INTRODUCTION: Diabetic macular edema (DME) is a leading cause of vision impairment in diabetes mellitus. Spectral-domain optical coherence tomography (SD-OCT) provides valuable biomarkers for assessing disease severity and treatment response. This study evaluates the visual outcomes and SD-OCT biomarker changes in patients treated with intravitreal ranibizumab at a tertiary hospital. MATERIALS AND METHODS: A prospective cohort study was conducted on 50 Type 2 diabetes mellitus patients with center-involving DME at Employees' State Insurance Corporation (ESIC) Medical College and Hospital, Hyderabad, from July 2022 to December 2023. Inclusion criteria were best-corrected visual acuity (BCVA) <
6/9 and central retinal thickness (CRT) ≥280 µm. Exclusion criteria included other retinal diseases, vision-impairing cataracts, or glaucoma. Patients received three monthly intravitreal ranibizumab injections and were followed up at one, two, three, and six months. BCVA, CRT, and SD-OCT biomarkers such as hyperreflective foci (HRF), subretinal neuroretinal detachment (SND), intraretinal cyst (IRC) size, disorganization of retinal inner layers (DRIL), ellipsoid zone (EZ) disruption, and external limiting membrane (ELM) disruption were assessed. Statistical analysis was performed using SPSS software, version 26 (IBM Corp., Armonk, NY). RESULTS: BCVA improved from 0.76±0.39 at baseline to 0.37±0.29 at six months (p<
0.00002). CRT reduced from 473.66±111.65 µm to 326.64±71.37 µm (p<
0.00002). HRF, SND, and IRC size showed significant regression. DRIL, EZ, and ELM disruption improved significantly (p<
0.00002). There was no statistically significant association between OCT biomarker features and BCVA improvement of more than three lines. CONCLUSION: Intravitreal ranibizumab significantly improves visual acuity and reduces retinal thickness in DME patients. SD-OCT biomarkers are valuable in monitoring treatment response and disease progression.