Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison with other treatment options for strabismus. OBJECTIVES: The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers on 6 July 2022, together with reference checking to identify additional studies. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) comparing botulinum toxin with strabismus surgery, botulinum toxin alternatives (i.e. bupivacaine) and conservative therapy such as orthoptic exercises, prisms, or lens therapy for people of any age with strabismus. All relevant RCTs identified in this update compared botulinum toxin with strabismus surgery. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane and assessed the certainty of the body of evidence using GRADE. MAIN RESULTS: We included four RCTs with 242 participants that enrolled adults with esotropia or exotropia, children with acquired esotropia, and children with infantile esotropia. The follow-up period ranged from six to 36 months. Two studies were conducted in Spain, and one each in Canada and South Africa. We judged the included studies to have a mixture of low, unclear and high risk of bias. We did not consider any of the included studies to be at low risk of bias for all domains. All four studies reported the proportion of participants who improved or corrected strabismus, defined as ≤ 10 prism diopters (PD) at six months (two studies) or ≤ 8 PD at one year (two studies). Low-certainty evidence suggested that participants treated with the surgery may be more likely to improve or correct strabismus compared with those who treated with botulinum toxin (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.53 to 0.99; I² = 50%; 4 studies, 242 participants; low-certainty evidence). One study, which enrolled 110 children with infantile esotropia, suggested that surgery may reduce the incidence of additional surgical intervention required, but the evidence was very uncertain (RR 3.05, 95% CI 1.34 to 6.91; 1 study, 101 participants; very low-certainty evidence). Two studies conducted in Spain compared botulinum toxin with surgery in children who required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that botulinum toxin may have little to no effect on achieving sensory fusion (RR 0.88, 95% CI 0.63 to 1.23; I² = 0%; 2 studies, 102 participants) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25; I² = 0%; 2 studies, 102 participants) compared with surgery. Three studies reported non-serious adverse events. Partial transient ptosis (range 16.7% to 37.0%) and transient vertical deviation (range 5.6% to 18.5%) were observed among participants treated with botulinum toxin in three studies. In one study, 44.7% participants in the surgery group experienced discomfort. No studies reported serious adverse events or postintervention quality of life. AUTHORS' CONCLUSIONS: It remains unclear whether botulinum toxin may be an alternative to strabismus surgery as an independent treatment modality among certain types of strabismus because we found only low and very low-certainty evidence in this review update. Low-certainty evidence suggests that strabismus surgery may be preferable to botulinum toxin injection to improve or correct strabismus when types of strabismus and different age groups are combined. We found low-certainty evidence suggesting botulinum toxin may have little to no effect on achievement of binocular single vision compared with surgery in children with acquired or infantile esotropia. We did not find sufficient evidence to draw any meaningful conclusions with respect to need for additional surgery, quality of life, and serious adverse events. We identified three ongoing trials comparing botulinum toxin with conventional surgeries in the varying types of strabismus, whose results will provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and cost-effectiveness should be examined in addition to clinical and safety outcomes.

Audio-visual stimulation for visual compensatory functions in stroke survivors with visual field defect: a systematic review.

BACKGROUND: Hemianopia is a complete or partial blindness in the visual fields of both eyes, commonly caused by cerebral infarction. It has been hypothesized that systematic audio-visual (AV) stimulation of the blind hemifield can improve accuracy and search times, probably due to the stimulation of bimodal representations in the superior colliculus (SC), an important multisensory structure involved in both the initiation and execution of saccades. METHODS: A narrative synthesis of the findings is presented to highlight how AV rehabilitation impacts on patients with hemianopia including visual oculomotor function, functional ability in activities of daily living, hemianopic dyslexia, visual scanning and searching tasks, maintaining of functional ability post training and the effect on brain multisensory integration by using neuroimaging. RESULTS: Sixteen studies were included (fourteen articles (188 participants) and two literature reviews). Results were grouped into AV training of hemianopia in adults and in children and then further grouped according to the AV task type: tasks measuring the training effects by comparing visual stimulation training to audio-visual training, localization abilities in homonymous hemianopia (HH) and AV integration in patients with HH. CONCLUSION: Systematic AV training may improve the processing of visual information by recruiting subcortical pathways, and because most of the patients with visual cortex damage have an intact SC, it might be useful to use the bimodal AV training to activate retinotectal functions. Nevertheless, the underlying mechanisms supporting the reported positive effects are not currently understood. Systematic functional and/or structural imaging studies may help in understanding the underlying mechanism and inform the design of optimal training paradigms.

"Eye" Don't See: An Analysis of Visual Symptom Reporting by Stroke Survivors from a Large Epidemiology Study.

AIM: The purpose was to explore the reported symptoms of post-stroke visual impairment from a large multi-centre prospective epidemiology study. METHODS: Visual assessment, including a case history, visual acuity, ocular alignment, ocular motility, visual fields, visual inattention and visual perception, was attempted for all stroke admissions to three acute stroke units. RESULTS: Of 1500 stroke admissions, 1204 received a visual assessment, of which 867 had one or more visual impairments. Of those identified with visual impairment 44.4% reported visual symptoms. The most common visual symptoms were blurred/altered vision (22.1%), field loss (12.6%), diplopia (9.9%) and reading difficulties (9.7%). 703 were identified to have a new visual impairment, 47.1% reported visual symptoms. No visual symptoms were reported by 38.4% and 14.5% were unable to report symptoms. Visual symptoms were first reported at a median of 3 days (IQR2-8) and mean of 16.0 days (SD39.8) from stroke onset. Those that reported symptoms were younger (p<0.001) and more independent (p<0.001) than those who were asymptomatic or unable to report. No significant difference was found between likelihood of reporting visual symptoms or not based on severity of reduced central vision, visual field loss or visual inattention. Stroke survivors with a manifest squint and cranial nerve palsies were significantly more likely to report symptoms. CONCLUSIONS: Almost 40% of stroke survivors with new onset visual impairment do not or cannot report visual symptoms. This highlights the importance of objective screening to ensure stroke survivors receive appropriate and timely referral to specialist services to access necessary treatment.

The Impact of Visual Impairment in Stroke (IVIS) Study - Evidence of Reproducibility.

Reporting generalisable data across stroke populations is important. We aimed to evaluate the Impact of Visual Impairment after Stroke (IVIS) visual assessment protocol in a different UK geographical area. This was a single-centre acute stroke unit, prospective study (IVIS-extension (IVIS-e) study) with comparison to a multi-centre acute stroke cohort (IVIS study). Orthoptists reviewed all stroke survivors with a standardised assessment of visual acuity, visual fields, ocular alignment, ocular motility, visual inattention and visual perception including a standardised follow-up strategy. 123 stroke survivors underwent visual screening: 42% women, 58% men, mean age 63.6 years and 86% ischaemic strokes. Ethnicity consisted of 68.3% white British and 28.5% being Pakistani, Indian, Caribbean, Bangladeshi, Black and Chinese. Two died and 28 could not be assessed. Of the 93 remaining, 10 stroke survivors (10.8%) had a normal visual assessment and 83 (89.2%) had visual impairments detected. Fifty-seven stroke survivors were assessed at their first orthoptic visit within 3 days of stroke onset; the remainder being assessed at subsequent orthoptic visits to the stroke unit. The visual profile was similar across the IVIS-e and original IVIS cohorts for most types of visual impairment although, overall, more visual impairment was detected in IVIS-e. Differences between the cohorts were primarily related to lower age and smaller white British ethnicity in the IVIS-e cohort. This likely relates to the differing population demographics for the two cohort geographical areas. Further roll-out of the IVIS assessment protocol to other regions and countries would improve detection of post-stroke visual impairment.

Stroke-Related Visual Impairment; is There an Association with Atrial Fibrillation?

BACKGROUND/OBJECTIVES: Stroke-related visual impairment and atrial fibrillation are both common following stroke. This study explores whether presence of visual impairment following stroke is associated with presence of atrial fibrillation (AF). SUBJECTS/METHODS: The Impact of Visual Impairment after Stroke (IVIS) study is a multi-centre, acute stroke unit, prospective epidemiology study. Standardised visual assessments included visual acuity, reading, visual fields, eye movements and visual perception. AF and blood pressure (BP) were measured on admission. Further data capture included stroke type, age, gender, stroke severity. Analysis included descriptive statistics, independent samples analysis and multivariate analysis for comparison of AF and visual impairment against covariates. RESULTS: 1500 stroke admissions were recruited of which 1204 stroke survivors had visual assessment. New onset stroke-related visual impairment (n = 703) was significantly associated with older age and stoke severity. AF and BP data were available for 889 stroke survivors. AF was present on admission for 258 stroke survivors and significantly associated with older age, stroke severity and discharge destination. A significant association was found for presence of AF and presence of visual impairment. However, stroke severity was a contributing factor for this association. High systolic BP (>140 mmHg) was present in 62% and high diastolic BP (>90 mmHg) in 29%, but not associated with presence of visual impairment. CONCLUSIONS: AF and visual impairment, independently, occur commonly in stroke. Although our results show an association between AF and visual impairment, this appears to be independently influenced by stroke severity. AF was not associated with type of visual impairment or extent of visual recovery. It remains unknown if AF causes more severe visual impairment.

Interventions for visual field defects in people with stroke.

BACKGROUND: Visual field defects are estimated to affect 20% to 57% of people who have had a stroke. Visual field defects can affect functional ability in activities of daily living (commonly affecting mobility, reading and driving), quality of life, ability to participate in rehabilitation, and depression and anxiety following stroke. There are many interventions for visual field defects, which are proposed to work by restoring the visual field (restitution); compensating for the visual field defect by changing behaviour or activity (compensation); substituting for the visual field defect by using a device or extraneous modification (substitution); or ensuring appropriate diagnosis, referral and treatment prescription through standardised assessment or screening, or both. OBJECTIVES: To determine the effects of interventions for people with visual field defects after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, the Cochrane Eyes and Vision Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, PsycINFO, and PDQT Databse, and clinical trials databases, including ClinicalTrials.gov and WHO Clinical Trials Registry, to May 2018. We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts. SELECTION CRITERIA: Randomised trials in adults after stroke, where the intervention was specifically targeted at improving the visual field defect or improving the ability of the participant to cope with the visual field loss. The primary outcome was functional ability in activities of daily living and secondary outcomes included functional ability in extended activities of daily living, reading ability, visual field measures, balance, falls, depression and anxiety, discharge destination or residence after stroke, quality of life and social isolation, visual scanning, adverse events, and death. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, extracted data and appraised trials. We undertook an assessment of methodological quality for allocation concealment, blinding of outcome assessors, method of dealing with missing data, and other potential sources of bias. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: Twenty studies (732 randomised participants, with data for 547 participants with stroke) met the inclusion criteria for this review. However, only 10 of these studies compared the effect of an intervention with a placebo, control, or no treatment group, and eight had data which could be included in meta-analyses. Only two of these eight studies presented data relating to our primary outcome of functional abilities in activities of daily living. One study reported evidence relating to adverse events.Three studies (88 participants) compared a restitutive intervention with a control, but data were only available for one study (19 participants). There was very low-quality evidence that visual restitution therapy had no effect on visual field outcomes, and a statistically significant effect on quality of life, but limitations with these data mean that there is insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control.Four studies (193 participants) compared the effect of scanning (compensatory) training with a control or placebo intervention. There was low-quality evidence that scanning training was more beneficial than control or placebo on quality of life, measured using the Visual Function Questionnaire (VFQ-25) (two studies, 96 participants, mean difference (MD) 9.36, 95% confidence interval (CI) 3.10 to 15.62). However, there was low or very-low quality evidence of no effect on measures of visual field, extended activities of daily living, reading, and scanning ability. There was low-quality evidence of no significant increase in adverse events in people doing scanning training, as compared to no treatment.Three studies (166 participants) compared a substitutive intervention (a type of prism) with a control. There was low or very-low quality evidence that prisms did not have an effect on measures of activities of daily living, extended activities of daily living, reading, falls, or quality of life, and very low-quality evidence that they may have an effect on scanning ability (one study, 39 participants, MD 9.80, 95% CI 1.91 to 17.69). There was low-quality evidence of an increased odds of an adverse event (primarily headache) in people wearing prisms, as compared to no treatment.One study (39 participants) compared the effect of assessment by an orthoptist to standard care (no assessment) and found very low-quality evidence that there was no effect on measures of activities of daily living.Due to the quality and quantity of evidence, we remain uncertain about the benefits of assessment interventions. AUTHORS' CONCLUSIONS: There is a lack of evidence relating to the effect of interventions on our primary outcome of functional ability in activities of daily living. There is limited low-quality evidence that compensatory scanning training may be more beneficial than placebo or control at improving quality of life, but not other outcomes. There is insufficient evidence to reach any generalised conclusions about the effect of restitutive interventions or substitutive interventions (prisms) as compared to placebo, control, or no treatment. There is low-quality evidence that prisms may cause minor adverse events.

Correction to: development of a core outcome set for amblyopia, strabismus and ocular motility disorders: a review to identify outcome measures.

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Development of a core outcome set for amblyopia, strabismus and ocular motility disorders: a review to identify outcome measures.

BACKGROUND: Core Outcome Sets (COS) are defined as the minimum sets of outcomes that should be measured and reported in all randomised controlled trials to facilitate combination and comparability of research. The aim of this review is to produce an item bank of previously reported outcome measures from published studies in amblyopia, strabismus and ocular motility disorders to initiate the development of COS. METHODS: A review was conducted to identify articles reporting outcome measures for amblyopia, strabismus and ocular motility disorders. Using systematic methods according to the COMET handbook we searched key electronic bibliographic databases from 1st January 2011 to 27th September 2016 using MESH terms and alternatives indicating the different subtypes of amblyopia, strabismus and ocular motility disorders in relation to treatment outcomes and all synonyms. We included Cochrane reviews, other systematic reviews, controlled trials, non-systematic reviews and retrospective studies. Data was extracted to tabulate demographics of included studies, primary and secondary outcomes, methods of measurement and their time points. RESULTS: A total of 142 studies were included; 42 in amblyopia, 33 in strabismus, and 68 in ocular motility disorders (one study overlap between amblyopia and strabismus). We identified ten main outcome measure domains for amblyopia, 14 for strabismus, and ten common "visual or motility" outcome measure domains for ocular motility disorders. Within the domains, we found variable nomenclature being used and diversity in methods and timings of measurements. CONCLUSION: This review highlights discrepancies in outcome measure reporting within published literature for amblyopia, strabismus and ocular motility and it generated an item bank of the most commonly used and reported outcome measures for each of the three conditions from recent literature to start the process of COS development. Consensus among all stakeholders including patients and professionals is recommended to establish a useful COS.

Development of a patient reported outcome measures for measuring the impact of visual impairment following stroke.

BACKGROUND: Among the available patient-reported outcome measures (PROMs) there is an absence of a PROM with a specific focus on the impact of the wide variety of visual impairments following stroke. Our aim was to develop a patient reported quality of life outcome measure for stroke survivors with visual impairment. METHODS: Potential items were sourced from a combination of existing PROMs from a systematic review and qualitative in-depth interviews, duplicates were removed and items shortlisted. The initial pilot instrument was created following a ranking exercise of these potential items and consultation with stroke survivors. Version 1 was piloted with 37 stroke survivors at acute and chronic stages. Version 2 was piloted with 243 stroke survivors with visual impairment at acute and chronic stages. This data was analysed using the Rasch measurement model. Simultaneously, items from Version 2 underwent a Delphi process with stroke survivors and stroke clinicians, to assess the importance of each item. Final consensus decisions on item removal were made using the combined analysis from the Rasch measurement model and Delphi process in a nominal group meeting. RESULTS: Due to the wide range of rank given to the majority of categories/items, only two items were discarded. Version 1 comprised of 102 items with 5 response categories relating to amount of difficulty. The pilot of Version 1 allowed item reduction based on analysis of floor/ceiling effects and not applicable responses. Version 2 comprised of 62 items. Within the nominal group meeting, the expert panel created a set of rules which aided them with decision making in addition to the Rasch and Delphi analysis data. This resulted in the removal of 43 items and the combination of seven items to create three new items. The expert panel also recommended the rewording of three items. CONCLUSION: The Brain Injury associated Visual Impairment Impact Questionnaire (BIVI-IQ-15), a 15-item instrument with 4 response categories has been developed for capturing vision-related quality of life of stroke survivors with any of the predominant types of visual impairment, in the presence of other impairments and for both inpatients and outpatients.

Interventions for eye movement disorders due to acquired brain injury.

BACKGROUND: 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. OBJECTIVES: 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). SEARCH METHODS: 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. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any intervention for ocular alignment or motility deficits (or both) due to acquired brain injury. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Programme choice for perimetry in neurological conditions (PoPiN): a systematic review of perimetry options and patterns of visual field loss.

BACKGROUND: Visual field loss occurs frequently in neurological conditions and perimetry is commonly requested for patients with suspected or known conditions. There are currently no guidelines for how visual fields in neurological conditions should be assessed. There is a wide range of visual field programs available and the wrong choice of program can potentially fail to detect visual field loss. We report the results of a systematic review of the existing evidence base for the patterns of visual field loss in four common neurological conditions and the perimetry programs used, to aid the design of future research and clinical practice guidelines. METHODS: A systematic search of the literature was performed. The inclusion criteria required studies testing and/or reporting visual field loss in one or more of the target conditions; idiopathic intracranial hypertension, optic neuropathy, chiasmal compression and stroke. Scholarly online databases and registers were searched. In addition articles were hand searched. MESH terms and alternatives in relation to the four target conditions and visual fields were used. Study selection was performed by two authors independently. Data was extracted by one author and verified by a second. RESULTS: This review included 330 studies; 51 in relation to idiopathic intracranial hypertension, 144 in relation to optic neuropathy, 105 in relation to chiasmal compression, 21 in relation to stroke and 10 in relation to a mixed neuro-ophthalmology population. CONCLUSIONS: Both the 30-2 and 24-2 program using the Humphrey perimeter were most commonly reported followed by manual kinetic perimetry using the Goldmann perimeter across all four conditions included in this review. A wide variety of other perimeters and programs were reported. The patterns of visual field defects differ much more greatly across the four conditions. Central perimetry is used extensively in neurological conditions but with little supporting evidence for its diagnostic accuracy in these, especially considering the peripheral visual field may be affected first whilst the central visual field may not be impacted until later in the progression. Further research is required to reach a consensus on how best to standardise perimetry for neurological conditions.

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. OBJECTIVES: The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We used standard methods expected by Cochrane and assessed the certainty of the evidence using GRADE. We defined ocular alignment as an angle of deviation of less than or equal to 10 prism dioptres. MAIN RESULTS: Six RCTs were eligible for inclusion. We judged the included studies as at a mixture of low, unclear and high risk of bias. We did not consider any of the included studies as at low risk of bias for all domains.Two trials conducted in Spain (102 people, number of eyes not specified) compared botulinum toxin with surgery in children that required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that children who received botulinum toxin may have a similar or slightly reduced chance of achieving ocular alignment (pooled risk ratio (RR) 0.91, 95% confidence interval (CI) 0.71 to 1.16), binocular single vision (RR 0.88, 95% CI 0.63 to 1.23), sensory fusion (RR 0.88, 95% CI 0.63 to 1.23) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25) compared with children who received surgery. One trial from Canada compared botulinum toxin with surgery in 30 adults (30 eyes) with horizontal strabismus and reported a reduced chance of ocular alignment with botulinum toxin (RR 0.38, 95% CI 0.17 to 0.85; low-certainty evidence).One trial in the UK suggested that botulinum toxin may result in a similar or slightly improved chance of ocular alignment in people with acute onset sixth nerve palsy compared with observation (RR 1.19, 95% CI 0.96 to 1.48; 47 participants, low-certainty evidence).Very low-certainty evidence from one trial from Brazil suggested that adjuvant botulinum toxin in strabismus surgery may increase the chances of ocular alignment compared with strabismus surgery alone (RR 1.83, 95% CI 0.41 to 8.11; 23 participants).One trial from China of 47 participants (94 eyes) suggested that people receiving botulinum toxin combined with sodium hyaluronate may have a similar or slightly reduced chance of achieving ocular alignment compared with botulinum toxin alone (RR 0.81, 95% CI 0.36 to 1.82; low-certainty evidence).Reported complications in people given botulinum toxin in the included trials included ptosis (range 9% to 41.66%) and vertical deviation (range 8.3% to 18.51%). Ptosis occurred less frequently when treated with botulinum toxin combined with sodium hyaluronate compared to botulinum toxin alone. AUTHORS' CONCLUSIONS: Most published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Six RCTs on the therapeutic use of botulinum toxin in strabismus, graded as low and very low-certainty evidence, have shown varying responses. These include a lack of evidence for effect of botulinum toxin on reducing visual symptoms in acute sixth nerve palsy, poor response in people with horizontal strabismus without binocular vision, similar or slightly reduced achievement of successful ocular alignment in children with esotropia and potential increased achievement of successful ocular alignment where surgery and botulinum toxin are combined. Further high quality trials using robust methodologies are required to compare the clinical and cost effectiveness of various forms of botulinum toxin (e.g. Dysport, Xeomin, etc), to compare botulinum toxin with and without adjuvant solutions and to compare botulinum toxin to alternative surgical interventions in strabismus cases with and without potential for binocular vision.

Vergence Neural Pathways: A Systematic Narrative Literature Review.

Research in the neural pathway for vergence is less understood in comparison to the other four visual eye movements. The aim of this study was to review the literature on vergence neural pathways and associated disorders. A review of previous published literature though to March 2016 was conducted. Intracranial pathologies that affect entire neural functioning were found to cause convergence insufficiencies. In contrast, pathologies with a more localised intracranial lesion cause more specific vergence disorders. There is debate as to the potential presence of a "divergence centre." Detailed information on the divergence pathway is lacking and warrants further research.

A Randomised Controlled Trial of Treatment for Post-Stroke Homonymous Hemianopia: Screening and Recruitment.

The authors report the screening process and recruitment figures for the VISION (Visual Impairment in Stroke; Intervention Or Not) trial. This is a prospective, randomised, single-blinded, three-arm controlled trial in 14 UK acute hospital stroke units. Stroke teams identified stroke survivors suspected as having homonymous hemianopia. Interventions included Fresnel prisms versus visual search training versus standard care (information only). Primary outcome was change in visual field assessment from baseline to 26 weeks. Secondary measures included change in quality-of-life questionnaires. Recruitment opened in May 2011. A total of 1171 patients were screened by the local principal investigators. Of 1171 patients, 178 (15.2%) were eligible for recruitment: 87 patients (7.4%) provided consent and were recruited; 91 patients (7.8%) did not provide consent, and 993 of 1171 patients (84.8%) failed to meet the eligibility criteria. Almost half were excluded due to complete/partial recovery of hemianopia (43.6%; n = 511). The most common ineligibility reason was recovery of hemianopia. When designing future trials in this area, changes in eligibility criteria/outcome selection to allow more patients to be recruited should be considered, e.g., less stringent levels of visual acuity/refractive error. Alternative outcomes measurable in the home environment, rather than requiring hospital attendance for follow-up, could facilitate increased recruitment.

Patient reported outcome measures for visual impairment after stroke: a systematic review.

PURPOSE: The aim of this review was to identify patient reported outcome measures (PROMs) for use in research and clinical practice involving individuals with visual impairment following stroke and to evaluate their content validity against quality assessment criteria. METHOD: A systematic review of the literature was conducted to identify articles related to the development and/or validation of PROMS. We searched scholarly online resources and hand searched journals. Search terms included MESH terms and alternatives relating to PROMs, visual impairments and quality of life. Data were extracted relating to the development and validation of the included instruments. The quality of the development process was assessed using a modified version of a PROM quality assessment tool. RESULTS: A total of 142 PROMs were identified, 34 vision-specific PROMs were relevant and available to be analysed in this review. Quality appraisal identified four highly rated instruments: the National Eye Institute Visual Functional Questionnaire (NEI-VFQ), Activity Inventory (AI), Daily Living Tasks Dependant on Vision (DLTV) and Veterans Affairs Low Visual Function Questionnaire (VA LV VFQ). The four instruments have only been used with either a limited number of stroke survivors or a sub-population within visual impairment following stroke. CONCLUSION: No instruments were identified which specifically targeted individuals with visual impairment following stroke. Further research is required to identify the items which a population of stroke survivors with visual impairment consider to be of most importance. The validation of a combination of instruments or a new instrument for use with this population is required.

Care provision for poststroke visual impairment.

BACKGROUND: We sought to explore the care provision for poststroke visual impairment and variations in this in the United Kingdom. METHODS: Survey questions were developed and piloted with clinicians, academics, and users. Questions addressed types of visual problems; how these were identified, treated, and followed up; care pathways in use; links with other professions; and referral options. The survey was accessed via a Weblink, which was circulated through UK professional organizations to multiprofessional members of ophthalmic and stroke teams. RESULTS: A total of 548 completed electronic surveys were obtained. In all, 49.5% of respondents represented stroke teams, 42.5% eye teams, and 8% from other teams, for example, emergency care. Many respondents (41%) saw patients within 1 week of stroke. Nineteen percent did not personally test vision: 11% had a visiting clinician to test vision, and 22% used screening tools. Validated tests were used for the assessment of visual acuity (39.5%), visual field (57.5%), eye movement (48.5%), and visual function (58.5%). Visual problems suspected by family or professionals were high (88.5%). Typical overall follow-up period of vision care was less than 3 months. In all, 46% of respondents used designated care pathways for stroke survivors with visual problems; 33.5% of respondents did not provide visual information leaflets. CONCLUSIONS: Significant inequality exists in care for stroke survivors who experience visual problems. There is great variability in how vision screening is undertaken, which vision tests are used, methods of referral to eye care services, how visual problems are managed, and what vision information is provided to stroke survivors/carers. Further work is required to ensure equality and effective care.

Detection of Visual Field Loss in Pituitary Disease: Peripheral Kinetic Versus Central Static.

Visual field assessment is an important clinical evaluation for eye disease and neurological injury. We evaluated Octopus semi-automated kinetic peripheral perimetry (SKP) and Humphrey static automated central perimetry for detection of neurological visual field loss in patients with pituitary disease. We carried out a prospective cross-sectional diagnostic accuracy study comparing Humphrey central 30-2 SITA threshold programme with a screening protocol for SKP on Octopus perimetry. Humphrey 24-2 data were extracted from 30-2 results. Results were independently graded for presence/absence of field defect plus severity of defect. Fifty patients (100 eyes) were recruited (25 males and 25 females), with mean age of 52.4 years (SD = 15.7). Order of perimeter assessment (Humphrey/Octopus first) and order of eye tested (right/left first) were randomised. The 30-2 programme detected visual field loss in 85%, the 24-2 programme in 80%, and the Octopus combined kinetic/static strategy in 100% of eyes. Peripheral visual field loss was missed by central threshold assessment. Qualitative comparison of type of visual field defect demonstrated a match between Humphrey and Octopus results in 58%, with a match for severity of defect in 50%. Tests duration was 9.34 minutes (SD = 2.02) for Humphrey 30-2 versus 10.79 minutes (SD = 4.06) for Octopus perimetry. Octopus semi-automated kinetic perimetry was found to be superior to central static testing for detection of pituitary disease-related visual field loss. Where reliant on Humphrey central static perimetry, the 30-2 programme is recommended over the 24-2 programme. Where kinetic perimetry is available, this is preferable to central static programmes for increased detection of peripheral visual field loss.

Systematic Review and Meta-Analysis of Prehospital Machine Learning Scores as Screening Tools for Early Detection of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction. METHODS AND RESULTS: Six bibliographic databases were searched from inception until October 10, 2023. Meta-analyses pooled the model performance using area under the curve (AUC), sensitivity, specificity, and summary receiver operating characteristic curve. Of 1544 studies screened, 8 retrospective studies were eligible, including 32 prehospital stroke scales and 21 ML models. Of the 9 prehospital scales meta-analyzed, the Rapid Arterial Occlusion Evaluation had the highest pooled AUC (0.82 [95% CI, 0.79-0.84]). Support Vector Machine achieved the highest AUC of 9 ML models included (pooled AUC, 0.89 [95% CI, 0.88-0.89]). Six prehospital stroke scales and 10 ML models were eligible for summary receiver operating characteristic analysis. Pooled sensitivity and specificity for any prehospital stroke scale were 0.72 (95% CI, 0.68-0.75) and 0.77 (95% CI, 0.72-0.81), respectively; summary receiver operating characteristic curve AUC was 0.80 (95% CI, 0.76-0.83). Pooled sensitivity for any ML model for LVO was 0.73 (95% CI, 0.64-0.79), specificity was 0.85 (95% CI, 0.80-0.89), and summary receiver operating characteristic curve AUC was 0.87 (95% CI, 0.83-0.89). CONCLUSIONS: Both prehospital stroke scales and ML models demonstrated varying accuracies in predicting LVO. Despite ML potential for improved LVO detection in the prehospital setting, application remains limited by the absence of prospective external validation, limited sample sizes, and lack of real-world performance data in a prehospital setting.

UK exceptional case driving application outcomes in post-stroke homonymous hemianopia: results from a clinical study.

PURPOSE: We report results in relation to returning to driving in the UK under the exceptional cases rule for visual field loss. METHODS: The Hemianopia Adaptation Study is a prospective clinical study recruiting adult stroke survivors with new onset homonymous hemianopia. The mobility assessment course (MAC) was used to measure navigational scanning. Car drivers were offered a 1-year post-stroke assessment to consider referral for driving assessment. RESULTS: Of 144 participants, 51 were eligible for driving assessment, with 13 (25.4%) accepting appointment for UK Driving and Vehicle Licensing Agency (DVLA) referral. A statistically significant difference in gender and baseline Barthel (stroke severity) scores was found between those requesting referral and those declining (p = 0.046; p < 0.001). MAC outcomes were significantly different, with those referred having a lower percentage of target omissions (9.0%) and faster mean course completion time (46.0 s), than those not referred (28.3%/72.5 s) (p = 0.006/p < 0.001). Twelve of the 13 referred were offered a driving assessment by the DVLA. All 12 passed and returned to driving. CONCLUSIONS: It is possible for individuals with post-stroke homonymous hemianopia to return to driving, where exceptional cases criteria are met. There is evidence to support use of the MAC as a clinical measurement of adaptation.IMPLICATIONS FOR REHABILITATIONIndividuals with post-stroke homonymous hemianopia should be fully informed regarding driving regulations that can differ between countries and sometimes different states within a country, as well as provided with the support and opportunity to consider a return to driving if appropriate.Professionals providing care within the stroke multi-disciplinary team should be aware that it is possible for patients with homonymous hemianopia to return to driving, when exceptional cases criteria are met.The mobility assessment course (MAC) should be considered as a clinical measurement of adaptation in homonymous hemianopia.A cut-off score of ≤25% omissions on MAC could be employed to determine those likely to adapt to hemianopia long-term and potentially return to driving.

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However it is unclear how effective its use is in comparison to other treatment options for strabismus. OBJECTIVES: To evaluate the efficacy of botulinum toxin in the treatment of strabismus compared with alternative treatment options, to investigate dose effect and complication rates. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 December 2011. We manually searched the Australian Orthoptic Journal and British and Irish Orthoptic Journal and ESA, ISA and IOA conference proceedings. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained. MAIN RESULTS: We found four RCTs that were eligible for inclusion. Two trials found that there was no difference between the use of botulinum toxin and surgery for patients requiring retreatment for acquired esotropia or infantile esotropia. There was no evidence for a prophylactic effect of botulinum toxin in a treatment trial of acute onset sixth nerve palsy. Botulinum toxin had a poorer response than surgery in a trial of patients requiring treatment for horizontal strabismus in the absence of binocular vision. Reported complications included ptosis and vertical deviation and ranged from 24% in a trial using Dysport™ to 52.17% and 55.54% in trials using Botox™. AUTHORS' CONCLUSIONS: The majority of published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Four RCTs on the therapeutic use of botulinum toxin in strabismus have shown varying responses ranging from a lack of evidence for prophylactic effect of botulinum toxin in acute sixth nerve palsy, to poor response in patients with horizontal strabismus without binocular vision, to no difference in response in patients that required retreatment for acquired esotropia or infantile esotropia. It was not possible to establish dose effect information. Complication rates for use of Botox™ or Dysport™ ranged from 24% to 55.54%.