Mutations in SOX2 cause anophthalmia.

A submicroscopic deletion containing SOX2 was identified at the 3q breakpoint in a child with t(3;11)(q26.3;p11.2) associated with bilateral anophthalmia. Subsequent SOX2 mutation analysis identified de novo truncating mutations of SOX2 in 4 of 35 (11%) individuals with anophthalmia. Both eyes were affected in all cases with an identified mutation.

Superior oblique tuck-effectiveness in reducing vertical deviations when performed as a primary versus secondary procedure in superior oblique paresis.

PURPOSE: To quantify the effectiveness of superior oblique tuck (SOT) surgery in patients with a hyperdeviation secondary to superior oblique paresis (SOP). Surgical outcomes were compared in patients undergoing SOT surgery as a primary procedure with those who had previously undergone ipsilateral inferior oblique weakening surgery. METHODS: This retrospective study assessed surgical outcomes from all patients undergoing SOT surgery for SOP between 2012 and 2021 across 2 hospitals. The effectiveness of SOT surgery in reducing the hyperdeviation was assessed in the primary position (PP) and in contralateral elevation and depression. Results were compared between those undergoing primary SOT surgery with those who had previously undergone ipsilateral inferior oblique weakening surgery. RESULTS: A total of 60 SOT procedures were performed between 2012 and 2021. 7 were removed due to incomplete data. The remaining 53 cases experienced a mean reduction in hyperdeviation of 6.5 prism dioptres (PD), 6.7PD and 12.0PD in the PP, contralateral elevation and contralateral depression respectively. In eyes with previous IO weakening, the reduction of hyperdeviation was larger than in those eyes with no previous IO weakening surgery, with mean reductions of 8.0PD vs 5.2PD, 7.4PD vs 6.2PD and 12.4PD vs 11.6PD in the PP, contralateral elevation and contralateral depression respectively. CONCLUSION: SOT surgery is a safe and effective procedure with high patient satisfaction and resolution of symptoms in those patients with troublesome diplopia in downgaze secondary to SOP. This is true in both unoperated eyes and in those who have previously undergone inferior oblique weakening surgery.

Modern approach to managing vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC), an allergic inflammation of the conjunctiva affecting mainly children and adolescents, is categorized under the rubric of allergic conjunctivitis. Lack of uniform diagnostic and predefined staging criteria has been a bottleneck in formulating fixed guidelines to treat VKC. This lack of consensus among clinicians/researchers regarding diagnostic and grading standards has prevented us from making comparisons between the outcomes of different studies. To treat VKC, selection of a drug from many available options should be based on the duration and frequency of symptoms, grade and inflammation of giant papillae, and severity of corneal involvement. Consideration also should be given to the patient's specific needs. The basic tenet of treatment is optimal control of symptoms with a minimum of toxic side effects resulting from prolonged use of medication.

Congenital fibrosis of the extra-ocular muscles (CFEOM) and the cranial dysinnervation disorders.

Congenital fibrosis of the extraocular muscles (CFEOM) is one of the congenital cranial dysinnervation disorders (CCDDs). This review discusses the characteristics of the CFEOM phenotypes and the CCDDs, the fibrosis associated with these disorders and the processes, and genes involved in the embryological development of cranial neuromuscular units. In particular, it focuses on the genetics of neural crest identity, axon guidance, and axon construction in relation to the CFEOMs and some consideration of treatment strategies.

Chronic anterior uveitis following bacille Calmette-Guérin vaccination: molecular mimicry in action?

A 13-year-old girl developed bilateral chronic anterior uveitis following bacille Calmette-Guérin (BCG) vaccination. HLA testing was negative for B27 but positive for DRB1 *0404, a variant of DR4 often associated with rheumatoid arthritis. The authors propose her HLA repertoire allowed for a BCG-induced abnormal autoimmune response by the mechanism of molecular mimicry.

A report of paracentric inversion of chromosome 8 in Moebius syndrome.

An eight-year-old girl with bilateral facial paresis and restricted eye movements was diagnosed with Moebius syndrome. A chromosomal analysis showed a paracentric inversion on the long arm of chromosome 8 (46, XX, inv(8) (q21.3q24.13)). Candidate genes have been found on chromosomes 3q21, 10q21, and 13q12. We discuss the genes which are known to have associated ocular movement dysfunction in the 8q21-24 region. We hope this case will add to the current body of knowledge regarding Moebius syndrome and its genetics.

The Cambridge Face Tracker: Accurate, Low Cost Measurement of Head Posture Using Computer Vision and Face Recognition Software.

PURPOSE: We validate a video-based method of head posture measurement. METHODS: The Cambridge Face Tracker uses neural networks (constrained local neural fields) to recognize facial features in video. The relative position of these facial features is used to calculate head posture. First, we assess the accuracy of this approach against videos in three research databases where each frame is tagged with a precisely measured head posture. Second, we compare our method to a commercially available mechanical device, the Cervical Range of Motion device: four subjects each adopted 43 distinct head postures that were measured using both methods. RESULTS: The Cambridge Face Tracker achieved confident facial recognition in 92% of the approximately 38,000 frames of video from the three databases. The respective mean error in absolute head posture was 3.34°, 3.86°, and 2.81°, with a median error of 1.97°, 2.16°, and 1.96°. The accuracy decreased with more extreme head posture. Comparing The Cambridge Face Tracker to the Cervical Range of Motion Device gave correlation coefficients of 0.99 (P < 0.0001), 0.96 (P < 0.0001), and 0.99 (P < 0.0001) for yaw, pitch, and roll, respectively. CONCLUSIONS: The Cambridge Face Tracker performs well under real-world conditions and within the range of normally-encountered head posture. It allows useful quantification of head posture in real time or from precaptured video. Its performance is similar to that of a clinically validated mechanical device. It has significant advantages over other approaches in that subjects do not need to wear any apparatus, and it requires only low cost, easy-to-setup consumer electronics. TRANSLATIONAL RELEVANCE: Noncontact assessment of head posture allows more complete clinical assessment of patients, and could benefit surgical planning in future.

Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I-BiT system.

BACKGROUND: Traditional treatment of amblyopia involves either wearing a patch or atropine penalisation of the better eye. A new treatment is being developed on the basis of virtual reality technology allowing either DVD footage or computer games which present a common background to both eyes and the foreground, containing the imagery of interest, only to the amblyopic eye. METHODS: A randomised control trial was performed on patients with amblyopia aged 4-8 years with three arms. All three arms had dichoptic stimulation using shutter glass technology. One arm had DVD footage shown to the amblyopic eye and common background to both, the second used a modified shooter game, Nux, with sprite and targets presented to the amblyopic eye (and background to both) while the third arm had both background and foreground presented to both eyes (non-interactive binocular treatment (non-I-BiT) games). RESULTS: Seventy-five patients were randomised; 67 were residual amblyopes and 70 had an associated strabismus. The visual acuity improved in all three arms by approximately 0.07 logMAR in the amblyopic eye at 6 weeks. There was no difference between I-BiT DVD and non-I-BiT games compared with I-BiT games (stated primary outcome) in terms of gain in vision. CONCLUSIONS: There was a modest vision improvement in all three arms. Treatment was well tolerated and safe. There was no difference between the three treatments in terms of primary stated outcomes but treatment duration was short and the high proportion of previously treated amblyopia and strabismic amblyopia disadvantaged dichoptic stimulation treatment. TRIAL REGISTRATION NUMBER: NCT01702727, results.

Surgical management of superior oblique paresis using inferior oblique anterior transposition.

BACKGROUND: Inferior oblique anterior transposition (IOAT) is an effective surgical procedure for weakening the inferior oblique muscle. The purpose of this study was to assess the effectiveness and complications of IOAT for superior oblique paresis at a single center over a period of 11 years. METHODS: The medical records of consecutive patients treated for congenital and acquired fourth nerve paresis with IOAT procedures at Addenbrookes Hospital, Cambridge, from 2001 to 2012 were retrospectively reviewed. All patients were examined before and after surgery: the vertical deviation in primary position and on contralateral gaze was measured, as were versions. The data collected included patient sex and age, presenting complaint, follow-up period, abnormal head position before and after surgery, postoperative complications, and further operative procedures. RESULTS: A total of 98 IOAT procedures were reviewed, with a mean follow-up of 5.8 months. The technique produced a mean correction of 9.5(Δ) in primary position and 17(Δ) in contralateral gaze. Inferior oblique overaction was reduced in all cases, with 20% having a residual overaction and 47% having an underaction. No patients had symptomatic antielevation syndrome. CONCLUSIONS: In this patient cohort, IOAT effectively managed appropriately selected patients with superior oblique paresis, improving the vertical deviation in primary position and contralateral gaze. The procedure induced limitation of elevation in some patients. No patient experienced major postoperative symptoms.

Evaluation and development of a novel binocular treatment (I-BiT™) system using video clips and interactive games to improve vision in children with amblyopia ('lazy eye'): study protocol for a randomised controlled trial.

BACKGROUND: Amblyopia (lazy eye) affects the vision of approximately 2% of all children. Traditional treatment consists of wearing a patch over their 'good' eye for a number of hours daily, over several months. This treatment is unpopular and compliance is often low. Therefore results can be poor. A novel binocular treatment which uses 3D technology to present specially developed computer games and video footage (I-BiT™) has been studied in a small group of patients and has shown positive results over a short period of time. The system is therefore now being examined in a randomised clinical trial. METHODS/DESIGN: Seventy-five patients aged between 4 and 8 years with a diagnosis of amblyopia will be randomised to one of three treatments with a ratio of 1:1:1 - I-BiT™ game, non-I-BiT™ game, and I-BiT™ DVD. They will be treated for 30 minutes once weekly for 6 weeks. Their visual acuity will be assessed independently at baseline, mid-treatment (week 3), at the end of treatment (week 6) and 4 weeks after completing treatment (week 10). The primary endpoint will be the change in visual acuity from baseline to the end of treatment. Secondary endpoints will be additional visual acuity measures, patient acceptability, compliance and the incidence of adverse events. DISCUSSION: This is the first randomised controlled trial using the I-BiT™ system. The results will determine if the I-BiT™ system is effective in the treatment of amblyopia and will also determine the optimal treatment for future development. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702727.

Brimonidine and apraclonidine as vasoconstrictors in adjustable strabismus surgery.

INTRODUCTION: Conjunctival and episcleral bleeding can interfere with visualization of anatomic structures during strabismus surgery. In the United Kingdom, dilute adrenaline (epinephrine) is routinely used to induce vasoconstriction at the beginning of strabismus surgery. Because it causes mydriasis and mildly inhibits accommodation, it is relatively contraindicated if early postoperative suture adjustment is planned. PURPOSE: To test whether topical alpha(2)-adrenergic agonists (brimonidine 0.2% and apraclonidine 1%) are useful alternatives to topical adrenaline (epinephrine) in adjustable suture strabismus surgery. METHODS: Prospective observational pilot study. Brimonidine 0.2% or apraclonidine 1% was applied to the medial or lateral conjunctiva of 10 consecutive adult patients undergoing strabismus surgery with adjustable sutures under general anesthesia. Video images were taken before and up to 20 minutes after instillation. The surface area of ocular surface blood vessels on the acquired images was quantified at selected intervals using imaging software. RESULTS: Both agents induced potent transient vasoconstriction of ocular surface vessels. Within 5 minutes of application, brimonidine reduces blood vessel surface area by 69.2% (95% CI, 50.4-88); this effect persists for 20 minutes. Apraclonidine reduces vessel area by 64.6% (95% CI, 57.2%-72%) within 10 minutes and begins to wear off over the following 10 minutes. CONCLUSIONS: Both brimonidine and apraclonidine may be useful alternatives to topical adrenaline (epinephrine) in adjustable suture strabismus surgery.

Mitomycin and amniotic membrane: a new method of reducing adhesions and fibrosis in strabismus surgery.

The effectiveness of complex strabismus surgery is often limited by the development of fibrosis postoperatively. The use of mitomycin C to reduce fibrosis in strabismus surgery has been reported, but the use of amniotic membrane has not. We describe a technique which uses both mitomycin C and amniotic membrane patches to reduce fibrosis. We describe this technique for two patients with complex strabismus who were treated with this technique.

SOX2 anophthalmia syndrome.

Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. Here we provide a detailed description of the clinical features associated with SOX2 mutations in the five individuals with reported mutations and four newly identified cases (including the first reported SOX2 missense mutation). The SOX2-associated ocular malformations are variable in type, but most often bilateral and severe. Of the nine patients, six had bilateral anophthalmia and two had anophthalmia with contralateral microphthalmia with sclerocornea. The remaining case had anophthalmia with contralateral microphthalmia, posterior cortical cataract and a dysplastic optic disc, and was the only patient to have measurable visual acuity. The relatively consistent extraocular phenotype observed includes: learning disability, seizures, brain malformation, specific motor abnormalities, male genital tract malformations, mild facial dysmorphism, and postnatal growth failure. Identifying SOX2 mutations from large cohorts of patients with structural eye defects has delineated a new, clinically-recognizable, multisystem disorder and has provided important insight into the developmental pathways critical for morphogenesis of the eye, brain, and male genital tract.