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- 1. Genetic Testing for Macular Degeneration Edwin M. Stone, M.D., Ph.D. The Howard Hughes Medical Institute The University of Iowa Institute for Vision Research
- 2. Financial Interests to Disclose None
- 3. AMD Prevalence 35% > Age 75
- 4. US Population over 75 years (will increase 44% by 2025) 19 million in 2012 27 million in 2025 From the US Census Bureau
- 5. Prevention is the Key
- 6. AMD is Genetic • More than 50% of all AMD is attributable to genetic factors • Several genes, especially CFH and ARMS2, have been significantly associated with the development of AMD
- 7. The Role of Genetics • Elucidate molecular mechanisms • Create in vitro and animal models • Enable novel mechanism-specific presymptomatic therapies • Identify patient populations for clinical trials of these therapies
- 9. Task Force Recommendation Avoid routine genetic testing for genetically complex disorders like age-related macular degeneration . . . until specific treatment or surveillance strategies have been shown in one or more published clinical trials to be of benefit to individuals with specific disease-associated genotypes. In the meantime, confine the genotyping of such patients to research studies. Ophthalmology. 2012 Nov;119(11):2408-10
- 10. Current AMD genetic tests have not been shown to improve clinical outcome • Less sensitive and specific than clinicians • There is no mechanism-specific therapy available • None of the tests can reliably distinguish between dry AMD and CNV
- 11. ARMS2 Normal vs AMD, p = 1.1 x 10-23 Dry vs CNV, p = 0.29 (NS) High Risk Het Low Risk
- 12. Complement Factor H Normal vs AMD, p = 3.8 x 10-19 Dry vs CNV, p = 0.36 (NS) High Risk Het Low Risk
- 13. PIIR Study (Pepose Institute, Illinois Retina) N. Holekamp, A. Almony, M. MacCumber • 103 subjects were tested for free by two commercial labs: Artic Dx (Macula Risk) and Sequenom (RetnaGene) • 97 subjects had sufficient genotypic and clinical information for comparison • 17/97 were normal controls (avg age 76.9 yrs) • 33/97 had dry AMD (avg age 79.3 yrs) • 47/97 had CNV (avg age 79.3 years)
- 14. Genotyping Errors • Artic Dx failed to detect the CFH H3 haplotype in any patients (this haplotype is present in about 30% of the population). • There were no detectable genotyping errors in the data provided by Sequenom.
- 15. Risk Comparison Method • Patients were assigned a risk rank from 1 (mildest) to 97 (most severe) based on the risk score assigned to them from each company. • These risk ranks were compared to each other and to the clinical phenotype assigned by the investigators.
- 21. Statistics Normal vs AMD Dry vs CNV Company 1 p = 1.4 x 10-5 p = 0.81 (NS) Company 2 p = 2.9 x 10-5 p = 0.74 (NS)
- 22. Conclusions • Avoid routine genetic testing for AMD until specific treatments have been shown in clinical trials to be of benefit to individuals with specific disease-associated genotypes. • For now, the standard clinical examination is more sensitive and specific for detecting treatable disease than any genetic test.