Acquired brain injury can cause eye movement disorders which may include: strabismus,
gaze deficits and nystagmus, causing visual symptoms of double, blurred or 'juddery'
vision and reading difficulties. A wide range of interventions exist that have potential
to alleviate or ameliorate these symptoms. There is a need to evaluate the effectiveness
of these interventions and the timing of their implementation. We aimed to assess
the effectiveness of any intervention and determine the effect of timing of intervention
in the treatment of strabismus, gaze deficits and nystagmus due to acquired brain
injury. We considered restitutive, substitutive, compensatory or pharmacological interventions
separately and compared them to control, placebo, alternative treatment or no treatment
for improving ocular alignment or motility (or both). We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) (containing the Cochrane Eyes and Vision Trials
Register) (2017, Issue 5), MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, AMED Ovid, PsycINFO
Ovid, Dissertations & Theses (PQDT) database, PsycBITE (Psychological Database for
Brain Impairment Treatment Efficacy), ISRCTN registry, ClinicalTrials.gov, Health
Services Research Projects in Progress (HSRProj), National Eye Institute Clinical
Studies Database and the World Health Organization (WHO) International Clinical Trials
Registry Platform (ICTRP). The databases were last searched on 26 June 2017. No date
or language restrictions were used in the electronic searches for trials. We manually
searched the Australian Orthoptic Journal, British and Irish Orthoptic Journal, and
ESA, ISA and IOA conference proceedings. We contacted researchers active in this field
for information about further published or unpublished studies. We included randomised
controlled trials (RCTs) of any intervention for ocular alignment or motility deficits
(or both) due to acquired brain injury. Two review authors independently selected
studies and extracted data. We used standard methods expected by Cochrane. We employed
the GRADE approach to interpret findings and assess the quality of the evidence. We
found five RCTs (116 participants) that were eligible for inclusion. These trials
included conditions of acquired nystagmus, sixth cranial nerve palsy and traumatic
brain injury‐induced ocular motility defects. We did not identify any relevant studies
of restitutive interventions. We identified one UK‐based trial of a substitutive intervention,
in which botulinum toxin was compared with observation in 47 people with acute sixth
nerve palsy. At four months after entry into the trial, people given botulinum toxin
were more likely to make a full recovery (reduction in angle of deviation within 10
prism dioptres), compared with observation (risk ratio 1.19, 95% CI 0.96 to 1.48;
low‐certainty evidence). These same participants also achieved binocular single vision.
In the injection group only, there were 2 cases of transient ptosis out of 22 participants
(9%), and 4 participants out of 22 (18%) with transient vertical deviation; a total
complication rate of 24% per injection and 27% per participant. All adverse events
recovered. We judged the certainty of evidence as low, downgrading for risk of bias
and imprecision. It was not possible to mask investigators or participants to allocation,
and the follow‐up between groups varied. We identified one USA‐based cross‐over trial
of a compensatory intervention. Oculomotor rehabilitation was compared with sham training
in 12 people with mild traumatic brain injury, at least one year after the injury.
We judged the evidence from this study to be very low‐certainty. The study was small,
data for the sham training group were not fully reported, and it was unclear if a
cross‐over study design was appropriate as this is an intervention with potential
to have a permanent effect. We identified three cross‐over studies of pharmacological
interventions for acquired nystagmus, which took place in Germany and the USA. These
studies investigated two classes of pharmacological interventions: GABAergic drugs
(gabapentin, baclofen) and aminopyridines (4‐aminopyridines (AP), 3,4‐diaminopyridine
(DAP)). We judged the evidence from all three studies as very low‐certainty because
of small numbers of participants (which led to imprecision) and risk of bias (they
were cross‐over studies which did not report data in a way that permitted estimation
of effect size). One study compared gabapentin (up to 900 mg/day) with baclofen (up
to 30 mg/day) in 21 people with pendular and jerk nystagmus. The follow‐up period
was two weeks. This study provides very low‐certainty evidence that gabapentin may
work better than baclofen in improving ocular motility and reducing participant‐reported
symptoms (oscillopsia). These effects may be different in pendular and jerk nystagmus,
but without formal subgroup analysis it is unclear if the difference between the two
types of nystagmus was chance finding. Quality of life was not reported. Ten participants
with pendular nystagmus chose to continue treatment with gabapentin, and one with
baclofen. Two participants with jerk nystagmus chose to continue treatment with gabapentin,
and one with baclofen. Drug intolerance was reported in one person receiving gabapentin
and in four participants receiving baclofen. Increased ataxia was reported in three
participants receiving gabapentin and two participants receiving baclofen. One study
compared a single dose of 3,4‐DAP (20 mg) with placebo in 17 people with downbeat
nystagmus. Assessments were made 30 minutes after taking the drug. This study provides
very low‐certainty evidence that 3,4‐DAP may reduce the mean peak slow‐phase velocity,
with less oscillopsia, in people with downbeat nystagmus. Three participants reported
transient side effects of minor perioral/distal paraesthesia. One study compared a
single dose of 4‐AP with a single dose of 3,4‐DAP (both 10 mg doses) in eight people
with downbeat nystagmus. Assessments were made 45 and 90 minutes after drug administration.
This study provides very low‐certainty evidence that both 3,4‐DAP and 4‐AP may reduce
the mean slow‐phase velocity in people with downbeat nystagmus. This effect may be
stronger with 4‐AP. The included studies provide insufficient evidence to inform decisions
about treatments specifically for eye movement disorders that occur following acquired
brain injury. No information was obtained on the cost of treatment or measures of
participant satisfaction relating to treatment options and effectiveness. It was possible
to describe the outcome of treatment in each trial and ascertain the occurrence of
adverse events. What is the aim of this review? The aim of this Cochrane Review was
to find out what treatments work well to improve eye position and eye movement disorders
due to acquired brain injury, and when is the best time to use them. Key messages
The evidence on the benefits and harms of treatments for eye movement disorders due
to acquired brain injury is currently very low‐certainty. What was studied in this
review? Acquired brain injury is any injury that occurs after birth and causes damage
to the brain's function. Strabismus is a condition in which the eyes are out of alignment,
with one or both eyes turned in, out, up or down. Ocular motility (eye movement) disorders
are defects that prevent normal movement of the eyes. Nystagmus is a condition where
the eye movements are not steady and, instead, the eyes wobble. Treatment options
include eye therapy, glasses, prisms, occlusion, botulinum toxin or surgery, to reduce
the deviation or movement of the eyes. Currently there are no clear recommendations
on when is best to provide these treatments, how much these treatments cost and whether
treatments are of benefit to people with eye alignment and movement disorders occurring
after acquired brain injury. What are the main results of this review? Cochrane researchers
found five relevant studies with a total of 116 participants. One study was from the
UK and looked at botulinum toxin compared to observation in people with recent onset
sixth nerve palsy. One study from the USA compared eye movement training with sham
(false) training in people with mild traumatic brain injury. Three studies took place
in Germany or the USA and compared medical drug treatments in people with acquired
nystagmus. The review provides: ∙ low‐certainty evidence that people with sixth nerve
palsy may have a slightly better chance of a reduction in visual symptoms when given
botulinum toxin compared with no treatment. ∙ very low‐certainty evidence on eye movement
treatment for people with brain injury due to trauma and use of medical drugs for
nystagmus, where treatments show slightly better improved symptoms. How up‐to‐date
is this review? Cochrane researchers searched for studies that had been published
up to 26 June 2017.