Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.

AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. RESULTS: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. DISCUSSION: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Fixed-combination brinzolamide 1%/brimonidine 0.2% vs monotherapy with brinzolamide or brimonidine in patients with open-angle glaucoma or ocular hypertension: results of a pooled analysis of two phase 3 studies.

PURPOSE: To describe pooled efficacy and safety data from two phase 3 studies comparing brinzolamide 1%/brimonidine 0.2% fixed combination (BBFC) with its component medications, brinzolamide and brimonidine, in patients with open-angle glaucoma or ocular hypertension. METHODS: Data were pooled from two nearly identical clinical trials comparing BBFC with its component medications, each given three times daily. The 3-month efficacy outcome was mean intraocular pressure (IOP) at 0800, 1000, 1500, and 1700 hours. Safety outcomes included adverse events (AEs), best-corrected visual acuity, examination of ocular structures, pachymetry, perimetry, and vital signs. RESULTS: A total of 1350 patients were enrolled and included in this analysis (BBFC, n=437; brinzolamide, n=458; brimonidine, n=455). Baseline mean IOP levels were similar among the three treatment groups. At 3 months, mean IOP of the BBFC group was significantly lower than that of either monotherapy group (P<0.0001) at all the four time points. A total of 272 patients (20.1%) experienced at least one treatment-related AE (BBFC, 24.6%; brinzolamide, 18.7%; brimonidine, 17.4%), the majority of which were ocular AEs. One serious AE, moderate intensity chest pain, was considered related to brinzolamide treatment and resulted in study discontinuation. CONCLUSIONS: This analysis strengthens the conclusions drawn from the two individual phase 3 studies showing that, in patients with open-angle glaucoma or ocular hypertension, BBFC had significantly superior IOP-lowering activity compared with either brinzolamide or brimonidine alone and a safety profile consistent with that of its individual components.

Anterior uveitis associated with latanoprost.

PURPOSE: To report the association of anterior uveitis with the use of latanoprost. METHODS: We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug. RESULTS: The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes. CONCLUSION: There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

Observer sensitivity to retinal vessel diameter and tortuosity in retinopathy of prematurity: a model system.

BACKGROUND: Abnormally increased diameter and tortuosity of retinal blood vessels in the posterior pole, or "plus disease," is recognized as a powerful predictor of poor outcome in eyes with retinopathy of prematurity (ROP). Although the diagnosis of plus disease depends upon the examiner's ability to examine retinal blood vessels, the ability of the human observer to identify changes in retinal blood vessel diameter and tortuosity accurately has not been studied. METHODS: Using computer-aided analysis of fundus photographs from eyes with a wide range of ROP severity, we generated tracings of posterior pole blood vessels which varied by quintiles of mean vessel diameter and tortuosity. Subjects (23 naive and 12 expert observers) ranked groups of tracings in order of increasing mean vessel diameter and tortuosity. These ranking tests were performed on tracings derived from the same fundus and tracings derived from distinct fundi. In a similar fashion, subjects also compared one designated standard fundus tracing with 25 distinct fundus tracings. RESULTS: Vessel diameter was assessed correctly more often than vessel tortuosity, both among similar (> 99% vs 92% of the time, respectively, P < 0.001), or among distinct (88% vs 78% of the time, respectively, P < 0.001) fundus images. The mean vessel diameter and tortuosity of 25 distinct fundus images were correctly ranked versus a standard image in 89% of attempts. Assessments of increments in vessel diameter and tortuosity were independent. Naive and expert subjects performed indistinguishably on all tests. CONCLUSIONS: Intelligent human observers have considerable ability to discern clinically relevant increments in blood vessel diameter and tortuosity. This ability may facilitate standardization in the diagnosis of plus disease in ROP.

Interruption in the medical interaction.

OBJECTIVES: To describe patterns of interruption in the physician-patient interaction; specifically, to determine who interrupts, to determine if a shift in control occurs as a result of interruption, and to characterize the information gained when patients interrupt physicians. DESIGN: Observational. SETTING: Community-based primary care practices in North Carolina. SUBJECTS: Internists and family physicians in private practice in North Carolina (six men and two women) and their patients (13 men and 27 women). INTERVENTIONS: None. MAIN OUTCOME MEASURE: The obtainment of control of the interaction, at least momentarily, as a result of interruption. RESULTS: Analysis of 40 audiotaped interactions revealed 833 interruptions (mean +/- SD, 20.8 +/- 12.2 per interaction): Patients initiated 55% of all interruptions. Physicians and patients each gained control of the conversation after 50% of interruptions. Patients gained control after 74% of patient-initiated interruptions, and physicians gained control after 79% of physician-initiated interruptions. Patients were more likely to gain control by interrupting late in the interaction, and 75% of patient-initiated interruptions resulted in new information (solicited and unsolicited) being contributed to the interaction. CONCLUSION: Interruption by patients can be an informative event.