What are the benefits and risks of different surgical procedures for infantile nystagmus syndrome (an eye disorder that develops shortly after birth)?

Why is this question important?
Infantile nystagmus syndrome (INS) is an eye disorder that causes involuntary movement of the eyes from side to side, up and down, or in circles. INS typically develops shortly after birth, and persists throughout life. It is often associated with visual problems, such as:
- long-sightedness (when people can see distant objects clearly, but near objects appear blurred);
- or short-sightedness (when people can see near objects clearly, but distant objects appear blurred).

There is currently no cure for INS. However, it is possible to reduce eye movement and improve people’s vision. One of the main options is eye surgery, which involves operating on the muscles that control eye movement. Several different surgical procedures can be used: some procedures involve detaching and reattaching the eye muscles, whereas others require complete removal of these muscles.  

It is unclear whether some surgical procedures for INS have more benefits or risks than others. To find out which surgical procedures work best, we reviewed the evidence from research studies. We were particularly interested in whether different surgical procedures could improve vision and quality of life in people with INS. We also wanted to know about any adverse (unwanted) effects.

How did we identify and evaluate the evidence?
First, we searched for randomised controlled studies, in which people were randomly divided into two or more treatment groups. This makes it less likely that any differences between treatment effects were actually due to differences in the people who received them (rather than due to the treatments themselves, which is what we wanted to find out).

We then compared the results, and summarised the evidence from all the studies. Finally, we rated our confidence in the evidence, based on factors such as study methods and sizes, and the consistency of findings across studies.

What did we find?
We found one study, set in India, that involved a total of 10 people with INS who were followed for six months after surgery. The study authors did not report any information about: 
- the age and gender of the people who took part in it;
- or the source of funding for the study.

The study compared two different surgical procedures: 
- one procedure in which two horizontal rectus muscles (eye muscles that control side-to-side eye movements) were moved from their original position to a position further back on the eyeball; and
- another procedure in which four horizontal rectus muscles were detached and reattached, in their original position.
The procedures were conducted in both eyes.

The study compared the effects of the treatments on:
- clarity of vision six months after surgery;
- intensity of eye movement six months after surgery;
- adverse events six months after surgery; and
- quality of life.  

The study did not investigate the effects of treatments on:
- head posture;
- the amount of time when the eye is still; or
- the time it takes to recognise objects.

We have very little confidence in the evidence from the study we found, because:
- it is based on a very small number of people; and
- the patients and researchers in the study knew which type of surgery each patient received. This knowledge may have influenced the study results.

We therefore cannot determine whether the two procedures investigated in the study had different benefits and risks.

What does this mean?
There is insufficient evidence to determine whether some surgical procedures are better than others for INS. We need researchers to conduct robust randomised controlled trials in future, so that we can compare different procedures. This would help clinicians, and people with INS, to make treatment decisions based on evidence from research.

How-up-to date is this review?
The evidence in this Cochrane Review is current to July 2020.

Authors' conclusions: 

This systematic review identified minimal high-quality evidence relating to the efficacy and safety of surgical interventions for INS. The limited availability of evidence must be considered by clinicians when treating INS, particularly given these procedures are irreversible and often performed on children. More high-quality RCTs are needed to better understand the efficacy and safety profile of surgical interventions for INS. This will assist clinicians, people with INS, and their parents or caregivers to make evidence-based treatment decisions.

Read the full abstract...
Background: 

Infantile nystagmus syndrome (INS) is a type of eye movement disorder that can negatively impact vision. Currently, INS cannot be cured, but its effects can potentially be treated pharmacologically, optically, or surgically. This review focuses on the surgical interventions for INS.

Despite the range of surgical interventions available, and currently applied in practice for the management of INS, there is no clear consensus, and no accepted clinical guidelines regarding the relative efficacy and safety of the various treatment options. A better understanding of these surgical options, along with their associated side effects, will assist clinicians in evidence-based decision-making in relation to the management of INS.

Objectives: 

To assess the efficacy and safety of surgical interventions for INS.

Search strategy: 

We searched CENTRAL, MEDLINE Ovid, Embase Ovid, ISRCTN registry, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to 3 July 2020, with no language restrictions.

Selection criteria: 

We included randomised controlled trials (RCTs) studying the efficacy and safety of surgical options for treating INS.

Data collection and analysis: 

Our prespecified outcome measures were the change from baseline in: binocular best-corrected distance visual acuity; head posture; amplitude, frequency, intensity, and foveation period durations of the nystagmus waveform; visual recognition times; quality of life and self-reported outcome measures; incidence of adverse effects with a probable causal link to treatment; and permanent adverse effects after surgery.

Two review authors independently screened titles and abstracts and full-text articles, extracted data from eligible RCTs, and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE approach.

Main results: 

We only identified one eligible RCT (N = 10 participants), undertaken in India. This trial randomised participants to receive either a large retro-equatorial recession of the horizontal rectus muscle of 9 mm on the medial rectus and 12 mm on the lateral rectus, or a simple tenotomy and resuturing of the four horizontal rectus muscles. We did not identify any RCTs comparing a surgical intervention for INS relative to no treatment.

In the single eligible RCT, both eyes of each participant received the same intervention. The participants’ age and gender were not reported, nor was information on whether participants were idiopathic or had sensory disorders. The study only included participants with null in primary position and did not explicitly exclude those with congenital periodic alternating nystagmus. The study did not report funding source(s) or author declaration of interests. The evaluation period was six months.

We judged this study at low risk for sequence generation and other sources of bias, but at high risk of bias for performance and detection bias. The risk of bias was unclear for selection bias, attrition bias, and reporting bias.

There is very uncertain evidence about the effect of the interventions on visual acuity and change in amplitude, frequency, and intensity of the nystagmus waveform. We were unable to calculate relative effects due to lack of data. None of the participants in either intervention group reported adverse effects at six-month follow-up (very low-certainty evidence). There was no quantitative data reported for quality of life, although the study reported an improvement in quality of life after surgery in both intervention groups (very low-certainty evidence).

Change in head posture, foveation period durations of the nystagmus waveform, visual recognition times, and permanent adverse effects after surgery were not reported in the included study.

We judged the certainty of the evidence, for both the primary and secondary efficacy outcomes, to be very low. Due to a lack of comprehensive reporting of adverse events, there was also very low-certainty of the safety profile of the evaluated surgical interventions in this population. As such, we are very uncertain about the relative efficacy and safety of these interventions for the surgical management of INS.