Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension

OBJECTIVE: To evaluate factors associated with Diabetic Retinopathy Severity Scale (DRSS) changes with less frequent ranibizumab after induction therapy. METHODS AND ANALYSIS: Post hoc analyses of RIDE/RISE and their open-label extension (OLE). Analyses included patients with diabetic retinopathy (DR)/diabetic macular oedema who completed the OLE. Comparisons were made between patients with improved/maintained (≥0 step decrease from OLE baseline (month 36) to month 48) versus worsened (≥1 step increase) DRSS during the OLE. DRSS changes over 12 months were compared between patients randomised to ranibizumab at RIDE/RISE baseline who improved to DRSS score ≤43 at OLE baseline (induced) versus those randomised to sham with DRSS score ≤43 at RIDE/RISE baseline (native). RESULTS: From OLE baseline to month 48, 72% (263/367) of patients improved/maintained DRSS scores. These patients had similar mean best-corrected visual acuity at RIDE/RISE (56.4 letters) and OLE baseline (68.6 letters) versus patients with worsened scores (58.2 and 70.8 letters). Patients who improved/maintained DRSS scores had similar mean central foveal thickness at RIDE/RISE (492 µm) and OLE baseline (196 µm) versus patients with worsened scores (441 and 167 µm). Patients who improved/maintained DRSS scores received a significantly higher (p<0.0001) mean number of pro re nata (PRN) injections (4.4) between OLE baseline and month 48 versus those with worsened scores (2.3). Patients with more severe DR at baseline who achieved mild-to-moderate non-proliferative DR (NPDR) induced by monthly ranibizumab injections were significantly more likely to worsen (p<0.0001) than those with mild-to-moderate NPDR at baseline randomised to sham injections (1.0-step versus 0.1-step worsening). CONCLUSIONS: Most patients improved/maintained DRSS scores with less-than-monthly PRN ranibizumab. Some minimum treatment/monitoring may be necessary to maintain improvements after induction therapy. TRIAL REGISTRATION NUMBERS: NCT00473382/NCT00473330.