Methodological quality of the review: Medium confidence
Author: Qiuming Hu, Haoyu Li, Yi Du, Jianfeng He
Region: Not reported
Subsector: Myopia treatment
Equity focus: No
Study population: >50 years
Type of programme: Hospital based
Review type: Other review
Quantitative synthesis method: Systematic review and meta-analysis
Qualitative synthesis method: Not applicable
Background: Macular choroidal neovascularisation (CNV) formation is one of the most common complications of central vision impairment in patients with pathological myopia. The prognosis of myopic CNV (mCNV) is poor. Antivascular endothelial growth factor (VEGF) therapy has become the first-line therapy for mCNV, and it might be a good treatment for nonsubfoveal CNV. The earliest report of intraocular injection of anti-VEGF drugs for the treatment of mCNV was in 2006, and short-term observations of this aspect become more and more common in recent years, and the conclusions support the effectiveness of anti-VEGF drugs against mCNV. Most previous studies reported that intraocular injections of VEGF inhibitors have resulted in significant anatomical and functional gains in mCNV treatment, such as improved visual acuity and central dark spots, but most studies lacked randomised control settings. The exact difference of efficacy between bevacizumab and ranibizumab in mCNV has not been determined.
Objectives: To evaluate the effect of intravitreal bevacizumab (IVB) and ranibizumab (IVR) for the treatment of choroidal neovascularisation (CNV) secondary to pathologic myopia (PM) by meta-analysis.
Main findings: Eventually, three eligible RCTs were included, a total of 158 eyes (79 for IVR and 79 for IVB), followed-up for 3 to 18 months. The three included studies are all prospective clinical randomised controlled studies. The performance bias is the most significant bias among the included studies. The same treatment and dose (0.05 ml 0.5 mg ranibizumab, 0.05 ml 1.25 mg bevacizumab) were used for the three studies. Two of the included studies considered that there was no significant difference in the therapeutic effect of IVR versus IVB on mCNV, and one study was deemed necessary to increase the sample size for further study; one study considered IVR to be more advantageous than IVB in the number and benefit of treatment. A significant increase of BCVA from baseline was observed in both groups in included studies. No heterogeneity between the IVR group and the IVB group was reported at 1 month (P=.23, I2=32%), 3 months (P=.36, I2=0), 6 months (P=.46, I2=0%) and 12 months (P=.87, I2=0%). No significant difference was reported between the two groups in increasing BCVA at 1 month (Z=0.30, 95% CI=-0.08 to 0.11, P=.76), 3 months (Z=0.36, 95% CI=-0.10 to 0.15, P=.72), 6 months (Z=0.17, 95% CI=-0.10 to 0.12, P=.86) and 12 months (Z=0.64, 95% CI=-0.15 to 0.08, P=.52). Results of analysis showed that the three articles were highly heterogeneous (P=.0008, I2=86%). Using the random effects model analysis, there was no significant difference between the number of injections in the IVR and IVB groups during the follow-up period (Z=1.13, 95% CI=-1.83 to 0.49, P=.26>0.05). Complete resolution fluorescein leakage was observed in all 16 eyes that received IVB treatment, and 15 out of 16 eyes received IVR treatment in Gharbiya’s study. Complete CNV stabilisation was observed in 21 out of 25 subjects that received IVB treatment, and all 23 subjects received IVR treatment in Iacono’s study.
Based on these findings, authors conclude that both IVR and IVB can significantly improve BCVA of eyes with mCNV, but there was no significant difference between the two therapies in the treatment of mCNV.
Published studies were included if they: compared the effects between intravitreal injection of ranibizumab and bevacizumab on treatment of myopic CNV; the study sample size was not <30 eyes and reported one or more of the following outcomes at month 1, 3, 6, 12 or longer observation time points: best corrected visual acuity (BCVA), central foveal thickness (CFT), CNV stabilisation, number of treatments, and ocular or systemic adverse events, though visual acuity was regarded as the primary outcome in the subsequent data analysis; and repetitive publications or documents of the same sample should be combined. All studies included should be randomised controlled trials and excluded potential publication bias. The titles and abstracts of retrieved articles were independently scanned by two authors to gather information and determine whether they met inclusion criteria.
Seven databases (retrieval of literature from PubMed, Embase, Web of Science, the Cochrane Library, CNKI, CQVIP and Wanfang) and ClinicalTrials.gov website were searched in November 2018. In conducting the search in the English database, retrieval keywords included pathologic myopia (myopia, degenerative), myopic choroid neovascularization, choroidal neovascularisation, bevacizumab (Avastin), ranibizumab (Lucentis); myopic choroidal neovascularisation was searched in ClinicalTrials gov. A bias risk assessment of included studies was performed.
In meta-analysis, the effect sizes of each study were presented as mean difference, with 95% confidence intervals (CIs) for continuous data and risk ratio (RR) with 95% CIs for discontinuous data. The statistical results of the combined effects were expressed as Z values, and the P values were obtained according to the Z values. P<.05 was considered statistically significant between the two groups.
Applicability/external validity: Regarding the external validity, the authors reported some limitations which need to be taken into account when using the results externally. The authors reported the bias and statistical difference in this review is due to the inconsistencies between the follow-up time of the included literatures and the termination event.
Geographic focus: Not discussed.
Summary of quality assessment:
Although authors used appropriate methods to analyse findings of included studies, literature searches were not thorough to ensure that all relevant studies were identified and included in the review, which may impact on the validity of review findings. Therefore, this review was attributed medium confidence.
Hu Q, Li H, Du Y, He J. Comparison of intravitreal bevacizumab and ranibizumab used for myopic choroidal neovascularization: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019 Mar;98(12):e14905.