Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial.

PURPOSE: Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. METHODS: We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. RESULTS: Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow-up and four (44%) showed further VA improvements. CONCLUSIONS: 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.

Transient improvements in fixational stability in strabismic amblyopes following bifoveal fixation and reduced interocular suppression.

PURPOSE: To test the hypothesis that fixational stability of the amblyopic eye in strabismics will improve when viewing provides both bifoveal fixation and reduced inter-ocular suppression by reducing the contrast to the fellow eye. METHODS: Seven strabismic amblyopes (Age: 29.2 ± 9 years; five esotropes and two exotropes) showing clinical characteristics of central suppression were recruited. Interocular suppression was measured by a global motion task. For each participant, a balance point was determined which defined contrast levels for each eye where binocular combination was optimal (interocular suppression minimal). When the balance point could not be determined, this participant was excluded. Bifoveal fixation was established by ocular alignment using a haploscope. Participants dichoptically viewed similar targets (a cross of 2.3° surrounded by a square of 11.3°) at 40 cm. Target contrasts presented to each eye were either high contrast (100% to both eyes) or balanced contrast (attenuated contrast in the fellow fixing eye). Fixation stability was measured over a 5 min period and quantified using bivariate contour ellipse areas in four different binocular conditions; unaligned/high contrast, unaligned/balance point, aligned/high contrast and aligned/balance point. Fixation stability was also measured in six control subjects (Age: 25.3 ± 4 years). RESULTS: Bifoveal fixation in the strabismics was transient (58.15 ± 15.7 s). Accordingly, fixational stability was analysed over the first 30 s using repeated measures anova. Post hoc analysis revealed that for the amblyopic subjects, the fixational stability of the amblyopic eye was significantly improved in aligned/high contrast (p = 0.01) and aligned/balance point (p < 0.01) conditions. Fixational stability of the fellow fixing eye was not different statistically across conditions. Bivariate contour ellipse areas of the amblyopic and fellow fixing eyes were therefore averaged for each amblyope in the four conditions and compared with normals. This averaged bivariate contour ellipse area was significantly greater (reduced fixational stability, p = 0.04) in amblyopes compared to controls except in the case of aligned and balanced contrast (aligned/balance point, p = 0.19). CONCLUSION: Fixation stability in the amblyopic eye appears to improve with bifoveal fixation and reduced interocular suppression. However, once initiated, bifoveal fixation is transient with the strabismic eye drifting away from foveal alignment, thereby increasing the angle of strabismus.

Impact of Global Optimization of Lens Constants on Absolute Prediction Error for Final IOL Power Selection When Using Intraoperative Aberrometry.

Purpose: To evaluate absolute prediction errors following phacoemulsification with implantation of a multifocal toric intraocular lens (IOL) using intraoperative aberrometry for IOL power selection and to compare findings with the globally optimized and manufacturer's recommended lens constants and regression coefficients. Methods: Data from the Optiwave Refractive Analysis (ORA SYSTEM) were analyzed retrospectively. Absolute prediction errors from surgeries performed before and after the first optimization of the manufacturer's recommended lens constant and non-optimized regression coefficients for the multifocal toric IOL (SND1T3-6) were compared. Optimization was based on outcomes of procedures performed using the ORA SYSTEM and archived in its database (AnalyzOR). Outcome measures included the proportion of eyes with absolute ORA SYSTEM prediction errors ≤0.25 D and ≤0.5 D and the mean and median absolute prediction errors. Results: The pre-optimization group included 1027 eyes operated on by 184 surgeons, and the optimized group included 419 eyes operated on by 143 surgeons. The proportions of eyes achieving absolute ORA SYSTEM prediction errors ≤0.25 D (52.5% vs 35.0%, p < 0.0001) and ≤0.50 D (83.1% vs 66.2%, p < 0.0001) were significantly higher in the optimized than in the pre-optimization group. The mean ± standard deviation (0.30 ± 0.25 D vs 0.43 ± 0.32 D, p < 0.0001) and median (0.24 D vs 0.36 D, p < 0.0001) absolute ORA SYSTEM prediction errors were significantly lower after than before optimization. Prediction errors following optimization were reduced more in eyes of average than of long and short axial lengths. Conclusion: Global optimization of the manufacturer's IOL lens constants and regression coefficients resulted in lower absolute prediction errors when compared with the initial manufacturer labeled lens constants and non-optimized regression coefficients. Reductions in absolute prediction error can result in lower postoperative residual refractive error, which can improve post-operative uncorrected visual acuity and provide the potential for greater patient satisfaction following cataract surgery.

Adherence to home-based videogame treatment for amblyopia in children and adults.

Clinical relevance: Home-based videogame treatments are increasingly popular for amblyopia treatment. However, at-home treatments tend to be done in short sessions and with frequent disruptions, which may reduce the effectiveness of binocular visual stimulation. These treatment adherence patterns need to be accounted for when considering dose-response relationships and treatment effectiveness.Background: Home-based videogame treatments are increasingly being used for various sensory conditions, including amblyopia ('lazy eye'), but treatment adherence continues to limit success. To examine detailed behavioural patterns associated with home-based videogame treatment, we analysed in detail the videogame adherence data from the Binocular tReatment of Amblyopia with VideOgames (BRAVO) clinical trial (ACTRN12613001004752).Methods: Children (7-12 years), teenagers (13-17 years) and adults (≥ 18 years) with unilateral amblyopia were loaned iPod Touch devices with either an active treatment or placebo videogame and instructed to play for a total of 1-2 hours/day for six weeks at home. Objectively-recorded adherence data from device software were used to analyse adherence patterns such as session length, daily distribution of gameplay, use of the pause function, and differences between age groups. Objectively-recorded adherence was also compared to subjectively-reported adherence from paper-based diaries.Results: One hundred and five of the 115 randomised participants completed six weeks of videogame training. Average adherence was 65% (SD 37%) of the minimum hours prescribed. Game training was generally performed in short sessions (mean 21.5, SD 11.2 minutes), mostly in the evening, with frequent pauses (median every 4.1 minutes, IQR 6.1). Children played in significantly shorter sessions and paused more frequently than older age groups (p < 0.0001). Participants tended to over-report adherence in subjective diaries compared to objectively-recorded gameplay time.Conclusion: Adherence to home-based videogame treatment was characterised by short sessions interspersed with frequent pauses, suggesting regular disengagement. This complicates dose-response calculations and may interfere with the effectiveness of treatments like binocular treatments for amblyopia, which require sustained visual stimulation.

Sighting ocular dominance magnitude varies with test distance.

BACKGROUND: Ocular dominance can be defined as the preference of an individual for viewing with one eye over the other for particular visual tasks. It is relevant to monovision contact lens wear, cataract surgery and sports vision. Clinically, the measurement of ocular dominance is typically done at an arbitrary distance using a sighting test, such as the hole-in-card method that has a binary outcome. We investigated the effect of test distance on ocular dominance measured using a binocular sighting test that provided a continuous measurement of dominance. METHODS: Ten participants with normal binocular vision took part in this study. Their binocular sighting ocular dominance and phorias were measured at one, two, four, eight and 10 metres. During the dominance tests participants made a binocular alignment judgment and then were asked to indicate the relative alignment of each eye using a visual analogue scale as a reference. RESULTS: Eight participants had strong ocular dominance (five right, three left). For these participants, there was a significant increase in the magnitude of dominance with increasing test distance (p < 0.001). This could not be fully explained by changes in convergence demand. Two participants showed very weak ocular dominance across all test distances (p > 0.05), despite changes in convergence demand. CONCLUSION: When ocular dominance is present, its magnitude varies significantly with test distance. This has significant implications for the accurate measurement of ocular dominance in the clinic and may reflect the neural processes that influence eye preference.

Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia: A Randomized Clinical Trial.

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 Participants: The 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 Measures: Change 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. Results: Of 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 Relevance: The 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. Trial Registration: anzctr.org.au Identifier: ACTRN12613001004752.

Regional Extent of Peripheral Suppression in Amblyopia.

Purpose: Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Methods: Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Results: Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). Conclusions: In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

Horizontal saccade dynamics across the human life span.

PURPOSE: To investigate saccade dynamics as a function of age to determine whether they follow the pattern of development and decline predicted by Weale's model of aging. METHODS: One hundred ninety-five participants between the ages of 3 and 86 years made visually guided horizontal prosaccades ranging in size from 1 degrees to 60 degrees in response to dot stimuli. Eye movements were recorded binocularly with a video-based eye tracker, sampling at 120 Hz. Saccadic latency, accuracy, and velocity were measured and analyzed as a function of age. RESULTS: Mean saccadic latency decreased from 439 ms at 3 years to 172 ms at 14 years, followed by a period of relative stability to age 50 and finally, gradually increased to 264 ms at >or=80 years. For saccadic accuracy (amplitude gain), there was a statistically significant (P<0.05) interaction between saccade size and age. Participants made increasingly hypometric saccades as age and saccade size increased. Average age group saccadic asymptotic peak velocity (Vmax) increased during childhood from 446 deg/s at age 3, to a peak of 610 deg/s at 14 years and then gradually declined with age to approximately 345 deg/s for participants>or=80 years. CONCLUSIONS: Age affected saccadic latency, accuracy, and velocity. For each parameter there was a different pattern of development and decline probably related to the way in which the portion of the brain that controls each function develops and ages.

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

BACKGROUND: Amblyopia 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/DESIGN: The 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. DISCUSSION: The 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 REGISTRATION: This trial was registered in Australia and New Zealand Clinical Trials Registry ( ACTRN12613001004752 ) on 10 September 2013.

Effect of age and pop out distracter on attended field of view.

PURPOSE: To investigate the functional field of view (FFOV) of younger and older individuals using the attended field of view (AFOV), a method which allows for eye and head movement. The impact of a pop out distracter and a dual task on the FFOV measure was also investigated. METHODS: Nine young adult (25±6 years) and 9 older participants (72±4 years) took part in the experiment. The AFOV test involved the binocular detection and localization of a white target (Landolt-C) in a field of 24 white rings (distracters). The further AFOV tests were modified to include the presence of a pop out distracter, a dual task condition, and a combination of the two. RESULTS: Older observers had lower viewing efficiency (log [1/presentation time]) in all conditions (pooled mean across conditions: older: 0.05±0.02; younger: 0.48±0.04) than the younger group. The addition of dual or a pop out distracter did not affect the older group (mean difference ∼104±150ms and ∼124±122ms respectively) but the additional pop out distracter reduced the efficiency of the younger group for targets near fixation (mean difference ∼68±35ms). CONCLUSION: Better viewing efficiency was observed in younger individuals compared to older individuals. Difficulty in disregarding irrelevant stimuli and thereby resorting to inefficient search strategy is proposed as the reason for the differences. The finding that both older and younger individuals are not affected significantly by the presence of the irrelevant pop out distracter has implications in situations such as driving or hazard avoidance. In such scenarios, search performance is likely not impaired beyond what is found with distracters (visual clutter) in the environment.

Time course of dichoptic masking in normals and suppression in amblyopes.

PURPOSE: To better understand the relationship between dichoptic masking in normal vision and suppression in amblyopia we address three questions: First, what is the time course of dichoptic masking in normals and amblyopes? Second, is interocular suppression low-pass or band-pass in its spatial dependence? And third, in the above two regards, is dichoptic masking in normals different from amblyopic suppression? METHODS: We measured the dependence of dichoptic masking in normal controls and amblyopes on the temporal duration of presentation under three conditions; monocular (the nontested eye-i.e., dominant eye of normals or nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the nontested eye seeing high-contrast visual noise). The subject had to detect a letter in the other eye, the contrast of which was varied. RESULTS: We found that threshold elevation relative to the patched condition occurred in both normals and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise, but not just mean luminance (i.e., there was no masking from the DC component that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg); longer presentation of the target (corresponding to lower temporal frequencies) produced greater threshold elevation. CONCLUSIONS: Dichoptic masking exhibits similar properties in both subject groups, being low-pass temporally and band-pass spatially, so that masking was greatest at the longest presentation durations and was not greatly affected by mean luminance in the nontested eye.