Ranibizumab Effective, Safe Long-Term Treatment for Diabetic Macular Edema, Study Says

Significant improvements in visual acuity and central retinal thickness (CRT) can be achieved in most patients after treatment with intravitreal ranibizumab injections, according to a study published in Clinical Ophthalmology. Improvements stabilized and injections were reduced in subsequent years, leading researchers to conclude that ranibizumab is an effective and safe long-term treatment for diabetic macular edema (DME).

According to the study’s findings the data confirms ranibizumab’s ability to prevent a decline in best corrected visual acuity (BCVA). It also demonstrated initial improvement and subsequent retention of BCVA in patients with DME at 36 months. 

Ranibizumab, an anti-vascular endothelial growth factor (VEGF) agent, has been used to treat several retinal diseases, including DME. Randomized controlled clinical trials have provided strong evidence of ranibizumab’s efficacy, but only limited data show actual treatment patterns and outcomes in daily clinical practice, according to investigators. 

To establish the long-term efficacy and safety, researchers conducted an open-label, observational, multicenter study in 9 Belgian outpatient ophthalmology clinics. Patients with visual impairment due to DME were treated with intravitreal ranibizumab (0.5 mg) per their ophthalmologist’s best clinical judgment. Since it was an observational study, there were no fixed time points for follow-up visits or required treatments. Follow-up intervals and treatment decisions, including retreatment, were at the discretion of the ophthalmologist.

Patients who had been treated with a VEGF inhibitor other than ranibizumab in the 90 days prior to study enrollment and those who were using other investigational drugs at the time of the study were excluded. The study included the primary treated eyes of 55 DME patients who were followed for approximately 3.5 years. Eyes were 21.8% treatment-naïve (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).

During the study, injections decreased from an average of 5.2 in year 1 to 0.8 in year 5. BCVA gains over baseline included a mean of +5.3 letters at year 1, +8.9 at year 2 and +5.8 at year 3. More specifically, at 12 months, BCVA increased (by 8.9±16.4 letters from 59.7±9.3 at baseline) in the TX-naïve cohort (P <.0001), as well as in the PRIOR-anti-VEGF group (by 11.8±9.9 from 61.6±8.5,  P =.03), and in the PRIOR-other group (by 4.2±10.6 from 58.2±14.6, P =.0002). 

BCVA remained stable for the remainder of follow-up in all groups, while CRT decreased in the first 2 months by monthly rates of -43.8 μm in the TX-naïve group (P =.04), -75.7 μm in the PRIOR-anti-VEGF group (P =.02), and -65.8 μm in the PRIOR-other eyes group (P =.0003), showing stability afterwards. 

No unknown adverse events were recorded. However, treatment intensity and BCVA and CRT outcomes in this study are lower than those seen in early efficacy trials. Investigators attribute the difference in efficacy to under-treatment.

Researchers identified several limitations with their study, including that it used a convenience sample, which may introduce selection bias. Similarly, attrition bias cannot be excluded due to the high drop-out rate. Additionally, because this was a study to assess ranibizumab, all patients were treated with that agent only and there was no randomization or comparator group of untreated patients or patients treated exclusively with other therapies. Lastly, the limited number of treatment-naïve patients and patients with prior anti-VEGF treatment may limit the reliability of the results, particularly beyond 24 months. 

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Van Aken E, Favreau M, Ramboer E, et al. Real-world outcomes in patients with diabetic macular edema treated long term with ranibizumab (VISION study). Clin Ophthalmol. 2020;14(12):4173-4185. doi:10.2147/OPTH.S281501.