Persistent diabetic macular edema after 6 months of anti-VEGF therapy is associated with diminished long-term improvement in vision: a post-hoc analysis of Protocol I

Abstract

Purpose : Previous studies have found inconsistent relationships between anatomic response and vision gain in diabetic macular edema (DME). In this analysis, we assess the association between anatomic response measured by duration of edema over the first 24 and 52 weeks of treatment and average vision improvement over 156 weeks of treatment, measured by the area under curve (AUC).

Methods : This post-hoc analysis of Protocol I stratified DME patients randomized to ranibizumab + prompt or deferred laser into 4 cohorts based duration of edema measured by the cumulative number of visits with central retinal thickness (CRT) ≥250µm, first at week 24 then week 52. The association with average change in best corrected visual acuity (BCVA) over the 156-week study duration, measured by AUC, was assessed in unadjusted and adjusted analyses.

Results : 367 eyes met inclusion criteria. Of 7 visits at week 24, CRT ≥250µm was observed in ≤1 visit (cohort 1) in n=56 (15.3%) eyes; 2-3 visits (cohort 2) in n=90 (24.5%) eyes; 4-5 visits (cohort 3) in n=57 (15.5%) eyes; and ≥6 visits (cohort 4) in n=164 (44.7%) eyes. Within eyes with persistent edema at week 24 (cohort 4), 65.9% had ≥6 visits with CRT ≥250µm over the second 24 weeks of treatment. After adjustment for potential confounders including baseline visual acuity, cohort 4 eyes gained on average 3.8 fewer letters (95% CI: -6.7, -0.8; p=0.012) compared with cohort 1 eyes over the first 156 weeks. (Table 1) Results, after adjustment, were consistent for eyes with persistent edema assessed after 52 weeks, where cohort 4 eyes gained on average 5.2 fewer letters than cohort 1 eyes (p<0.001) (Table 1).

Conclusions : This post-hoc analysis found a statistically significant association between duration of edema at week 24, and decreased average vision improvement at week 156, after adjusting for key potential confounders such as baseline BCVA. These data suggest that increased duration of edema over the first 6 months following anti-VEGF therapy is associated with worse long-term improvement in vision — supporting timely consideration of additional or alternative treatments in patients with persistent edema.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.