Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

IMPORTANCE Binocular amblyopia treatment using contrast-rebalanced stimuli showed promise in laboratory studies and requires clinical trial investigation in a home-based setting.OBJECTIVE To compare the effectiveness of a binocular video game with a placebo video game for improving visual functions in older children and adults. DESIGN, SETTING, AND PARTICIPANTSThe Binocular Treatment of Amblyopia Using Videogames clinical trial was a multicenter, double-masked, randomized clinical trial. Between March 2014 and June 2016, 115 participants 7 years and older with unilateral amblyopia (amblyopic eye visual acuity, 0.30-1.00 logMAR; Snellen equivalent, 20/40-20/200) due to anisometropia, strabismus, or both were recruited. Eligible participants were allocated with equal chance to receive either the active or the placebo video game, with minimization stratified by age group (child, age 7 to 12 years; teenager, age 13 to 17 years; and adult, 18 years and older).INTERVENTIONS Falling-blocks video games played at home on an iPod Touch for 1 hour per day for 6 weeks. The active video game had game elements split between eyes with a dichoptic contrast offset (mean [SD] initial fellow eye contrast, 0.23 [0.14]). The placebo video game presented identical images to both eyes. MAIN OUTCOMES AND MEASURESChange in amblyopic eye visual acuity at 6 weeks. Secondary outcomes included compliance, stereoacuity, and interocular suppression. Participants and clinicians who measured outcomes were masked to treatment allocation. RESULTSOf the 115 included participants, 65 (56.5%) were male and 83 (72.2%) were white, and the mean (SD) age at randomization was 21.5 (13.6) years. There were 89 participants (77.4%) who had prior occlusion. The mean (SD) amblyopic eye visual acuity improved 0.06 (0.12) logMAR from baseline in the active group (n = 56) and 0.07 (0.10) logMAR in the placebo group (n = 59). The mean treatment difference between groups, adjusted for baseline visual acuity and age group, was −0.02 logMAR (95% CI, −0.06 to 0.02; P = .25). Compliance with more than 25% of prescribed game play was achieved by 36 participants (64%) in the active group and by 49 (83%) in the placebo group. At 6 weeks, 36 participants (64%) in the active group achieved fellow eye contrast greater than 0.9 in the binocular video game. No group differences were observed for any secondary outcomes. Adverse effects included 3 reports of transient asthenopia. CONCLUSIONS AND RELEVANCEThe specific home-based binocular falling-blocks video game used in this clinical trial did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play. More engaging video games with considerations for compliance may improve effectiveness.

Friedreich ataxia (FRDA), the commonest of the inherited ataxias, is a multisystem neurodegenerative condition that affects ocular motor function. We assessed eye movement abnormalities in 20 individuals with genetically confirmed FRDA and compared these results to clinical measures. All subjects were assessed with infrared oculography. Fifteen individuals underwent a full protocol of eye movement recordings. Ten subjects were analysed using two-dimensional scleral coil equipment and five using three-dimensional scleral coil recording equipment. We also recorded visual quality of life, Sloan low contrast letter acuity and Friedreich Ataxia Rating Scale scores to compare to the visual measures. Whilst saccadic velocity was essentially normal, saccadic latency was prolonged. The latency correlated with clinical measures of disease severity, including the scores for the Friedreich Ataxia Rating Scale and the Sloan low contrast letter acuity tests. Fixation abnormalities consisting of square wave jerks and ocular flutter were common, and included rare examples of vertical square wave jerks. Vestibular abnormalities were also evident in the group, with markedly reduced vestibulo-ocular reflex gain and prolonged latency. The range of eye movement abnormalities suggest that neurological dysfunction in FRDA includes brainstem, cortical and vestibular pathways. Severe vestibulopathy with essentially normal saccadic velocity are hallmarks of FRDA and differentiate it from a number of the dominant spinocerebellar ataxias. The correlation of saccadic latency with FARS score raises the possibility of its use as a biomarker for FRDA clinical trials.

Improvements from optical treatment resulted in one-fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.

Head injuries are frequently associated with ophthalmic problems. The commonest problems seen in this series of 161 patients with head injury were problems with poor accommodation (1 6% of patients; 58% of these persisted), convergence (14% of patients; 35% of these persisted), pseudomyopia (1 9%; 55% persisted) and optic atrophy (26% of the patients; 78% of these were mild and easily missed on routine testing, and 22% were severe).Motility disorders were common, especially cranial nerve palsies. Other less frequent motility disturbances included apparent inferior oblique palsy, comitant esotropia, and exotropia which was often of the convergence insufficiency type.

BackgroundAmblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment.Methods/designThe BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7–12, 13–17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at baseline, 3, 6, 12 and 24 weeks post randomisation. Treatment compliance and acceptability will also be assessed along with quality of life for adult participants.DiscussionThe BRAVO study is the first randomised controlled trial of a home-based videogame treatment for older children and adults with amblyopia. The results will indicate whether a binocular approach to amblyopia treatment conducted at home is effective for patients aged 7 years or older.Trial registrationThis trial was registered in Australia and New Zealand Clinical Trials Registry (ACTRN12613001004752) on 10 September 2013.

A case is presented of a patient with high myopia who developed vertical binocular diplopia after decentred laser in situ keratomileusis (LASIK) surgery with associated decompensation of pre-existing exophoria into an exotropia. A 40-year-old man underwent LASIK surgery for high myopia in his right eye. Preoperatively, he was approximately -26.00/-2.00 x 35 degrees with visual acuity of 6/12(-2) in that eye. He also had an asymptomatic exophoria. After LASIK surgery, he achieved a refraction of -3.25/-0.50 x 80 degrees with 6/21 best-corrected visual acuity. He also developed binocular diplopia. The ablation zone had been decentred upwards and there was also an exo- and hypo-deviation of his right eye. He was able to superimpose the two images in free space with vertical and horizontal prisms.A hard contact lens also resulted in superimposition of the two images. Vertical decentration of the ablation zone can induce a vertical prism effect after LASIK surgery and result in vertical diplopia. This together with abnormal optics also caused loss of best-corrected vision and decompensation of his pre-existing exophoria into an exotropia.

Botulinum Toxin as a medical therapy was introduced by Dr Alan Scott more than 20 years ago. The first clinical applications of Botulinum Toxin type A (BT-A) were for the treatment of strabismus and for periocular spasms. Botulinum Toxin type A is often effective in small to moderate angle convergent strabismus (esotropia) of any cause, and may be an alternative to surgery in these cases. Botulinum Toxin type A may have a role in acute or chronic fourth and sixth nerve palsy, childhood strabismus and thyroid eye disease. The use of BT-A for strabismus varies enormously in different cities and countries for no apparent reason. Botulinum Toxin type A may be particularly useful in situations where strabismus surgery is undesirable. This may be in elderly patients unfit for general anaesthesia, when the clinical condition is evolving or unstable, or if surgery has not been successful. Botulinum Toxin type A can give temporary symptomatic relief in many instances of bothersome diplopia irrespective of the cause. Ptosis and acquired vertical deviations are the commonest complications encountered. Vision-threatening complications are rare. Repeated use of BT-A is safe.