Vergence and accommodation responses in the control of intermittent exotropia.

PURPOSE: Individuals with different types of intermittent exotropia (IXT) may use neurally coupled accommodation and vergence responses differently from those without exotropia to achieve eye alignment. This study examined the relationship between simultaneously recorded accommodation and vergence responses in children and young adults with a range of types of IXT while aligned and deviated. METHODS: Responses of 29 participants with IXT (4-31 years) and 24 age-matched controls were recorded using simultaneous eye-tracking and eccentric photorefraction while they watched a movie in binocular or monocular viewing at varying viewing distances. Gradient response AC/A ratios and fusional vergence ranges were also assessed. Eight participants had divergence or pseudo-divergence excess type IXT, 5 had convergence insufficiency and 16 had basic IXT. RESULTS: Control and IXT participants accommodated similarly both in monocular and binocular-aligned conditions to visual targets at 80 and 33 cm. When deviated in binocular viewing, most participants with IXT exhibited changes in accommodation <0.5D relative to alignment. Gradient response AC/A ratios were similar for control [0.56 MA/D (IQR: 0.51 MA/D)] and IXT participants [0.42 MA/D (0.54 MA/D); p  = 0.60]. IXT participants showed larger vergence to accommodation ratios with changes from distance to near fixation [1.19 MA/D (1.45 MA/D)] than control participants [0.78 MA/D (0.60 MA/D); p = 0.02], especially among IXT participants with divergence or pseudo-divergence excess. Participants with IXT exhibited typical fusional divergence ranges beyond their dissociated position [8.86 Δ (7.10 Δ)] and typical fusional convergence ranges from alignment [18 Δ (15.75 Δ)]. CONCLUSIONS: This study suggests that control of IXT is typically neither driven by accommodative convergence alone nor associated with over-accommodation secondary to fusional convergence efforts. These simultaneous measurements confirmed that proximal vergence contributed significantly to IXT control, particularly for divergence or pseudo-divergence excess type IXT. For IXT participants in this study, achieving eye alignment did not conflict with having clear vision.

Longitudinal Evaluation of Accommodation During Treatment for Unilateral Amblyopia.

Purpose: Retinal image quality is dependent on accommodative performance. This longitudinal observational study of children with unilateral amblyopia evaluated the accommodative performance of the amblyopic eye during treatment. Methods: Twenty-six participants with unilateral amblyopia and 10 participants with typical vision aged 3 to 10 years participated. Accommodative response was measured using modified Nott retinoscopy in monocular and binocular viewing conditions for target distances of 50, 33, and 25 cm, at enrollment and each follow-up visit. Results: Participants with amblyopia accommodated less accurately when viewing with their amblyopic eye in monocular than in binocular conditions. Over the course of amblyopia treatment, accommodative performance improved with amblyopic eye visual acuity (VA) improvement, although this was not consistent across individual participants. A linear mixed model showed that accommodative error worsened with increasing depth of amblyopia for monocular viewing with the amblyopic eye (0.14 diopter [D] per line of acuity loss, P = 0.001), with an interaction between VA and stimulus demand (0.09 D of additional lag per diopter of stimulus, per line of acuity loss, P < 0.001). Participant age, patching duration, length of time in the study, history of strabismus, and stereoacuity were not significant predictors of accommodative performance. Conclusions: Overall, poor monocular accommodative performance of the amblyopic eye was associated with worse amblyopia and improved simultaneously with VA improvement, although there was variability across the study cohort. Further research is needed to determine the causal relationship between amblyopic eye VA and accommodation and its impact on amblyopia treatment.

A Randomized Trial of a Binocular iPad Game Versus Part-Time Patching in Children Aged 13 to 16 Years With Amblyopia.

PURPOSE: To compare visual acuity (VA) improvement in teenagers with amblyopia treated with a binocular iPad game vs part-time patching. METHODS: One hundred participants aged 13 to <17 years (mean 14.3 years) with amblyopia (20/40 to 20/200, mean ∼20/63) resulting from strabismus, anisometropia, or both were enrolled into a randomized clinical trial. Participants were randomly assigned to treatment for 16 weeks of either a binocular iPad game prescribed for 1 hour per day (n = 40) or patching of the fellow eye prescribed for 2 hours per day (n = 60). The main outcome measure was change in amblyopic eye VA from baseline to 16 weeks. RESULTS: Mean amblyopic eye VA improved from baseline by 3.5 letters (2-sided 95% confidence interval [CI]: 1.3-5.7 letters) in the binocular group and by 6.5 letters (2-sided 95% CI: 4.4-8.5 letters) in the patching group. After adjusting for baseline VA, the difference between the binocular and patching groups was -2.7 letters (95% CI: -5.7 to 0.3 letters, P = .082) or 0.5 lines, favoring patching. In the binocular group, treatment adherence data from the iPad device indicated that only 13% of participants completed >75% of prescribed treatment. CONCLUSIONS: In teenagers aged 13 to <17 years, improvement in amblyopic eye VA with the binocular iPad game used in this study was not found to be better than patching, and was possibly worse. Nevertheless, it remains unclear whether the minimal treatment response to binocular treatment was owing to poor treatment adherence or lack of treatment effect.

Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome.

Relatively few patients with Cornelia de Lange syndrome (CdLS) due to SMC1A mutation have been reported, limiting understanding of the full extent of the phenotype. Compared to children with classic NIPBL-associated CdLS, patients with SMC1A-associated CdLS have a milder physical phenotype with prominent intellectual disability, high rate of cleft palate and absence of limb reductions. We present a patient with SMC1A-associated CdLS who had typical features including developmental delay, seizure disorder, feeding difficulties, hirsutism, and cleft palate. She also was found to have three novel features: (i) left ventricular non-compaction (LVNC) cardiomyopathy; (ii) microform cleft lip; and (iii) severe hyperopia and astigmatism. These features have implications regarding potential insight into the pathogenesis of the disorder, screening, and medical management. Hypertrophic cardiomyopathy has previously been reported in SMC1A-associated CdLS, but to our knowledge this is the first reported child with LVNC. Previous reports have included children with isolated clefts of the palate without involvement of the lip. When cleft palate alone is associated with a disorder, the underlying pathophysiology for clefting is sometimes secondary due to mechanical blocking of the fusion of the palatal shelves with the developing tongue. The presence of microform cleft lip in this patient suggests that the pathophysiology of clefting in SMC1A is primary rather than secondary. Few studies report ophthalmologic findings specific to SMC1A. Based on these findings, LVNC cardiomyopathy and cleft lip should be considered features of SMC1A-associated CdLS. All patients should receive echocardiogram and undergo thorough ophthalmologic evaluation as part of routine CdLS care. © 2016 Wiley Periodicals, Inc.

Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia: A Randomized Clinical Trial.

IMPORTANCE: A binocular approach to treating anisometropic and strabismic amblyopia has recently been advocated. Initial studies have yielded promising results, suggesting that a larger randomized clinical trial is warranted. OBJECTIVE: To compare visual acuity (VA) improvement in children with amblyopia treated with a binocular iPad game vs part-time patching. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, noninferiority randomized clinical trial was conducted in community and institutional practices from September 16, 2014, to August 28, 2015. Participants included 385 children aged 5 years to younger than 13 years with amblyopia (20/40 to 20/200, mean 20/63) resulting from strabismus, anisometropia, or both. Participants were randomly assigned to either 16 weeks of a binocular iPad game prescribed for 1 hour a day (190 participants; binocular group) or patching of the fellow eye prescribed for 2 hours a day (195 participants; patching group). Study follow-up visits were scheduled at 4, 8, 12, and 16 weeks. A modified intent-to-treat analysis was performed on participants who completed the 16-week trial. INTERVENTIONS: Binocular iPad game or patching of the fellow eye. MAIN OUTCOMES AND MEASURES: Change in amblyopic-eye VA from baseline to 16 weeks. RESULTS: Of the 385 participants, 187 were female (48.6%); mean (SD) age was 8.5 (1.9) years. At 16 weeks, mean amblyopic-eye VA improved 1.05 lines (2-sided 95% CI, 0.85-1.24 lines) in the binocular group and 1.35 lines (2-sided 95% CI, 1.17-1.54 lines) in the patching group, with an adjusted treatment group difference of 0.31 lines favoring patching (upper limit of the 1-sided 95% CI, 0.53 lines). This upper limit exceeded the prespecified noninferiority limit of 0.5 lines. Only 39 of the 176 participants (22.2%) randomized to the binocular game and with log file data available performed more than 75% of the prescribed treatment (median, 46%; interquartile range, 20%-72%). In younger participants (aged 5 to <7 years) without prior amblyopia treatment, amblyopic-eye VA improved by a mean (SD) of 2.5 (1.5) lines in the binocular group and 2.8 (0.8) lines in the patching group. Adverse effects (including diplopia) were uncommon and of similar frequency between groups. CONCLUSIONS AND RELEVANCE: In children aged 5 to younger than 13 years, amblyopic-eye VA improved with binocular game play and with patching, particularly in younger children (age 5 to <7 years) without prior amblyopia treatment. Although the primary noninferiority analysis was indeterminate, a post hoc analysis suggested that VA improvement with this particular binocular iPad treatment was not as good as with 2 hours of prescribed daily patching. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT02200211.

Accommodative performance of children with unilateral amblyopia.

PURPOSE: The purpose of this study was to compare the accommodative performance of the amblyopic eye of children with unilateral amblyopia to that of their nonamblyopic eye, and also to that of children without amblyopia, during both monocular and binocular viewing. METHODS: Modified Nott retinoscopy was used to measure accommodative performance of 38 subjects with unilateral amblyopia and 25 subjects with typical vision from 3 to 13 years of age during monocular and binocular viewing at target distances of 50, 33, and 25 cm. The relationship between accommodative demand and interocular difference (IOD) in accommodative error was assessed in each group. RESULTS: The mean IOD in monocular accommodative error for amblyopic subjects across all three viewing distances was 0.49 diopters (D) (95% confidence interval [CI], ±1.12 D) in the 180° meridian and 0.54 D (95% CI, ±1.27 D) in the 90° meridian, with the amblyopic eye exhibiting greater accommodative errors on average. Interocular difference in monocular accommodative error increased significantly with increasing accommodative demand; 5%, 47%, and 58% of amblyopic subjects had monocular errors in the amblyopic eye that fell outside the upper 95% confidence limit for the better eye of control subjects at viewing distances of 50, 33, and 25 cm, respectively. CONCLUSIONS: When viewing monocularly, children with unilateral amblyopia had greater mean accommodative errors in their amblyopic eyes than in their nonamblyopic eyes, and when compared with control subjects. This could lead to unintended retinal image defocus during patching therapy for amblyopia.