Dataset Information

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

ABSTRACT:

Purpose

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG).

Design

Secondary analyses using longitudinal data from 2 randomized controlled trials.

Participants

A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Methods

Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements.

Main outcome measures

Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression.

Results

Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001).

Conclusions

Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management.

SUBMITTER: Schell GJ

PROVIDER: S-EPMC4495761 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

Schell Greggory J GJ Lavieri Mariel S MS Helm Jonathan E JE Liu Xiang X Liu Xiang X Musch David C DC Van Oyen Mark P MP Stein Joshua D JD

Ophthalmology 20140404 8

<h4>Purpose</h4>To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG).<h4>Design</h4>Secondary analyses using longitudinal data from 2 randomized controlled trials.<h4>Participants</h4>A total of 571 participants from the Advanced Glaucoma Inter ...[more]

PMID: 24704136

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Project description:PurposeTo generate personalized forecasts of how patients with open-angle glaucoma (OAG) experience disease progression at different intraocular pressure (IOP) levels to aid clinicians with setting personalized target IOPs.DesignSecondary analyses using longitudinal data from 2 randomized controlled trials.ParticipantsParticipants with moderate or advanced OAG from the Collaborative Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention Study (AGIS).MethodsBy using perimetric and tonometric data from trial participants, we developed and validated Kalman Filter (KF) models for fast-, slow-, and nonprogressing patients with OAG. The KF can generate personalized and dynamically updated forecasts of OAG progression under different target IOP levels. For each participant, we determined how mean deviation (MD) would change if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or 24 mmHg) over the next 5 years. We also model and predict changes to MD over the same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the level attained in the trials.Main outcome measuresPersonalized estimates of the change in MD under different target IOP levels.ResultsA total of 571 participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same target IOPs and time frame. When using our tool to quantify the OAG progression dynamics for all 571 patients, we found no statistically significant differences over 5 years between progression for black versus white, male versus female, and CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all).ConclusionsTo our knowledge, this is the first clinical decision-making tool that generates personalized forecasts of the trajectory of OAG progression at different target IOP levels. This approach can help clinicians determine appropriate, personalized target IOPs for patients with OAG.

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

Project description:ImportanceGlaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients.ObjectiveTo summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews.Data sourcesThe Cochrane Database of Systematic Reviews including studies published before June 1, 2021.Study selectionReviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy.Data extraction and synthesisData were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted.Main outcomes and measuresThe proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up.ResultsSix eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results.Conclusions and relevanceBased on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.

Dataset Information

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

Similar Datasets

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