Aim Evaluate long-term real-world treatment patterns and associated effectiveness and safety outcomes in patients with diabetic macular edema (DME) treated ≥36 months with 0.5mg ranibizumab. Methods Open-label observational effectiveness study in 9 Belgian clinics. Included were primary treated eyes of 55 DME patients between August 2014 and March 2015 and followed for 3.5±1.8 years. Eyes were 21.8% treatment (TX)-naïve, 9.1% non-naïve with exclusive prior anti-VEGF treatment (PRIOR-anti-VEGF), and 63.6% non-naïve with other prior treatments (PRIOR-other). Intravitreal injections with ranibizumab were administered per ophthalmologists’ best clinical judgment. Trend testing of changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over time occurred using mixed regression analysis. Results The mean±SD number of treatments in the first year was 5.1±3.0 (TX-naïve), 4.5±2.7 (PRIOR-anti-VEGF) and 5.6±3.1 (PRIOR-other). At 12 months, BCVA increased by 8.9±16.4 letters from 59.7±9.3 at baseline in TX-naïve (p<0.0001), by 11.8±9.9 from 61.6±8.5 in PRIOR-anti-VEGF (p=0.03), and by 4.2±10.6 from 58.2±14.6 in PRIOR-other groups (p=0.0002). BCVA remained stable for the remainder of follow-up in all groups. CRT decreased over the first 2 months by monthly rates of −43.8µm in TX-naïve (p=0.04), −75.7µm in PRIOR-anti-VEGF (p=0.02), and −65.8µm in PRIOR-other eyes (p=0.0003), showing stability afterwards. No unknown adverse events were recorded; a painful eye following injection was registered with a possible relationship to the treatment. Conclusion This real-world study confirms the effectiveness of ranibizumab in preventing a decline in BCVA and demonstrated initial improvement and subsequent retention of BCVA in DME patients ≥36 months. Ranibizumab initially reduced and then maintained CRT. However, these data reveal that treatment intensity and BCVA and CRT outcomes are lower than those found in early efficacy trials. Under-treatment likely accounts for this efficacy-effectiveness gap. Yet, intravitreal ranibizumab is an effective and safe long-term treatment for DME under conditions of significant heterogeneity in patients and treatment patterns.

Purpose: To evaluate long-term, real-world treatment patterns and outcomes of ranibizumab 0.5 mg for neovascular age-related macular degeneration (nAMD) in a Belgian cohort. Patients and Methods: This Belgian (BE) cohort of the 5-year global observational LUMINOUS study included 229 patients with nAMD. Outcomes included visual acuity (VA), central retinal thickness (CRT) and safety. Results: The mean age was 79.5±7.7 years. The majority of patients (67.7%) were female and all patients were Caucasian. Most patients previously received ranibizumab with only 17.5% of patients being treatment-naïve. The injection frequency declined over time irrespective of prior treatment status (p<0.0001), with treatment-naïve eyes receiving a mean of 4.2±2.9 yearly injections and prior-ranibizumab eyes 3.6±2.7. Regression analysis confirmed first-year VA increases for treatment-naïve eyes (p=0.002) followed by a slight decrease of −1.8 letters per year. For prior-ranibizumab eyes, the visual changes over 1 year were statistically non-significant (p=0.90) but declined slightly after year one (p<0.0001). Anatomically, the CRT of treatment-naïve eyes decreased over time from baseline (p<0.0001), whereas the CRT of prior-ranibizumab eyes remained stable (p=0.43). No new safety findings were identified. Conclusion: LUMINOUS-BE reconfirms the well-characterized benefit-risk profile of ranibizumab for nAMD treatment. The observed low injection frequency reflects a need for more rigorous treatment in real-world settings. Clinical Trial Registration: NCT01318941.