atment was reinitiated when a reduction in BCVA due to DME progression was observed. Laser photocoagulation was administered at baseline on the same day, at least 30 minutes before injection of ranibizumab, and then as needed based on ETDRS criteria.
Key outcome measures are summarised in Table 4 and Figure 2.
Table 4 Outcomes at Month 12 in study D2301 (RESTORE)
Outcome measure compared to baseline
Ranibizumab
0.5 mg
n=115
Ranibizumab
0.5 mg + Laser
n=118
Laser
n=110
Mean average change in BCVA from Month 1 to Month 12a (±SD)
6.1 (6.4)
5.9 (7.9)
0.8 (8.6)
Gain of ≥10 letters or BCVA ≥84a (%)
37.4
43.2
15.5
Gain of ≥15 letters or BCVA ≥84 (%)
22.6
22.9
8.2
p-value
0.0032
0.0021
ap<0.0001
Figure 2 Mean change in visual acuity from baseline over time in study D2301 (RESTORE)
BL=baseline; SE=standard error of mean
* Difference in least square means, p<0.0001/0.0004 based on two-sided stratified Cochran-Mantel-Haenszel test
The effect was consistent in most subgroups. However, subjects with a fairly good baseline BCVA (>73 letters) together with macular oedema with central retinal thickness of <300 μm did not appear to benefit from treatment with ranibizumab compared to laser photocoagulation.
The improvement in visual acuity seen with Lucentis 0.5 mg at 12 months was accompanied by patient-reported benefits with regards to most vision-related functions as measured by the National Eye Institute Visual Function Questionnaire (VFQ-25) scores. For other subscales of this questionnaire no treatment differences could be established. The difference between Lucentis 0.5 mg and the control group was assessed with p-values of 0.0137 (ranibizumab mono) and 0.0041 (ranibizumab+laser) for the VFQ-25 composite score.
In both studies, the improvement of vision was accompanied by a continuous decrease in the macular oedema as measured by central retinal thickness (CRT).
Treatment of visual impairment due to macular oedema secondary to RVO
The clinical safety and efficacy of Lucentis in patients with visual impairment due to macular oedema secondary to RVO have been assessed in the randomised, double-masked, controlled studies BRAVO and CRUISE that recruited subjects with BRVO (n=397) and CRVO (n=392), respectively. In both studies, subjects received either 0.3 mg or 0.5 mg intravitreal ranibizumab or sham injections. After 6 months, patients in the sham-control arms were crossed over to 0.5 mg ranibizumab. In BRAVO, laser photocoagulation as rescue was allowed in all arms from Month 3.
Key outcome measures from BRAVO and CRUISE are summarised in Tables 5 and 6 and Figures 3 and 4.
Table 5 Outcomes at Month 6 and 12 (BRAVO)
Sham/Lucentis 0.5 mg
(n=132)
Lucentis 0.5 mg
(n=131)
Mean change in visual acuity at Month 6a (letters) (SD) (primary endpoint)
7.3 (13.0)
18.3 (13.2)
Mean change in BCVA at Month 12 (letters) (SD)
12.1 (14.4)
18.3 (14.6)
Gain of ≥15 letters in visual acuity at Month 6a (%)
28.8
61.1
Gain of ≥15 letters in visual acuity at Month 12 (%)
43.9
60.3
Proportion (%) receiving laser rescue over 12 month
