This retrospective study evaluated the association of hyperreflective foci (HRF) with treatment response in diabetic macular oedema (DME) after anti-vascular endothelial growth factor (VEGF) therapy. The medical records, including of ophthalmologic examinations and optical coherence tomography (OCT) images, of 106 patients with DME treated with either intravitreal ranibizumab or aflibercept were reviewed. The correlations between best-corrected visual acuity (BCVA) changes and HRF along with other OCT biomarkers were analysed. The mean logMAR BCVA improved from 0.696 to 0.461 after an average of 6.2 injections in 1 year under real-world conditions. Greater visual-acuity gain was noted in patients with a greater number of HRF in the outer retina at baseline (p = 0.037), along with other factors such as poor baseline vision (p < 0.001), absence of epiretinal membrane (p = 0.048), and presence of subretinal fluid at baseline (p = 0.001). The number of HRF after treatment was correlated with the presence of hard exudate (p < 0.001) and baseline haemoglobin A1C (p = 0.001). Patients with proliferative diabetic retinopathy had greater HRF reduction after treatment (p = 0.018). The number of HRF in the outer retina, in addition to other baseline OCT biomarkers, could be used to predict the treatment response in DME after anti-VEGF treatment.