1 Disclosures Supported by the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases under award numbers UG1EY014231 and UG1EY023207 Regeneron provided aflibercept for the study and funds to the DRCR Retina Network to defray the studys clinical site ID: 1044065
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1. DRCR Retina NetworkEffect of Initial Aflibercept, Laser, or Observation on Low-Contrast Visual Acuity in Eyes with Diabetic Macular Edema and Good Vision: Ancillary Study Within a Randomized Clinical Trial (Protocol V)1
2. DisclosuresSupported by the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases under award numbers UG1EY014231 and UG1EY023207. Regeneron provided aflibercept for the study and funds to the DRCR Retina Network to defray the study’s clinical site costs.2
3. Low-Contrast Visual Acuity: Protocol VLow-contrast VA (contrast sensitivity) is important for driving at night, recognizing faces, identifying objects, and seeing in low-light situationsDRCR Retina Network Protocol V was a randomized clinical trial of 702 participants (eyes) comparing initial treatment with aflibercept, focal/grid laser, and observation for diabetic macular edema in eyes with high-contrast VA 20/25 or better*Eyes starting with laser or observation could receive aflibercept if VA loss met pre-specified criteriaNo significant difference between groups in the percentage of eyes with ≥ 5-letter high-contrast VA loss from baseline at 2 years52 of 91 sites comprising 387 of 702 participants (55%) measured LCVA3*DRCR Retina Network. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: A randomized clinical trial. JAMA. 2019;321(19):1880-1894.
4. Contrast Sensitivity, DME, + Anti-VEGFA small RCT (N = 41 eyes) treated eyes with DME and VA impairment (20/40 to 20/200) with bevacizumab or sham at baseline and 6 weeks*Compared with sham, bevacizumab showed significant improvement in contrast sensitivity at 2 weeks and a non-significant trend at 12 weeksPost hoc analysis of 468 eyes from RIDE/RISE trials showed a mean 2.5-letter improvement in contrast sensitivity at 2 years among eyes treated with ranibizumab**Data from the sham group were not reported4* Motta AAL, Bonanomi M, Ferraz DA, et al. Short-term effects of intravitreal bevacizumab in contrast sensitivity of patients with diabetic macular edema and optimizing glycemic control. Diabetes Res Clin Pract. 2019;149:170-178.** Ip MS, Zhang J, Ehrlich JS. The clinical importance of changes in diabetic retinopathy severity score. Ophthalmology. 2017;124(5):596-603.
5. ObjectivesEvaluate deficits in low-contrast VA among eyes with good high-contrast VA despite center-involved DMECompare treatment strategies in Protocol V with respect to change in low-contrast VA at 2 yearsEvaluate correlations of low-contrast VA with high-contrast VA and OCT central subfield thickness5
6. Participant Baseline CharacteristicsEyes with Baseline Low-Contrast VAAfliberceptN = 112Initial LaserN = 146Initial ObservationN = 129Age (y), median596062Female/Male sex45% / 55%32% / 68%37% / 63%Type 2 Diabetes92%91%91%HbA1c (%), median7.67.77.5Race/EthnicityWhite67%68%75%Black/African American13%11%10%Hispanic or Latino19%18%12%Other2%3%2%6
7. 7Low-Contrast Visual Acuity ChartWaldman AT, Lavery AM, Liu GW, et al. High- and Low-Contrast Letter Acuity Perception Matures With Age in Normally Sighted Children. J Neuroophthalmol. 2020;40(2):148‐156.2.5% low-contrast acuityETDRS high-contrast acuity
8. Ocular Baseline CharacteristicsEyes with Baseline Low-Contrast VAInitiation WithAfliberceptN = 112LaserN = 146ObservationN = 129High-Contrast VA Letter ScoreMean, letters (Snellen)85 (20/20)85 (20/20)85 (20/20)Low-Contrast VA Letter ScoreMean, letters (Snellen)45 (20/125)49 (20/125)48 (20/125)≥2 SD below age-specific norms, %*30%23%17%OCT Central Subfield Thickness (Stratus Equivalent)Mean, µm3173163128*Pineles SL, Velez FG, Yu F, Demer JL, Birch E. Normative reference ranges for binocular summation as a function of age for low contrast letter charts. Strabismus. 2014;22(4):167-175.
9. Mean Change in Low-Contrast VA Letter Score from BaselineN = 112N = 146N = 129N = 93N = 117N = 1042-Year1-Year2 Years: Adjusted Treatment Group Comparisons* Aflibercept vs. Laser: 5.3 (-0.2 to 10.8), P = .06Aflibercept vs. Observation: 5.5 (-0.2 to 11.2), P = .06Laser vs. Observation: 0.2 (-4.6 to 5.0), P = .94+2.7-2.0-3.1Error bars represent 95% confidence intervals9Baseline*Adjusted for baseline visual acuity and DME treatment in the non-study eye within 4 months before or after randomization.
10. Impaired Low-Contrast VA10*Pineles SL, Velez FG, Yu F, Demer JL, Birch E. Normative reference ranges for binocular summation as a function of age for low contrast letter charts. Strabismus. 2014;22(4):167-175.% of eyes ≥2 SD below age-specific norm
11. Interpreting CorrelationsEvans (1996)* proposed the following: .01-.19 “very weak”.20-.39 “weak”.40-.59 “moderate”.60-.79 “strong“.80-1.0 “very strong”11*Evans, J.D. 1996. Straightforward Statistics for the Behavioral Sciences. Brooks/Cole Publishing; Pacific Grove, Calif.: 1996.
12. 12High-Contrast VA vs. Low-Contrast VAr = 0.47 (95% CI 0.38 to 0.55)Moderate correlationr = 0.58 (95% CI, 0.51 to 0.65)Moderate correlation2 YearsChange from Baseline to 2 Years
13. 13Central Subfield Thickness vs. Low-Contrast VA r = -0.20 (95% CI, -0.30 to -0.09)Weak correlationr = -0.07 (95% CI, -0.18 to 0.04)No significant correlation2 YearsChange from Baseline to 2 Years
14. SummaryObjective #1: Evaluate deficits LCVA among eyes with good high-contrast VA despite center-involved DMEAt baseline, among eyes with good HCVA (≥20/25), 23% had a deficit in LCVAAfter treatment with aflibercept, laser, or observation, only the aflibercept group saw a numeric decline in the percentage of eyes with a deficit in LCVA at 2 years compared with baseline14
15. SummaryObjective #2: Compare treatment strategies in Protocol V with respect to change in low-contrast VA at 2 yearsChange in low-contrast VA from baseline was not statistically different between the three treatment strategiesAflibercept vs. Laser 95% CI: -0.2 to 10.8Aflibercept vs. Observation 95% CI: -0.2 to 11.2The study was conducted at only a subset of sites in Protocol V and not powered for this objective15
16. SummaryObjective #3: Evaluate correlations of low-contrast VA with high-contrast VA and OCT central subfield thicknessWhile low-contrast VA and high-contrast VA were moderately correlated, some patients had good HCVA but poor LCVA, which can interfere with overall visual functionThere was no significant correlation between low-contrast VA and OCT central subfield thickness in cross section at 2 years; there was a weak correlation between changes from baseline16
17. ConclusionThere was no significant difference between treatment groups in low-contrast VA change from baseline to 2 yearsConsidering the range of the 95% confidence intervals, however, the study may have been underpowered to detect a clinically meaningful benefit between treatment groups17
18. Thank You on Behalf of the DRCR Retina Network18