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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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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.
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).
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.
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.
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