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Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study.

ABSTRACT: Three types of open-angle glaucoma (OAG)--primary, pigmentary and pseudoexfoliative--are frequently encountered. The aim of this study was to compare demographic, ocular and systemic medical information collected on people with these three OAG types at diagnosis, and determine if the OAG type affected the prognosis.Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterised their demographic, ocular and medical status at diagnosis. Comparisons were made using analysis of variance and ?(2) or Fisher's exact tests. Multinomial, mixed and logistic regression analyses were also performed.Relative to people with primary OAG, those with pigmentary OAG were younger, more likely to be white, less likely to have a family history of glaucoma, and were more myopic. Those with pseudoexfoliative OAG were older, more likely to be white, more likely to be women, less likely to have bilateral disease, and presented with higher intraocular pressure (IOP) and better visual acuity. The type of glaucoma was not associated with IOP or visual field progression during follow-up.Characteristics of newly diagnosed enrollees differed by the type of OAG. While some of these differences relate to the pathogenesis of OAG type, other differences are noteworthy for further evaluation within population-based samples of subjects with newly diagnosed OAG.

SUBMITTER: Musch DC

PROVIDER: S-EPMC3480313 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study.

Musch David C DC Shimizu Takayuki T Niziol Leslie M LM Gillespie Brenda W BW Cashwell L Frank LF Lichter Paul R PR

The British journal of ophthalmology 20120706 9

<h4>Background/aims</h4>Three types of open-angle glaucoma (OAG)--primary, pigmentary and pseudoexfoliative--are frequently encountered. The aim of this study was to compare demographic, ocular and systemic medical information collected on people with these three OAG types at diagnosis, and determine if the OAG type affected the prognosis.<h4>Methods</h4>Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterised their ...[more]

PMID: 22773091

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Project description:ImportanceRecent studies indicate that alcohol consumption is linked to increased intraocular pressure and higher prevalence of open-angle glaucoma (OAG). However, there is insufficient evidence to establish any correlation between alcohol abstinence and improved outcomes in patients with OAG.ObjectiveTo evaluate the association between alcohol consumption status (and its changes) and risk of incident severe visual impairment (VI) or blindness in patients with newly diagnosed OAG.Design, setting, and participantsThis retrospective, nationwide, population-based cohort study used the Korean National Health Insurance Service's claims and health examination database to enroll patients who were newly diagnosed with OAG between January 1, 2010, and December 31, 2011, and had been alcohol drinkers before their OAG diagnosis. The cohort was followed up until December 2020. The data were analyzed from February to December 2022.ExposuresThe patients were categorized into 2 groups based on their post-OAG diagnosis alcohol consumption status: sustainers and abstainers. The risks of severe VI or blindness were compared using weighted Cox proportional hazards regression models along with inverse probability of treatment weighting.Main outcomes and measuresIncident severe VI or blindness.ResultsAmong 13 643 patients with newly diagnosed OAG (mean [SD] age, 53.7 [11.9] years; 12 066 men [88.4%]) who were drinkers, 2866 (21.0%) quit drinking after the diagnosis. During 91 366 person-years of follow-up, patients abstaining from alcohol after their OAG diagnosis had a lower risk of severe VI or blindness than did those who had sustained drinking (adjusted hazard ratio [AHR] after inverse probability of treatment weighting, 0.63; 95% CI, 0.45-0.87). Among the sustained drinkers, both mild consumption (<105 g/wk; AHR, 1.52; 95% CI, 1.01-2.28) and moderate to heavy consumption (≥105 g/wk; AHR, 1.78; 95% CI, 1.11-2.86) after OAG diagnosis were associated with higher risk of severe VI or blindness relative to abstainers. Frequent drinking (≥4 d/wk) also was associated with a higher risk of severe VI or blindness (AHR, 2.56; 95% CI, 1.52-4.33) compared with abstinence.Conclusions and relevanceIn this cohort study of patients with OAG who were drinkers, abstaining from alcohol after an OAG diagnosis was associated with lower risk of severe VI or blindness. These findings suggest that lifestyle interventions, such as alcohol abstinence, could be essential for patients with newly diagnosed OAG.

Project description:PurposeTo determine the extent of geographic variation in the proportion of patients with newly diagnosed open-angle glaucoma (OAG) undergoing visual field (VF) testing, fundus photography (FP), and other ocular imaging (OOI) among patients residing in different US communities.DesignRetrospective, longitudinal cohort study.ParticipantsAll enrollees with newly diagnosed OAG enrolled in a managed care network between 2001 and 2014.MethodsWe identified all persons in the plan with incident OAG residing in 201 communities across the United States. All communities contributed ≥20 enrollees. The proportion of enrollees undergoing ≥1 VF test, FP, OOI, and no testing of any type in the 2 years after first OAG diagnosis was determined for each community, and comparisons were made to assess the extent of variation in use of diagnostic testing among patients residing in the different communities.Main outcome measuresReceipt of VF testing, FP, OOI, or none of these tests in the 2 years after initial OAG diagnosis.ResultsOf the 56675 enrollees with newly diagnosed OAG, the mean proportion of patients undergoing VF testing within 2 years of initial diagnosis was 74%±7%, ranging from as low as 51% in Rochester, Minnesota, to as high as 95% in Lancaster, Pennsylvania. The mean proportion undergoing OOI was 63%±10% and varied from 34% in Palm Springs/Rancho Mira, California, to 85% in Charleston, South Carolina. The mean proportion receiving FP was 26%±10% and ranged from as low as 3% in Fresno, California, to as high as 57% in Harlingen, Texas. The proportion undergoing no glaucoma testing ranged from 0% in Binghamton, New York, to as high as 35% in 2 other communities.ConclusionsIn many US communities, a high proportion of patients are undergoing testing according to established practice guidelines. However, in several communities, less than 60% of patients with newly diagnosed OAG are undergoing VF testing in the 2 years after initial OAG diagnosis, and in a few communities >1 in 4 patients have no record of glaucoma diagnostic testing of any type. Additional research is needed to understand factors driving this variation in practice patterns and its impact on patient outcomes.

Project description:The total RNA from control and POAG optic nerve lamina cribrosa region was isolated and subjected to analysis on U133A 2.0 affymetrix microarray chip. The results from these two analysis was compared to determine whether PAD II RNA level is altered. Purpose of the study. This study was done to determine which RNA transcripts undergo significant changes in the optic nerve between normal and cadaver primary open-angle glaucoma donors. Using donor tissues from NDRI we have performed proteomic analyses (which will be published shortly), we intend a comparison between the proteomic and RNA changes for select proteins in our study. Sample Collection and Preparation of Labeled Copy RNA; The total RNA from optic nerve was obtained using TRIZOL (Invitrogen Inc., Carlsbad, CA) with modification of recommended protocols. The optic nerve from donor eyes were carefully excised and minced into small pieces first using a scissor and then a scalpel. Prior to use tissue was washed with DEPC water and all solutions were prepared in DEPC water. The minced tissue was placed in a glass homogenizer with 1 ml TRIZOL per 100 mg of tissue and homogenized in a glass homogenizer DUALL 20 (Kimble Kontes Glass Co, Vineland, NJ) with 10 strokes cycles each at room temperature and after freezing with liquid nitrogen for 1 min for 40 cycles. This RNA was extracted with chloroform, isoamylalcohol and precipitated with sodium citrate/sodium chloride and isopropanol. The final air-dried RNA precipitate was suspended in DEPC water and stored in â??80oC prior to use. RNA was prepared for hybridization according to the GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA). The hybridization was performed at Gene Expression Array Core Facility at Case Western Reserve University (www.geacf.net). The RNA sample was cleaned using a column from a Qiagen RNeasy kit, (part # 74104 ) in accordance with the manufacturerâ??s instructions. The volume of DEPC water used to elute the RNA from the Qiagen column was dictated by the nominal mass of the loaded RNA sample. Samples were eluted in 100ml of water, precipitated with 0.5 volume of 7.5M Ammonium Acetate and 2.5 volumes of 100% ethanol at -20oC for 1 hr and centrifuged for 10 min at room temperature. The pellet was drained and washed twice in 500Âµl of 70% ethanol. Supernatant was aspirated. The pellet was dried briefly (less than 1 min) in a speeedvac (Savant) and re-suspended in a small volume (~ 12â??15ml) of DEPC water. A small aliquot (2ml) of the sample was used for quantitation. Cleaned RNA samples were annotated as â??clnRNAâ?? and stored at -20oC. cDNA Synthesis; The protocol recommended by Affymetrix Inc. for cDNA synthesis was used at all times. The reaction was primed by annealing an oligo-dT primer coupled to a T7 RNA polymerase promoter to the RNA sample. Whenever possible, 8 mg of clnRNA were reverse transcribed using Superscript II reverse transcriptase in a 20ml reaction at 42oC for 1 hr. Second strand synthesis was carried out immediately in a total reaction volume of 150ml in the presence of E. coli DNA polymerase I, RNAse H and DNA ligase. The reaction mixture incubated for 2 hrs at 16oC and for a further 5 min in the presence of T4 DNA pol.. The reaction was terminated by the addition of EDTA. The sample was cleaned with a Qiagen cDNA clean-up column according to the manufacturers directions. The elution buffer volume was 14ml. The eluted samples were stored overnight at -20oC. In-Vitro Transcription (IVT) reaction; In a 0.5ml microfuge tube, complementary RNA (cRNA) was generated in an IVT reaction using a BioArray High Yield ENZO kit (Affymetrix). The 40ml reaction contained 10ml of cDNA sample and was incubated at 37oC in the heating block for 4-5hrs. Samples were mixed by flicking, pulse-centrifuged and returned to the incubator once every 40 minutes. Upon completion of the reaction, IVT samples were adjusted to a volume of 100ml with DEPC-treated water and cleaned using Qiagen RNA clean-up columns. Samples were eluted in 45ml of DEPC-treated water. A 2ml-aliquot was used for quantitation. Corrected concentrations of cRNA (minus the input clnRNA) were determined. A standard fragmentation reaction volume was 40ml in a 0.5 ml microfuge tube and used 20mg of overall IVT RNA in 1X fragmentation buffer (40mM Tris acetate, pH 8.1, 100mM KOAc, 30mM MgOAc). The reaction was incubated at 94oC for 35min in a heat block. After the 35 min incubation the fragmented samples were placed on ice. The standard hybridization cocktail volume was 300ml. 150ml of 2X hybridization buffer was added (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20) Herring sperm and acetylated BSA were added to a final concentration of 0.1 and 0.5mg/ml respectively. The amount of fragmentation reaction containing 15mg of cRNA was added to the cocktail and the remaining volume was made up with molecular biology grade water. A 15ml aliquot of a 20X mixture of in-vitro transcripts of bacterial genes BioB BioC BioD and cre as external controls (spikes) were added to the cocktail to give final concentrations of 1.5, 5, 25 and 100pM respectively. Control oligonucleotide (5ml) was added to a final concentration of 50pM. Array Hybridization; Sample Hyridization cocktails (300ml) were removed from storage at â??20oC and thawed in a 45oC temperature block. The samples were incubated at 45oC for 5 min, incubated at 45oC for 5 min and then centrifuged at 15,000g for 5 min. This study used commercially available Affymetrix HG U133A 2.0 arrays only. These are in situ synthesized, high density oligonucleotide arrays which can interrogate 22,777 gene entities. The part number is 900444 more detailed information may be found at www.affymetrix.com website. Meanwhile, the affymetrix chip arrays were taken from their storage at 4oC and allowed to come to room temperature. The chamber was filled with 1X hybridization buffer (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20). The chip was then preconditioned by incubation in the hybridization oven at 45oC for 10 min. The chip was removed and the chamber drained. Sample cocktails (200ml) were then introduced into the chamber of the chips. The ports were sealed with tough-spots stickers and placed in the hybridization oven and incubated at 45oC with rotation overnight. Next day (16hr later), the incubation was terminated and the chips removed from the oven. Samples were retrieved from the chips and stored again in a freezer at -20oC. The chips were filled with buffer A and placed in a module of Fluidics 400 wash station. The chips were subjected to the Affymetrix â??EuKws4 ver 2â?? programmed series of stringent post hybridization washes, staining and post-staining washes in accordance with Affy protocols. Upon completion of the wash series (approximately 2 hrs), the chips were removed from the Fluidics station. The chips were inspected. Chips were scanned using an Agilent Gene Array scanner 3000 driven by Affymetrix GCOS software. Generation of Expression Values; Microarray Suite, version 5 (Affymetrix), was used to generate *.cel files, and a computer program (Probe Profiler, ver. 1.3.11; Corimbia Inc., Berkeley, CA) developed specifically for the GeneChip system (Affymetrix) was used to convert intensity data into quantitative estimates of gene expression for each probe set. The software identifies informative probe pairs, and down-weights the signal contribution of probe pairs that are subject to differential cross-hybridization effects or that consistently produce no signal. The software also detects and corrects for saturation artifacts, outliers, and chip defects. A probability statistic was generated for each probe set. The probability is associated with the null hypothesis that the expression level of the probe set is equal to zero (background). Genes not significantly expressed above background in any of the samples (P > 0.05) were

Dataset Information

Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study.

Publications

Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study.

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