Baseline visual acuity strongly predicts visual acuity gain in patients with diabetic macular edema following anti-vascular endothelial growth factor treatment across trials

Abstract

Objective: This study was designed to evaluate the correlation of baseline visual acuity (VA) with VA outcome in response to anti-vascular endothelial growth factor (VEGF) in diabetic macular edema using a retrospective analysis of nine clinical trials. The result will help assess the relevance of VA gain comparisons across trials.

Methods: A correlation analysis was performed between mean baseline VA and VA gain at month 12 for 1,616 diabetic macular edema patients across nine randomized clinical trials (RESOLVE, RISE, RIDE, RESTORE, RETAIN, DRCR.net Protocol I, DA VINCI, VIVID, VISTA) with anti-VEGF treatment regimens ranibizumab 0.5 mg and aflibercept 2 mg.

Results: The mean baseline VA ranged from 56.9 to 64.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The mean VA gain at month 12 ranged from 6.8 to 13.1 ETDRS letters across trials. There was a strong inverse correlation between mean baseline VA and VA gain at month 12 (r=-0.85). The mean VA at 12 months plateaued at ~70 (68.5-73.0) ETDRS letters (20/40 Snellen VA equivalent) for the anti-VEGF treatment groups from all trials, regardless of dosing regimens and agents.

Conclusion: Cross-trial comparisons based on changes in best-corrected visual acuity should be done cautiously and only after adjusting for best-corrected visual acuity at baseline. Furthermore, the total VA afforded by treatment appears to be subject to a plateau effect, which warrants further exploration.

Keywords: aflibercept; anti-vascular endothelial growth factor; best-corrected visual acuity; cross-trial comparison; diabetic macular edema; ranibizumab.

Figure 1

The mean BCVA gain across nine clinical trials of anti-VEGF agents in DME. Note: ^a24-month data. Abbreviations: BCVA, best-corrected visual acuity; VEGF, vascular endothelial growth factor; DME, diabetic macular edema; ETDRS, Early Treatment Diabetic Retinopathy Study; T&E, treat and extend; PRN, pro re nata; def laser, deferred laser; 2q8, 2 mg intravitreal aflibercept every 8 weeks; 2q4, 2 mg intravitreal aflibercept every 4 weeks; 2PRN, 2 mg intravitreal aflibercept pro re nata.

Figure 2

Regression analysis of mean BCVA gains versus mean baseline BCVA in the nine trials. Abbreviations: BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.

Figure 3

Baseline, gained, and final BCVA by trial and regimen. Notes: ^aMedian. ^b24-month data. Abbreviations: BCVA, best-corrected visual acuity; VA, visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; 2q8, 2 mg intravitreal aflibercept every 8 weeks; 2q4, 2 mg intravitreal aflibercept every 4 weeks; 2PRN, 2 mg intravitreal aflibercept pro re nata; PRN, pro re nata; def laser, deferred laser; T&E, treat and extend.

Figure 4

Mean change in BCVA from baseline to month 12 by baseline BCVA. Note: Data from RESTORE. Abbreviations: BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.

Figure 5

Mean change in BCVA from baseline to months 12 and 24 by baseline BCVA. Note: Data from RETAIN (on file). Abbreviations: BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; T&E, treat and extend; PRN, pro re nata.