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S.G. Schwartz, S. Gerzenstein, J. Ayala–Haedo, M. Polk, A.S. Venkatraman, C.A. Puliafito, M.E. Fini; Glucocorticoid Receptor Polymorphisms and Corticosteroid–Induced Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):205.
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Elevated intraocular pressure (IOP) is an important complication of intravitreal triamcinolone acetonide (IVTA). The mechanism of IOP elevation is largely unknown. Single nucleotide polymorphisms in the glucocorticoid receptor may play a role. There are 5 identified polymorphisms. The best studied is an AAT to AGT point mutation at cDNA position 1220. This results in an asparagine (Asn) to serine (Ser) substitution at codon 363 in about 6% of the population. This polymorphism may have clinical relevance, as Ser363 carriers demonstrate increased sensitivity to exogenously administered corticosteroids as compared with Asn363 homozygotes.
Patients with a history of glaucoma, iris neovascularization, or pars plana vitrectomy in the study eye were excluded. Baseline IOP was measured prior to IVTA. The glucocorticoid receptor genotype at codon 363 was determined by an investigator masked to the clinical data, using peripheral blood by polymerase chain reaction with restriction fragment length polymorphisms. Patients were followed as clinically indicated, and follow–up IOPs were recorded. The maximum IOP during the follow–up period was determined. Change in IOP was calculated as maximum follow–up IOP minus baseline IOP, with a positive value indicating an increase in IOP.
As of this writing, 15 patients with various retinal diseases requiring IVTA have been prospectively enrolled. Seven patients have completed at least 4 weeks of follow–up (range, 4 to 11) and have had genetic analysis. During the follow–up period, no patient underwent any therapy intended to lower IOP. Of the 7 patients fully studied, mean age was 57 + 18 years (range, 22 to 70). Four (57%) patients were male. The treated eye was OD in 5 (71%) patients and OS in 2 (29%). There were there were 7 Asn363 homozygotes (100%) and 0 Ser363 carriers (0%). Mean baseline IOP was 17.4 + 5.3 mmHg (range, 12 to 27). Mean maximum follow–up IOP was 22.4 + 5.0 mmHg (range, 16 to 29). Mean change in IOP was +5.0 + 4.2 mmHg (range, –3 to +10).
In this small, prospective series, we have thus far been unable to demonstrate a correlation between genotype at codon 363 of the glucocorticoid receptor gene and short–term IOP elevation following IVTA. We have not identified any Ser363 carriers as of this writing. Recruitment continues at this time.
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