Surgery at early versus late for intermittent exotropia: a meta-analysis and systematic review

Author: Dong Y, Nan L, Liu YY.

Geographical coverage: United States of America (USA), South Korea, Canada, Egypt, China, Iran, Korea and Singapore.

Sector: Treatment

Sub-sector: Postoperative outcomes

Equity focus: Children

Study population: Children

Review type: Other review

Quantitative synthesis method: Narrative synthesis and meta-analysis

Qualitative synthesis method: Not applicable


Intermittent exotropia (IXT) is a common form of childhood exotropia. It is characterised by the intermittent outward deviation of either eye that, if untreated, can gradually become constant in about one-third of the cases. The age of onset for IXT coincides with the age of the visual maturation in children, which is between 3 and 6 years old. Surgery is the mainstay approach for restoring binocular single vision and enhancing cosmetic appearance in patients with IXT. However, studies focused on the relationship between age at surgery and the surgical response have shown contradictory results.


To compare the outcomes between early surgery and late surgery for intermittent exotropia (IXT) with a meta-analysis.

Main findings:

Given high heterogeneity within included studies, authors performed a random-effect model for the pool of the first and final follow-up. Authors found no significant difference when comparing early and late surgical procedures in IXT patients (OR First follow-up = 0.88, 95%CI 0.53-1.44, p = 0.61; OR Final follow-up = 1.48, 95%CI 0.94-2.31, p = 0.09). However, these results did not withstand the sensitivity analysis. After omitting one study, the pooled analysis showed the final follow-ups were more promising for early surgery (OR = 1.71, 95%CI 1.17-2.49). However, authors emphasise the need of more extensive cohort studies to validate these findings.

Based on the subgroup analysis, authors found that early surgery has a better outcome in the 4-year boundary subgroup and BLR sub-group related to the final follow-up (OR4y = 2.64, 95%CI 1.57-4.44, p = 0.00; ORBLR = 2.25, 95%CI 1.36-3.74, p = 0.00).

Authors found no obvious evidence of publication bias according to Begg’s and Egger’s tests.

Overall, authors conclude that early surgery is able to provide a better long-term postoperative outcome when patients are younger than 4 years old or patients that chose BLR surgical method.


Inclusion criteria consisted of studies which: 1) grouped patients by age at surgery; 2) included precise data for early or late surgery; 3) defined the criteria of success; and 4) specified patient inclusion criteria and excluded paralytic or restrictive strabismus, congenital systemic anomalies, neurological disorders, history of previous strabismus surgery. Studies were excluded if other types of strabismus were detected, in which the surgical outcomes for IXT could not be extracted separately.

Authors conducted a search on PubMed, EMBASE, Web of Science, Cochrane and China National Knowledge Infrastructure with the following free words and MeSH terms: “intermittent exotropia”, “X(T)”, “surgery”, “age factors”, “early”, “late”. Searches were supplemented by screening references of all retrieved studies. Bibliographies of all included studies were reviewed to identify additional citations. The language was not limited to English. The search was conducted by two authors independently.

Data extraction was conducted by two reviewers independently and disagreements regarding inclusion of studies were resolved with other study authors. Data extracted included: first author, publication year, country, type of surgery, follow-up period, definition of success, the boundary of age at surgery.

Quality assessment of studies was assessed using an 11-item checklist, based on a pre-established scale provided by the Agency for Healthcare Research and Quality. An item would be scored 0 if the answer was ‘no’ or ‘unclear’; the article quality was assessed as follows: low quality: 0-3; moderate quality: 4-7; and high quality 8-11.

Authors conducted a statistical analysis of included studies. A p-value <0.05 was considered statistically significant. Forest plots were created to summarise the composite data, generating odds ratios and corresponding 95% confidence intervals for the outcome of the first and last follow-up. The heterogeneity among the studies included in the meta-analysis was assessed and quantified using the Chi-square based Q statistic test and the I2 metric. Findings were considered statistically significant if PQ ≤0.10 or I2 >50%. If there was statistically significant heterogeneity among the studies, a random-effects model would be used. If not, data would be pooled using a fixed-effects model. The sensitivity of the pooled results was assessed by omitting each study one at a time.

Applicability/external validity: Authors note that early surgery is able to provide a better long-term postoperative outcome when patients were younger than 4 years old, or patients chose the BLR method.

Geographic focus: This study focuses on several countries, however, authors do not report how findings may be applicable to low and middle countries.

    Summary of quality assessment:

This review used an appropriate approach to analyse the findings of included studies, addressed heterogeneity, used appropriate methods to extract data of included studies, and assess the risk of bias of included studies. However, major limitations were identified. Authors did not conduct a thorough search of the literature to ensure that all relevant studies were identified and therefore included in the review. Furthermore, it is not clear if the review covers an appropriate time period, and authors do not report the methods used to screen studies for inclusion in the review. Therefore, low confidence was attributed to the conclusions about the effects of this review.

Publication Source:

Dong Y, Nan L, Liu YY. Surgery at early versus late for intermittent exotropia: a meta-analysis and systematic review. Int J Ophthalmol. 2021 Apr 18;14(4):582-588. d