Dataset Information

Association of Baseline Characteristics and Early Vision Response with 2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT).

ABSTRACT:

Purpose

To evaluate the association of baseline characteristics and early visual acuity (VA) response with visual outcomes at years 1 or 2 in the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT).

Design

Secondary analysis of CATT.

Participants

The 1185 CATT participants with baseline VA of 20/25 to 20/320.

Methods

Participants were assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of baseline characteristics and early VA response (week 4 or 12) with VA response at years 1 or 2 were assessed by R(2) from linear regression analyses. Patients who had a poor initial response (VA 20/40 or worse with persistent fluid and without ≥1-line VA gain) were defined as candidates for changing treatment.

Main outcome measures

Visual acuity change from baseline.

Results

Statistically significant (P < 0.05) baseline predictors for less VA gain at year 2 were older age, VA of 20/40 or better, larger choroidal neovascularization area, presence of geographic atrophy, total foveal thickness ≤325 μm or ≥425 μm, and elevation of retinal pigment epithelium. Among 176 eyes gaining ≥3 lines at week 12, 78% had a ≥3-line gain at year 2, whereas among 113 eyes losing ≥1 line at week 12, 27% improved to a ≥1-line gain at year 2. Visual acuity response at week 12 was more predictive of VA response at year 2 (R(2) = 0.30) than VA response at week 4 (R(2) = 0.17) and baseline predictors (R(2) = 0.13; P < 0.0001). Among 126 candidates for changing treatment drug at week 12, mean VA improved by 2.8 letters (P = 0.050), mean total retinal thickness decreased 53 μm (P < 0.0001), and fluid resolved in 33% (P < 0.0001) between week 12 and year 1 with continued use of the same drug and regimen. Similar improvements were observed among 83 candidates for changing drugs at week 24.

Conclusions

Visual acuity response at week 12 is more predictive of 2-year vision outcomes than either several baseline characteristics or week 4 response. Eyes with poor initial response may benefit from continued treatment without switching to another drug.

SUBMITTER: Ying GS

PROVIDER: S-EPMC4658285 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Baseline Characteristics and Early Vision Response with 2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT).

Ying Gui-shuang GS Maguire Maureen G MG Daniel Ebenezer E Ferris Frederick L FL Jaffe Glenn J GJ Grunwald Juan E JE Toth Cynthia A CA Huang Jiayan J Martin Daniel F DF

Ophthalmology 20150915 12

<h4>Purpose</h4>To evaluate the association of baseline characteristics and early visual acuity (VA) response with visual outcomes at years 1 or 2 in the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT).<h4>Design</h4>Secondary analysis of CATT.<h4>Participants</h4>The 1185 CATT participants with baseline VA of 20/25 to 20/320.<h4>Methods</h4>Participants were assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of baseline characteristi ...[more]

PMID: 26383996

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Project description:PurposeTo evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD.DesignClinical trial.ParticipantsEight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers.MethodsEach patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA).Main outcomes measuresGenotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P≤0.01 was considered statistically significant.ResultsNo statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing.ConclusionsAlthough specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.

Project description:PurposeTo determine baseline predictors of visual acuity (VA) outcomes at 5 years after initiating treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).DesignSecondary analysis of data from a cohort study.ParticipantsPatients enrolled in the Comparison of AMD Treatments Trials (CATT) who completed a 5-year follow-up visit.MethodsParticipants were randomly assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After two years, patients were released from the clinical trial protocol, and were recalled for examination at 5 years. Trained readers evaluated baseline lesion features, fluid and thickness. Baseline predictors were determined using univariate and multivariate regression analysis.Main outcome measuresVA score and change from baseline, ≥3-line gain, and VA 20/200 or worse at 5 years.ResultsAmong 647 patients with VA measured at 5 years, mean VA score in the study eye was 58.9 letters (≈20/63), mean decrease from baseline was 3.3 letters, 17.6% eyes gained ≥3 lines, and 19.9% had VA of 20/200 or worse. In multivariate analysis, worse baseline VA was associated with worse VA, more VA gain, higher percentage with ≥3-line gain, and higher percentage with 20/200 or worse at 5 years (all p<0.001). Larger baseline CNV lesion area was associated with worse VA, greater VA loss, and higher percentage with 20/200 or worse at 5 years (all p<0.05). Absence of baseline subretinal fluid was associated with worse VA (p=0.03) and more VA loss (p=0.03). Female gender, bevacizumab treatment in the first 2 years, and absence of RPE elevation were associated with higher percentage with ≥3-line gain. Cigarette smoking was associated with a higher percentage with 20/200 or worse. None of the 21 SNPs evaluated were associated with VA outcomes.ConclusionsFive years after initiating treatment with ranibizumab or bevacizumab in CATT participants, worse baseline VA, larger baseline CNV lesion area, and presence of baseline RPE elevation remained independently associated with worse VA at 5 years. In addition, male gender, cigarette smoking, absence of subretinal fluid and treatment with ranibizumab in the first 2 years were independently associated with worse vision outcomes at 5 years.

Project description:PurposeTo determine the prevalence of, risk factors for, and visual acuity (VA) correlations with outer retinal tubulation (ORT) seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) after anti-vascular endothelial growth factor (VEGF) therapy.DesignProspective cohort study within a randomized clinical trial.ParticipantsPatients with SD OCT images at weeks 56 and 104 in the Comparison of AMD Treatments Trials (CATT).MethodsParticipants in the CATT were assigned randomly to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a monthly or pro re nata (PRN) injection-dosing regimen. A subset of eyes was imaged with SD OCT beginning at week 56. Cirrus 512×128 or Spectralis 20°×20° volume cube scan protocols were used to acquire SD OCT images. Two independent readers at the CATT OCT reading center graded scans, and a senior reader arbitrated discrepant grades. The prevalence of ORT, identified as tubular structures seen on at least 3 consecutive Cirrus B scans or 2 consecutive Spectralis B scans, was determined. The associations of patient-specific and ocular features at baseline and follow-up with ORT were evaluated by univariate and multivariate analyses.Main outcome measuresOuter retinal tubulations.ResultsSeven of 69 eyes (10.1%) at 56 weeks and 64 of 368 eyes (17.4%) at week 104 had ORTs. Absence of diabetes, poor VA, blocked fluorescence, geographic atrophy, greater lesion size, and presence of subretinal hyperreflective material at baseline were associated independently with greater risk of ORT at 104 weeks (P < 0.05). Neither drug nor dosing regimen were associated significantly with ORT. The mean VA of eyes with ORT at week 104 (58.5 Early Treatment Diabetic Retinopathy Study letters) was worse than the mean VA of eyes without ORT (68.8 letters; P < 0.0001).ConclusionAt 2 years after initiation of anti-VEGF therapy for neovascular AMD, ORTs are present in a substantial proportion of eyes. We identified baseline features that independently predict ORTs. It is important to identify ORTs because eyes with ORTs have worse VA outcomes than those without this finding.

Project description:PurposeTo apply machine learning models for predicting the number of pro re nata (PRN) injections of antivascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD) in two years in the Comparison of AMD (age-related macular degeneration) Treatments Trials.MethodsThe data from 493 eligible participants randomized to PRN treatment of ranibizumab or bevacizumab were used for training (n = 393) machine learning models including support-vector machine (SVM), random forest, and extreme gradient boosting (XGBoost) models. Model performances of prediction using clinical and image data from baseline, weeks 4, 8, and 12 were evaluated by the area under the receiver operating characteristic curve (AUC) for predicting few (≤8) or many (≥19) injections, by R2 and mean absolute error (MAE) for predicting the total number of injections in two years. The best model was selected for final validation on a test dataset (n = 100).ResultsUsing training data up to week 12, the models achieved AUCs of 0.79-0.82 and 0.79-0.81 for predicting few and many injections, respectively, with R2 of 0.34-0.36 (MAE = 4.45-4.58 injections) for predicting total injections in two years from cross-validation. In final validation on the test dataset, the SVM model had AUCs of 0.77 and 0.82 for predicting few and many injections, respectively, with R2 of 0.44 (MAE = 3.92 injections). Important features included fluid in optical coherence tomography, lesion characteristics, and treatment trajectory in the first three months.ConclusionsMachine learning models using loading dose phase data have the potential to predict two-year anti-VEGF demand for nAMD and quantify feature importance for these predictions.Translational relevancePrediction of anti-VEGF injections using machine learning models from readily available data, after further validation on independent datasets, has the potential to help optimize treatment protocols and outcomes for nAMD patients in an individualized manner.

Project description:PurposeTo compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs.DesignProspective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).ParticipantsPatients with NVAMD.MethodsReading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features.Main outcome measuresVisual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years.ResultsRetinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P < 0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 μm vs. -161 μm; P < 0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P < 0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025).ConclusionsAt both 1 and 2 years after initiation of anti-VEGF treatment in CATT, eyes with RAP were less likely to have fluid, FA leakage, scar, and SHRM and more likely to have GA than eyes without RAP. Mean improvement in VA was similar at 2 years.

Project description:ImportanceRetinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated.ObjectiveTo determine the incidence and progression of non-GA (NGA) and associated risk factors.Design, setting, and participantsThis study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019.InterventionsParticipants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Participants were treated according to best medical judgement thereafter.Main outcomes and measuresIncidence of nAMD-associated NGA (hypopigmentation and hyperpigmentation in color images) and progression; adjusted risk ratios (aRR) for baseline characteristics.ResultsAmong 1107 participants, risk of NGA was 35% (391 eyes), 59% (246 eyes), and 81% (122 eyes) at 1, 2, and 5 years, respectively. Risk factors for NGA included worse visual acuity (20/200-20/320: aRR, 1.74 [95% CI, 1.24-2.43], compared with ≤20/40; P = .006), larger neovascularization area (>4 disc areas: aRR, 1.31 [95% CI, 1.01-1.71], compared with ≤1 disc areas; P = .007), switched drug regimen (aRR, 1.28 [95% CI, 1.06-1.54], compared with as-needed injections; P = .02), and single-nucleotide variants Age-Related Maculopathy Susceptibility 2 (ARMS2) (TT variant: relative risk [RR], 1.53 [95% CI, 1.22-1.93]; P = .001) and HtrA Serine Peptidase 1 (HTRA1) (AG variant: RR, 1.23 [95% CI, 1.01-1.48]; AA variant: RR, 1.51 [95% CI, 1.20-1.91]; P = .002). Sub-retinal pigment epithelium thickness was protective (>275 μm: aRR, 0.59 [95% CI, 0.46-0.75], compared with ≤75 μm; P < .001). Among 389 eyes with NGA by 2 years and subsequent color images, risk of progression to GA was 29%, 43%, and 50% at 1, 3, and 4 years, respectively. Risk factors for progression to GA included worse visual acuity (20/200-20/320: aRR, 2.75 [95% CI, 1.54-4.93], compared with ≤20/40; P < .001), worse fellow-eye visual acuity (<20/40: aRR, 1.77 [95% CI, 1.12-2.79], compared with ≥20/40; P = .01), fellow-eye GA (aRR, 1.71 [95% CI, 1.06-2.75]; P = .03), and pseudodrusen in either eye (aRR, 1.65 [95% CI, 1.17-2.34]; P = .005). Subretinal fluid was associated with a decreased risk of progression (aRR, 0.42 [95% CI, 0.28-0.63]; P < .001).Conclusions and relevanceIn this study, after 2 years of protocol-guided anti-vascular endothelial growth factor treatment for nAMD, more than half of the eyes in the study developed NGA in the location of nAMD. After 3 additional years of regular care, half of them progressed to GA.Trial registrationClinicalTrials.gov Identifier: NCT00593450.

Dataset Information

Association of Baseline Characteristics and Early Vision Response with 2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT).

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Association of Baseline Characteristics and Early Vision Response with 2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT).

Similar Datasets

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