A pilot randomized controlled trial comparing effectiveness of prism glasses, visual search training and standard care in hemianopia.

OBJECTIVE: Pilot trial to compare prism therapy and visual search training, for homonymous hemianopia, to standard care (information only). METHODS: Prospective, multicentre, parallel, single-blind, three-arm RCT across fifteen UK acute stroke units. PARTICIPANTS: Stroke survivors with homonymous hemianopia. INTERVENTIONS: Arm a (Fresnel prisms) for minimum 2 hours, 5 days per week over 6 weeks. Arm b (visual search training) for minimum 30 minutes, 5 days per week over 6 weeks. Arm c (standard care-information only). INCLUSION CRITERIA: Adult stroke survivors (>18 years), stable hemianopia, visual acuity better than 0.5 logMAR, refractive error within ±5 dioptres, ability to read/understand English and provide consent. OUTCOMES: Primary outcomes were change in visual field area from baseline to 26 weeks and calculation of sample size for a definitive trial. Secondary measures included Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual, Short Form-12 questionnaires and Radner reading ability. Measures were post-randomization at baseline and 6, 12 and 26 weeks. RANDOMIZATION: Randomization block lists stratified by site and partial/complete hemianopia. BLINDING: Allocations disclosed to patients. Primary outcome assessor blind to treatment allocation. RESULTS: Eighty-seven patients were recruited: 27-Fresnel prisms, 30-visual search training and 30-standard care; 69% male; mean age 69 years (SD 12). At 26 weeks, full results for 24, 24 and 22 patients, respectively, were compared to baseline. Sample size calculation for a definitive trial determined as 269 participants per arm for a 200 degree2 visual field area change at 90% power. Non-significant relative change in area of visual field was 5%, 8% and 3.5%, respectively, for the three groups. Visual Function Questionnaire responses improved significantly from baseline to 26 weeks with visual search training (60 [SD 19] to 68.4 [SD 20]) compared to Fresnel prisms (68.5 [SD 16.4] to 68.2 [18.4]: 7% difference) and standard care (63.7 [SD 19.4] to 59.8 [SD 22.7]: 10% difference), P=.05. Related adverse events were common with Fresnel prisms (69.2%; typically headaches). CONCLUSIONS: No significant change occurred for area of visual field area across arms over follow-up. Visual search training had significant improvement in vision-related quality of life. Prism therapy produced adverse events in 69%. Visual search training results warrant further investigation.

A randomised controlled trial to compare the clinical and cost-effectiveness of prism glasses, visual search training and standard care in patients with hemianopia following stroke: a protocol.

INTRODUCTION: Homonymous hemianopia is a common and disabling visual problem after stroke. Currently, prism glasses and visual scanning training are proposed to improve it. The aim of this trial is to determine the effectiveness of these interventions compared to standard care. METHODS AND ANALYSIS: The trial will be a multicentre three arm individually randomised controlled trial with independent assessment at 6 week, 12 week and 26 week post-randomisation. Recruitment will occur in hospital, outpatient and primary care settings in UK hospital trusts. A total of 105 patients with homonymous hemianopia and without ocular motility impairment, visual inattention or pre-existent visual field impairment will be randomised to one of three balanced groups. Randomisation lists will be stratified by site and hemianopia level (partial or complete) and created using simple block randomisation by an independent statistician. Allocations will be disclosed to patients by the treating clinician, maintaining blinding for outcome assessment. The primary outcome will be change in visual field assessment from baseline to 26 weeks. Secondary measures will include the Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual-5D and Short Form-12 questionnaires. Analysis will be by intention to treat. ETHICS AND DISSEMINATION: This study has been developed and supported by the UK Stroke Research Network Clinical Studies Group working with service users. Multicentre ethical approval was obtained through the North West 6 Research ethics committee (Reference 10/H1003/119). The trial is funded by the UK Stroke Association. Trial Registration: Current Controlled Trials ISRCTN05956042. Dissemination will consider usual scholarly options of conference presentation and journal publication in addition to patient and public dissemination with lay summaries and articles. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05956042.

Surgical correction of large-angle exotropia in adults.

AIM: A retrospective and longitudinal review of the outcome of strabismus surgery for adults with large- and very-large-angle manifest exodeviations, using two-, three- and four muscle horizontal recti surgery with adjustable sutures. METHODS: A total of 26 consecutive adult patients undergoing surgery for socially noticeable strabismus comprising five primary, 16 consecutive, and five secondary constant exotropias with a mean near deviation of 58 prism dioptres and a mean distance deviation of 55Delta were evaluated preoperatively and at various time intervals postoperatively. Surgery involved two muscles in seven cases, three muscles in 13 cases, and four muscles in six cases; and 25 of 26 had adjustable sutures. There was a horizontal preoperative ocular movement deficit in 17 that was asymmetrical in four cases. RESULTS: Binocularity was restored in eight patients (31%), 20 (77%) were within 10Delta of orthotropia, and 24 (92%) were happy with their cosmesis. Two had symptomatic asymmetrical ocular motility deficits postoperatively following a two-muscle procedure and one required reoperation. A total of 19 patients undergoing three- or four-muscle surgery were asymptomatic postoperatively. A total of 22 patients had follow-up of 8 months or more. CONCLUSION: In adults with large-angle manifest exodeviations, adjustable suture surgery involving three or more horizontal recti successfully restores primary position alignment, a high degree of patient satisfaction, and can be expected to be associated with a low incidence of symptomatic postoperative asymmetrical ocular movement deficits.

In vivo role of truncated trkb receptors during sensory ganglion neurogenesis.

The mammalian trkB locus undergoes alternative splicing to produce two different types of brain-derived neurotrophic factor receptors. The first type is the full-length receptor tyrosine kinase (TrkB(Tk+); the second type is a truncated receptor lacking the intracellular tyrosine kinase domain (TrkB(Tk-)). To investigate the function of both types of TrkB receptor in vivo, we have generated knockout mice lacking all isoforms of the TrkB receptor (trkB-/-) and compared sensory neuron survival in these mice to that in the previously described TrkB kinase domain knockout mice (trkB(k)-/-). We observed that the presence of truncated TrkB receptors in trkB(k)-/- mice results in more severe sensory neuron losses. Increased neuron losses associated with the presence of truncated TrkB were most severe in regions where neuron survival is most dependent on brain-derived neurotrophic factor and neurotrophin-3. Our data suggest that truncated TrkB receptors negatively influence neuron survival by interfering with the function of catalytic TrkB receptors.

Unilateral inferior oblique muscle myectomy and recession in the treatment of inferior oblique muscle overaction: a longitudinal study.

BACKGROUND: The comparable long-term outcomes of inferior oblique muscle myectomy and recession for the treatment of superior oblique underaction (in primary position and straight right and left gaze) have not been well documented in the literature. The purpose of this study was to compare longitudinally these two procedures in a similar, patient population with binocular single vision, when both operations were performed by the same surgeon, with a minimum follow-up period of 12 months. METHODS: A total of 24 patients who randomly underwent either a unilateral myectomy (at the temporal border of the inferior rectus muscle) or a standard recession for inferior oblique muscle overaction associated with long-standing superior oblique underaction were evaluated preoperatively at 2 weeks, 4 months, and 12 months postoperatively by the same orthoptist. RESULTS: A total of 23 patients met the study criteria, (12 myectomies and 11 recessions). All but one patient had demonstrable binocular single vision. The average preoperative hyperdeviation in contralateral gaze was 26.5 prism dioptres (Delta) in the myectomies and 20 Delta in the recessions. This was reduced at 12 months postoperatively to 1.75 Delta in the myectomies and to 3 Delta in the recessions. Both procedures were largely self-grading, so that the larger the preoperative hyperdeviation, the greater the effect of surgery. CONCLUSIONS: Single inferior oblique muscle-weakening procedures were effective in the vast majority of patients, even when the preoperative primary position hyperdeviation was 15 Delta or more. An improvement occurred in both groups immediately after surgery and in many throughout the follow-up period represented by a continuing drift towards orthotropia, but there was a recurrence of the hyperdeviation in some of the recession patients.

Neurotrophins are not required for normal embryonic development of olfactory neurons.

Neurons of the vertebrate olfactory epithelium (OE) regenerate continuously throughout life. The capacity of these neurons to regenerate and make new and precise synaptic connections in the olfactory bulb provides a useful model to study factors that may control or mediate neuronal regeneration. Expression and in vitro studies have suggested potential roles for the neurotrophins in the olfactory system. To directly examine whether neurotrophins are required for olfactory neuron development, we characterized in vivo the role of the neurotrophins in the primary olfactory system. For this, we generated mutant mice for TrkA, TrkB, TrkC, and also for BDNF and NT3 together with P2-IRES-tau-LacZ trangenic mice. Histochemical staining for beta-galactosidase at birth allowed in vivo analysis of the P2 subpopulation of olfactory neurons as well as their projections to the olfactory bulb. Our data indicate that Trk signaling is not required for normal embryonic development of the olfactory system.

A molecular basis for estrogen-induced cryptorchidism.

Male sexual differentiation relies upon testicular secretion of the hormones testosterone, Mullerian inhibiting substance, and insulin-3 (Insl3). Insl3 is responsible for testicular descent through virilization and outgrowth of the embryonic gubernaculum. In mouse, prenatal exposure to 17beta-estradiol and the nonsteroidal synthetic estrogen diethylstilbestrol (DES) disturbs the endocrine balance, causing demasculinizing and feminizing effects in the male embryo, including impaired testicular descent (cryptorchidism). In the current study, we show that maternal exposure to estrogens, including 17alpha- and beta-estradiol, as well as DES, specifically down regulates Insl3 expression in embryonic Leydig cells, thereby providing a mechanism for cryptorchidism. These experiments may have implications for the widespread use of estrogenic substances in agriculture and the environment.

Cardiac death and stored electrograms in patients with third-generation implantable cardioverter-defibrillators.

OBJECTIVES: We sought to utilize terminal stored intracardiac electrograms (EGMs) to study the electrophysiologic events that accompany mortality in patients with third-generation implantable cardioverter-defibrillators (ICDs). BACKGROUND: Despite their ability to effectively terminate ventricular tachyarrhythmias, cardiac mortality in patients with ICDs remains high. The mechanisms and modes of death in these patients are not well understood. METHODS: We retrospectively analyzed clinical data and stored EGMs from patients enrolled in the clinical trial of the Ventritex Cadence ICD. Of the 1,729 patients 119 died during 6 years of follow-up. The final recorded EGM was reviewed. Postimplant EGMs as well as 50 control EGMs were used to define normal EGM characteristics. RESULTS: There were 36 noncardiac deaths (30%) and 83 cardiac deaths (70%). Of the cardiac deaths, 55 (66%) were nonsudden and 28 (34%) were sudden. When cardiac deaths were analyzed, 46 (55%) had no stored EGMs within 1 h of death, implying that the deaths were not directly related to tachyarrhythmias. In 37 cardiac deaths (18 nonsudden, 19 sudden), stored EGMs were present within 1 h of death. In these 37 deaths, the final EGM recorded was wide (>158 ms) in 33 (89%). Wide EGMs were interpreted as ventricular tachycardia in 27 and ventricular fibrillation in 6. In 13 of the 33 patients (39%) with wide EGMs, therapy was not delivered by the ICD, as it incorrectly detected a spontaneous termination of the arrhythmia. EGMs were significantly wider if recorded within 1 h, as compared with those recorded from 1 to 48 h before death (261+/-124 vs. 181+/-93 ms, p=0.04). CONCLUSIONS: Only 37 patients (31%) who died after placement of an ICD had a stored EGM within 1 h of the time of death, suggesting that the majority of deaths (69%) were not the immediate result of a tachyarrhythmia. When EGMs were recorded, they were wide in 89% of patients. These wide EGMs most likely represent intracardiac recordings of electromechanical dissociation. Thus, of the 119 deaths, 112 (94%) were not the immediate result of a tachyarrhythmia.

Convergence insufficiency in thyroid eye disease.

The incidence of convergence insufficiency in patients with thyroid ophthalmopathy and their response to convergence exercise is unknown. Twenty-seven consecutive patients with thyroid eye disease (TED) were evaluated prospectively. Six patients with symptomatic convergence insufficiency obtained varying degrees of subjective and objective benefit from treatment. None of the six had other TED-related complaints that required therapeutic intervention. The study findings should alert the clinician to consider convergence insufficiency in patients with TED and nonspecific ophthalmic symptoms.

Long-term outcome with the automatic implantable cardioverter-defibrillator.

The automatic implantable cardioverter-defibrillator was implanted in 270 patients because of life-threatening arrhythmias over a 7 year period. There was a history of sustained ventricular tachycardia or fibrillation, or both, in 96% of these patients, 80% had one or more prior cardiac arrests and 78% had coronary artery disease as their underlying diagnosis. The average ejection fraction was 34%, and 96% of these patients had had an average of 3.4 antiarrhythmic drug failures per patient before defibrillator implantation. There were four perioperative deaths and eight patients had generator infection or generator erosion, or both, during the perioperative period or during long-term follow-up. Concomitant antiarrhythmic drug therapy was given to 69% of patients. Shocks from the device were given to 58% of patients. and 20% received "problematic" shocks. The device was removed from 16 patients during long-term follow-up for a variety of reasons. There were 7 sudden cardiac deaths and 30 nonsudden cardiac deaths, 18 of which were secondary to congestive heart failure. The actuarial incidence of sudden death, total cardiac death and total mortality from all causes was 1%, 7% and 8%, respectively, at 1 year, and 4%, 24% and 26% at 5 years. The automatic implantable cardioverter-defibrillator nearly eliminates sudden death over a long-term follow-up period in a high risk group of patients. It has an acceptable rate of complications or problems, or both, and most late deaths in these patients are nonsudden and of cardiovascular origin.