Non-medical treatment for late age-related macular degeneration
DOI: 10.32364/2311-7729-2021-21-4-215-219
A.K. Drakon1, A.G. Kurguzova1, V.M. Sheludchenko1, N.B. Korchazhkina2
1Scientific Research Institute of Eye Diseases, Moscow, Russian Federation
2Academician B.V. Petrovskiy Russian Scientific Center of Surgery, Moscow, Russian Federation
Age-related macular degeneration (AMD) is the leading cause of blindness in people over 55 in developed countries. Moreover, the number of these patients will increase growth as life expectancy increases. It is estimated that late AMD accounts for half of blindness and low vision cases in European countries. A myriad of studies is currently underway to discover cutting-edge, effective therapeutic modalities. Gene therapy is a novel alternative to regular intravitreal injections of anti-VEGF agents for late wet AMD. This technique’s heart is a specific gene delivery to target cells to generate natural VEGF inhibitors. Gene therapy affecting the complement system to deactivate its end product, the membrane attack complex, is reasonable in late atrophic AMD. Studies on stem cell therapy for late atrophic AMD undergo as well. It was demonstrated that retinal pigment epithelium (RPE) cells derived from human embryonic stem cells or induced pluripotent stem cells express typi cal RPE markers that can phagocytize photoreceptor segments. Electrical stimulation and magnet therapy are already introduced into clinical practice to rehabilitate patients with late AMD. Magnetic and electrical fields improve impulse transmitting, activate intracellular and tissue regeneration of the retina. Recent findings are promising but require further in-depth studies.
Keywords: age-related macular degeneration, retinal scar, gene therapy, stem cells, physiotherapy, rehabilitative medicine.
For citation: Drakon A.K., Kurguzova A.G., Sheludchenko V.M., Korchazhkina N.B. Non-medical treatment for late age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2021;21(4):215–219 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-215-219.
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35. Schwartz S.D., Tan G., Hosseini H., Nagiel A. Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. Invest Ophthalmol Vis Sci. 2016; ;57(5):ORSFc1–9. DOI: 10.1167/iovs.15-18681.
36. Falkner-Radler C.I., Krebs I., Glittenberg C. et al. Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study. British Journal of Ophthalmology. 2011;95(3):370–375. DOI: 10.1136/bjo.2009.176305.
37. Dang Y., Zhang C., Zhu Y. Stem cell therapies for age-related macular degeneration: the past, present, and future. Clinical Interventions in Aging. 2015;10:255–264. DOI: 10.2147/CIA.S73705.
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39. Kokkinaki M., Sahibzada N., Golestaneh N. Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells. 2011;29(5):825–835. DOI: 10.1002/stem.635.
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43. Fernandes R.A., Diniz B., Ribeiro R., Humayun M. Artificial vision through neuronal stimulation. Neurosci Lett. 2012;519(2):122–128. DOI: 10.1016/j.neulet.2012.01.063.
2. Wong W.L., Su X., Li X., Cheung C.M. et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2(2):106–116. DOI: 10.1016/S2214- 109X(13)70145-1.
3. Нероев В.В. Российское наблюдательное эпидемиологическое неинтервенционное исследование пациентов с «влажной» формой возрастной макулярной дегенерации. Российский офтальмологический журнал. 2011;4(2):4–9. [Neroev V.V. Russia’s nationwide epidemiological noninvasive study of patients with wet age-related macular degeneration. Russian Ophthalmological Journal. 2011:4(2):4–9 (in Russ.)].
4. Cruess A.F., Zlateva G., Xu X., Soubrane G. et al. Economic burden of bilateral neovascular age-related macular degeneration: multi-country observational study. Pharmacoeconomics. 2008;26(1):57–73. DOI: 10.2165/00019053-200826010-00006.
5. Li J.Q., Welchowski T., Schmid M., Mauschitz M.M. et al. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. Br J Ophthalmol. 2020;104(8):1077–1084. DOI: 10.1136/bjophthalmol-2019-314422.
6. Congdon N., O’Colmain B., Klaver C.C. et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477–485. DOI: 10.1001/archopht.122.4.477.
7. Lim L.S., Mitchell P., Seddon J.M. et al. Age-related macular degeneration. Lancet. 2012;379(9827):1728–1738. DOI: 10.1016/S0140-6736(12)60282-7.
8. Klein R., Klein B.E., Lee K.E. et al. Changes in visual acuity in a population over a 15-year period: The Beaver Dam Eye Study. Am J Ophthalmol. 2006;142(4):539–549. DOI: 10.1016/j.ajo.2006.06.015.
9. Файзрахманов Р.Р., Будзинская М.В. Макулярные пигменты при дегенеративных процессах сетчатки. Вестник офтальмологии. 2018;134(5):135–140. [Faizrakhmanov R.R., Budzinskaya M.V. Macular pigments in retinal degenerative processes. Vestnik oftal’mologii. 2018;134(5):135–140 (in Russ.)]. DOI: 10.17116/oftalma2018134051135.
10. Мирзабекова К.А. Возрастная макулярная дегенерация: профилактика и лечение. Обзор. Офтальмология. 2014;11(2):4–9. [Mirzabekova K.A. Age-related macular degeneration: prevention and treatment. A review. Ophthalmology in Russia. 2014;11(2):4–9 (in Russ.)]. DOI: 10.18008/1816-5095-2014-2-4-9.
11. Ferrara N., Gerber H.P., LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–676. DOI: 10.1038/nm0603-669.
12. Wang Q., Zhao H.S., Li L. Association between complement factor I gene polymorphisms and the risk of age-related macular degeneration: a meta-analysis of literature. Int J Ophthalmol. 2016;9(2):298–305. DOI: 10.18240/ijo.2016.02.23.
13. Wu M., Guo Y., Ma Y., Zheng Z., Wang Q., Zhou X. Association of two polymorphisms, rs1061170 and rs1410996, in complement factor H with age-related macular degeneration in an Asian population: a meta-analysis. Ophthalmic Res. 2016;55(3):135–144. DOI: 10.1159/000442257.
14. Thakkinstian A., Han P., McEvoy M. et al. Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration. Hum Mol Genet. 2006;15(18):2784–2790. DOI: 10.1093/hmg/ddl220.
15. Velilla S., García-Medina J.J., García-Layana A. et al. Smoking and age-related macular degeneration: review and update. J Ophthalmol. 2013;2013:895147. DOI: 10.1155/2013/895147.
16. Myers C.E., Klein B.E., Gangnon R., Sivakumaran T.A. et al. Cigarette smoking and the natural history of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology. 2014;121:1949–1955. DOI: 10.1016/j.ophtha.2014.04.040.
17. Ni Dhubhghaill S.S., Cahill M.T., Campbell M., Cassidy L. et al. The pathophysiology of cigarette smoking and age-related macular degeneration. Adv Exp Med Biol. 2010;664:437–446. DOI: 10.1007/978-1-4419-1399-9_50.
18. Cano M., Thimmalappula R., Fujihara M. et al. Cigarette smoking, oxidative stress, the anti-oxidant response through Nrf2 signaling, and age-related macular degeneration. Vision Res. 2010;50(7):652–664. DOI: 10.1016/j.visres.2009.08.018.
19. Beatty S., Koh H., Phil M., Henson D., Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000;45(2):115–134. DOI: 10.1016/s0039-6257(00)00140-5.
20. Schaumberg D.A., Hankinson S.E., Guo Q., Rimm E. et al. A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch Ophthalmol. 2007;125(1):55–62. DOI: 10.1001/archopht.125.1.55.
21. Rennie C.A., Stinge A., King E.A., Sothirachagan S. et al. Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study. Eye (Lond.). 2012;6(1):109–118. DOI: 10.1038/eye.2011.256.
22. Guymer R.H., Chong E.W. Modifiable risk factors for age-related macular degeneration. Med J Aust. 2006;184(9):455–458. DOI: 10.5694/j.1326-5377.2006.tb00318.x.
23. Hyman L., Neborsky R. Risk factors for age-related macular degeneration: an update. Curr Opin Ophthalmol. 2002;13(3):171–175. DOI: 10.1097/00055735-200206000-00007.
24. Wilde C., Poostchi A., Mehta R.L., MacNab H.K. et al. Prevalence of age-related macular degeneration in an elderly UK Caucasian population-The Bridlington Eye Assessment Project: a cross-sectional study. Eye (Lond.). 2017;31(7):1042–1050. DOI: 10.1038/eye.2017.30.
25. Joachim N., Colijn J.M., Kifley A., Lee K.E. et al. Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report. Br J Ophthalmol. 2017;101(9):1185–1192. DOI: 10.1136/bjophthalmol-2016-309729.
26. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.Age-Related Eye Disease Study Research Group. Arch Ophthalmol. 2001;119(10):1417–1436. DOI: 10.1001/archopht.119.10.1417.
27. Keenan T.D., Agrón E., Domalpally A., Clemons T.E. et al. AREDS2 Research Group. Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16. Ophthalmology. 2018 Dec;125(12):1913–1928. DOI: 10.1016/j.ophtha.2018.05.028.
28. Rosenfeld P.J., Brown D.M., Heier J.S., Boyer D.S. et al.; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 20065;355(14):1419–1431. DOI: 10.1056/NEJMoa054481.
29. Brader H.S., Ying G.S., Martin E.R., Maguire M.G.; Complications of Age-Related Macular Degeneration Prevention Trial-CAPT Research Group. New grading criteria allow for earlier detection of geographic atrophy in clinical trials. Invest Ophthalmol Vis Sci. 2011;52(12):9218–9225. DOI: 10.1167/iovs.11-7493.
30. Schmitz-Valckenberg S., Sahel J.A., Danis R., Fleckenstein M. et al. Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study). Ophthalmology. 2016;123(2):361–368. DOI: 10.1016/j.ophtha.2015.09.036. Epub 2015.
31. Bordet T., Behar-Cohen F. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov Today. 2019;24(8):1685–1693. DOI: 10.1016/j.drudis.2019.05.038.
32. Heier J.S., Kherani S., Desai S. et al. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: A phase 1, open-label trial. Lancet. 2017;390:50–61. DOI: 10.1016/S0140-6736(17)30979-0.
33. Liu Y., Fortmann S.D., Shen J. et al. AAV8-antiVEGFfab ocular gene transfer for neovascular age-related macular degeneration. Mol Ther. 2018;26:542–549. DOI: 10.1016/j.ymthe.2017.12.002.
34. Mu Y., Zhao M., Su G. Stem cell-based therapies for age-related macular degeneration: current status and prospects. Int J Clin Exp Med. 2014;7(11):3843–3852.
35. Schwartz S.D., Tan G., Hosseini H., Nagiel A. Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. Invest Ophthalmol Vis Sci. 2016; ;57(5):ORSFc1–9. DOI: 10.1167/iovs.15-18681.
36. Falkner-Radler C.I., Krebs I., Glittenberg C. et al. Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study. British Journal of Ophthalmology. 2011;95(3):370–375. DOI: 10.1136/bjo.2009.176305.
37. Dang Y., Zhang C., Zhu Y. Stem cell therapies for age-related macular degeneration: the past, present, and future. Clinical Interventions in Aging. 2015;10:255–264. DOI: 10.2147/CIA.S73705.
38. Cho M.S., Kim S.J., Ku S.Y. et al. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses. Stem Cell Research. 2012;9(2):101–109. DOI: 10.1016/j.scr.2012.05.002.
39. Kokkinaki M., Sahibzada N., Golestaneh N. Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells. 2011;29(5):825–835. DOI: 10.1002/stem.635.
40. Zhao T., Zhang Z. N., Rong Z., Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;474(7350):212–215. DOI: 10.1038/nature10135.
41. Йойлева Е.Э., Филатова Е.В., Голубева О.В., Гаврилова Н.А., Гаджиева Н.С. Физиотерапевтическая реабилитация пациентов с возрастной макулярной дегенерацией: Учебное пособие для клинических ординаторов, врачей-офтальмологов и врачей-физиотерапевтов. М.: МГМСУ им. А.И. Евдокимова; 2017:19–28. [Ioileva E.Eh., Filatova E.V., Golubeva O.V., Gavrilova N.A., Gadzhieva N.S. Fizioterapevticheskaya reabilitatsiya patsientov s vozrastnoi makulyarnoi degeneratsiei: Uchebnoe posobie dlya klinicheskikh ordinatorov, vrachei oftal’mologov i vrachei-fizioterapevtov. M.: MGMSU im. A.I. Evdokimova; 2017:18–24 (in Russ.)].
42. Manthey A.L., Liu W., Jiang Z.X. et al. Using Electrical Stimulation to Enhance the Efficacy of Cell Transplantation Therapies for Neurodegenerative Retinal Diseases: Concepts, Challenges, and Future Perspectives. Cell Transplant. 2017;26(6):949–965. DOI: 10.3727/096368917X694877.
43. Fernandes R.A., Diniz B., Ribeiro R., Humayun M. Artificial vision through neuronal stimulation. Neurosci Lett. 2012;519(2):122–128. DOI: 10.1016/j.neulet.2012.01.063.
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