参考文献/References:
［1］ YANG K,LIANG Y B,GAO L Q,PENG Y,SHEN R.Prevalence of age-related macular degeneration in a rural Chinese population：the Handan eye study［J］.Ophthalmology,2011,118(7)：1395-1401.
［2］ GBD 2019 Blindness and Vision Impairment Collaborators,Vision Loss Expert Group of the Global Burden of Disease Study.Causes of blindness and vision impairment in 2020 and trends over 30 years,and prevalence of avoidable blindness in relation to VISION 2020：the right to sight：an analysis for the global burden of disease study［J］.Lancet Glob Health,2021,9(2)：e144-e160.
［3］ CONNOLLY E,RHATIGAN M,O’HALLORAN A M,MULDREW K A,CHAKRAVARTHY U,CAHILL M,et al.Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population［J］.Br J Ophthalmol,2018,102(12)：1691-1695.
［4］ WONG W L,SU X,LI X,CHEUNG C M,KLEIN R,CHENG C Y,et al.Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040：a systematic review and meta-analysis［J］.Lancet Glob Health,2014,2(2)：e106-e116.
［5］ RAIMUNDO M,MIRA F,CACHULO M,BARRETO P,RIBEIRO L,FARINHA C,et al.Adherence to a mediterranean diet,lifestyle and age-related macular degeneration：the Coimbra Eye Study-report 3［J］.Acta Ophthalmol (Copenh),2018,96(8)：e926-e932.
［6］ WONG W C,YANAGI Y,LEE W K,OGURA Y,YEO I,WONG T Y,et al.Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians［J］.Prog Retin Eye Res,2016,53：107-139.
［7］ KHAN K N,MAHROO O A,KHAN R S,MOHAMED M D,MCKIBBIN M,BIRD A,et al.Differentiating drusen：drusen and drusen-like appearances associated with ageing,age-related macular degeneration,inherited eye disease and other pathological processes［J］.Prog Retin Eye Res,2016,53：70-106.
［8］ FLECKENSTEIN M,MITCHELL P,FREUND K B,SADDA S,HOLZ F G,BRITTAIN C,et al.The progression of geographic atrophy secondary to age-related macular degeneration［J］.Ophthalmology,2018,125(3)：369-390.
［9］ VERBRAAK F D,PONSIOEN D L,TIGCHELAAR-BESLING O,NGUYEN V,GILLIES M C,BARTHELMES D,et al.Real-world treatment outcomes of neovascular age-related macular degeneration in the Netherlands［J］.Acta Ophthalmol,2021,99(6)：e884-e892.
［10］ HOLZ F G,SADDA S R,STAURENGHI G,LINDNER M,BIRD A C,BLODI B,et al.Imaging protocols in clinical studies in advanced age-related macular degeneration：recommendations from classification of atrophy consensus meetings［J］.Ophthalmology,2017,124(4)：464-478.
［11］ LAMBERT N G,ELSHELMANI H,SINGH M K,MANSERGH F C,WRIDE M A,PADILLA M,et al.Risk factors and biomarkers of age-related macular degeneration［J］.Prog Retin Eye Res,2016,54：64-102.
［12］ FRITSCHE L G,IGL W,BAILEY J N,GRASSMANN F,SENGUPTA S,BRAGG-GRESHAM J L,et al.A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants［J］.Nat Genet,2016,48(2)：134-143.
［13］ VAN ASTEN F,SIMMONS M,SINGHAL A,KEENAN T D,RATNAPRIYA R,AGRN E,et al.A deep phenotype association study reveals specific phenotype associations with genetic variants in age-related macular degeneration：age-related eye disease study 2 (AREDS2) report no.14［J］.Ophthalmology,2018,125(4)：559-568.
［14］ GOLESTANEH N,CHU Y,XIAO Y Y,STOLERU G L,THEOS A C.Dysfunctional autophagy in RPE,a contributing factor in age-related macular degeneration［J］.Cell Death Dis,2017,8(1)：e2537.
［15］ WANG L A,LUKAS T J,YUAN M,NEUFELD A H.Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid［J］.Mol Vis,2008,14：644-651.
［16］ WALDSTEIN S M,VOGL W D,BOGUNOVIC H,SADEGHIPOUR A,RIEDL S,SCHMIDT-ERFURTH U.Characterization of drusen and hyperreflective foci as biomarkers for disease progression in age-related macular degeneration using artificial intelligence in optical coherence tomography［J］.JAMA Ophthalmol,2020,138(7)：740-747.
［17］ BEHNKE V,WOLF A,LANGMANN T.The role of lymphocytes and phagocytes in age-related macular degeneration (AMD)［J］.Cell Mol Life Sci,2020,77(5)：781-788.
［18］ JOHANSSON I,MONSEN V,PETTERSEN K,MILDENBERGER J,MISUND K.The Marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells［J］.Autophagy,2015,11(9)：1636-1651.
［19］ FELSZEGHY S,VIIRI J,PATERNO J,HYTTINEN J,KOSKELA A.Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration［J］.Redox Biol,2019,20：1-12.
［20］ KIM S H,PARK J W.Morin hydrate attenuates CSE-induced lipid accumulation,ER stress,and oxidative stress in RPE cells：implications for age-related macular degeneration［J］.Free Radic Res,2019,53(8)：865-874.
［21］ LI J,CAI X,XIA Q,YAO K,CHEN J,ZHANG Y,et al.Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration［J］.Toxicol Sci,2015,143(1)：196-208.
［22］ YASUDA H,TANAKA M,NISHINAKA A,NAKAMURA S,SHIMAZAWA M,HARA H.Role of activating transcription factor 4 in murine choroidal neovascularization model［J］.Int J Mol Sci,2021,22(16)：8890.
［23］ PERUSEK L,SAHU B,PARMAR T,MAENO H,ARAI E,LE Y Z,et al.Di-retinoid-pyridinium-ethanolamine (A2E) accumulation and the maintenance of the visual cycle are independent of Atg7-mediated autophagy in the retinal pigmented epithelium［J］.J Biol Chem,2015,290(48)：29035-29044.
［24］ JY S,FAN B,CHE L,PAN Y R,ZHANG S M,WANG Y,et al.Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury［J］.Aging,2020,12(16)：16579-16596.
［25］ DEMISHTEIN A,FRAIBERG M,BERKO D,TIROSH B,ELAZAR Z,NAVON A.SQSTM1/p62-mediated autophagy compensates for loss of proteasome polyubiquitin recruiting capacity［J］.Autophagy,2017,13(10)：1697-1708.
［26］ WANG Y,HANUS J W,ABU-ASAB M S,SHEN D,OGILVY A,OU J,et al.NLRP3 upregulation in retinal pigment epithelium in age-related macular degeneration［J］.Int J Mol Sci,2016,17(1)：73.
［27］ BLACK J R,CLARK S J.Age-related macular degeneration：genome-wide association studies to translation［J］.Genet Med,2016,18(4)：283-289.
［28］ COUGHLIN B,SCHNABOLK G,JOSEPH K,RAIKWAR H,KUNCHITHAPAUTHAM K.Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells［J］.Sci Rep,2016,6:23794..
［29］ MULLINS R F,SCHOO D P,SOHN E H,FLAMME-WIESE M J,WORKAMELAHU G,JOHNSTON R M,et al.The membrane attack complex in aging human choriocapillaris：relationship to macular degeneration and choroidal thinning［J］.Am J Pathol,2014,184(11)：3142-3153.
［30］ WOODELL A,JONES B W,WILLIAMSON T,SCHNABOLK G,TOMLINSON S,ATKINSON C,et al.A targeted inhibitor of the alternative complement pathway accelerates recovery from smoke-induced ocular injury［J］.Invest Ophthalmol Vis Sci,2016,57(4)：1728-1737.
［31］ CHEREPANOFF S,MCMENAMIN P,GILLIES M C,KETTLE E,SARKS S H.Bruch’s membrane and choroidal macrophages in early and advanced age-related macular degeneration［J］.Br J Ophthalmol,2010,94(7)：918-925.
［32］ LAD E M,COUSINS S W,VAN A J,PROIA A D.Abundance of infiltrating CD163(+) cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration［J］.Graefes Arch Clin Exp Ophthalmol,2015,253(11)：1941-1945.
［33］ LEVY O,CALIPPE B,LAVALETTE S,HU S J,RAOUL W,DOMINGUEZ E,et al.Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration［J］.EMBO Mol Med,2015,7(2)：211-226.
［34］ SENNLAUB F,AUVYNET C,CALIPPE B,LAVALETTE S,POUPEL L,HU S J,et al.CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice［J］.EMBO Mol Med,2013,5(11)：1775-1793.
［35］ KROGH N M,SUBHI Y,MOLBECH C R,FALK M K,NISSEN M H,SRENSEN T L.Chemokine profile and the alterations in CCR5-CCL5 axis in geographic atrophy secondary to age-related macular degeneration［J］.Invest Ophthalmol Vis Sci,2020,61(4)：28.
［36］ KROGH N M,SUBHI Y,MOLBECH C R,FALK M K,SINGH A,NISSEN M H,et al.Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes［J］.Clin Exp Ophthalmol,2019,47(1)：69-78.
［37］ XI H,KATSCHKE K J,LI Y,TRUONG T,LEE W P,DIEHL L,et al.IL-33 amplifies an innate immune response in the degenerating retina［J］.J Exp Med,2016,213(2)：189-207.
［38］ Age-Related Eye Disease Study Research Group.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［J］.Arch Ophthalmol,2001,119(10):1417-1436.
［39］ 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.
［40］ WU J,CHO E,GIOVANNUCCI E L,ROSNER B,SASTRY S M,WILLETT W C,et al.Dietary intakes of eicosapentaenoic acid and docosahexaenoic acid and risk of age-related macular degeneration［J］.Ophthalmology,2017,124(5)：634-643.
［41］ ROMDHONIYYAH D F,HARDING S P,CHEYNE C P,BEARE N.Metformin,a potential role in age-related macular degeneration：a systematic review and meta-analysis［J］.Ophthalmol Ther,2021,10(2)：245-260.
［42］ RICHER S,PATEL S,SOCKANATHAN S,ULANSKI L J 2nd,MILLER L,PODELLA C.Resveratrol based oral nutritional supplement produces long-term beneficial effects on structure and visual function in human patients［J］.Nutrients,2014,6(10)：4404-4420.
［43］ SHAW L T,MACKIN A,SHAH R,JAIN S,JAIN P,NAYAK R,et al.Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema［J］.Expert Opin Investig Drugs,2020,29(6)：547-554.
［44］ EHLERS J P,YEH S,MAGUIRE M G,SMITH J R,MRUTHYUNJAYA P,JAIN N,et al.Intravitreal pharmacotherapies for diabetic macular edema：a report by the American academy of ophthalmology［J］.Ophthalmology,2022,129(1):88-99.
［45］ LEUNG E,LANDA G.Update on current and future novel therapies for dry age-related macular degeneration［J］.Expert Rev Clin Pharmacol,2013,6(5):565-579.
［46］ WONG W T,DRESNER S,FOROOGHIAN F,GLASER T,DOSS L,ZHOU M,et al.Treatment of geographic atrophy with subconjunctival sirolimus：results of a phase I/II clinical trial［J］.Invest Ophthalmol Vis Sci,2013,54(4):2941-2950.
［47］ YEHOSHUA Z,DE AMORIM G C,NUNES R P,GREGORI G,PENHA F M,MOSHFEGHI A A,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.
［48］ KASSA E,CIULLA T A,HUSSAIN R M,DUGEL P U.Complement inhibition as a therapeutic strategy in retinal disorders［J］.Expert Opin Biol Ther,2019,19(4):335-342.
［49］ GJ J,WESTBY K,CSAKY K G,MONS J,PEARLMAN J A,PATEL S S,et al.C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration：a randomized pivotal phase 2/3 trial［J］.Ophthalmology,2021,128(4)：576-586.
［50］ HOLZ F G,SADDA S R,BUSBEE B,CHEW E Y,MITCHELL P,TUFAIL A,et al.Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration：chroma and spectri phase 3 randomized clinical trials［J］.JAMA Ophthalmol,2018,136(6)：666-677.
［51］ ROSENFELD P J,BERGER B,REICHEL E,DANIS R P,GRESS A,YE L,et al.A randomized phase 2 study of an anti-amyloid β monoclonal antibody in geographic atrophy secondary to age-related macular degeneration［J］.Ophthalmol Retina,2018,2(10)：1028-1040.
［52］ ZHANG K,HOPKINS J J,HEIER J S,BIRCH D G,HALPERIN S,ALBINI T,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 U S A,2011,108(15)：6241-6245.
［53］ KUPPERMANN B D,PATEL S S,BOYER D S,AUGUSTIN A J,FREEMAN W R,KERR K J,et al.Phase 2 study of the safety and efficacy of brimonidine drug delivery system (brimo dds) generation 1 in patients with geographic atrophy secondary to age-related macular degeneration［J］.Retina,2021,41(1)：144-155.
［54］ COLLIER R J,WANG Y,SMITH S S,MARTIN E,ORNBERG R,RHOADES K,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.
［55］ JAFFE G J,SCHMITZ-VALCKENBERG S,BOYER D,HEIER J,WOLF-SCHNURRBUSCH U,STAURENGHI G,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.
［56］ DO K V,KAUTZMANN M I,JUN B,GORDON W C,NSHIMIYIMANA R,YANG R,et al.Elovanoids counteract oligomeric β-amyloid-induced gene expression and protect photoreceptors［J］.Proc Natl Acad Sci U S A,2019,116(48)：24317-24325.
［57］ FONTAINE V,MONTEIRO E,FOURNI M,BRAZHNIKOVA E,BOUMEDINE T,VIDAL C,et al.Systemic administration of the diapocarotenoid norbixin (BIO201) is neuroprotective,preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease［J］.Aging,2020,12(7)：6151-6171.
［58］ ELLIS S A,BUCHBERGER J,HOLDER E,ORHAN J.GT005,a gene therapy for the treatment of dry age-related macular degeneration (AMD)［J］.Invest Ophthalmol Vis Sci,2020,61(7)：2295.
［59］ CASHMAN S,GRACIAS J,ADHI M,KUMAR-SINGH R.Adenovirus-mediated delivery of factor H attenuates complement C3 induced pathology in the murine retina：a potential gene therapy for age-related macular degeneration［J］.J Gene Med,2015,2015：229-243.
［60］ HO A,CHANG T,SAMUEL M,WILLIAMSON P,WILLENBUCHER R.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.
［61］ HEIER J S,HO A C,SAMUEL M A,CHANG T,RIEMANN C D,KITCHENS J W,et al.Safety and efficacy of subretinally administered palucorcel for geographic atrophy of age-related macular degeneration：phase 2b study［J］.Ophthalmol Retina,2020,4(4)：384-393.
［62］ SCHWARTZ S D,REGILLO C D,LAM B L,ELIOTT D,ROSENFELD P J,GREGORI N Z,et al.Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy：follow-up of two open-label phase 1/2 studies［J］.Lancet,2015,385(9967)：509-516.
［63］ HOLAN V,PALACKA K,HERMANKOVA B.Mesenchymal stem cell-based therapy for retinal deg enerative diseases：experimental models and clinical trials［J］.Cells,2021,10(3)：588.
［64］ KASHANI A H,LEBKOWSKI J S,RAHHAL F M,AVERY R L,SALEHI-HAD H,DANG W,et al.A bioengineered retinal pigment epithelial monolayer for advanced,dry age-related macular degeneration［J］.Sci Transl Med,2018,10(435)：eaao4097.
［65］ WEISS J N,LEVY S.Stem cell ophthalmology treatment study (Scots)：bone marrow-derived stem cells in the treatment of age-related macular degeneration［J］.Medicines (Basel),2020,7(4)：16.
［66］ COTRIM C,TOSCANO L,MESSIAS A,JORGE R,SIQUEIRA R.Intravitreal use of bone marrow mononuclear fraction containing CD34 stem cells in patients with atrophic age-related macular degeneration［J］.Clin Ophthalmol,2017：931-938.
［67］ VESSEY K A,HO T,JOBLING A,MILLS S A,TRAN M X,BRANDLI A,et al.Nanosecond laser treatment for age-related macular degeneration does not induce focal vision loss or new vessel growth in the retina［J］.Invest Ophthalmol Vis Sci,2018,59(2)：731-745.
［68］ AUGUSTIN A J,DIEHM C,GRIEGER F,BENTZ J.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.
［69］ THOMAS C N,SIM D A,LEE W H,ALFAHAD N,DICK A D,DENNISTON A K,et al.Emerging therapies and their delivery for treating age-related macular degeneration［J］.Br J Pharmacol,2021.［Epub ahead of print］.
［70］ MARKOWITZ S N,DEVENYI R G,MUNK M R,CROISSANT C L,TEDFORD S E,RCKERT R,et al.A double-masked,randomized,sham-controlled,single-center study with photobiomodulation for the treatment of dry age-related macular degeneration［J］.Retina,2020,40(8)：1471-1482.