Table 2.
Clinical characteristics of included studies in the meta-analysis
| Study | Mean age in years (range) | Number of injections prior to conversion (range) | Time between last anti-VEGF treatment and conversion (range) | Mean number of aflibercept injections (range) | Treatment regimen |
|---|---|---|---|---|---|
| Aghdam et al25 | 73.95±10.65 (56–91) | 9.55±6.91 (6–30) | Not <4 weeks or >6 weeks | 7.27±1.98 (4–12) | Loading phase of aflibercept every 4 weeks for 3 months followed by PRN |
| Arcinue et al30 | 81.00 (IQR 76–87) | 13.00 (IQR 7–22) | Median 6 weeks (range 4–18) | Those treated every 8 weeks =4 (4–6) 21 eyes were switched to every 4-weekly treatment |
8 weekly aflibercept injections without loading phase In case of persistent fluid regimen, changed to every 4 weeks |
| Bakall et al42 | 79.00 (60–88) | 25.60 (6–74) 10.6 for ranibizumab group 15.0 for bevacizumab group |
4 weeks | 5.72 (in 9 eyes treatment was stopped prior to 6 months: in 8 patients after the fifth injection and in 1 patient after the fourth injection) | Loading phase of aflibercept every 4–6 weeks for 3 months, followed by PRN |
| Barthelmes et al31 | N/A | N/A | N/A | 6.60 | N/A |
| Broadhead et al22 | 78.70 | 34.80 | N/A | 8.00 | Loading phase of aflibercept every 4 weeks for 3 months, followed by 8 weekly injections |
| Chan et al32 | 83.40 | Bevacizumab group: 4.80 over 6 months prior to switch Ranibizumab group: 8.60 over 6 months prior to switch Mixed group: 4.90 over 6 months prior to switch |
N/A | 5.40 5.40 bevacizumab group 5.50 ranibizumab group 5.50 mixed group |
3 monthly loading doses, and then treat- and-observe strategy |
| Chang et al24 | 77.80±7.50 | 34.90±16.10 | >30 days | 5.00 | Loading phase of 3 monthly injections plus mandatory injection at weeks 16 and 24 |
| Chang et al23 | 77.80±7.50 | 34.90±16.10 | 36 days | 8.00 | Loading phase of 3 monthly injections plus mandatory injection every 2 months at months 4, 6, 8, 10, and 12 |
| Chatziralli et al43 | 78.60±8.20 | 7.00±4.50 (3–36) | N/A | 6.80 | 8 weekly aflibercept injections. No loading dose |
| Cho et al41 | 81.00 (62–95) | 20.20±7.60 (7–37) | 28–35 days | 4.40 (3–6) | Loading phase of 3 monthly injections, and then every 6–8 weeks for 21 eyes (75%) |
| de Massougnes et al33 | 78.80±7.10 | 26.10±12.00 | N/A | N/A | 3 monthly loading doses, and then treat-and -observe strategy |
| Eadie et al34 | 79.90 | 3–38 | 5.88 weeks (4–10) | 5.53 (2–11) | Treat + extend approach, or every 4 weeks due to persistent exudation |
| Gerding45 | 80.60±7.70 (60.9–100) | 21.50±11.70 (9–54) | 46.5 days | 4.01±1.14 (2–6) | PRN |
| Gharbiya et al35 | 70.10±8.10 (60–86) | 34.40±11.90 (15–50) | 4.90±0.80 weeks (4–6) | 4.50±1.30 (3–6) | Loading dose of 3 injections and retreatment according to following factors: 1) VA loss of at least 5 letters with OCT evidence of fluid, 2) persistent or recurrent IRF/SRF on OCT, and 3) new SR hemorrhage from CNV |
| Grewal et al26 | 80.70±4.50 | 29.80±17.10 (6–70) | Not <28 days | 10.20±1.20 (10–12) | Loading phase of 3 monthly injections plus bimonthly injections in case of resolution of the edema or monthly in case of edema |
| Hall et al36 | 80.40±1.45 | 14.90±2.01 (2–53) | N/A | 6.27±0.37 (4–11) (6-month follow-up: 30 patients received 4.50±0.11 injections; 9 month follow-up: 26 patients received 6.00±0.23; 12-month follow-up: 22 patients received 7.17±0.38) | In the presence of SRF at the time of the switch: loading phase of 3 monthly injections, and then treat-and-extend regimen. In absence of SRF at the time of the switching: treat-and -extend regimen |
| Hariri et al46 | 81.00 (60–97) | 18.00 | 35.80±5.04 days (28–42) | N/A | N/A |
| He et al47 | 82.90±8.15 | 17.46±10.07 (3–46) | N/A | 7.51±1.65 | 82 eyes: standard therapy: 3 monthly loading doses and bimonthly doses thereafter 34 eyes: Rx with less than standard therapy, undergoing injections further apart 26 eyes: Rx with more than standard: monthly or every 6 week injections |
| Kanesa-Thasan et al37 | 80.70±4.38 | 25.70±20.10 (6–70) | N/A | 15.10±2.47 18 months (12–19) |
Minimum 3 monthly aflibercept, and then switched to a bimonthly interval if complete resolution of SRF or IRF, or kept at an interval at which complete resolution was maintained, based on treat–and -extend approach |
| Kumar et al38 | 79.00±8.00 (72–84) | 28.60±20.10 (IQR 11–43) | 34.40±5.00 days (IQR 32–37) | 5.30±0.60 (IQR 5–6) | Loading phase of 3 monthly injections followed by PRN treatment |
| Major et al48 | 81.20 (60–95) | 24.80 (2–66) | 36 days (27–65) | N/A | N/A |
| Mantel et al27 | 76.00 | 20.70 Group A (aflibercept n=10 eyes): 21.30 Group R (ranibizumab n=11 eyes): 20.10 |
N/A | 10.70 Group A (aflibercept): 10.70 Group R (ranibizumab): 10.70 |
3 monthly injections and then observe-and -extend regimen for 12 months |
| Narayan and Muecke39 | 83.20±7.00 | N/A | N/A | 7.58 | 48 eyes (60%): 8 weekly; 25 eyes (31%): 6 weekly; 6 eyes (7.5%): 4 weekly; 1 eye: initially 4 weekly extended to 12 weekly |
| Pinheiro-Costa et al44 | 76.60 (61–92) | 12.40 16.50 (6–24) bevacizumab group 8.90 (3–39) ranibizumab group |
N/A | 5.10±1.70 (range 3–9) Bevacizumab group: 4.50±1.60 Ranibizumab group: 5.60±1.60 |
Treat and extend |
| Ricci et al49 | 79.00 (59–93) PRN group 77 (52–85) fixed regimen group |
5.00 (4.5–7.50) PRN group 6.50 (4–9.5) fixed regimen group |
N/A | 3.50±1.60 (1–7) PRN group 7.00 fixed regimen group |
36 eyes (50%): PRN regimen; 36 eyes (50%): loading dose of 3 monthly injections followed by fixed bimonthly injection |
| Sarao et al28 | 78.30±8.20 | 15.20±1.90 | N/A | 3.50±1.80 | Initial injection of aflibercept and then reviewed every 4 weeks. Rx at investigators’ discretion |
| Thorell et al40 | 76.20±8.70 | 30.70±15.50 | N/A | 4.50±1.00 | Treat-and -extend strategy, starting from every 4-week treatment |
| Wykoff et al29 | 77.80 (55–95) | 42.00 (19–67) | 33.30 days (28–68) | 5.60 | Loading phase of 3 monthly injections, one mandatory dose at month 4 and PRN doses at months 3 and 5 |
Abbreviations: CNV, choroidal neovascularization; IQR, interquartile range; IRF, intraretinal fluid; N/A, not available; OCT, optical coherence tomography; PRN, pro re nata; Rx, treatment; SRF, subretinal fluid; SR, subretinal; VA, visual acuity; VEGF, vascular endothelial growth factor.