Search

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63-0.75], p = 1.86×10⁻¹⁸), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21-1.43], p = 3.87×10⁻¹¹). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50-0.67], p = 1.17×10⁻¹²) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53-0.72], p = 8.88×10⁻¹⁰). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.

DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI -1.1-12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

Purpose. To evaluate potential risk factors for developing tube shunt exposure in glaucoma patients. Patients and Methods. Forty-one cases from 41 patients that had tube shunt exposure from 1996 to 2005 were identified from the Robert Cizik Eye Clinic and Bascom Palmer Eye Institute. Each case was matched with 2 controls of the same gender and with tube shunts implanted within 6 months of the index case. Conditional logistic regression was used to determine risk factors. Results. The study cohort includes a total of 121 eyes from 121 patients. The mean age was 63.6 ± 19.7 years, ranging from 1 to 96 years. The average time to exposure was 19.29 ± 23.75 months (range 0.36–85.74 months). Risk factors associated with tube exposure were Hispanic ethnicity (P=0.0115; OR = 3.6; 95% CI, 1.3–9.7), neovascular glaucoma (P=0.0064; OR = 28.5; 95% CI, 2.6–316.9), previous trabeculectomy (P=0.0070; OR = 5.3; 95% CI, 1.6–17.7), and combined surgery (P=0.0381; OR = 3.7; 95% CI, 1.1–12.7). Conclusions. Hispanic ethnicity, neovascular glaucoma, previous trabeculectomy, and combined surgery were identified as potential risk factors for tube shunt exposure. These potential risk factors should be considered when determining the indication for performing tube shunt implantation and the frequency of long-term followup.

Abstract Optical coherence tomography (OCT) has moved to the forefront of imaging modalities in the management of glaucoma and retinal diseases. It is modifying how glaucoma and glaucoma progression are diagnosed clinically and augmenting our understanding of the disease. OCT provides multiple parameters from various anatomic areas for glaucoma diagnosis, evaluation of treatment efficacy, and progression monitoring. While the use of multiple parameters has increased the likelihood of detecting early structural changes, diagnosing glaucoma in early stages is often challenging when the damages are subtle and not apparent on OCT scans, in addition to the fact that assessment of OCT parameters often yields conflicting findings. One promising approach is to combine multiple individual parameters into a composite parameter from the same test to improve diagnostic accuracy, sensitivity, and specificity. This review presents current evidence regarding the value of spectral domain OCT composite parameters in diagnosing early glaucoma.

AIM: To evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma.METHODS: The medical records of 92 eyes (89 patients) that underwent PPV-BGI were retrospectively reviewed, including 43 eyes with neovascular glaucoma (NVG) and 49 eyes with other types of glaucoma (non-NVG).RESULTS: Outcome measures were visual acuity (VA), intraocular pressure (IOP), glaucoma medical therapy, complications, and success [VA>hand motions (HM), IOP≥6 mm Hg and ≤21 mm Hg, no subsequent glaucoma surgery]. Cumulative success rates for the non-NVG group and NVG group were 79% and 40% at 1y, respectively (P=0.038). No difference in the rates of surgical success were found between pars plana and anterior chamber tube placement. Preoperative IOP (mean±SD) was 30.3±11.7 mm Hg in the Non-NVG group and 40.0±10.6 mm Hg in the NVG group, and IOP was reduced to 15±9.5 mm Hg in the non-NVG group and 15±10.5 mm Hg in the NVG at 1y. Number of glaucoma medications (mean±SD) decreased from 2.7±1.3 in the non-NVG group and 2.8±1.3 in the NVG group preoperatively to 0.76±1.18 in the non-NVG group and 0.51±1.00 in the NVG group at 1y. Improvement in VA of ≥2 Snellen lines was observed in 25 (27%) eyes, although only 33% of non-NVG eyes and 2.3% of NVG eyes maintained VA better than 20/200 at 1y. Nonclearing vitreous hemorrhage was the most common postoperative complication occurring in 16 (17%) eyes, and postoperative suprachoroidal hemorrhages developed in 5 (5.4%) eyes.#$NLCONCLUSION: PPV-BGI is a viable surgical option for eyes with refractory glaucoma, but visual outcomes are frequently poor because of ocular comorbidities, especially in eyes with NVG. The location of tube placement does not influence surgical outcome and should be left to the discretion of the surgeon.