May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Possible Pharmacogenomic Associations With Intraocular Pressure Response Following Intravitreal Triamcinolone Acetonide
Author Affiliations & Notes
  • S. G. Schwartz
    Bascom Palmer Eye Institute, Univ of Miami Miller Sch of Medicine, Naples, Florida
  • M. E. Fini
    Bascom Palmer Eye Institute, Univ of Miami Miller Sch of Medicine, Miami, Florida
  • M. T. Pletcher
    Translational Research Institute, The Scripps Research Institute-Scripps Florida, Jupiter, Florida
  • S. Gerzenstein
    Bascom Palmer Eye Institute, Univ of Miami Miller Sch of Medicine, Miami, Florida
  • Miami Pharmacogenomics Team
    Bascom Palmer Eye Institute, Univ of Miami Miller Sch of Medicine, Naples, Florida
  • Footnotes
    Commercial Relationships  S.G. Schwartz, University of Miami, P; M.E. Fini, University of Miami, P; M.T. Pletcher, None; S. Gerzenstein, None.
  • Footnotes
    Support  American Health Assistance Foundation, Prevent Blindness America, NIH P30-EY014801, and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5612. doi:
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    • Get Citation

      S. G. Schwartz, M. E. Fini, M. T. Pletcher, S. Gerzenstein, Miami Pharmacogenomics Team; Possible Pharmacogenomic Associations With Intraocular Pressure Response Following Intravitreal Triamcinolone Acetonide. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5612.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The phenomenon of increased intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem with a poorly understood etiology. We sought possible pharmacogenomic associations in an attempt to predict the steroid response for individual patients.

Methods: : A small DNA bank was created using peripheral blood samples from 53 patients treated with IVTA for a variety of retinal diseases. IOP was measured at baseline and at each subsequent visit for up to 1 year, or until the eye was treated with intraocular surgery, another intravitreal injection, or any medical therapy intended to lower IOP. We defined ΔIOP as the highest post-injection IOP minus the baseline IOP, with a positive value indicating a rise in IOP following IVTA. The peripheral blood samples were subjected to genome-wide DNA screening using the GeneChip® Human Mapping 500K Array Set (Affymetrix, Santa Clara, CA).

Results: : Over 440,000 genes were screened. Forty-eight different single nucleotide polymorphisms (SNPs) within 33 genes were found to correlate (p<0.001) with magnitude of ΔIOP following IVTA. The strongest association involves a SNP within an as-yet poorly described G-protein coupled receptor (p=3.05x10-8). Four individual SNPs within a single transporter gene were identified (p between 5.59x10-4 and 2.81x10-5). Other genes with multiple SNPs included a translation elongation factor, an F-box protein, an oxysterol binding protein, and a solute carrier family gene. One group of 18 SNPs (FDR-corrected p=0.000709) divided the 53 samples into two groups, one containing the samples with the two highest ΔIOPs and one containing the other 51 samples.

Conclusions: : With this small, pilot DNA bank study, we have identified several novel SNPs which appear to correlate with magnitude of IOP response following IVTA to a highly statistically significant degree. Further studies are necessary to validate these associations and to identify the relevant genes. However, these data may indicate a potential future ability to predict IOP elevation following IVTA for individual patients.

Keywords: gene screening • corticosteroids • clinical (human) or epidemiologic studies: outcomes/complications 
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