Identification of systemic risk factors and genetic biomarkers for intravitreal steroid induced ocular hypertension

Abstract

Initially, to determine the incidence and risk factors associated with newlineSI-OHT in the Indian population, a retrospective study was performed to newlineinvestigate the steroid response upon 1549 TA and Dex administrations in newline1075 eyes of 897 patients at a tertiary ophthalmic hospital, Chennai, India. newlineIOP values were extracted from the hospital s electronic medical records newline(EMR) before steroid administration (baseline IOP), day-1, month-1, month- newline3, and month-6 post injections. Glaucoma patients and suspects, uveitis, newlinetrauma cases were excluded from the study. Patients were categorized as newlinesteroid-responders (SR): IOP and#8804; 21mmHg and steroid non-responders (NR): newlineIOP and#8804; 20mmHg based on the IOP values. The incidence rate, the time and newlinemagnitude of the IOP rise, and treatment details were compared between TASR newlineand Dex-SR cohorts. Ocular and systemic parameters associations with newlineSI-OHT were compared between SR and NR of TA-treated and Dex-treated newlinegroups. Further, to identify the genetic and molecular determinants associated newlinewith SI-OHT, blood samples were collected from 66- TA and 60-Dex treated newlinesubjects after obtaining informed consent. Plasma and DNA samples were newlineisolated. An enzyme-linked immunosorbent assay (ELISA) was performed to newlineidentify the role of eight circulatory inflammatory cytokines in SI-OHT newlineprogression from the isolated plasma samples. Further, the genetic newlinedeterminants associated with SI-OHT were identified based on genotyping of newlineknown SNPs identified among Caucasian subjects and the GWAS for novel newlineSNP identification identification among Indian subjects. Thereby a newlinepreliminary validation study for the 48 SNPs identified from the Caucasian newlinepopulation was performed among TA (n=54) and Dex (n=47) treated Indian newlinepatients. In this analysis, the genotypic frequencies were calculated and a newlinesignificant association with OHT was compared between the following newlinegroups; a) steroid-treated versus reference healthy controls; b) SR versus NR; newlinec) influence of time, severity, and gender on IOP rise. newline