Abstract
Purpose :
Age-related macular degeneration (AMD) is a multifactorial disease with known genetic associations. The ability to forecast morphological changes and treatment response based on genetic and clinical risk factors would be a valuable tool for clinicians. This study evaluated the association between the number of risk alleles for AMD and drusen volume change over two years in a group of AMD subjects taking curcumin.
Methods :
Participants were recruited from the office of Zaparackas and Knepper, Ltd. in Chicago, IL after IRB approval and informed consent. All participants (n=17) had drusen ≥63 µm without geographic atrophy or choroidal neovascularization. Participants took oral curcumin (2.66 g/day) and were imaged using OCT for a period of two years. Drusen were categorized by width as 63-124 µm, 125-249 µm, and ≥250 µm. Genetic samples were analyzed by Arctic Medical Laboratories (Grand Rapids, MI). AMD risk alleles evaluated included C2, C3, CFB, CFH (rs412852, rs3766405, rs1048663), CFI, ABCA1, APOE, ARMS2, CETP, COL8A1, LIPC, and TIMP3. Drusen volume was measured in mm3. Pearson’s correlations were used to assess the associations between number of AMD risk alleles and change in drusen volume during the study.
Results :
A lower number of overall risk alleles (r=0.65, p=0.009) and of complement system risk alleles (r=0.68, p=0.005) was correlated with a larger decrease in drusen volume after two years. Individually, a lower number of ARMS2 (r=0.55, p=0.04) and CFH rs3766405 (r=0.61, p=0.02) risk alleles was correlated with a larger decrease in volume. A high-risk genetic profile composed of the number of risk alleles for ARMS2, CFH rs412852, CFH rs3766405, C3, and CFI significantly predicted smaller changes in volume over time (r=0.75, p=0.001). The number of risk alleles overall, in complement system genes, and in ARMS2 and CFH were correlated with volume change in drusen 125-249 µm and ≥250 µm but not in drusen 63-124 µm.
Conclusions :
The response of drusen to curcumin supplementation is associated with the genetic profile of the patient. A higher number of certain risk alleles is associated with a worse response to curcumin. This explains the variable responses of AMD patients to supplementation with other antioxidants such as AREDS.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.