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

Authors：

Liu Yang ^1,2 , Wang Junwen ² , Li Yin ² ,  Li Tuo ²

1. Graduate School, Hubei University of Medicine, Shiyan 442000, China;
2. Department of Ophthalmonogy, Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China;

Corresponding author：

Li Tuo, Email: 13986840088@139.com

Keywords：

Age-related macular degeneration; Atrophic age-related macular degeneration; Drusen; Treatment; Review

DOI：

10.3760/cma.j.cn511434-20240717-00273

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss. There are two primary forms of AMD: exudative age-related macular degeneration (WAMD) and atrophic AMD (DAMD). While numerous medications are currently available for the treatment of WAMD, yielding significant therapeutic outcomes, effective treatments for DAMD remain scarce. Various animal studies and clinical trials on DAMD treatment have been conducted, focusing primarily on antioxidants, complement pathway inhibitors, mitochondrial protectors, visual cycle inhibitors, neuroprotectants, amphiphilic polymer-based drug delivery systems, cell therapy, photobiomodulation therapy, gene therapy, surgical interventions, and traditional Chinese medicine. Among these, antioxidant supplementation with vitamins and complement pathway inhibitor APL-2 and ACP have received Food and Drug Administration approval for the treatment of DAMD. With the continuous development of the medical field, the future will explore the treatment methods with little trauma, good efficacy and good patient compliance, and successfully achieve clinical transformation.

Citation： Liu Yang, Wang Junwen, Li Yin, Li Tuo. Advances in the treatment of atrophic age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2024, 40(12): 969-974. doi: 10.3760/cma.j.cn511434-20240717-00273 Copy

1.	Palanker D. Electronic retinal prostheses[J/OL]. Cold Spring Harb Perspect Med, 2023, 13(8): a041525[2023-08-01]. https://pubmed.ncbi.nlm.nih.gov/36781222/. DOI: 10.1101/cshperspect.a041525.
2.	Guymer RH, Campbell TG. Age-related macular degeneration[J]. Lancet, 2023, 401(10386): 1459-1472. DOI: 10.1016/S0140-6736(22)02609-5.
3.	Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis[J/OL]. Lancet Glob Health, 2014, 2(2): e106-e116[2014-01-03]. https://pubmed.ncbi.nlm.nih.gov/25104651/. DOI: 10.1016/S2214-109X(13)70145-1.
4.	Ye H, Zhang Q, Liu X, et al. Prevalence of age-related macular degeneration in an elderly urban Chinese population in China: The Jiangning Eye Study[J]. Invest Ophthalmol Vis Sci, 2014, 55(10): 6374-6380. DOI: 10.1167/iovs.14-14899.
5.	Girgis S, Lee LR. Treatment of dry age-related macular degeneration: a review[J]. Clin Exp Ophthalmol, 2023, 51(8): 835-852. DOI: 10.1111/ceo.14294.
6.	Han S, Chen J, Hua J, et al. MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium[J/OL]. Redox Biol, 2020, 34: 101537[2020-04-16]. https://pubmed.ncbi.nlm.nih.gov/32361183/. DOI: 10.1016/j.redox.2020.101537.
7.	Tang Y, Kang Y, Zhang X, et al. Mesenchymal stem cell exosomes as nanotherapeutics for dry age-related macular degeneration[J]. J Control Release, 2023, 357: 356-370. DOI: 10.1016/j.jconrel.2023.04.003.
8.	Li F, Lang F, Zhang H, et al. Apigenin alleviates endotoxin-induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy[J/OL]. Oxid Med Cell Longev, 2017, 2017: 2302896[2017-07-30]. https://pubmed.ncbi.nlm.nih.gov/28828145/. DOI: 10.1155/2017/2302896.
9.	Zhang Y, Yang Y, Yu H, et al. Apigenin protects mouse retina against oxidative damage by regulating the Nrf2 pathway and autophagy[J/OL]. Oxid Med Cell Longev, 2020, 2020: 9420704[2020-05-13]. https://pubmed.ncbi.nlm.nih.gov/32509154/. DOI: 10.1155/2020/9420704.
10.	Wang B, Wang L, Gu S, et al. D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration[J]. Signal Transduct Target Ther, 2020, 5(1): 20. DOI: 10.1038/s41392-020-0122-1.
11.	Pardue MT, Allen RS. Neuroprotective strategies for retinal disease[J]. Prog Retin Eye Res, 2018, 65: 50-76. DOI: 10.1016/j.preteyeres.2018.02.002.
12.	Rhoades W, Dickson D, Do DV. Potential role of lampalizumab for treatment of geographic atrophy[J]. Clin Ophthalmol, 2015, 9: 1049-1056. DOI: 10.2147/opth.S59725.
13.	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.
14.	Garg A, Nanji K, Tai F, et al. The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: a living systematic review and meta-analysis[J]. Surv Ophthalmol, 2024, 69(3): 349-361. DOI: 10.1016/j.survophthal.2023.11.008.
15.	Danzig CJ, Khanani AM, Loewenstein A. C5 inhibitor avacincaptad pegol treatment for geographic atrophy: a comprehensive review[J]. Immunotherapy, 2024, 29: 1-12. DOI: 10.1080/1750743x.2024.2368342.
16.	Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration[J]. Ophthalmology, 2021, 128(4): 576-586. DOI: 10.1016/j.ophtha.2020.08.027.
17.	Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial[J]. Lancet, 2023, 402(10411): 1449-1458. DOI: 10.1016/s0140-6736(23)01583-0.
18.	Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration[J]. Ophthalmology, 2014, 121(3): 693-701. DOI: 10.1016/j.ophtha.2013.09.044.
19.	Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials[J]. Lancet, 2023, 402(10411): 1434-1448. DOI: 10.1016/s0140-6736(23)01520-9.
20.	Yang P, Shao Z, Besley NA, et al. Risuteganib protects against hydroquinone-induced injury in human RPE cells[J]. Invest Ophthalmol Vis Sci, 2020, 61(10): 35. DOI: 10.1167/iovs.61.10.35.
21.	Boyer DS, Gonzalez VH, Kunimoto DY, et al. Safety and efficacy of intravitreal risuteganib for non-exudative AMD: a multicenter, phase 2a, randomized, clinical trial[J]. Ophthalmic Surg Lasers Imaging Retina, 2021, 52(6): 327-335. DOI: 10.3928/23258160-20210528-05.
22.	Lad EM, Boyer DS, Heier JS, et al. Color vision and microperimetry changes in nonexudative age-related macular degeneration after risuteganib treatment: exploratory endpoints in a multicenter phase 2a double-masked, randomized, sham-controlled, crossover clinical trial[J]. Ophthalmic Surg Lasers Imaging Retina, 2022, 53(8): 430-438. DOI: 10.3928/23258160-20220725-02.
23.	Camardo J. The rapamune era of immunosuppression 2003: the journey from the laboratory to clinical transplantation[J]. Transplant Proc, 2003, 35(3): 18-24. DOI: 10.1016/s0041-1345(03)00356-7.
24.	Wong WT, Dresner S, Forooghian F, et al. Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase Ⅰ/Ⅱ clinical trial[J/OL]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2941-2950[2014-04-26]. https://pubmed.ncbi.nlm.nih.gov/23548622/. DOI: 10.1167/iovs.13-11650.
25.	Suri R, Neupane YR, Mehra N, et al. Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration[J]. Int J Biol Macromol, 2021, 191: 548-559. DOI: 10.1016/j.ijbiomac.2021.09.069.
26.	Mettu PS, Allingham MJ, Cousins SW. Phase 1 clinical trial of elamipretide in dry age-related macular degeneration and noncentral geographic atrophy: ReCLAIM NCGA Study[J/OL]. Ophthalmol Sci, 2022, 2(1): 100086[2021-11-27]. https://pubmed.ncbi.nlm.nih.gov/36246181/. DOI: 10.1016/j.xops.2021.100086.
27.	Bavik C, Henry SH, Zhang Y, et al. Visual cycle modulation as an approach toward preservation of retinal integrity[J/OL]. PLoS One, 2015, 10(5): e0124940[2015-05-13]. https://pubmed.ncbi.nlm.nih.gov/25970164/. DOI: 10.1371/journal.pone.0124940.
28.	Rosenfeld PJ, Dugel PU, Holz FG, et al. Emixustat hydrochloride for geographic atrophy secondary to age-related macular degeneration[J]. Ophthalmology, 2018, 125(10): 1556-1567. DOI: 10.1016/j.ophtha.2018.03.059.
29.	Sparrow JR, Vollmer-Snarr HR, Zhou J, et al. A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation[J]. J Biol Chem, 2003, 278(20): 18207-18213. DOI: 10.1074/jbc.M300457200.
30.	Conley B, O'Shaughnessy J, Prindiville S, et al. Pilot trial of the safety, tolerability, and retinoid levels of N-(4-hydroxyphenyl) retinamide in combination with tamoxifen in patients at high risk for developing invasive breast cancer[J]. J Clin Oncol, 2000, 18(2): 275-283. DOI: 10.1200/jco.2000.18.2.275.
31.	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.
32.	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.
33.	Ma L, Kaufman Y, Zhang J, et al. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease[J]. J Clin Oncol, 2011, 286(10): 7966-7674. DOI: 10.1074/jbc.M110.178657.
34.	Xu XL, Zhang W, Rao GW. Clinical application and synthesis methods of deuterated drugs[J]. Curr Med Chem, 2023, 30(36): 4096-4129. DOI: 10.2174/0929867330666221122123201.
35.	Kauper K, McGovern C, Sherman S, et al. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases[J]. Invest Ophthalmol Vis Sci, 2012, 53(12): 7484-7491. DOI: 10.1167/iovs.12-9970.
36.	Wen R, Tao W, Li Y, et al. CNTF and retina[J]. Prog Retin Eye Res, 2012, 31(2): 136-151. DOI: 10.1016/j.preteyeres.2011.11.005.
37.	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.
38.	Kuppermann BD, Patel SS, Boyer DS, et al. Phase 2 study of safety and efficacy of brimonidine drug delivery system (BRIMO DDS) generation 1 in patients with geographic atrophy secondary to age-related macular degenetation[J]. Retina, 2021, 41(1): 144-155. DOI: 10.1097/iae.0000000000002789.
39.	Freeman WR, Bandello F, Souied E, et al. Randomized phase Ⅱb study of brimonidine drug delivery system generation 2 for geographic atrophy in age-related macular degeneration[J]. Ophthalmol Retina, 2023, 7(7): 573-585. DOI: 10.1016/j.oret.2023.03.001.
40.	Jiang Y, Fu X, Shao M, et al. Eyedrop delivery of therapeutic proteins with zwitterionic polymers to treat dry age-related macular degeneration[J/OL]. Biomaterials, 2024, 305: 122429[2023-12-22]. https://pubmed.ncbi.nlm.nih.gov/38150770/. DOI: 10.1016/j.biomaterials.2023.122429.
41.	Trincão-Marques J, Ayton LN, Hickey DG, et al. Gene and cell therapy for age-related macular degeneration: a review[J]. Surv Ophthalmol, 2024, 69(5): 665-676. DOI: 10.1016/j.survophthal.2024.05.002.
42.	Maeda T, Sugita S, Kurimoto Y, et al. Trends of stem cell therapies in age-related macular degeneration[J/OL]. J Clin Med, 2021, 10(8): 1785[2024-04-20]. https://pubmed.ncbi.nlm.nih.gov/33923985/. DOI: 10.3390/jcm10081785.
43.	Ho AC, Chang TS, Samuel M, et al. Experience with a subretinal cell-based therapy in patients with geographic atrophy secondary to age-related macular degeneration[J]. Am J Ophthalmol, 2017, 179: 67-80. DOI: 10.1016/j.ajo.2017.04.006.
44.	Kashani AH, Lebkowski JS, Rahhal FM, et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration[J/OL]. Sci Transl Med, 2018, 10(435): eaao4097[2018-04-04]. https://pubmed.ncbi.nlm.nih.gov/29618560/. DOI: 10.1126/scitranslmed.aao4097.
45.	Hashmi JT, Huang YY, Sharma SK, et al. Effect of pulsing in low-level light therapy[J]. Lasers Surg Med, 2010, 42(6): 450-466. DOI: 10.1002/lsm.20950.
46.	Albarracin R, Eells J, Valter K. Photobiomodulation protects the retina from light-induced photoreceptor degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(6): 3582-3592. DOI: 10.1167/iovs.10-6664.
47.	Ivandic BT, Ivandic T. Low-level laser therapy improves vision in patients with age-related macular degeneration[J]. Photomed Laser Surg, 2008, 26(3): 241-245. DOI: 10.1089/pho.2007.2132.
48.	Merry GF, Munk MR, Dotson RS, et al. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration[J/OL]. Acta Ophthalmologica, 2016, 95(4): e270-e277[2016-12-18]. https://pubmed.ncbi.nlm.nih.gov/27989012/. DOI: 10.1111/aos.13354.
49.	Markowitz SN, Devenyi RG, Munk MR, et al. A double-masked, randomized, sham-controlled, single-center study with photobiomodulation for the treatment of dry age-related macular degenetation[J]. Retina, 2020, 40(8): 1471-1482. DOI: 10.1097/iae.0000000000002632.
50.	Ertl HCJ. Immunogenicity and toxicity of AAV gene therapy[J/OL]. Front Immunol, 2022, 13: 975803[2022-08-12]. https://pubmed.ncbi.nlm.nih.gov/36032092/. DOI: 10.3389/fimmu.2022.975803.
51.	Cabral de Guimaraes TA, Daich Varela M, Georgiou M, et al. Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions[J]. Br J Ophthalmol, 2022, 106(3): 297-304. DOI: 10.1136/bjophthalmol-2020-318452.
52.	Dreismann AK, McClements ME, Barnard AR, et al. Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells[J]. Gene Ther, 2021, 28(5): 265-276. DOI: 10.1038/s41434-021-00239-9.
53.	Khanani AM, Thomas MJ, Aziz AA, et al. Review of gene therapies for age-related macular degeneration[J]. Eye (Lond), 2022, 36(2): 303-311. DOI: 10.1038/s41433-021-01842-1.
54.	Kumar-Singh R. The role of complement membrane attack complex in dry and wet AMD-from hypothesis to clinical trials[J]. Exp Eye Res, 2019, 184: 266-277. DOI: 10.1016/j.exer.2019.05.006.
55.	Fusco A, Cashman SM, Ramo K, et al. A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration[J/OL]. PLoS One, 2011, 6(4): e19078[2011-04-28]. https://pubmed.ncbi.nlm.nih.gov/21552568/. DOI: 10.1371/journal.pone.0019078.
56.	Cheng DL, Greenberg PB, Borton DA. Advances in retinal prosthetic research: a systematic review of engineering and clinical characteristics of current prosthetic initiatives[J]. Curr Eye Res, 2017, 42(3): 334-347. DOI: 10.1080/02713683.2016.1270326.
57.	Palanker D, Le Mer Y, Mohand-Said S, et al. Photovoltaic restoration of central vision in atrophic age-related macular degeneration[J]. Ophthalmology, 2020, 127(8): 1097-1104. DOI: 10.1016/j.ophtha.2020.02.024.
58.	Palanker D, Le Mer Y, Mohand-Said S, et al. Simultaneous perception of prosthetic and natural vision in AMD patients[J]. Nat Commun, 2022, 13(1): 513. DOI: 10.1038/s41467-022-28125-x.
59.	Coleman DJ, Silverman RH, Rondeau MJ, et al. Age-related macular degeneration: choroidal ischaemia?[J]. Br J Ophthalmol, 2013, 97(8): 1020-1023. DOI: 10.1136/bjophthalmol-2013-303143.
60.	Lylyk I, Bleise C, Lylyk PN, et al. Ophthalmic artery angioplasty for age-related macular degeneration[J]. J Neurointerv Surg, 2022, 14(10): 968-972. DOI: 10.1136/neurintsurg-2021-018222.
61.	冯思齐, 周欣, 张元钟, 等. 驻景丸加减方治疗肝肾不足型干性年龄相关性黄斑变性的临床研究[J]. 南京中医药大学学报, 2024, 40(5): 521-526. DOI: 10.14148/j.issn.1672-0482.2024.0521.Feng SQ, Zhou X, Zhang YZ, et al. Clinical study on the treatment of dry age-related macular degeneration of liver and kidney insufficiency type with modified Zhujing pills[J]. J Nanjing UnivTradit Chin Medicine, 2024, 40(5): 521-526. DOI: 10.14148/j.issn.1672-0482.2024.0521.
62.	王漫峤, 邵彦, 李筱荣. 藏花醛治疗干性年龄相关性黄斑变性机制的研究进展[J]. 中国中医眼科杂志, 2024, 34(3): 275-279. DOI: 10.3969/j.issn. zgzyykzz.2024.03.016. DOI: 10.3969/j.issn.zgzyykzz.2024.03.016.Wang MQ, Shao Y, Li XR. Research progress on the mechanisms of safranal in treating dry age-related macular degeneration[J]. Chinese Journal of Chinese Ophthalmology, 2024, 34(3): 275-279. DOI: 10.3969/j.issn. zgzyykzz.2024.03.016. DOI: 10.3969/j.issn.zgzyykzz.2024.03.016.
63.	王龙龙, 刘蓓蓓. 养血益睛汤治疗早期干性年龄相关性黄斑变性疗效观察[J]. 安徽中医药大学学报, 2021, 40(5): 24-27. DOI: 10.14148/j.issn.2095-7246.2021.05.007.Wang LL, Liu BB. Clinical effect of Yangxue Yij ing decoction in treatment of early-stage dry age-related macular degeneration[J]. J Anhui Univ Chinese Med, 2021, 40(5): 24-27. DOI: 10.14148/j.issn.2095-7246.2021.05.007.
64.	梁振华. 增视明目汤治疗干性年龄相关性黄斑变性(肝肾阴虚证)的临床疗效[J]. 中西医结合心血管病电子杂志, 2020, 8(12): 158. DOI: 10.16282/j.cnki.cn11-9336/r.2020.12.142.Liang ZH. Clinical effect of Zengshi Mingmu decoction on dry age-related macular degeneration (syndrome of Yin deficiency of liver and kidney)[J]. Cardiovascular Disease Journal of Integrated Traditional Chinese and Western Medicine(Electronic), 2020, 8(12): 158. DOI: 10.16282/j.cnki.cn11-9336/r.2020.12.142.
65.	李雅萍, 吴利龙, 孙洋, 等. 加味十全明目片治疗干性年龄相关性黄斑变性50眼临床观察[J]. 湖南中医杂志, 2018, 34(12): 59-61. DOI: 10.16808/j.cnki.issn1003-7705.2018.12.025.Li YP, Wu LL, Sun Y, et al. Clinical observation of 50 eyes of dry age-related macular degeneration treated with modified Shianyu Mingmu tablet[J]. Hunan Journal of Traditional Chinese Medicine, 2018, 34(12): 59-61. DOI: 10.16808/j.cnki.issn1003-7705.2018.12.025.

1. Palanker D. Electronic retinal prostheses[J/OL]. Cold Spring Harb Perspect Med, 2023, 13(8): a041525[2023-08-01]. https://pubmed.ncbi.nlm.nih.gov/36781222/. DOI: 10.1101/cshperspect.a041525.
2. Guymer RH, Campbell TG. Age-related macular degeneration[J]. Lancet, 2023, 401(10386): 1459-1472. DOI: 10.1016/S0140-6736(22)02609-5.
3. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis[J/OL]. Lancet Glob Health, 2014, 2(2): e106-e116[2014-01-03]. https://pubmed.ncbi.nlm.nih.gov/25104651/. DOI: 10.1016/S2214-109X(13)70145-1.
4. Ye H, Zhang Q, Liu X, et al. Prevalence of age-related macular degeneration in an elderly urban Chinese population in China: The Jiangning Eye Study[J]. Invest Ophthalmol Vis Sci, 2014, 55(10): 6374-6380. DOI: 10.1167/iovs.14-14899.
5. Girgis S, Lee LR. Treatment of dry age-related macular degeneration: a review[J]. Clin Exp Ophthalmol, 2023, 51(8): 835-852. DOI: 10.1111/ceo.14294.
6. Han S, Chen J, Hua J, et al. MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium[J/OL]. Redox Biol, 2020, 34: 101537[2020-04-16]. https://pubmed.ncbi.nlm.nih.gov/32361183/. DOI: 10.1016/j.redox.2020.101537.
7. Tang Y, Kang Y, Zhang X, et al. Mesenchymal stem cell exosomes as nanotherapeutics for dry age-related macular degeneration[J]. J Control Release, 2023, 357: 356-370. DOI: 10.1016/j.jconrel.2023.04.003.
8. Li F, Lang F, Zhang H, et al. Apigenin alleviates endotoxin-induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy[J/OL]. Oxid Med Cell Longev, 2017, 2017: 2302896[2017-07-30]. https://pubmed.ncbi.nlm.nih.gov/28828145/. DOI: 10.1155/2017/2302896.
9. Zhang Y, Yang Y, Yu H, et al. Apigenin protects mouse retina against oxidative damage by regulating the Nrf2 pathway and autophagy[J/OL]. Oxid Med Cell Longev, 2020, 2020: 9420704[2020-05-13]. https://pubmed.ncbi.nlm.nih.gov/32509154/. DOI: 10.1155/2020/9420704.
10. Wang B, Wang L, Gu S, et al. D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration[J]. Signal Transduct Target Ther, 2020, 5(1): 20. DOI: 10.1038/s41392-020-0122-1.
11. Pardue MT, Allen RS. Neuroprotective strategies for retinal disease[J]. Prog Retin Eye Res, 2018, 65: 50-76. DOI: 10.1016/j.preteyeres.2018.02.002.
12. Rhoades W, Dickson D, Do DV. Potential role of lampalizumab for treatment of geographic atrophy[J]. Clin Ophthalmol, 2015, 9: 1049-1056. DOI: 10.2147/opth.S59725.
13. 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.
14. Garg A, Nanji K, Tai F, et al. The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: a living systematic review and meta-analysis[J]. Surv Ophthalmol, 2024, 69(3): 349-361. DOI: 10.1016/j.survophthal.2023.11.008.
15. Danzig CJ, Khanani AM, Loewenstein A. C5 inhibitor avacincaptad pegol treatment for geographic atrophy: a comprehensive review[J]. Immunotherapy, 2024, 29: 1-12. DOI: 10.1080/1750743x.2024.2368342.
16. Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration[J]. Ophthalmology, 2021, 128(4): 576-586. DOI: 10.1016/j.ophtha.2020.08.027.
17. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial[J]. Lancet, 2023, 402(10411): 1449-1458. DOI: 10.1016/s0140-6736(23)01583-0.
18. Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration[J]. Ophthalmology, 2014, 121(3): 693-701. DOI: 10.1016/j.ophtha.2013.09.044.
19. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials[J]. Lancet, 2023, 402(10411): 1434-1448. DOI: 10.1016/s0140-6736(23)01520-9.
20. Yang P, Shao Z, Besley NA, et al. Risuteganib protects against hydroquinone-induced injury in human RPE cells[J]. Invest Ophthalmol Vis Sci, 2020, 61(10): 35. DOI: 10.1167/iovs.61.10.35.
21. Boyer DS, Gonzalez VH, Kunimoto DY, et al. Safety and efficacy of intravitreal risuteganib for non-exudative AMD: a multicenter, phase 2a, randomized, clinical trial[J]. Ophthalmic Surg Lasers Imaging Retina, 2021, 52(6): 327-335. DOI: 10.3928/23258160-20210528-05.
22. Lad EM, Boyer DS, Heier JS, et al. Color vision and microperimetry changes in nonexudative age-related macular degeneration after risuteganib treatment: exploratory endpoints in a multicenter phase 2a double-masked, randomized, sham-controlled, crossover clinical trial[J]. Ophthalmic Surg Lasers Imaging Retina, 2022, 53(8): 430-438. DOI: 10.3928/23258160-20220725-02.
23. Camardo J. The rapamune era of immunosuppression 2003: the journey from the laboratory to clinical transplantation[J]. Transplant Proc, 2003, 35(3): 18-24. DOI: 10.1016/s0041-1345(03)00356-7.
24. Wong WT, Dresner S, Forooghian F, et al. Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase Ⅰ/Ⅱ clinical trial[J/OL]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2941-2950[2014-04-26]. https://pubmed.ncbi.nlm.nih.gov/23548622/. DOI: 10.1167/iovs.13-11650.
25. Suri R, Neupane YR, Mehra N, et al. Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration[J]. Int J Biol Macromol, 2021, 191: 548-559. DOI: 10.1016/j.ijbiomac.2021.09.069.
26. Mettu PS, Allingham MJ, Cousins SW. Phase 1 clinical trial of elamipretide in dry age-related macular degeneration and noncentral geographic atrophy: ReCLAIM NCGA Study[J/OL]. Ophthalmol Sci, 2022, 2(1): 100086[2021-11-27]. https://pubmed.ncbi.nlm.nih.gov/36246181/. DOI: 10.1016/j.xops.2021.100086.
27. Bavik C, Henry SH, Zhang Y, et al. Visual cycle modulation as an approach toward preservation of retinal integrity[J/OL]. PLoS One, 2015, 10(5): e0124940[2015-05-13]. https://pubmed.ncbi.nlm.nih.gov/25970164/. DOI: 10.1371/journal.pone.0124940.
28. Rosenfeld PJ, Dugel PU, Holz FG, et al. Emixustat hydrochloride for geographic atrophy secondary to age-related macular degeneration[J]. Ophthalmology, 2018, 125(10): 1556-1567. DOI: 10.1016/j.ophtha.2018.03.059.
29. Sparrow JR, Vollmer-Snarr HR, Zhou J, et al. A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation[J]. J Biol Chem, 2003, 278(20): 18207-18213. DOI: 10.1074/jbc.M300457200.
30. Conley B, O'Shaughnessy J, Prindiville S, et al. Pilot trial of the safety, tolerability, and retinoid levels of N-(4-hydroxyphenyl) retinamide in combination with tamoxifen in patients at high risk for developing invasive breast cancer[J]. J Clin Oncol, 2000, 18(2): 275-283. DOI: 10.1200/jco.2000.18.2.275.
31. 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.
32. 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.
33. Ma L, Kaufman Y, Zhang J, et al. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease[J]. J Clin Oncol, 2011, 286(10): 7966-7674. DOI: 10.1074/jbc.M110.178657.
34. Xu XL, Zhang W, Rao GW. Clinical application and synthesis methods of deuterated drugs[J]. Curr Med Chem, 2023, 30(36): 4096-4129. DOI: 10.2174/0929867330666221122123201.
35. Kauper K, McGovern C, Sherman S, et al. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases[J]. Invest Ophthalmol Vis Sci, 2012, 53(12): 7484-7491. DOI: 10.1167/iovs.12-9970.
36. Wen R, Tao W, Li Y, et al. CNTF and retina[J]. Prog Retin Eye Res, 2012, 31(2): 136-151. DOI: 10.1016/j.preteyeres.2011.11.005.
37. 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.
38. Kuppermann BD, Patel SS, Boyer DS, et al. Phase 2 study of safety and efficacy of brimonidine drug delivery system (BRIMO DDS) generation 1 in patients with geographic atrophy secondary to age-related macular degenetation[J]. Retina, 2021, 41(1): 144-155. DOI: 10.1097/iae.0000000000002789.
39. Freeman WR, Bandello F, Souied E, et al. Randomized phase Ⅱb study of brimonidine drug delivery system generation 2 for geographic atrophy in age-related macular degeneration[J]. Ophthalmol Retina, 2023, 7(7): 573-585. DOI: 10.1016/j.oret.2023.03.001.
40. Jiang Y, Fu X, Shao M, et al. Eyedrop delivery of therapeutic proteins with zwitterionic polymers to treat dry age-related macular degeneration[J/OL]. Biomaterials, 2024, 305: 122429[2023-12-22]. https://pubmed.ncbi.nlm.nih.gov/38150770/. DOI: 10.1016/j.biomaterials.2023.122429.
41. Trincão-Marques J, Ayton LN, Hickey DG, et al. Gene and cell therapy for age-related macular degeneration: a review[J]. Surv Ophthalmol, 2024, 69(5): 665-676. DOI: 10.1016/j.survophthal.2024.05.002.
42. Maeda T, Sugita S, Kurimoto Y, et al. Trends of stem cell therapies in age-related macular degeneration[J/OL]. J Clin Med, 2021, 10(8): 1785[2024-04-20]. https://pubmed.ncbi.nlm.nih.gov/33923985/. DOI: 10.3390/jcm10081785.
43. Ho AC, Chang TS, Samuel M, et al. Experience with a subretinal cell-based therapy in patients with geographic atrophy secondary to age-related macular degeneration[J]. Am J Ophthalmol, 2017, 179: 67-80. DOI: 10.1016/j.ajo.2017.04.006.
44. Kashani AH, Lebkowski JS, Rahhal FM, et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration[J/OL]. Sci Transl Med, 2018, 10(435): eaao4097[2018-04-04]. https://pubmed.ncbi.nlm.nih.gov/29618560/. DOI: 10.1126/scitranslmed.aao4097.
45. Hashmi JT, Huang YY, Sharma SK, et al. Effect of pulsing in low-level light therapy[J]. Lasers Surg Med, 2010, 42(6): 450-466. DOI: 10.1002/lsm.20950.
46. Albarracin R, Eells J, Valter K. Photobiomodulation protects the retina from light-induced photoreceptor degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(6): 3582-3592. DOI: 10.1167/iovs.10-6664.
47. Ivandic BT, Ivandic T. Low-level laser therapy improves vision in patients with age-related macular degeneration[J]. Photomed Laser Surg, 2008, 26(3): 241-245. DOI: 10.1089/pho.2007.2132.
48. Merry GF, Munk MR, Dotson RS, et al. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration[J/OL]. Acta Ophthalmologica, 2016, 95(4): e270-e277[2016-12-18]. https://pubmed.ncbi.nlm.nih.gov/27989012/. DOI: 10.1111/aos.13354.
49. Markowitz SN, Devenyi RG, Munk MR, et al. A double-masked, randomized, sham-controlled, single-center study with photobiomodulation for the treatment of dry age-related macular degenetation[J]. Retina, 2020, 40(8): 1471-1482. DOI: 10.1097/iae.0000000000002632.
50. Ertl HCJ. Immunogenicity and toxicity of AAV gene therapy[J/OL]. Front Immunol, 2022, 13: 975803[2022-08-12]. https://pubmed.ncbi.nlm.nih.gov/36032092/. DOI: 10.3389/fimmu.2022.975803.
51. Cabral de Guimaraes TA, Daich Varela M, Georgiou M, et al. Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions[J]. Br J Ophthalmol, 2022, 106(3): 297-304. DOI: 10.1136/bjophthalmol-2020-318452.
52. Dreismann AK, McClements ME, Barnard AR, et al. Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells[J]. Gene Ther, 2021, 28(5): 265-276. DOI: 10.1038/s41434-021-00239-9.
53. Khanani AM, Thomas MJ, Aziz AA, et al. Review of gene therapies for age-related macular degeneration[J]. Eye (Lond), 2022, 36(2): 303-311. DOI: 10.1038/s41433-021-01842-1.
54. Kumar-Singh R. The role of complement membrane attack complex in dry and wet AMD-from hypothesis to clinical trials[J]. Exp Eye Res, 2019, 184: 266-277. DOI: 10.1016/j.exer.2019.05.006.
55. Fusco A, Cashman SM, Ramo K, et al. A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration[J/OL]. PLoS One, 2011, 6(4): e19078[2011-04-28]. https://pubmed.ncbi.nlm.nih.gov/21552568/. DOI: 10.1371/journal.pone.0019078.
56. Cheng DL, Greenberg PB, Borton DA. Advances in retinal prosthetic research: a systematic review of engineering and clinical characteristics of current prosthetic initiatives[J]. Curr Eye Res, 2017, 42(3): 334-347. DOI: 10.1080/02713683.2016.1270326.
57. Palanker D, Le Mer Y, Mohand-Said S, et al. Photovoltaic restoration of central vision in atrophic age-related macular degeneration[J]. Ophthalmology, 2020, 127(8): 1097-1104. DOI: 10.1016/j.ophtha.2020.02.024.
58. Palanker D, Le Mer Y, Mohand-Said S, et al. Simultaneous perception of prosthetic and natural vision in AMD patients[J]. Nat Commun, 2022, 13(1): 513. DOI: 10.1038/s41467-022-28125-x.
59. Coleman DJ, Silverman RH, Rondeau MJ, et al. Age-related macular degeneration: choroidal ischaemia?[J]. Br J Ophthalmol, 2013, 97(8): 1020-1023. DOI: 10.1136/bjophthalmol-2013-303143.
60. Lylyk I, Bleise C, Lylyk PN, et al. Ophthalmic artery angioplasty for age-related macular degeneration[J]. J Neurointerv Surg, 2022, 14(10): 968-972. DOI: 10.1136/neurintsurg-2021-018222.
61. 冯思齐, 周欣, 张元钟, 等. 驻景丸加减方治疗肝肾不足型干性年龄相关性黄斑变性的临床研究[J]. 南京中医药大学学报, 2024, 40(5): 521-526. DOI: 10.14148/j.issn.1672-0482.2024.0521.Feng SQ, Zhou X, Zhang YZ, et al. Clinical study on the treatment of dry age-related macular degeneration of liver and kidney insufficiency type with modified Zhujing pills[J]. J Nanjing UnivTradit Chin Medicine, 2024, 40(5): 521-526. DOI: 10.14148/j.issn.1672-0482.2024.0521.
62. 王漫峤, 邵彦, 李筱荣. 藏花醛治疗干性年龄相关性黄斑变性机制的研究进展[J]. 中国中医眼科杂志, 2024, 34(3): 275-279. DOI: 10.3969/j.issn. zgzyykzz.2024.03.016. DOI: 10.3969/j.issn.zgzyykzz.2024.03.016.Wang MQ, Shao Y, Li XR. Research progress on the mechanisms of safranal in treating dry age-related macular degeneration[J]. Chinese Journal of Chinese Ophthalmology, 2024, 34(3): 275-279. DOI: 10.3969/j.issn. zgzyykzz.2024.03.016. DOI: 10.3969/j.issn.zgzyykzz.2024.03.016.
63. 王龙龙, 刘蓓蓓. 养血益睛汤治疗早期干性年龄相关性黄斑变性疗效观察[J]. 安徽中医药大学学报, 2021, 40(5): 24-27. DOI: 10.14148/j.issn.2095-7246.2021.05.007.Wang LL, Liu BB. Clinical effect of Yangxue Yij ing decoction in treatment of early-stage dry age-related macular degeneration[J]. J Anhui Univ Chinese Med, 2021, 40(5): 24-27. DOI: 10.14148/j.issn.2095-7246.2021.05.007.
64. 梁振华. 增视明目汤治疗干性年龄相关性黄斑变性(肝肾阴虚证)的临床疗效[J]. 中西医结合心血管病电子杂志, 2020, 8(12): 158. DOI: 10.16282/j.cnki.cn11-9336/r.2020.12.142.Liang ZH. Clinical effect of Zengshi Mingmu decoction on dry age-related macular degeneration (syndrome of Yin deficiency of liver and kidney)[J]. Cardiovascular Disease Journal of Integrated Traditional Chinese and Western Medicine(Electronic), 2020, 8(12): 158. DOI: 10.16282/j.cnki.cn11-9336/r.2020.12.142.
65. 李雅萍, 吴利龙, 孙洋, 等. 加味十全明目片治疗干性年龄相关性黄斑变性50眼临床观察[J]. 湖南中医杂志, 2018, 34(12): 59-61. DOI: 10.16808/j.cnki.issn1003-7705.2018.12.025.Li YP, Wu LL, Sun Y, et al. Clinical observation of 50 eyes of dry age-related macular degeneration treated with modified Shianyu Mingmu tablet[J]. Hunan Journal of Traditional Chinese Medicine, 2018, 34(12): 59-61. DOI: 10.16808/j.cnki.issn1003-7705.2018.12.025.

Previous Article
Research progress of hydroxychloroquine related retinal toxicity
Next Article
Research progress on the role and mechanism of lactate in retinal diseases

Chinese Journal of Ocular Fundus Diseases

Advances in the treatment of atrophic age-related macular degeneration

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content