BACKGROUND: Age-related macular degeneration (AMD) is a common retinal disease in older people. In Europe, about 1.6% of persons over age 65 and more than 13% of persons over age 85 have late-stage AMD, which can severely impair vision. The development of AMD is influenced both by environmental factors and by a strong hereditary component. METHOD: We selectively searched the PubMed database for articles published between April 2001 and November 2013 with the key words "age-related macular degeneration," "risk factor," "complement," and "therapy." The website www.clinicaltrials.gov was also used to search for relevant clinical trials. RESULTS: Old age and smoking are confirmed risk factors for AMD. Moreover, genetic association studies have pointed to signaling pathways in which the complement system, a part of the individual's innate immune system, takes on a central role in the pathogenesis of the disease. Several clinical trials designed to interfere specifically with these pathomechanisms have yielded rather disappointing results, although a phase II study of the monoclonal antibody lampalizumab showed that blocking complement factor D lessened the progression of geographic atrophy. A risk model based on 13 genetic markers was found to have positive predictive values in predisposed individuals that ranged from 5.1% (in persons aged 65 to 69) to 91.7% (in persons aged 85 or older). It should be borne in mind that 50% of patients with AMD are not carriers of risk-associated markers. CONCLUSION: There is no rationale at present for genetic testing to estimate the individual risk of developing AMD. Several recent clinical trials have incorporated current pathophysiological knowledge, but nearly all of these trials have yielded negative findings, with only one exception.
BACKGROUND: Age-related macular degeneration (AMD) is a common retinal disease in older people. In Europe, about 1.6% of persons over age 65 and more than 13% of persons over age 85 have late-stage AMD, which can severely impair vision. The development of AMD is influenced both by environmental factors and by a strong hereditary component. METHOD: We selectively searched the PubMed database for articles published between April 2001 and November 2013 with the key words "age-related macular degeneration," "risk factor," "complement," and "therapy." The website www.clinicaltrials.gov was also used to search for relevant clinical trials. RESULTS: Old age and smoking are confirmed risk factors for AMD. Moreover, genetic association studies have pointed to signaling pathways in which the complement system, a part of the individual's innate immune system, takes on a central role in the pathogenesis of the disease. Several clinical trials designed to interfere specifically with these pathomechanisms have yielded rather disappointing results, although a phase II study of the monoclonal antibody lampalizumab showed that blocking complement factor D lessened the progression of geographic atrophy. A risk model based on 13 genetic markers was found to have positive predictive values in predisposed individuals that ranged from 5.1% (in persons aged 65 to 69) to 91.7% (in persons aged 85 or older). It should be borne in mind that 50% of patients with AMD are not carriers of risk-associated markers. CONCLUSION: There is no rationale at present for genetic testing to estimate the individual risk of developing AMD. Several recent clinical trials have incorporated current pathophysiological knowledge, but nearly all of these trials have yielded negative findings, with only one exception.
Authors: Robert J Klein; Caroline Zeiss; Emily Y Chew; Jen-Yue Tsai; Richard S Sackler; Chad Haynes; Alice K Henning; John Paul SanGiovanni; Shrikant M Mane; Susan T Mayne; Michael B Bracken; Frederick L Ferris; Jurg Ott; Colin Barnstable; Josephine Hoh Journal: Science Date: 2005-03-10 Impact factor: 47.728
Authors: Johanna Jakobsdottir; Yvette P Conley; Daniel E Weeks; Tammy S Mah; Robert E Ferrell; Michael B Gorin Journal: Am J Hum Genet Date: 2005-07-26 Impact factor: 11.025
Authors: Andrea Rivera; Sheila A Fisher; Lars G Fritsche; Claudia N Keilhauer; Peter Lichtner; Thomas Meitinger; Bernhard H F Weber Journal: Hum Mol Genet Date: 2005-09-20 Impact factor: 6.150
Authors: Jonathan L Haines; Michael A Hauser; Silke Schmidt; William K Scott; Lana M Olson; Paul Gallins; Kylee L Spencer; Shu Ying Kwan; Maher Noureddine; John R Gilbert; Nathalie Schnetz-Boutaud; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance Journal: Science Date: 2005-03-10 Impact factor: 47.728
Authors: W Smith; J Assink; R Klein; P Mitchell; C C Klaver; B E Klein; A Hofman; S Jensen; J J Wang; P T de Jong Journal: Ophthalmology Date: 2001-04 Impact factor: 12.079
Authors: Frank G Holz; Erich C Strauss; Steffen Schmitz-Valckenberg; Menno van Lookeren Campagne Journal: Ophthalmology Date: 2014-01-14 Impact factor: 12.079
Authors: Boglarka Racz; Andras Varadi; Jian Kong; Rando Allikmets; Paul G Pearson; Graham Johnson; Christopher L Cioffi; Konstantin Petrukhin Journal: J Biol Chem Date: 2018-06-05 Impact factor: 5.157
Authors: Diana Pauly; Benedikt M Nagel; Jörg Reinders; Tobias Killian; Matthias Wulf; Susanne Ackermann; Boris Ehrenstein; Peter F Zipfel; Christine Skerka; Bernhard H F Weber Journal: PLoS One Date: 2014-05-05 Impact factor: 3.240