Study IDa | |||||||
---|---|---|---|---|---|---|---|
Korobelnik 2015 [13] | Régnier 2014 [14] | Zhang 2016 [15] | Muston 2018 [16] | Virgili 2018 [17] | |||
Protocol identified | x | x | x | x | √ | ||
Search | Cochrane | √ | √ | √ | √ | √ | |
EMBASE | √ | √ | √ | √ | √ | ||
MEDLINE | √b | √b | √c | √b | √ | ||
Others | d | e | f | g | h | ||
Date | 01/2013 | 02/2014 | 08/2015 | 12/2016 | 04/2017 | ||
Number of studies | 11 | 8 | 21 | 13 | 24 | ||
Statistics | Network model | Bayesian | Bayesian | Bayesian | Bayesian | Frequentist | |
Sensitivity analysis | Heterogeneous studies; ethnic group | Ethnic group | Heterogeneous studies; ethnic group | Studies at higher risk of biasi | |||
Covariates | Baseline BCVA and/or CRT | Baseline BCVA and/or CRT | Baseline BCVA and/or CRT | ||||
Others | Some IPD | ||||||
Participants | Diabetic macular oedema | √ | √ | √ | √ | √ | |
Significant, focal or diffuse; DME secondary to diabetes involving the centre of the macula; Retinal thickening due to DME/clinically significant macula oedema with DR | Baseline BCVA and CRT varied—24–78 letters | Non-specific | As for Korobelnik 2015 | Baseline visual acuity between 20/200 and 20/40; Previously received central/peripheral laser or treatment naïve included | |||
Interventionsk | Aflibercept | 2q4 or 2q8 | 2 mg; bimonthly | Intravitreal | 2q8 | 2 mgj | |
+ Laser | √ | √ | |||||
Ranibizumab | 0.5 mg, PRN | 0.5 mg, PRN | Intravitreal | 0.5 mg PRN or 0.5 mg T&E or 0.3 mg q4 | 0.5 mg or 0.3 mg | ||
+ Laser | √ | √ | √ | Deferred | |||
Prompt | |||||||
Dexamethasone (continued) | Implants | Implants | |||||
Bevacizumab | Intravitreal | 1.25 mg | 1.25 mg | ||||
+ Laser | √ | √ | √ | ||||
Triamcinolone acetonide | Intravitreal | 4 mg q4/PRN or 4 mg q4 | |||||
+ Laser | √ | √ | √ | ||||
Pegaptanib | 0.3 mg | ||||||
Laser | √ | √ | √ | √ | |||
+ Sham injection | √ | ||||||
Sham | √ | √ | |||||
Outcomes | Binary | ETDRS letters in BCVA | > 10 and > 15 gain; > 10 and > 15 loss | > 10 gain | > 10 and > 15 gain; > 10 and > 15 loss | > 15 gain | |
AEs | √ | √ | √ | ||||
Continuous (average change) | In BCVA using ETDRS charts | √ | √ | √ | √ | ||
CMT | CRT measured using OCT | ||||||
Conclusions | Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons | Ranibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser | Our analysis confirms that intravitreal aflibercept is the most favourable with both BCVA improvement and CMT decrease than other current therapies in the management of DME within 12 months. Vascular endothelial growth factor inhibitors for DME should be used with caution due to systematic AEs. Combined intravitreal triamcinolone with LASER has a stronger efficacy in decreasing CMT than the other interventions in the early stage after injection | This NMA, which incorporated IPD to improve analytic robustness, showed evidence of the superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA | Anti-VEGF drugs given by injection into the eye improve vision in people with diabetic macular oedema as compared to no average improvement with laser photocoagulation. One of these drugs, aflibercept, probably works slightly better after 1 year. There did not appear to be important harms from any of these drugs | ||
Key results | There was an increase in the mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN. IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants | The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept. Ranibizumab and aflibercept were statistically superior to laser monotherapy. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser | Intravitreal ranibizumab improved BCVA most significantly in 6 months and intravitreal aflibercept in 12 months. Intravitreal triamcinolone combined with LASER decreased CMT most significantly in 6 months and intravitreal aflibercept in 12 months. Compared with the relatively high rate of ocular AEs in the groups with administration of steroids, systematic AEs occurred more frequently in the groups with vascular endothelial growth factor inhibitors involved | IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for the mean change in BCVA, ≥ 15 ETDRS letter gain, and ≥ 10 ETDRS letter loss. IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA | All three anti-VEGF drugs prevent visual loss and improve vision in people with DMO (high-certainty evidence) People receiving ranibizumab were probably slightly less likely to improve vision compared with aflibercept at 1 year after the start of treatment (moderate-certainty evidence). Approximately three in 10 people improve vision by 3 or more lines with ranibizumab, and one in 10 additional people can achieve this with aflibercept. People receiving ranibizumab and bevacizumab probably have a similar visual outcome at 1 year after the start of treatment (moderate certainty evidence). Aflibercept, ranibizumab, and bevacizumab are similar for common and serious systemic harms (such as any disease leading to hospitalisation, disability, or death) (moderate- or high-certainty evidence) but is less certain for arterial thromboembolic events (mainly stroke, myocardial infarction, and vascular death) and death of any cause (very low-certainty evidence) |