Progress in the treatment of atrophic age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

Xue Rong ,  Wan Guangming

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China;

Corresponding author：

Wan Guangming, Email: wgm6608@163.com

Keywords：

Macular degeneration/therapy; Geographic atrophy; Review

DOI：

10.3760/cma.j.issn.1005-1015.2019.01.023

Video：

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Abstract Full text Figures/Tables Video References Cited by

Atrophic age-related macular degeneration (AMD) does not show obvious loss of visual function in the early stage, so it is not easy to be taken seriously. In the advanced stage, most of the patients suffered from macular area retinal map atrophy, which affected night vision and central vision. Drugs currently used in clinical or clinical trials to treat atrophic AMD include drugs for improving choroidal perfusion, reducing the accumulation of harmful substances, preventing oxidative stress injury, inhibiting inflammatory reactions, as well as neuroprotectants and lipid metabolism drugs. Stem cell transplantation for atrophic AMD is currently the most promising treatment. In theory, it is feasible to replace atrophic AMD with retinal photoreceptor cells and RPE cells derived from human stem cell differentiation. However, there are still many problems to be solved, such as how to improve the efficiency of directional differentiation of seed cells and how to ensure the safe and effective RPE cell transplantation and survival after transplantation. At present, several studies have found that multiple locus mutations are associated with atrophic AMD, so gene therapy also plays an important role in the development of the disease.

Citation： Xue Rong, Wan Guangming. Progress in the treatment of atrophic age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2019, 35(1): 94-98. doi: 10.3760/cma.j.issn.1005-1015.2019.01.023 Copy

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2. Patel HR, Hariprasad SM, Eichenbaum D. Geographic atrophy: clinical impact and emerging treatments[J]. Ophthalmic Surg Lasers Imaging Retina, 2015, 46(1): 8-13. DOI: 10.3928/23258160-20150101-01.
3. Chew EY, Clemons TE, Agron E, et al. Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration: AREDS report no.35[J]. Ophthalmology, 2013, 120(8): 1604-1611. DOI: 10.1016/j.ophtha.2013.01.021.
4. Hanus J, Zhang H, Wang Z, et al. Induction of necrotic cell death by oxidative stress in retinal pigment epithelial cells[J/OL]. Cell Death Dis, 2013, 4: 965[2013-12-18]. http://dx.doi.org/10.1038/cddis.2013.478. DOI: 10.1038/cddis.2013.478.
5. Datta S, Cano M, Ebrahimi K, et al. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD[J]. Prog Retin Eye Res, 2017, 60: 201-218. DOI: 10.1016/j.preteyeres.2017.03.002.
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7. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration[J]. Science, 2005, 308(5720): 385-389. DOI: 10.1126/science.1109557.
8. Jakobsdottir J, Conley YP, Weeks DE, et al. Susceptibility genes for age-related maculopathy on chromosome 10q26[J]. Am J Hum Genet, 2005, 77(3): 389-407. DOI: 10.1086/444437.
9. Spencer KL, Olson LM, Anderson BM, et al. C3 R102G polymorphism increases risk of age-related macular degeneration[J]. Hum Mol Genet, 2008, 17(12): 1821-1824. DOI: 10.1093/hmg/ddn075.
10. Augustin AJ, Diehm C, Grieger F, et al. Alprostadil infusion in patients with dry age related macular degeneration: a randomized controlled clinical trial[J]. Expert Opin Investig Drugs, 2013, 22(7): 803-812. DOI: 10.1517/13543784.2013.794782.
11. Grunwald JE, Metelitsina TI, Dupont JC, et al. Reduced foveolar choroidal blood flow in eyes with increasing AMD severity[J]. Invest Ophthalmol Vis Sci, 2005, 46(3): 1033-1038. DOI: 10.1167/iovs.04-1050.
12. Pemp B, Garhofer G, Lasta M, et al. The effects of moxaverine on ocular blood flow in patients with age-related macular degeneration or primary open angle glaucoma and in healthy control subjects[J]. Acta Ophthalmol, 2012, 90(2): 139-145. DOI: 10.1111/j.1755-3768.2010.01878.x.
13. Schmidl D, Pemp B, Lasta M, et al. Effects of orally administered moxaverine on ocular blood flow in healthy subjects[J]. Graefe’s Arch Clin Exp Ophthalmol, 2013, 251(2): 515-520. DOI: 10.1007/s00417-012-2207-1.
14. Harris A, Kagemann L, Ehrlich R, et al. The effect of sildenafil on ocular blood flow[J]. Br J Ophthalmol, 2008, 92(4): 469-473. DOI: 10.1136/bjo.2007.131789.
15. Metelitsina TI, Grunwald JE, DuPont JC, et al. Effect of Viagra on the foveolar choroidal circulation of AMD patients[J]. Exp Eye Res, 2005, 81(2): 159-164. DOI: 10.1016/j.exer.2005.01.017.
16. Radu RA, Han Y, Bui TV, et al. Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: a potential therapy for treatment of lipofuscin-based retinal diseases[J]. Invest Ophthalmol Vis Sci, 2005, 46(12): 4393-4401. DOI: 10.1167/iovs.05-0820.
17. Mata NL, Lichter JB, Vogel R, et al. Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration[J]. Retina, 2013, 33(3): 498-507. DOI: 10.1097/IAE.0b013e318265801d.
18. Dugel PU, Novack RL, Csaky KG, et al. Phase Ⅱ, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular degeneration[J]. Retina, 2015, 35(6): 1173-1183. DOI: 10.1097/IAE.0000000000000606.
19. Ding JD, Johnson LV, Herrmann R, et al. Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration[J]. Proc Natl Acad Sci USA, 2011, 108(28): 279-287. DOI: 10.1073/pnas.1100901108.
20. Pfizer. Efficacy, safety and tolerability study of RN6G in subjects with geographic atrophy secondary to age-related macular degeneration. In: ClinicalTrials.gov [cited 2017-01-06].
21. GlaxoSmithKline. Clinical study to investigate safety and efficacy of GSK933776 in adult patients with geographic atrophy secondary to agerelated macular degeneration. In: ClinicalTrials.gov [cited 2017-01-06].
22. Rhee KD, Nusinowitz S, Chao K, et al. CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Muller glial cells[J]. Proc Natl Acad Sci USA, 2013, 110(47): 4520-4529. DOI: 10.1073/pnas.1303604110.
23. Zhang K, Hopkins JJ, Heier JS, et al. Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration[J]. Proc Natl Acad Sci USA, 2011, 108(15): 6241-6245. DOI: 10.1073/pnas.1018987108.
24. Lai RK, Chun T, Hasson D, et al. Alpha-2 adrenoceptor agonist protects retinal function after acute retinal ischemic injury in the rat[J]. Vis Neurosci, 2002, 19(2): 175-185. DOI: 10.1017/S0952523802191152.
25. Allergan. A safety and efficacy study of brimonidine intravitreal implant in geographic atrophy secondary to age-related macular degeneration (BEACON). In: ClinicalTrials.gov [cited 2017-01-06].
26. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial[J]. JAMA, 2013, 309(19): 2005-2015. DOI: 10.1001/jama.2013.4997.
27. Maccarone R, Di Marco S, Bisti S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina[J]. Invest Ophthalmol Vis Sci, 2008, 49(3): 1254-1261. DOI: 10.1167/iovs.07-0438.
28. Zhu W, Wu Y, Meng YF, et al. Effect of curcumin on aging retinal pigment epithelial cells[J]. Drug Des Devel Ther, 2015, 9: 5337-5344. DOI: 10.2147/DDDT.S84979.
29. Collier RJ, Wang Y, Smith SS, et al. Complement deposition and microglial activation in the outer retina in light-induced retinopathy: inhibition by a 5-HT1A agonist[J]. Invest Ophthalmol Vis Sci, 2011, 52(11): 8108-8116. DOI: 10.1167/iovs.10-6418.
30. Jaffe GJ, Schmitz-Valckenberg S, Boyer D, et al. Randomized trial to evaluate tandospirone in geographic atrophy secondary to age-related macular degeneration: the GATE Study[J]. Am J Ophthalmol, 2015, 160(6): 1226-1234. DOI: 10.1016/j.ajo.2015.08.024.
31. Borrelli E, Diadori A, Zalaffi A, et al. Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study[J]. Int J Ophthalmol, 2012, 5(6): 708-713. DOI: 10.3980/j.issn.2222-3959.2012.06.11.
32. Danis RP, Lavine JA, Domalpally A. Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects[J]. Clin Ophthalmol, 2015, 9: 2159-2174. DOI: 10.2147/OPTH.S92359.
33. Anderson DH, Mullins RF, Hageman GS, et al. A role for local inflammation in the formation of drusen in the aging eye[J]. Am J Ophthalmol, 2002, 134(3): 411-431. DOI: 10.1016/S0002-9394(02)01624-0.
34. Thomas TC, Rollins SA, Rother RP, et al. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv[J]. Mol Immunol, 1996, 33(17-18): 1389-1401. DOI: 10.1016/S0161-5890(96)00078-8.
35. Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study[J]. Ophthalmology, 2014, 121(3): 693-701. DOI: 10.1016/j.ophtha.2013.09.044.
36. Potentia Pharmaceuticals Inc. Safety of intravitreal POT-4 therapy for patients with neovascular age-related macular degeneration (AMD) (ASaP). In: ClinicalTrials.gov [cited 2017-01-06].
37. Le KN, Gibiansky L, van Lookeren Campagne M, et al. Population pharmacokinetics and pharmacodynamics of lampalizumab administered intravitreally to patients with geographic atrophy[J]. CPT Pharmacometrics Syst Pharmacol, 2015, 4(10): 595-604. DOI: 10.1002/psp4.12031.
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