Assessment of foveal avascular zone and macular vascular plexus density in children with unilateral amblyopia: a systematic review and meta-analysis

Authors: Gao L, Gao Y, Hong F, Zhang P and Shu X.

Geographical coverage: China, Turkey, the USA, Japan and Portugal.

Sector: Burden of disease

Sub-sector: Epidemiology

Equity focus: Children

Study population: Children with amblyopia

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Studies suggest amblyopia affects the postnatal reduction of ganglion cells, potentially leading to a thicker circumpapillary retinal nerve fibre layer. A meta-analysis of Optical Coherence Tomography (OCT) studies found a thicker foveola in amblyopic eyes. However, it’s unclear if this is linked to changes in blood flow or microvessel density. OCT Angiography (OCTA), a non-invasive imaging technique, provides high-resolution blood flow information and angiographic images of the retina and choroid. While OCTA has been used in studies on amblyopic eyes, results are inconsistent, and no meta-analysis exists to synthesize the quantitative measurements of OCTA in children with amblyopia.

Objectives: To examine the quantitative measurements of OCTA in children with amblyopia using the meta-analysis methodology – to provide a firmer basis for the use of OCTA for the management of amblyopia.

Main findings:

In summary, the authors discovered that, based on OCTA, amblyopic eyes exhibited a lower vessel density in the parafoveal SCP and DCP compared to healthy control eyes, but this was not the case when compared to their fellow eyes. Furthermore, no significant differences were observed in the area of the foveal avascular zone and the thickness of the fovea between amblyopic and non-amblyopic eyes.

Twelve studies were included in this review, including eight cross-sectional studies, one longitudinal study, one cohort study, one case-control study and one undefined. A total of 1,744 patients were included. All 12 studies were of high quality, according to the Newcastle-Ottawa scale (NOS).

When considering the parafovea, according to the authors the microvessel density was reduced in amblyopic eyes compared with healthy control eyes in the superficial capillary plexus (SCP) in 6 x 6 volume scan (Weighted mean differences (WMD) = -2.12, 95%CI: -3.24, -0.99) but not SCP in 3 x 3 volume scan (WMD = -1.43, 95%CI: -2.96, 0.11). In the deep capillary plexus (DCP), authors revealed that amblyopia did not decrease vessel density in the 6 x 6 volume scan (WMD = -2.22, 95%CI: -5.86, 1.42; I² = 79.6%, p = 0.008), but a difference was observed in the whole eye 3 × 3 (WMD = -1.95, 95%CI: -3.23, -0.67; I² = 27.5%, p = 0.252). Authors found no significant differences in the foveal avascular zone area and foveal thickness between amblyopic eyes and healthy control eyes. Furthermore, authors note no significant differences in microvessel density, foveal avascular zone area, and foveal thickness between amblyopic eyes and fellow eyes.

OCTA is a recent technology; the area is still being explored, and the number of studies is small. Therefore, study authors note that future studies should provide additional data, especially clinical trials.

Methodology:

Study eligibility criteria were as follows: (1) children with amblyopia in one eye as the case group, compared with the contralateral eyes or healthy control eyes; (2) quantitative measurement of the foveal avascular zone and macular vascular plexus density using OCTA; (3) language limited to English; and (4) the outcomes could be extracted.

Authors searched on the following databases: PubMed, EMBASE, and the Cochrane Library for available papers up to March 2021 using the MeSH terms and key words pertinent to “amblyopia” and “optical coherence tomography angiography”.

The selection and inclusion of studies were performed in two stages by two independent reviewers. This included, first, the analysis of the titles and abstracts, followed by the full-texts. Any disagreements were resolved by a third reviewer.

The observational studies were evaluated according to the NOS. All analyses were performed using Stata SE 14.0. WMDs and corresponding 95% confidence intervals (CIs) were used to compare the retina parameters between the eyes with amblyopia and the contralateral eyes or healthy control eyes. Statistical heterogeneity among these studies was calculated using Cochran’s Q-test and the I² index. Q-test with p <0.10 and I² >50% indicated high heterogeneity, and the random-effects model was then used; otherwise, the fixed-effects model was used. The publication bias was analysed using funnel plots; p-values <0.05 were considered statistically significant.

Applicability/external validity:

The review does not explicitly report the applicability and external validity of the findings. However, it does discuss some factors that may affect the generalizability of the results, such as: high heterogeneity; lack of standardized definitions and measurements of foveal avascular zone and macular density across the studies; and potential confounding effects of refractive error, axial length, and ocular alignment pn OCTA parameters.

Geographic focus: Authors included studies from low- and middle-income countries such as China, Turkey and Japan.

Summary of quality assessment:

The study employed two independent reviewers to minimize bias in article selection and evaluated the quality of the included studies. However, the search was somewhat restricted as it did not encompass non-English or unpublished materials, and there was no mention of scrutinising the reference lists of the included studies. Despite the generally robust analysis methods, the inclusion of only 12 studies inherently limited the scope of the review. Given these limitations in the search strategy, we have low confidence in the review’s results.