Long-Term Incidence And Timing Of Intraocular Hypertension After Intravitreal Triamcinolone Acetonide Injection

Purpose: To describe the long-term incidence and timing of steroid-induced ocular hypertension after intravitreal triamcinolone acetonide (IVTA) therapy. Design: Retrospective case series of 929 eyes of 841 patients. Participants: Patients with a variety of posterior segment disorders in a single group practice. Intervention: Pars plana injection of IVTA. Main Outcome Measures: Intraocular pressure (IOP) and requirement for glaucoma surgery. Results: Overall, 929 eyes received ≥1 injections (mean, 1.6) of 4 mg of IVTA. During a mean follow-up period of 14±6.9 months, the Kaplan-Meier cumulative incidences of IOP elevations \u3e21 mmHg at 6, 12, 18, and 24 months post-injection were 28.2%, 34.6%, 41.2%, and 44.6%, respectively; similarly, the incidences of eyes with IOP measurements \u3e25 mmHg were 14.6%, 19.1%, 24.1%, and 28.2%, respectively. At the same time points, lOP-lowering medications were required byl3.0%, 16.9%, 20.7%, and 24.2% of eyes, respectively. Only 3 eyes (0.3%) required lOP-lowering surgery. Preexisting glaucoma, younger age, and a history of an IOP elevation after a previous IVTA injection were risk factors for IOP elevations after IVTA injection. The minimum and maximum follow-up were 3 weeks and 37 months. The mean rate of attrition in this study was 3% per month. Conclusions: Elevations in IOP after IVTA injection are common. Younger patients and eyes with preexisting glaucoma or a history of a steroid response should be monitored more closely for IOP elevations after IVTA therapy

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society

Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED)

Estrogen pathway polymorphisms in relation to primary open angle glaucoma: An analysis accounting for gender from the United States

Purpose Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender. Methods: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP 0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01). Conclusions: The estrogen SNP pathway was associated with POAG among women

CDKN2B-AS1 Genotype–Glaucoma Feature Correlations in Primary Open-Angle Glaucoma Patients From the United States

To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients

Hypothesis-independent pathway analysis implicates GABA and Acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets

Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets

Purpose Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters.

Funder: All funders per study are acknowledged in the Supplementary FileA new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH