Methodological quality of the review: Medium confidence
Authors: Lin Z, Huang S, Xie B, Zhong Y
Region: Japan, Canada, China, USA, Korea, Germany and Belgium.
Sector: Open-angle glaucoma
Sub-sector: Risk factors
Equity focus: None specified
Review type: Other review
Quantitative synthesis method: Meta-analysis
Qualitative synthesis method: Not applicable
Glaucoma is becoming more common than expected, which is characterized by loss of retinal nerve fiber layers and an associated change in visual field, resulting in irreversible blindness worldwide. The total number of people aged 40–80 years diagnosed as having primary open-angle glaucoma (POAG) is predicted to increase to 79.76 million in 2040, approximately 85% of the glaucomatous population. The pathogenesis of open-angle glaucoma (OAG) has not been fully interpreted yet and accumulating evidence suggests that it is associated with the reduced blood perfusion to the optic nerve. As the peripapillary choroid branches are the main source of blood supply to this region, it has been proposed that an abnormal choroid circulation could be involved in the occurrence of glaucomatous optic neuropathy. However, it is specifically challenging to study because it is located beneath the retinal pigment epithelium (RPE).
To investigate the potential relationship between open-angle glaucoma (OAG) and peripapillary choroidal thickness (PPCT).
A total of 13 studies were included in the meta-analysis. Out of the 13 studies, four were conducted in Korea, two studies each were conducted in USA, Japan and China, and one study each was conducted in Canada, Germany and Belgium. Instruments used in these studies varied between Heidelberg, RTVue-100 SD-OCT, Cirrus HD-OCT, and swept-source OCT. The authors attributed all included studies a low risk of bias.
Using a random-effect, the authors showed that the average PPCT in OAG patients was reduced significantly compared to the healthy individuals (weighted mean difference (WMD) = −24.07, 95% confidence interval (CI): −34.29, −13.85).
The authors reported heterogeneity among studies reporting OAG and four-quadrant PPCT. Meta-analysis of each sector showed, according to the authors, a significant reduction of PPCT between the two groups in the superior (WMD = −28.87, 95% CI: −44.96, −12.78) and nasal (WMD = −21.75, 95% CI: −41.52, −1.98) parts was identified, but PPCT in the inferior (WMD= −9.57, 95% CI: −36.55, 17.40) and temporal (WMD = −13.85, 95% CI: −35.40, 7.70) sectors was not significantly different in OAG patients compared to the control group.
Subgroup analysis was carried by according to the type of glaucoma and the authors reported a significant different of average PPCT between primary open-angle glaucoma (POAG) patients and controls (WMD= −14.60, 95%CI: −23.41, −5.80) with no heterogeneity; the authors observed a similar result in NTG patients (WMD = −37.18, 95% CI: −66.13, −8.22) but with significant heterogeneity.
Findings did not change significantly at sensitivity analysis; and the authors report that no obvious publication bias was identified (Begg’s test, P=0.499; Egger’s test, P = 0.859).
The authors included published studies if they were in cross-sectional or case-control design comparing the differences in peripapillary choroidal thickness measured by OCT between patients with OAG and healthy controls. Abstracts from conferences, case reports, duplicate publications, letters, and reviews were excluded.
The authors conducted a search of PubMed, EMBASE, ISI Web of Knowledge, and the Cochrane Library without language or time restrictions. The final search was performed in January 2016. Systematic searches were conducted using the following key words in different combinations: “peripapillary choroidal thickness”, “optical coherence tomography”, and “open-angle glaucoma”. In addition, the reviewers also went through the reference lists of relevant published articles manually for any additional study. Two authors independently extracted data of included studies.
The authors used the Newcastle-Ottawa Scale (NOS) to quality assess included studies. A score of 6 or higher shows adequate quality.
Statistical analysis was performed using Revman software. The authors note, as the PPCT showed continuous outcomes, the effect sizes were measured using the WMD and 95% CI. We examined heterogeneity among the studies using the Chi2 test and I2 test. If I2 > 50, then the authors used a random-effect model and subgroup analysis was conducted.
Sensitivity analysis was used to explore stability and reliability of findings. To detect potential publication bias the authors used funnel plots, Begg’s and Egger’s test.
The authors emphasize that findings from this review is contrary to previously conducted meta-analysis. Glaucoma is often manifested with focal optic disc damage; authors note that none of the included studies addressed the morphological patterns of optic disc damage which might be highly related with the choroidal thickness around the optic nerve head. Therefore, current knowledge does not seem to give an exact explanation. The authors note that further investigations, focused on the relationship between the type of glaucomatous disc damage and the distribution of peripapillary choroidal thickness, are required to address this problem.
Applicability of findings to low- and middle- income countries were not discussed.
Summary of quality assessment:
Medium confidence was attributed in conclusions about the effects of this study. The authors used appropriate methods to analyse evidence of included studies. However, literature searches were not comprehensive enough to ensure that all relevant studies were identified and included in the review. In addition, it is not clear if the authors avoided biases whilst screening studies for inclusion.