. Dynamic indocyanine green angiography-guided focal thermal laser treatment of fibrotic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2008;246(12):1677-1683. https://doi.org/10.1007/s00417-008-0905-5
  21. Bearelly S, Espinosa-Heidmann DG, Cousins SW. The role of dynamic indocyanine green angiography in the diagnosis and treatment of retinal angiomatous proliferation. Br J Ophthalmol. 2008;92(2):191-196.  https://doi.org/10.1136/bjo.2007.118760
  22. Grossniklaus HE, Kang SJ, Berglin L. Animal models of choroidal and retinal neovascularization. Prog Retin Eye Res. 2010;29(6):500-519.  https://doi.org/10.1016/j.preteyeres.2010.05.003
  23. Espinosa-Heidmann DG, Suner I, Hernandez EP, Frazier WD, Csaky KG, Cousins SW. Age as an independent risk factor for severity of experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2002;43(5): 1567-1573.
  24. Espinosa-Heidmann DG, Malek G, Mettu PS, Caicedo A, Saloupis P, Gach S, Dunnon AK, Hu P, Spiga MG, Cousins SW. Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization. Invest Ophthalmol Vis Sci. 2013; 54(12):7439-7449. https://doi.org/10.1167/iovs.13-12546
  25. McLeod DS, Bhutto I, Edwards MM, Silver RE, Seddon JM, Lutty GA. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2016; 57(14):5843-5855. https://doi.org/10.1167/iovs.16-20049
  26. Kent D, Sheridan C. Choroidal neovascularization: a wound healing perspective. Mol Vis. 2003;9:747-755. 
  27. Reddy VM, Zamora RL, Kaplan HJ. Distribution of growth factors in subfoveal neovascular membranes in age-related macular degeneration and presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1995;120(3): 291-301.  https://doi.org/10.1016/s0002-9394(14)72158-0
  28. Miller DM, Espinosa-Heidmann DG, Legra J, et al. The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am J Ophthalmol. 2004;138(3):323-328.  https://doi.org/10.1016/j.ajo.2004.03.018
  29. Nikitina E, Larionova I, Choinzonov E, Kzhyshkowska J. Monocytes and Macrophages as Viral Targets and Reservoirs. Int J Mol Sci. 2018;19(9):2821. https://doi.org/10.3390/ijms19092821
  30. Mettu PS, Saloupis P, Cousins SW. PAMP Stimulation of Macrophages Promotes Neovascular Remodeling in Experimental Choroidal Neovascularization. Invest Ophthalmol Vis Sci. 2014;55(13):1198.
  31. Yuan F, Fu X, Shi H, Chen G, Dong P, Zhang W. Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2/STAT3 pathway. PLoS One. 2014;9(9):e107063. https://doi.org/10.1371/journal.pone.0107063
  32. Yang XF, Yin Y, Wang H. Vascular inflammation and atherogenesis are activated via receptors for PAMPs and suppressed by regulatory T cells. Drug Discov Today Ther Strateg. 2008;5(2):125-142.  https://doi.org/10.1016/j.ddstr.2008.11.003
  33. McGeer PL, Sibley J. Sparing of age-related macular degeneration in rheumatoid arthritis. Neurobiol Aging. 2005;26(8):1199-1203. https://doi.org/10.1016/j.neurobiolaging.2005.02.003
  34. Ishibashi T, Miki K, Sorgente N, Patterson R, Ryan SJ. Effects of Intravitreal Administration of Steroids on Experimental Subretinal Neovascularization in the Subhuman Primate. Arch Ophthalmol. 1985;103(5):708-711.  https://doi.org/10.1001/archopht.1985.01050050100026
  35. Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013;13(6):438-451.  https://doi.org/10.1038/nri3459
  36. Budzinskaya MV, Gurova IV, Schegoleva IV, Loschenov VB, Shevchik SA, Kuzjmin SG, Vorogtsov GN. Combined modality therapy for exsudative form of age-related macular degeneration. Photodynamic Therapy and Photodyagnosis = Fotodinamicheskaya terapiya i fotodiagnostika. 2013;2(1):20-24 (In Russ.).
  37. Bobykin EV, Morozova OV, Beresneva NS. Treatment of macular diseases: an overview of key randomized clinical trials. Russian Ophthalmological Journal = Rossiyskiy oftal’mologicheskiy zhurnal. 2021;14(4):137-148 (In Russ.). https://doi.org/10.21516/2072-0076-2021-14-4-137-148
  38. Koh A, Lai TYY, Takahashi K, et al. Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2017; 135(11):1206-1213. https://doi.org/10.1001/jamaophthalmol.2017.4030
  39. Wong TY, Ogura Y, Lee WK, et al. Efficacy and safety of intravitreal Aflibercept for polypoidal choroidal vasculopathy: two-year results of the Aflibercept in polypoidal choroidal vasculopathy study. Am J Ophthalmol. 2019; 204:80-89.  https://doi.org/10.1016/j.ajo.2019.02.027
  40. Shen J, Frye M, Lee BL, et al. Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature. J Clin Invest. 2014;124(10):4564-4576. https://doi.org/10.1172/JCI74527
  41. Hussain RM, Neiweem AE, Kansara V, Harris A, Ciulla TA. Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. Expert Opin Investig Drugs. 2019;28(10):861-869.  https://doi.org/10.1080/13543784.2019.1667333
  42. Dugel PU, Boyer DS, Antoszyk AN, et al. Phase 1 Study of OPT-302 Inhibition of Vascular Endothelial Growth Factors C and D for Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2020;4(3):250-263.  https://doi.org/10.1016/j.oret.2019.10.008
  43. Cabral T, Lima LH, Mello LGM, et al. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018;2(1):31-37.  https://doi.org/10.1016/j.oret.2017.04.004
  44. Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother. 2019;20(15):1879-1891. https://doi.org/10.1080/14656566.2019.1636031
  45. Peden MC, Suñer IJ, Hammer ME, Grizzard WS. Long-term outcomes in eyes receiving fixed-interval dosing of anti-vascular endothelial growth factor agents for wet age-related macular degeneration. Ophthalmology. 2015; 122(4):803-808.  https://doi.org/10.1016/j.ophtha.2014.11.018
  46. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG; HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020;127(1):72-84.  https://doi.org/10.1016/j.ophtha.2019.04.017
  47. Espinosa-Heidmann DG, Reinoso MA, Pina Y, Csaky KG, Caicedo A, Cousins SW. Quantitative enumeration of vascular smooth muscle cells and endothelial cells derived from bone marrow precursors in experimental choroidal neovascularization. Exp Eye Res. 2005;80(3):369-378.  https://doi.org/10.1016/j.exer.2004.10.005
  48. Caicedo A, Espinosa-Heidmann DG, Piña Y, Hernandez EP, Cousins SW. Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization. Exp Eye Res. 2005;81(1): 38-47.  https://doi.org/10.1016/j.exer.2005.01.013
  49. Lad EM, Cousins SW, Van Arnam JS, Proia AD. Abundance of infiltrating CD163+ cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2015;253 (11):1941-1945. https://doi.org/10.1007/s00417-015-3094-z
  50. Allingham MJ, Mettu PS, Cousins, SW. Elamipretide, a Mitochondrial-Targeted Drug, for the Treatment of Vision Loss in Dry AMD with High Risk Drusen: Results of the Phase 1 ReCLAIM Study. Invest Ophthalmol Vis Sci. 2019;60(9):361. 
  51. Cousins SW, Allingham MJ, Mettu PS. Elamipretide, a Mitochondria-Targeted Drug, for the Treatment of Vision Loss in Dry AMD with Noncentral Geographic Atrophy: Results of the Phase 1 ReCLAIM Study. Invest Ophthalmol Vis Sci. 2019;60(9):974. 
  52. Mettu PS, Allingham MJ, Cousins SW. Effects of the Mitochondria-Targeted Drug Elamipretide on Leakage-Independent Vision Loss in Fellow Eyes with Neovascular AMD in the ReCLAIM Study. Invest Ophthalmol Vis Sci. 2019;60(9):358. 
  53. Fursova AZh, Derbeneva AS, Tarasov MS, Nikulich IF, Devyatkin VA, Telegina DV, Kolosova NG, Kozhevnikova OS. Leukocyte Telomere Length and Response to Antiangiogenic Therapy in Patients with Neovascular Age-Related Macular Degeneration. Advances in Gerontology = Uspekhi gerontologii. 2021;34(6):823-830.  https://doi.org/10.34922/AE.2021.34.6.002
  54. Avitabile T, Boscia F, Dell’Erba A, Introini U, Lanzetta P, Locatelli P, Ricci F, Staurenghi G, Varano M, Zotti F. Definition of indicators of appropriateness in the management of neovascular age-related macular degeneration: An expert opinion. Eur J Ophthalmol. 2020;30(4):795-804.  https://doi.org/10.1177/1120672120915685
  55. Okada M, Wong TY, Mitchell P, Eldem B, Talks SJ, Aslam T, Daien V, Rodriguez FJ, Gale R, Barratt J, Finger RP, Loewenstein A. Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2021;139(7):769-776.  https://doi.org/10.1001/jamaophthalmol.2021.1660
  56. Monés J. Non-responders neovascular AMD concept and spectrum. Presentation at the EURETINA 2021 Virtual (Instructional Course 8: Non-Responders in Neovascular AMD, 09.09.2021).
  57. FDA Approves Genentech’s Port Delivery System, Susvimo, a First-of-Its-Kind Therapeutic Approach for Wet AMD. Accessed October 26, 2021. https://eyewire.news/news/fda-approves-genentechs-port-delivery-system-susvimo-a-first-of-its-kind-therapeutic-approach-for-wet-amd
  58. Wong DT, Lambrou GN, Loewenstein A, Pearce I, Okada AA. Vision Academy Steering Committee. Suspending treatment of neovascular age-related macular degeneration in cases of futility. Retina. 2020;40(6):1010-1020. https://doi.org/10.1097/IAE.0000000000002713
  59. Schneiderman LJ. Defining Medical Futility and Improving Medical Care. J Bioeth Inq. 2011;8(2):123-131.  https://doi.org/10.1007/s11673-011-9293-3
  60. The Royal College of Ophthalmologists. Age-related macular degeneration: guidelines for management. September 2013. Accessed October 21, 2021. https://www.rcophth.ac.uk/wp-content/uploads/2014/12/2013-SCI-318-RCOphth-AMD-Guidelines-Sept-2013-FINAL-2.pdf
  61. Ross AH, Downey L, Devonport H, Gale RP, Kotagiri A, Mahmood S, Mehta H, Narendran N, Patel PJ, Parmar N, Jain N. Recommendations by a UK expert panel on an aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration. Eye (Lond). 2020; 34(10):1825-1834. https://doi.org/10.1038/s41433-019-0747-x
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.