Treating diabetic macular oedema

Anti-VEGF treatment for clinically significant diabetic macular oedema with intravitreal ranibizumab (Lucentis, Genentech) provides a rapid and robust increase in visual acuity that is sustained for 24 months with monthly injections, reported David M Brown MD (The Methodist Hospital, Houston, Texas), at the annual meeting of the Association for Research in Vision and Ophthalmology. Dr Brown reviewed the results from the RISE and RIDE trials that randomised 377 and 382 patients, respectively, to monthly intravitreal injections with ranibizumab 0.3mg, 0.5mg, or sham. Ranibizumab treatment at both doses produced statistically significant increases of three or more lines of BCVA at month 24 in both studies.

Ranibizumab’s benefit for improving visual acuity was already seen at the first follow-up visit at one week when patients in all ranibizumab groups achieved a mean BCVA gain of more than one line. A statistically significant difference compared with sham persisted at all monthly evaluations. Ranibizumab treatment also reduced the rate of significant BCVA loss (≥3 lines) to less than five per cent in all arms. The functional benefits corresponded with anatomic improvements in macular thickness and resolution of fluorescein leakage.

The ocular safety of intravitreal ranibizumab was consistent with prior Phase III studies for treatment of exudative age-related macular degeneration (AMD) and retinal vein occlusion. There were no new significant systemic safety findings, although there were a few more strokes among patients treated with ranibizumab 0.5mg, and a few more deaths in the pooled ranibizumab groups compared with controls.

“Since the results of the Early Treatment Diabetic Retinopathy Study (ETDRS) were published in 1985, photocoagulation has been the standard of care for DME, and photocoagulation became the standard because it significantly reduced the risk of loss of three or more lines of BCVA and not because of its improved visual acuity. This type of functional loss is what causes patients to stop working, and photocoagulation reduced its incidence by more than half to just 10 per cent,†commented Dr Brown, who was a Phase III study investigator and is a vitreoretinal specialist in private practice.

“With ranibizumab treatment, we are seeing a further significant reduction in the rate of moderate vision loss in eyes with clinically significant DME for the first time since 1985.â€

Dr Brown said the pivotal studies are not powered to detect significant differences between groups in systemic adverse events potentially related to VEGF. “However, it is important to look carefully at this issue because patients being treated for diabetic retinopathy are relatively sick. Rates of serious adverse events were low in all groups, and we hope that the small increase in cases of stroke and death among ranibizumab-treated patients are related to chance.â€

The RISE and RIDE trials enrolled patients with central subfield thickness ≥275 microns and ETDRS BCVA between 20/40 and 20/320 in the study eye. The treatment groups in the two studies were well matched at baseline. Patients averaged 60 years of age and had diabetes for about 15 years. Baseline VA averaged around 20/80 and mean centre point thickness was about 440 to 480 microns across the groups. About two-thirds of patients had prior focal/grid laser treatment and in the two studies, about one-fourth to one-third received intraocular steroid.

At 24 months, mean BCVA improvement exceeded two lines in all ranibizumab groups compared with less than three letters in the control groups. Rates of BCVA loss of three lines or more were 2.4 per cent for both ranibizumab arms and 10 per cent for the controls in RISE, and 1.6 per cent, 3.9 per cent, and 8.5 per cent, respectively, for the ranibizumab 0.3mg, 0.5mg and sham groups in RIDE. The benefit of ranibizumab treatment corresponded with anatomic improvement and was achieved with much lower rates of laser treatment. Centre point thickness decreased rapidly and immediately in the ranibizumab arms and only gradually decreased over time in the control group. Overall, the ranibizumab-treated eyes achieved about a 250 micron reduction in centre point thickness at 24 months versus 133 microns in the control group.

All patients were eligible for focal laser treatment beginning at month three if centre point thickness was greater than 250 microns and the investigator thought the treatment could be beneficial.