What are the benefits and risks of different treatments for intermittent exotropia (an eye co-ordination problem that starts in childhood)?

Key messages

· Covering one eye with a patch improves the eye co-ordination of children with intermittent exotropia more effectively than regular monitoring by an eye specialist.

· Few studies have compared other treatments for intermittent exotropia, and those that have do not provide clear answers about their benefits and risks.

· Well-conducted studies are needed in this area to improve the management of intermittent exotropia.

What is intermittent exotropia?

Intermittent exotropia is an eye condition that develops in the first year of life. It causes one or both eyes to turn out toward the ear, typically when a child looks into the distance, daydreams, is tired, or is in bright sunlight. Only one eye turns out at a time, while the other eye points straight forwards. This can happen infrequently, or regularly throughout the day.

What treatments are available for intermittent exotropia?

Regular monitoring (observation) by an eye specialist may be all that is needed when a child’s eyes point in the same direction most of the time, or when intermittent exotropia does not affect vision.

For children with more severe intermittent exotropia, several treatments are available, including:

· eye exercises, to improve a child’s control over their eye movements;

· glasses, to encourage the eyes to work together;

· eye muscle surgery, to adjust the position of the eyes; and

· covering one eye with a patch, to strengthen the other eye.

What did we want to find out?

We wanted to find out:

· which treatment works best for intermittent exotropia; and

· whether treatments cause any unwanted (adverse) effects.

What did we do?

We searched for studies that compared different treatments for intermittent exotropia against each other. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 6 studies that involved a total of 890 people who were mostly children aged 12 months to 10 years. The studies followed people for between six months and three years, and took place in the USA (four studies), India (one study), and Turkey (one study). The studies compared:

· patching against observation (two studies); and

· different treatments involving surgery (four studies).

Patching compared to observation

The evidence:

· shows that patching is better than observation for improving eye co-ordination; and

· suggests that patching and observation may have similar effects on sharpness of near vision.

Different surgical procedures

The evidence suggests that:

· surgery on the muscles that control the outward movement of both eyes is probably better for improving eye co-ordination than surgery on the muscles that control both inward and outward movement in one eye;

· these two procedures may have similar effects on sharpness of near vision and quality of life, and may lead to similar numbers of adverse effects (such as small lumps under the skin); and

· there may be little to no difference in effect on eye co-ordination when looking at distant objects between surgical procedures on the inside of the eye (‘plication’ and ‘resection’) when combined with surgery on the outside of the eye.

What are the limitations of the evidence?

The evidence is based on a small number of studies, and several studies may have used methods likely to introduce errors in their results. In general, the studies provided limited information about the benefits and risks of different treatments for intermittent exotropia. For example, they often did not investigate adverse effects or effects on sharpness of vision at a distance and quality of life.

How up-to-date is this evidence?

The evidence is current to January 2021.

Authors' conclusions: 

Patching confers a clinical benefit in children aged 12 months to 10 years of age with basic- or distance-type X(T) compared with active observation. There is insufficient evidence to determine whether interventions such as bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection; lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection; and prism adaptation test prior to eye muscle surgery versus eye muscle surgery alone may confer any benefit.

Read the full abstract...
Background: 

The clinical management of intermittent exotropia (X(T)) has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for intervention, the most effective form of treatment, and whether there is an optimal time in the evolution of the disease at which any given treatment should be carried out.

Objectives: 

The objective of this review was to analyze the effects of various surgical and non-surgical treatments in randomized controlled trials (RCTs) of participants with intermittent exotropia, and to report intervention criteria and determine whether the treatment effect varies by age and subtype of X(T).

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 1), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Science Information database (LILACS); the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. The date of the search was 20 January 2021. We performed manual searches of the British Orthoptic Journal up to 2002, and the proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA), and American Association for Pediatric Ophthalmology and Strabismus meeting (AAPOS) up to 2001.

Selection criteria: 

We included RCTs of any surgical or non-surgical treatment for intermittent exotropia.

Data collection and analysis: 

We followed standard Cochrane methodology.

Main results: 

We included six RCTs, four of which took place in the United States, and the remaining two in Asia (Turkey, India). A total of 890 participants with basic or distance X(T) were included, most of whom were children aged 12 months to 10 years. Three of these six studies were from the 2013 version of this review. Overall, the included studies had a high risk of performance bias as masking of participants and personnel administering treatment was not possible.

Two RCTs compared bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection, but only one RCT (n = 197) reported on the primary outcomes of this review. Bilateral lateral rectus recession likely results in little difference in motor alignment at near (MD 1.00, 95% CI −2.69 to 4.69) and distance (MD 2.00, 95% CI −1.22 to 5.22) fixation as measured in pupillary distance using PACT (moderate-certainty evidence). Bilateral lateral rectus recession may result in little to no difference in stereoacuity at near fixation (risk ratio (RR) 0.77, 95% CI 0.35 to 1.71), adverse events (RR 7.36, 95% CI 0.39 to 140.65), or quality of life measures (low-certainty evidence).

We conducted a meta-analysis of two RCTs comparing patching (n = 249) with active observation (n = 252), but were unable to conduct further meta-analyses due to the clinical and methodological heterogeneity in the remaining trials. We found evidence that patching was clinically more effective than active observation in improving motor alignment at near (mean difference (MD) −2.23, 95% confidence interval (CI) −4.02 to −0.44) and distance (MD −2.00, 95% CI −3.40 to −0.61) fixation as measured by prism and alternate cover test (PACT) at six months (high-certainty evidence). The evidence suggests that patching results in little to no difference in stereoacuity at near fixation (MD 0.00, 95% CI −0.07 to 0.07) (low-certainty evidence). Stereoacuity at distance, motor fusion test, and quality of life measures were not reported. Adverse events were also not reported, but study authors explained that they were not anticipated due to the non-surgical nature of patching.

One RCT (n = 38) compared prism adaptation test with eye muscle surgery versus eye muscle surgery alone. No review outcomes were reported.

One RCT (n = 60) compared lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection. Lateral rectus recession and medial rectus plication may not improve motor alignment at distance (MD 0.66, 95% CI −1.06 to 2.38) (low-certainty evidence). The evidence for the effect of lateral rectus recession and medial rectus plication on motor fusion test performance is very uncertain (RR 0.92, 95% CI 0.48 to 1.74) (very low-certainty evidence).