Background
Methods
Protocol
Eligibility criteria
Information sources
Literature search
Screening process
Data extraction process
Data items
Risk of bias assessment
Data analysis
Results
Literature search
Study and patient characteristics
Number of studies (n = 92) | % of studies | ||
---|---|---|---|
Study characteristics | |||
Year of publication | 2000–2006 | 8 | 8.7% |
2007–2011 | 31 | 33.7% | |
2012–2017 | 42 | 45.7% | |
2018–2019 | 11 | 11.9% | |
Geographic region | Europe | 33 | 35.9% |
North America | 29 | 31.5% | |
Asia | 19 | 20.7% | |
Multi | 8 | 8.7% | |
Australia/New Zealand | 3 | 3.3% | |
Study design | Parallel RCT | 91 | 98.9% |
Cluster RCT | 1 | 1.1% | |
Setting | Multi-centre | 55 | 59.8% |
Single-centre | 36 | 39.1% | |
Sample Size | < 50 | 25 | 30% |
50–149 | 31 | 33% | |
150–249 | 9 | 11% | |
250–499 | 13 | 9% | |
500–999 | 8 | 4% | |
≥ 1000 | 14 | 15.5% | |
Study duration (months)a | < 12 | 18 | 19.6% |
12 | 58 | 63.0% | |
13–23 | 4 | 4.3% | |
24 | 10 | 10.9% | |
36 | 2 | 2.2% | |
Frequency of interventions examined | Aflibercept | 5 | 6% |
Bevacizumab | 27 | 34% | |
Bevacizumab+IVTA+PDT | 1 | 1% | |
Bevacizumab+PDT | 5 | 6% | |
Brolucizumab | 2 | 2% | |
Conbercept | 1 | 1% | |
DXM | 1 | 1% | |
DXM+PDT+ranibizumab | 1 | 1% | |
DXM+ranibizumab | 3 | 4% | |
IVTA | 4 | 5% | |
IVTA+Bevacizumab | 2 | 3% | |
IVTA+PDT | 7 | 9% | |
IVTA+ranibizumab | 1 | 1% | |
PDT | 15 | 19% | |
PDT+ranibizumab | 10 | 13% | |
Placebo | 8 | 10% | |
Ranibizumab | 42 | 53% | |
Number of studies by outcome | Vision gain | 48 | 61% |
Vision loss | 51 | 65% | |
Mean BCVA | 77 | 97% | |
Legal blindness | 8 | 10% | |
Vision-related function | 6 | 8% | |
All-cause mortality | 45 | 57% | |
Arterial thromboembolic events | 18 | 23% | |
Venous thromboembolic events | 11 | 14% | |
Bacterial endophthalmitis | 24 | 30% | |
Retinal detachment | 20 | 25% | |
AE | 22 | 28% | |
Serious AE | 23 | 29% | |
Withdrawals due to AE | 16 | 20% | |
Patient characteristics | |||
Total # patients: 24,717 Mean number of patients (range): 655.77 (7–4300) Mean age in years (range): 75.3 (60.0–83.0)a % Female (range): 0.0–74.0% | |||
Mean age (years)b | 60-70 | 3 | 4% |
70-75 | 7 | 9% | |
75-80 | 21 | 27% | |
> 80 | 1 | 1% | |
NR | 45 | 57% | |
% female | < 47.0% | 14 | 18% |
48.0–57.0% | 13 | 17% | |
58.0–62.0% | 19 | 24% | |
62.5–65.0% | 11 | 14% | |
66.0–74.0% | 13 | 16% | |
NR | 9 | 11% | |
% patients with hypertension | 0.0–50.0% | 4 | 5% |
51.0–78.0% | 3 | 4% | |
NR | 72 | 91% | |
Lens status | Mixed | 6 | 8% |
Pseudophakic | 4 | 5% | |
Phakic | 1 | 1% | |
NR | 79 | 87% |
Risk of bias results
Statistical analysis results
Treatment comparison | NMA estimate (95% CrI) (95% PrI) |
---|---|
Proportion of patients experiencing vision gain (≥ 15 ETDRS letters) 34 RCTs, 8809 patients, 12 treatments + placebo No inconsistency was observed in the overall NMA (chi-square = 1.79, p = 0.41) Between-study variance: 0.02 (0.00–0.14) | |
Bevacizumab vs aflibercept | 0.96 [(0.64–1.39) (0.54–1.62)] |
Ranibizumab vs aflibercept | 1.09 [(0.78–1.47) (0.65–1.76)] |
Ranibizumab vs bevacizumab | 1.14 [(0.9–1.43) (0.73–1.8)] |
Brolucizumab vs aflibercept | 1.2 [(0.85–1.71) (0.71–2.03)] |
Brolucizumab vs bevacizumab | 1.26 [(0.76–2.14) (0.67–2.44)] |
Brolucizumab vs ranibizumab | 1.11 [(0.71–1.8) (0.61–2.07)] |
Conbercept vs aflibercept | 0.19 [(0.06–0.65) (0.05–0.68)]a |
Conbercept vs bevacizumab | 0.2 [(0.06–0.69) (0.06–0.73)]a |
Conbercept vs ranibizumab | 0.17 [(0.05–0.59) (0.05–0.63)]a |
Conbercept vs brolucizumab | 0.15 [(0.05–0.56) (0.04–0.59)]a |
Proportion of patients experiencing vision loss of ≥ 15 ETDRS letters 36 RCTs, 9081 patients, 13 treatments + placebo No inconsistency was observed in the overall NMA (chi-square = 0.25, p = 0.88) Between-study variance: 0.02 (0.00–0.13) | |
Bevacizumab vs aflibercept | 0.94 [(0.51–1.67) (0.47–1.81)] |
Ranibizumab vs aflibercept | 0.9 [(0.55–1.43) (0.5–1.59)] |
Ranibizumab vs bevacizumab | 0.96 [(0.69–1.35) (0.6–1.57)] |
Brolucizumab vs aflibercept | 0.96 [(0.57–1.63) (0.51–1.79)] |
Brolucizumab vs bevacizumab | 1.03 [(0.47–2.27) (0.44–2.43)] |
Brolucizumab vs ranibizumab | 1.08 [(0.53–2.19) (0.49–2.36)] |
Conbercept vs aflibercept | 0.24 [(0–4.29) (0–4.4)] |
Conbercept vs bevacizumab | 0.26 [(0–4.65) (0–4.67)] |
Conbercept vs ranibizumab | 0.27 [(0–4.67) (0–4.79)] |
Conbercept vs brolucizumab | 0.24 [(0–4.71) (0–4.85)] |
Mortality 24 RCTs, 10 treatments + placebo, 8875 patients No inconsistency in the network (chi-squared = 0.69, p-value = 0.71) Between study variance: 0.01 (0.00-0.17) | |
Bevacizumab vs aflibercept | 0.58 [(0.15–1.98) (0.15–2.09)] |
Ranibizumab vs aflibercept | 0.59 [(0.17–1.8) (0.16–1.9)] |
Ranibizumab vs bevacizumab | 1.02 [(0.6–1.73) (0.54–1.94)] |
Brolucizumab vs aflibercept | 0.7 [(0.24–1.91) (0.23–2558)] |
Brolucizumab vs bevacizumab | 1.21 [(0.24–6.49) (0.23–2558)] |
Brolucizumab vs ranibizumab | 1.19 [(0.25–5.98) (0.24–2558)] |
Difference in mean change in BCVA 26 RCTs, 10 treatments + placebo, 5916 patients No inconsistency in the network (chi-squared = 2.62, p-value = 0.27) Between-study variance: 6.29 (3.28–11.27) | |
bevacizumab vs aflibercept | 2.21 [(− 1.1 to 5.42) (− 3.96 to 8.22)] |
ranibizumab vs aflibercept | 1.09 [(− 1.53 to 3.7) (− 4.62 to 6.81)] |
ranibizumab vs bevacizumab | − 1.11 [(− 3.07 to 0.92) (− 6.5 to 4.28)] |
brolucizumab vs aflibercept | − 0.46 [(− 4.26 to 3.33) (− 6.84 to 5.81)] |
brolucizumab vs bevacizumab | − 2.68 [(− 7.69 to 2.43) (− 9.72 to 4.54)] |
brolucizumab vs ranibizumab | − 1.57 [(− 6.12 to 3.07) (− 8.34 to 5.32)] |
conbercept vs aflibercept | − 15.17 [(− 23.8 to − 6.5) (− 25.35 to − 4.89)] a |
conbercept vs bevacizumab | − 17.35 [(− 25.84 to − 8.57) (− 27.14 to − 7.16)] a |
conbercept vs ranibizumab | − 16.23 [(− 24.57 to − 7.74) (− 25.97 to − 6.25)] a |
conbercept vs brolucizumab | − 14.68 [(− 24.01 to − 5.17) (− 25.48 to − 3.94)] a |
Adverse events (AEs) 15 RCTs, 8 treatments + placebo, 5785 patients No inconsistency in the network (chi-squared = 0.01, p-value = 0.93) Between-study variance: 0.01 (0.00–0.15) | |
Bevacizumab vs aflibercept | 1.11 [(0.53–2.1) (0.49–2.25)] |
Ranibizumab vs aflibercept | 1.23 [(0.76–1.93) (0.67–2.16)] |
Ranibizumab vs bevacizumab | 1.11 [(0.71–1.87) (0.63–2.12)] |
Brolucizumab vs aflibercept | 1.07 [(0.77–1.46) (0.67–1.69)] |
Brolucizumab vs bevacizumab | 0.97 [(0.48–2.14) (0.45–2.34)] |
Brolucizumab vs ranibizumab | 0.87 [(0.5–1.55) (0.46–1.72)] |
Conbercept vs aflibercept | 0.74 [(0.28–2) (0.26–2.09)] |
Conbercept vs bevacizumab | 0.67 [(0.22–2.15) (0.21–2.3)] |
Conbercept vs ranibizumab | 0.61 [(0.22–1.68) (0.21–1.77)] |
Conbercept vs brolucizumab | 0.69 [(0.25–1.96) (0.23–2.08)] |
Arterial thromboembolic events (ATE) 15 RCTs, 8 treatments + placebo, 6365 patients No source of inconsistency in the network (no closed loops) Between-study variance: 0.03 (0.00–0.48) | |
Bevacizumab vs aflibercept | 1.13 [(0.31–4.32) (0.29–4.78)] |
Ranibizumab vs aflibercept | 1.81 [(0.61–5.86) (0.54–6.68)] |
Ranibizumab vs bevacizumab | 1.6 [(0.85–3.15) (0.7–3.85)] |
Brolucizumab vs aflibercept | 0.66 [(0.28–1.52) (0.24–1.82)] |
Brolucizumab vs bevacizumab | 0.58 [(0.12–2.61) (0.11–2.93)] |
Brolucizumab vs ranibizumab | 0.36 [(0.09–1.42) (0.08–1.57)] |
Conbercept vs aflibercept | 0.73 [(0.01–38.5) (0.01–39.9)] |
Conbercept vs bevacizumab | 0.66 [(0.01–31.63) (0.01–32.15)] |
Conbercept vs ranibizumab | 0.41 [(0.01–19.15) (0.01–20.03)] |
Conbercept vs brolucizumab | 1.1 [(0.02–62.85) (0.02–64.99)] |