Age-related macular degeneration

Macular degeneration is the physical breakdown of the central portion of the retina called the macula. Age-related macular degeneration (AMD/ARMD) is the leading cause of blindness. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. In AMD, there are two phenotypes, atrophic/ dry and neovascular/ wet. The former is characterized by the geographic atrophy due to death of retinal pigment epithelium, and the latter is usually characterized by the abnormal growth of new blood vessels under the macula, which causes severe loss of vision. While wet AMD can be treated by the inhibition of vascular endothelial growth factor or photodynamic therapy, so far there are no available treatments for dry AMD.

Nervous system disease

(ARMD1) HMCN1 [HSA:83872] [KO:K17341]
(ARMD2) ABCA4 [HSA:24] [KO:K05644]
(ARMD3) FBLN5 [HSA:10516] [KO:K17340]
(ARMD4) HF1 [HSA:3075] [KO:K04004]
(ARMD5) ERCC6 [HSA:2074] [KO:K10841]
(ARMD6) RAX2 [HSA:84839] [KO:K09333]
(ARMD7) HTRA1 [HSA:5654] [KO:K08784]
(ARMD8) ARMS2 [HSA:387715]
(ARMD9) C3 [HSA:718] [KO:K03990]
(ARMD10) TLR4 [HSA:7099] [KO:K10160]
(ARMD11) CST3 [HSA:1471] [KO:K13899]
(ARMD12) CX3CR1 [HSA:1524] [KO:K04192]
(ARMD13) CFI [HSA:3426] [KO:K01333]
(ARMD14) C2 [HSA:717] [KO:K01332]
(ARMD14) CFB [HSA:629] [KO:K01335]
CFHR1 [HSA:3078] [KO:K23815]
CFHR3 [HSA:10878] [KO:K23815]

Aflibercept [DR:D09574]
Verteporfin [DR:D01162]
Pegaptanib sodium [DR:D05386]
Ranibizumab [DR:D05697]
Brolucizumab [DR:D11083]

A haplotype carrying deletion of the complement factor H-related genes CFHR1 and CFHR3 is also associated with reduced risk of ARMD.

PMID:18097986

Montezuma SR, Sobrin L, Seddon JM

Review of genetics in age related macular degeneration.

Semin Ophthalmol 22:229-40 (2007)
DOI:10.1080/08820530701745140

PMID:21072178

Baas DC, Despriet DD, Gorgels TG, Bergeron-Sawitzke J, Uitterlinden AG, Hofman A, van Duijn CM, Merriam JE, Smith RT, Barile GR, ten Brink JB, Vingerling JR, Klaver CC, Allikmets R, Dean M, Bergen AA

The ERCC6 gene and age-related macular degeneration.

PLoS One 5:e13786 (2010)
DOI:10.1371/journal.pone.0013786

PMID:12160730

Ayyagari R, Demirci FY, Liu J, Bingham EL, Stringham H, Kakuk LE, Boehnke M, Gorin MB, Richards JE, Sieving PA

X-linked recessive atrophic macular degeneration from RPGR mutation.

Genomics 80:166-71 (2002)
DOI:10.1006/geno.2002.6815

PMID:3718916

Giuffre G, Lodato G

Vitelliform dystrophy and pattern dystrophy of the retinal pigment epithelium: concomitant presence in a family.

Br J Ophthalmol 70:526-32 (1986)
DOI:10.1136/bjo.70.7.526

PMID:20393116

Michaelides M, Gaillard MC, Escher P, Tiab L, Bedell M, Borruat FX, Barthelmes D, Carmona R, Zhang K, White E, McClements M, Robson AG, Holder GE, Bradshaw K, Hunt DM, Webster AR, Moore AT, Schorderet DF, Munier FL

The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.

Invest Ophthalmol Vis Sci 51:4771-80 (2010)
DOI:10.1167/iovs.09-4561

PMID:18685559

Fagerness JA, Maller JB, Neale BM, Reynolds RC, Daly MJ, Seddon JM

Variation near complement factor I is associated with risk of advanced AMD.

Eur J Hum Genet 17:100-4 (2009)
DOI:10.1038/ejhg.2008.140

PMID:16518403

Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R

Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.

Nat Genet 38:458-62 (2006)
DOI:10.1038/ng1750

PMID:16998489

Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U

A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.

Nat Genet 38:1173-7 (2006)
DOI:10.1038/ng1890

PMID:21546780 (drug)

Koss MJ, Lewicka-Chomont A, Schramm K, Rejdak R, Ohrloff C, Koch FH

Quadruple therapy leads to a sustained improvement of vision in patients with wet age-related macular degeneration.

Ophthalmologica 226:45-50 (2011)
DOI:10.1159/000327702

PMID:21623685 (drug)

Mitchell P

A systematic review of the efficacy and safety outcomes of anti-VEGF agents used for treating neovascular age-related macular degeneration: comparison of ranibizumab and bevacizumab.

Curr Med Res Opin 27:1465-75 (2011)
DOI:10.1185/03007995.2011.585394

PMID:17636773

Virgili G, Bini A

Laser photocoagulation for neovascular age-related macular degeneration.

Cochrane Database Syst Rev CD004763 (2007)
DOI:10.1002/14651858.CD004763.pub2

PMID:18462575 (drug)

Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A

Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation.

Health Technol Assess 12:iii-iv, ix-201 (2008)
DOI:10.3310/hta12160

PMID:23440797 (drug)

Geltzer A, Turalba A, Vedula SS

Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration.

Cochrane Database Syst Rev 1:CD005022 (2013)
DOI:10.1002/14651858.CD005022.pub3