GOOD RESULTS FROM PHASE 111 REVEAL STUDY

Results from the Phase III REVEAL study establish that Intravitreal ranibizumab (Lucentis, Genentech) is safe and effective for improving vision and reducing central retinal thickness in Asian patients with diabetic macular oedema (DME), reported Adrian Koh MD, at the 12th EURETINA Congress, citing results of the Phase III REVEAL study.

Conducted at centres in China, Hong Kong, Taiwan, Republic of Korea, Japan and Singapore, REVEAL randomised 396 patients equally into three arms to receive ranibizumab 0.5mg + sham focal grid laser, ranibizumab 0.5mg + active laser, or sham injection + active laser. Injections (ranibizumab or sham) were given to all patients monthly for three months and as needed thereafter based on ETDRS BCVA stability and DME progression. Laser photocoagulation (active or sham) was performed based on ETDRS guidelines and was repeated no more than once every three months. Almost 90 per cent of patients completed the 12-month study.

Significant differences

Both the ranibizumab monotherapy and laser combined arms were significantly superior to laser alone in the primary endpoint analysis of mean average change in BCVA from baseline to month one to 12 (+5.9 and +5.7 vs. +1.7 letters). In addition, there were significant differences favouring both the ranibizumab monotherapy and combined laser arms compared with laser alone in analyses of mean change from baseline to month 12 in BCVA (+6.6 and +6.4 vs. +1.8 letters) and CRT (-132 and -164 vs. -58.6 microns).

Safety data showed the most common ocular and non-ocular adverse events were minor. Rates of serious adverse events were generally similar across all study groups.

“REVEAL is the first randomised, clinical trial designed to assess the efficacy and safety of ranibizumab in Asian patients with DME, and the results are consistent with those observed in RESTORE, one of the pivotal studies that led to approval of ranibizumab for treatment of DME in Europe and Asia,†said Dr Koh, founding partner and senior consultant, Eye & Retina Surgeons, Camden Medical Centre, Singapore.

“It was encouraging to see there were no new safety signals in this study, and particularly given the concern about the potential for adverse events thought to be related to systemic VEGF inhibition in patients with diabetes. Ranibizumab was well tolerated, and there was no increase in rates of cerebrovascular events or cardiovascular morbidity and mortality in this population of diabetic patients receiving repeated anti-VEGF injections.â€

Analyses of treatments received showed the mean number of injections (ranibizumab or sham) was similar across all three groups (range 7.0 to 7.8) as were the mean number of laser treatments (active or sham, range 1.5 to 1.9). “The study was initiated with the expectation that adjunctive laser would reduce the burden of ranibizumab injections. However, that has not been observed in any clinical trials, and in fact, there has even been some suggestion that applying laser too early will limit visual gains with ranibizumab,†said Dr Koh.

However, he noted that clinicians should not forget that laser has an important place in management of diabetic eye disease. “DME does not arise in isolation and it should not be the sole focus of treatment. Very often patients have progression of diabetic retinopathy or significant peripheral nonperfusion for which laser photocoagulation plays a role,†Dr Koh said. He added that it was also feared initially that prolonged anti-VEGF therapy might increase ischemia to the eye. Rather, the reverse appears to be true. “In giving anti-VEGF therapy on a regular basis, the perfusion status seems to improve for most diabetics,†Dr Koh said.