Electrophysiological and Genetic Aspects of Age-Related Macular Degeneration (AMD): Treatment Implications

  • Author / Creator
    Dimopoulos, Ioannis
  • Age-related macular degeneration (AMD) is considered a heterogeneous group of disorders. Although many genes influence susceptibility to disease, none has shown to be the primary contributor. To identify genetic contributors, distinct AMD phenotypes need to be established. We relied on electrophysiological testing (ERG) to detect homogeneous subgroups for future genotype-phenotype association studies. We also classified AMD patients based on refractoriness to anti-VEGF treatment to investigate genetic associations with known high-risk single nucleotide polymorphisms (SNPs). Our results suggest that generalized cone dysfunction and delayed rod phototransduction activation characterizes a subset of AMD patients, while impaired dark adaptation constitutes a universal feature of the disease. We were unable to unify all patients unresponsive to anti- VEGF monotherapy under a single SNP haplotype, highlighting the genetic complexity underlying the disorder and its treatment prediction. By applying a novel approach to investigate potential pharmacogenetic interactions, we provided evidence that variation in multiple susceptibility loci may better explain differential response to anti-VEGF therapy. Treatment with prolonged VEGF blockade was found to result in inner retina dysfunction in a subset of AMD patients. Therefore, pharmacogenetic research holds promise in developing individualized approaches for AMD treatment in the future, which will not only optimize final patient outcome, but also reduce the risk of adverse effects.

  • Subjects / Keywords
  • Graduation date
    Fall 2014
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.