PurposeTo determine the average time-point at which it is best to define 'sub-optimal response' after ranibizumab treatment for diabetic macular edema (DME) based on the data obtained from real-life clinical practice.MethodsIn this retrospective observational study, 322 consecutive treatment naïve eyes with DME were treated with three loading doses of intravitreal ranibizumab followed by re-treatment based on decision of the treating physician on a case-by-case basis. The demographic data, clinic-based visual acuity measurements and central subfield thickness (CST) assessed on spectral domain optical coherence tomography (OCT) were evaluated at baseline (month 0), 1, 2, 3, 6, and 12 months.ResultsOn an average, the improvement in visual acuity and CST was first seen after the loading dose. However, the maximal response in terms of proportion of patients with improvement in visual acuity and/ or CST in this cohort was observed at 12 months. Patients who presented with low visual acuity at baseline (<37 ETDRS letters) were unlikely to attain driving vision with ranibizumab therapy.ConclusionsOn an average, a 'sub-optimal response' after ranibizumab therapy is best defined at month 12 as patients may continue to improve with treatment.