Residual Edema With Ranibizumab 0.5 mg and 2.0 mg for DME
Residual Edema With Ranibizumab 0.5 mg and 2.0 mg for DME
In all, 43 patients (43 eyes) were enrolled into this clinical trial (Table 1). Included patients had a mean (standard deviation (SD)) age of 64.0 (±10.1) years and 23 (53.5%) patients were male. Twenty patients had proliferative diabetic retinopathy and 23 patients had nonproliferative diabetic retinopathy. In addition to previous bevacizumab treatment, patients had previously received a mean (SD) of 0.3 (±0.9) intravitreal triamcinolone injections, and 20 of 43 eyes had prior focal photocoagulation with a mean (SD) of 2.5 (±2.1) sessions of laser treatment. Patients received a mean (SD) of 4.7 (±2.4) intravitreal bevacizumab injections before the study, and the mean (SD) 1-mm CST before and after two consecutive bevacizumab injections was 475.8 (±128.7) μm and 469.5 (±133.1) μm, respectively (Supplementary Figure 1 http://www.nature.com/eye/journal/v29/n4/suppinfo/eye2014338s1.html).
The mean (SD) visual acuity at baseline was 58.8 (±9.7) letters and improved by a mean of +6.8 (±7.4) letters at month 3 and by +8.8 (±9.3) letters at month 6. The improvement in visual acuity from baseline was statistically significant at both time points (P<0.0001) (Figure 2a). At month 3, 25/43 (58.1%) patients improved by 5 or more letters, 15/43 (34.9%) patients improved by 10 or more letters, and 5/43 (11.6%) patients improved by 15 or more letters from baseline. At month 6, 31/43 (72.1%) patients improved by 5 or more letters, 23/43 (53.5%) patients improved by 10 or more letters, and 9/43 (20.9%) patients improved by 15 or more letters from baseline.
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Figure 2.
(a) Mean change in visual acuity through 6 months compared with baseline. (b) Mean CST from baseline to month 6. Baseline through month 6: n = 42; 4 patients did not receive ranibizumab 2.0-mg during months 3 to 5. Vertical bars ± standard deviation of the mean. BL, baseline; ETDRS, Early Treatment Diabetic Retinopathy Study.
The mean (SD) 1-mm CST at baseline was 500.6 (±129.1) μm. At month 3, it decreased to 387.0 (±99.2) μm (P<0.001), and further decreased to 335.2 (±91.5) μm at month 6 (P<0.001) (Figure 2b).
There were 13 partial responders and 30 nonresponders to treatment with intravitreal bevacizumab administered before enrollment in REEF. After nonresponders received three intravitreal ranibizumab 0.5-mg injections (at baseline and months 1 and 2), 1 patient showed complete resolution of DME, 22 patients showed partial resolution of DME, and 6 patients demonstrated no resolution or had worsening of DME compared with baseline. One patient died because of acute hypoxemic respiratory failure after 1 month in the study and was not included in the analysis. At months 3, 4, and 5, 28/29 bevacizumab nonresponders received three consecutive monthly intravitreal ranibizumab 2.0-mg injections. Of these 28 patients, 15 (53.6%) demonstrated an additional reduction of DME (>10% reduction compared with CST at month 3), and 13 (46.4%) showed no resolution or had worsening of DME. At month 6, 10 (35.7%) patients did not require additional treatment for DME (Figure 3). In the six patients who showed a reduction of less than 10% in CST following monthly bevacizumab and three doses of ranibizumab 0.5-mg, the administration of three doses of ranibizumab 2.0-mg resulted in three (50.0%) patients achieving a reduction of more than 10% in CST (Figure 4).
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Figure 3.
Complete, partial, and minimal or nonresponse following three ranibizumab 0.5-mg injections and three ranibizumab 2.0-mg injections. *One death, patient not included in analysis.
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Figure 4.
Percent change in CST through 6 months in six nonresponders following three ranibizumab 0.5-mg injections. The six patients showed minimal reduction in CST following three consecutive ranibizumab 0.5-mg injections; three of six patients showed reduction in CST following ranibizumab 2.0-mg treatment. BL, baseline.
All patients were stratified according to the number of pre-trial bevacizumab injections received (≤4 vs ≥5 bevacizumab injections in total). The mean (SD) change in visual acuity was +9.1 (±9.0) letters in the four or fewer injections group compared with +8.3 (±9.8) letters in the five or more group; this difference was not statistically significant (P=0.538). Mean (SD) CST reduction in the four or fewer injections group was –189.4 (±148.1) μm vs –122.0 (±90.2) μm in the five or more group; this difference also was not statistically different (P=0.404).
In the partial responder group, 11 (84.6%) patients treated with intravitreal injections of ranibizumab 0.5-mg for 3 months showed partial or no reduction and 2 (15.4%) showed complete resolution of DME. The 11 patients were treated with intravitreal ranibizumab 2.0-mg for 3 months; of these, 7 (63.6%) showed further reduction (>10% compared with CST value at month 3) and 5 (45.5%) did not require treatment at month 6.
Outcomes from the WPAI:SHP questionnaire showed that at baseline, 27.5% of all patients were employed; this percentage was slightly increased at month 3 and month 12 (30.8% and 29.7%, respectively). In all patients, both overall work impairment and activity impairment were reduced at month 12 compared with baseline. The percentage of patients who reported overall work impairment decreased from 23.3 to 15.0%, and reported activity impairment decreased from 24.3 to 16.8% (Supplementary Figure 2 http://www.nature.com/eye/journal/v29/n4/suppinfo/eye2014338s1.html).
Results
In all, 43 patients (43 eyes) were enrolled into this clinical trial (Table 1). Included patients had a mean (standard deviation (SD)) age of 64.0 (±10.1) years and 23 (53.5%) patients were male. Twenty patients had proliferative diabetic retinopathy and 23 patients had nonproliferative diabetic retinopathy. In addition to previous bevacizumab treatment, patients had previously received a mean (SD) of 0.3 (±0.9) intravitreal triamcinolone injections, and 20 of 43 eyes had prior focal photocoagulation with a mean (SD) of 2.5 (±2.1) sessions of laser treatment. Patients received a mean (SD) of 4.7 (±2.4) intravitreal bevacizumab injections before the study, and the mean (SD) 1-mm CST before and after two consecutive bevacizumab injections was 475.8 (±128.7) μm and 469.5 (±133.1) μm, respectively (Supplementary Figure 1 http://www.nature.com/eye/journal/v29/n4/suppinfo/eye2014338s1.html).
The mean (SD) visual acuity at baseline was 58.8 (±9.7) letters and improved by a mean of +6.8 (±7.4) letters at month 3 and by +8.8 (±9.3) letters at month 6. The improvement in visual acuity from baseline was statistically significant at both time points (P<0.0001) (Figure 2a). At month 3, 25/43 (58.1%) patients improved by 5 or more letters, 15/43 (34.9%) patients improved by 10 or more letters, and 5/43 (11.6%) patients improved by 15 or more letters from baseline. At month 6, 31/43 (72.1%) patients improved by 5 or more letters, 23/43 (53.5%) patients improved by 10 or more letters, and 9/43 (20.9%) patients improved by 15 or more letters from baseline.
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Figure 2.
(a) Mean change in visual acuity through 6 months compared with baseline. (b) Mean CST from baseline to month 6. Baseline through month 6: n = 42; 4 patients did not receive ranibizumab 2.0-mg during months 3 to 5. Vertical bars ± standard deviation of the mean. BL, baseline; ETDRS, Early Treatment Diabetic Retinopathy Study.
The mean (SD) 1-mm CST at baseline was 500.6 (±129.1) μm. At month 3, it decreased to 387.0 (±99.2) μm (P<0.001), and further decreased to 335.2 (±91.5) μm at month 6 (P<0.001) (Figure 2b).
There were 13 partial responders and 30 nonresponders to treatment with intravitreal bevacizumab administered before enrollment in REEF. After nonresponders received three intravitreal ranibizumab 0.5-mg injections (at baseline and months 1 and 2), 1 patient showed complete resolution of DME, 22 patients showed partial resolution of DME, and 6 patients demonstrated no resolution or had worsening of DME compared with baseline. One patient died because of acute hypoxemic respiratory failure after 1 month in the study and was not included in the analysis. At months 3, 4, and 5, 28/29 bevacizumab nonresponders received three consecutive monthly intravitreal ranibizumab 2.0-mg injections. Of these 28 patients, 15 (53.6%) demonstrated an additional reduction of DME (>10% reduction compared with CST at month 3), and 13 (46.4%) showed no resolution or had worsening of DME. At month 6, 10 (35.7%) patients did not require additional treatment for DME (Figure 3). In the six patients who showed a reduction of less than 10% in CST following monthly bevacizumab and three doses of ranibizumab 0.5-mg, the administration of three doses of ranibizumab 2.0-mg resulted in three (50.0%) patients achieving a reduction of more than 10% in CST (Figure 4).
(Enlarge Image)
Figure 3.
Complete, partial, and minimal or nonresponse following three ranibizumab 0.5-mg injections and three ranibizumab 2.0-mg injections. *One death, patient not included in analysis.
(Enlarge Image)
Figure 4.
Percent change in CST through 6 months in six nonresponders following three ranibizumab 0.5-mg injections. The six patients showed minimal reduction in CST following three consecutive ranibizumab 0.5-mg injections; three of six patients showed reduction in CST following ranibizumab 2.0-mg treatment. BL, baseline.
All patients were stratified according to the number of pre-trial bevacizumab injections received (≤4 vs ≥5 bevacizumab injections in total). The mean (SD) change in visual acuity was +9.1 (±9.0) letters in the four or fewer injections group compared with +8.3 (±9.8) letters in the five or more group; this difference was not statistically significant (P=0.538). Mean (SD) CST reduction in the four or fewer injections group was –189.4 (±148.1) μm vs –122.0 (±90.2) μm in the five or more group; this difference also was not statistically different (P=0.404).
In the partial responder group, 11 (84.6%) patients treated with intravitreal injections of ranibizumab 0.5-mg for 3 months showed partial or no reduction and 2 (15.4%) showed complete resolution of DME. The 11 patients were treated with intravitreal ranibizumab 2.0-mg for 3 months; of these, 7 (63.6%) showed further reduction (>10% compared with CST value at month 3) and 5 (45.5%) did not require treatment at month 6.
Outcomes from the WPAI:SHP questionnaire showed that at baseline, 27.5% of all patients were employed; this percentage was slightly increased at month 3 and month 12 (30.8% and 29.7%, respectively). In all patients, both overall work impairment and activity impairment were reduced at month 12 compared with baseline. The percentage of patients who reported overall work impairment decreased from 23.3 to 15.0%, and reported activity impairment decreased from 24.3 to 16.8% (Supplementary Figure 2 http://www.nature.com/eye/journal/v29/n4/suppinfo/eye2014338s1.html).