Dataset Information

Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies.

ABSTRACT: BACKGROUND/AIMS:To evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ?43, 47, and ?53 in VIVID-DME and VISTA-DME. METHODS:Patients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2?mg every 4 weeks (2q4), intravitreal aflibercept 2?mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups were also pooled. RESULTS:748 patients had a baseline DRSS score based on fundus photographs (?43, n=301; 47, n=153; ?53, n=294). At week 100, the least squares mean difference between treatment groups (effect of intravitreal aflibercept above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9 (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95%?CI 7.96 to 14.1) letters in those with baseline DRSS scores ?43, 47, and ?53, respectively. The proportions of patients with ?2?step DRSS score improvement were greater in the intravitreal aflibercept group versus laser, respectively, for those with baseline DRSS scores of ?43 (13% vs 5.9%), 47 (25.8% vs 4.5%), and ?53 (64.5% vs 28.4%). CONCLUSIONS:Regardless of baseline DRSS score, functional outcomes were superior in intravitreal aflibercept-treated patients, demonstrating consistent treatment benefit across various baseline levels of retinopathy. TRIAL REGISTRATION NUMBERS:NCT01331681 and NCT01363440, Post-results.

SUBMITTER: Staurenghi G

PROVIDER: S-EPMC6047149 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies.

Staurenghi Giovanni G Feltgen Nicolas N Arnold Jennifer J JJ Katz Todd A TA Metzig Carola C Lu Chengxing C Holz Frank G FG

The British journal of ophthalmology 20171019 7

<h4>Background/aims</h4>To evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ≤43, 47, and ≥53 in VIVID-DME and VISTA-DME.<h4>Methods</h4>Patients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every v ...[more]

PMID: 29051325

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Project description:BACKGROUND:Diabetic macular edema (DME) shows a gradual and sustained functional and morphologic response to anti-vascular endothelial growth factor (VEGF) drugs, but the optimal schedule for initiation of anti-VEGF therapy is not known. This study evaluates the treatment response behavior of DME in the Phase 3 trials of intravitreal aflibercept, with 5 initial intravitreal aflibercept injections (IAI), 2 mg every 4 weeks (2q4), in the upload phase. METHODS:This post hoc pooled analysis of the VISTA-DME (NCT01363440) and VIVID-DME (NCT01331681) trials evaluated the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the upload phase, using pooled data from both IAI treatment groups [2q4 and 2 mg every 8 weeks (2q8)]. The mean visit-to-visit change in BCVA and CRT, and the respective rate of gainers and losers was calculated for each successive visit. A secondary analysis compared the visit-to-visit change in BCVA between the 2q4 and 2q8 treatment arms during the upload period and the first year treatment period. RESULTS:The majority of eyes showed a continuing improvement of BCVA after the first IAI. The proportions of eyes gaining BCVA (?5 letters) at each visit compared with the previous visit during the IAI 2q4 upload phase were 60 (4-weeks), 19 (8-weeks), 16 (12-weeks), 15 (16-weeks), and 14 % (20-weeks). In contrast, the proportions of eyes losing BCVA (?5 letters) were 3 (4-weeks), 7 (8-weeks), 7 (12-weeks), 9 (16-weeks), and 8 % (20-weeks), respectively. The odds of BCVA (?5 letters) gain/loss exceeded 1.7 at each visit (range 1.7-20). Overall, the proportion of patients with BCVA gain ?5 letters at week 20 (compared with baseline) was 76 and 80 % in the 2q4 and 2q8 groups, respectively. The proportions of eyes showing a visit-to-visit decrease in CRT of ?30 µm during the first 5 IAI were 77 (4-weeks), 27 (8-weeks), 21 (12-weeks), 17 (16-weeks), and 12 % (20-weeks). In the secondary analysis, the BCVA outcomes were similar for the 2q8 and 2q4 treatment arms. CONCLUSIONS:The data presented here are consistent with continual functional and anatomic improvement following the fourth and fifth initial 2q4 injections, suggesting that an intensive and sufficiently long upload may be beneficial. Trial registration VIVID-DME: Clinicaltrials.gov: NCT01331681; VISTA-DME: Clinicaltrials.gov: NCT01363440.

Project description:BackgroundThe Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (DRSS) is a standard approach to measure diabetic retinopathy (DR) severity. Many clinical trials evaluating drug intervention for DR rely upon demonstration of a therapeutic effect through measurement of a 2- or 3-step improvement or progression on the DRSS; however, these binary endpoints require a relatively large sample size for a reliable estimate of therapeutic efficacy, especially when the SOC (eg, anti-VEGF) is used as a control. This study was designed to evaluate the sensitivity and statistical efficiency of detecting a drug effect in DR across different DRSS endpoints, and present alternative analytical approaches to enable smaller-size DR trials for detecting a reliable efficacy signal before moving into larger confirmatory DR trials.MethodsData from two randomized, double-blinded, controlled Phase III trials, that enrolled patients with decreased vision due to center-involved DME and the presence of macular edema documented on optical coherence tomography and simulated data, were used for this study. Changes in DRSS steps during a 3-month period from patients (n=205) with no active intervention were used to confirm the reliability of DRSS outcomes. A simulation study compared sensitivity and statistical efficiency across different DRSS endpoints.ResultsThe standard deviation of step change between baseline and month 3 DRSS across different steps at baseline were all within 1 step, confirming the reliability of DRSS measure by each step. Efficiency of detecting reliable therapeutic efficacy was augmented when treatment effect in improvement and progression was evaluated together; highest sensitivity was observed when change in DRSS steps was used directly as an endpoint.ConclusionDRSS step change may provide more robust sensitivity and statistical efficiency. It is therefore a more cost-effective endpoint for the detection of therapeutic efficacy signal in drug discoveries in DR.

Project description:ImportanceModerate to substantial agreement between Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field imaging and ultrawide-field (UWF) imaging has been suggested in single-center studies. Comparing images obtained by multiple centers could increase confidence that UWF images can be used reliably in place of ETDRS imaging in future clinical trials.ObjectiveTo compare diabetic retinopathy (DR) severity from modified ETDRS 7-field imaging and UWF imaging.Design, setting, and participantsThis preplanned, cross-sectional analysis included modified ETDRS 7-field images obtained using the Diabetic Retinopathy Clinical Research Network acquisition protocol and UWF images obtained captured with the Optos 200Tx system (Optos, PLC) from adult participants (≥18 years old) with type 1 or type 2 diabetes. Both image types were evaluated by trained graders masked to clinical data. Data collection occurred from February 2015 to December 2015, and data analysis from June 2016 to December 2017.Main outcomes and measuresAgreement between UWF images, UWF images masked to include only the ETDRS 7-field area, and ETDRS 7-field images were calculated using κ statistics.ResultsA total of 764 eyes from 385 participants were included; participants had a median (IQR) age of 62.2 (53.6-69.2) years, 194 (50.4%) were women, and 256 (66.5%) were white. Of 742 eyes with both ETDRS 7-field images and UWF masked images graded, 359 (48.4% [95% CI, 44.4%-52.4%]) eyes had exact agreement, and 653 eyes (88.0% [95% CI, 85.2%-90.3%]) agreed within 1 step (weighted κ, 0.51 [95% CI, 0.44-0.58]). After open adjudication by an independent senior grader of all images with more than a 2-step discrepancy, perfect agreement was found in 435 eyes (59.0% [95% CI, 55.1%-62.8%]) and agreement within 1 step in 714 eyes (96.9% [95% CI, 95.1%-98.0%]; κ, 0.77 [95% CI, 0.73-0.82]). Ability of the imaging modalities to detect retinopathy severity in an individual eye was considered similar in 59 eyes (50.9% [95% CI, 41.3%-60.4%]), better for ETDRS 7-field imaging in 22 eyes (19.0% [95% CI, 12.5%-27.7%]), and better for UWF-masked images in 31 eyes (26.7% [95% CI 18.8%-36.5%]). Comparing UWF masked and unmasked images, 94 of 751 eyes (12.5%) had DR graded as at least 1 step more severe on UWF unmasked images vs UWF masked images. Predominantly peripheral DR lesions were present in 308 of 751 eyes (41.0%); this suggested increased DR severity by 2 or more steps in 34 eyes (11.0%).Conclusions and relevanceImaging by the ETDRS 7-field and UWF imaging systems have moderate to substantial agreement when determining the severity of DR within the 7 standard fields. Disparities in an individual eye are equivalently distributed between imaging modalities and can be better or worse on 1 or the other. Longitudinal follow-up will evaluate the primary outcome of this study to determine if peripheral retinal findings are associated with future retinopathy outcomes.

Dataset Information

Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies.

Publications

Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies.

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