Eight-Year Outcomes of Bilateral Lateral Rectus Recessions versus Unilateral Recession-Resection in Childhood Basic-Type Intermittent Exotropia.

PURPOSE: To report 8-year outcomes from a randomized controlled trial (RCT) comparing bilateral lateral rectus muscle recession (BLRc) with unilateral recession-resection (R&R) for childhood intermittent exotropia (IXT). DESIGN: Eight-year follow-up of RCT cohort. PARTICIPANTS: Of 197 randomized participants, 123 agreed to continue follow-up after the 3-year outcome visit (baseline age, 3-< 11 years; basic-type IXT, 15-40 prism diopters [Δ] by prism and alternate cover test [PACT]; baseline stereoacuity, ≤ 400 arcsec; no prior surgery). METHODS: After the RCT primary outcome at 3 years, annual follow-up from 4 through 8 years with treatment at investigator discretion. MAIN OUTCOME MEASURES: Suboptimal surgical outcome by 8 years after randomization, defined as any of the following at any visit: exotropia of 10 Δ or more by simultaneous prism cover test (SPCT) at distance or near, constant esotropia (ET) of 6 Δ or more by SPCT at distance or near, loss of near stereoacuity by 0.6 log arcsec or more from baseline, or reoperation. Secondary outcomes included (1) reoperation by 8 years and (2) complete or near-complete resolution at 8 years, defined as exodeviation of less than 10 Δ by SPCT and PACT at distance and near and 10 Δ or more reduction from baseline by PACT at distance and near, ET of less than 6 Δ at distance and near, no decrease in stereoacuity by 0.6 log arcsec or more from baseline, and no reoperation or nonsurgical treatment for IXT. RESULTS: The Kaplan-Meier cumulative probability of suboptimal surgical outcome through 8 years was 68% (55 events among 101 at risk) for BLRc and 53% (42 events among 96 at risk) for R&R (difference, 15%; 95% confidence interval [CI], -2% to 32%; P = 0.08). Complete or near-complete resolution at 8 years occurred in 15% (7/46) for BLRc and 37% (16/43) for R&R (difference, -22%; 95% CI, -44% to -0.1%; P = 0.049). The cumulative probability of reoperation was 30% for BLRc and 11% for R&R (difference, 19%; 95% CI, 2%-36%; P = 0.049). CONCLUSIONS: Despite no significant difference for the primary outcome, the 95% CI did not exclude a moderate benefit of R&R, which together with secondary outcomes suggests that unilateral R&R followed by usual care may yield better long-term outcomes than BLRc followed by usual care for basic-type childhood IXT using these surgical doses. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Baseline factors associated with myopia progression and axial elongation over 30 months in children 5 to 12 years of age.

PURPOSE: This study aimed to identify baseline factors associated with greater myopia progression and axial elongation in children with myopia. METHODS: This study performed a post hoc analysis of data from a 30-month randomized trial of atropine 0.01% versus placebo in children 5 to <13 years old with baseline spherical equivalent refractive error (SER) of -1.00 to -6.00 D, astigmatism of ≤1.50 D, and anisometropia of <1.00 D SER. Data from atropine 0.01% and placebo groups were pooled given outcomes were similar. Baseline factors of age, SER, axial length, race, sex, parental myopia, and iris color were evaluated for association with changes in SER and with changes in axial length at 30 months (24 months on treatment and then 6 months off) using backward model selection. RESULTS: Among 187 randomized participants, 175 (94%) completed 30 months of follow-up. The mean change in SER was greater among younger children (-0.19 D per 1 year younger; 95% confidence interval [CI], -0.25 to -0.14 D; p<0.001) and children with higher myopia (-0.14 D per 1 D more myopia at baseline; 95% CI, -0.23 to -0.05 D; p=0.002). The mean change in axial length was also greater among younger children (0.13 mm per 1 year younger; 95% CI, 0.10 to 0.15 mm; p<0.001) and children with higher baseline myopia (0.04 mm per 1 D more myopia; 95% CI, 0.002 to 0.08; p=0.04). CONCLUSIONS: Younger children with higher myopia had greater myopic progression and axial elongation over 30 months than older children with lower myopia. Developing effective treatments to slow the faster myopic progression in younger children should be a target of further research.

A Pilot Randomized Clinical Trial of Base-in Relieving Prism Spectacle Treatment of Intermittent Exotropia.

SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.

Rasch-calibrated Intermittent Exotropia Symptom Questionnaire for Children.

SIGNIFICANCE: A rigorously designed and calibrated symptom questionnaire for childhood intermittent exotropia would be useful for clinical care and for research. PURPOSE: The aim of this study was to Rasch-calibrate and evaluate the previously developed Child Intermittent Exotropia Symptom Questionnaire using data gathered as part of a randomized clinical trial. METHODS: The questionnaire was administered to 386 children aged 3 to 10 years with intermittent exotropia who were enrolled in a randomized clinical trial comparing overminus with nonoverminus spectacles. Participants were followed at 6 and 12 months while on treatment and at 18 months off treatment. Factor analysis determined dimensionality, and Rasch analysis evaluated questionnaire performance. Logit values were converted to 0 (best) to 100 (worst). We evaluated differences in questionnaire scores between treatment groups and time points, and correlations with control scores. RESULTS: The Child Intermittent Exotropia Symptom Questionnaire was unidimensional. Rasch analysis indicated that there was no notable local dependence and no significant differential item functioning for sex or age. There was suboptimal targeting (mean logit, -1.62), and person separation was somewhat poor (0.95). There were no significant differences in the Child Intermittent Exotropia Symptom score between overminus spectacles and nonoverminus spectacles at 6, 12, and 18 months. Combining data from both treatment groups, there was significant improvement from baseline at all follow-up visits (e.g., mean change from baseline to 12 months, -6.6 points; 95% confidence interval, -8.6 to -4.6). Child Intermittent Exotropia Symptom scores were not correlated with distance or near control scores at 12 months. CONCLUSIONS: The seven-item Rasch-scored Child Intermittent Exotropia Symptom Questionnaire is limited by suboptimal performance. Future study is needed to determine whether it may be useful for clinical practice and for research.

Three-year observation of children 12 to 35 months old with untreated intermittent exotropia.

PURPOSE: To describe the clinical course of untreated intermittent exotropia (IXT) in children 12-35 months of age followed for 3 years. METHODS: We enrolled 97 children 12-35 months of age with previously untreated IXT who had been randomly assigned to the observation arm of a randomised trial of short-term occlusion versus observation. Participants were observed unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, and 6-month intervals thereafter for 3 years. The primary outcome was deterioration of the IXT by 3 years, defined as (1) a constant exotropia ≥10 prism dioptres (∆) at distance and near (i.e., motor deterioration) or (2) treatment prescribed despite not having met motor deterioration. The primary analysis used the Kaplan-Meier method to determine the cumulative proportion of participants meeting deterioration by three years and 95% confidence interval (CI). RESULTS: The cumulative probability of deterioration by 3 years was 28% (95% CI = 20%-39%). Of the 24 participants meeting the primary outcome of deterioration, seven met motor deterioration and 17 were prescribed treatment without meeting motor deterioration. The cumulative probability of motor deterioration by 3 years was 10% (95% CI = 5%-19%). CONCLUSIONS: Given the modest rate of motor deterioration over three years, watchful waiting may be a reasonable management approach in 12- to 35-month-old children with IXT. To confirm this recommendation would require a long-term randomised trial of immediate treatment versus observation followed by deferred treatment if needed.

A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus Unilateral Recess and Resect for Basic-Type Intermittent Exotropia.

PURPOSE: To compare long-term outcomes after bilateral lateral rectus recession (BLRc) or unilateral lateral rectus recession combined with medial rectus resection in the same eye (R&R) for primary treatment of childhood intermittent exotropia (IXT). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: One hundred ninety-seven children 3 to younger than 11 years of age with basic-type IXT, a largest deviation by prism and alternate cover test at any distance of 15 to 40 prism diopters (PD), and near stereoacuity of at least 400 seconds of arc. METHODS: Random assignment to BLRc or R&R and masked examinations conducted every 6 months after surgery for 3 years. MAIN OUTCOME MEASURES: Proportion of participants meeting suboptimal surgical outcome by 3 years, defined as: (1) exotropia of 10 PD or more at distance or near using simultaneous prism and cover test (SPCT); or (2) constant esotropia of 6 PD or more at distance or near using SPCT; (3) loss of 2 octaves or more of stereoacuity from baseline, at any masked examination; or (4) reoperation without meeting any of these criteria. RESULTS: Cumulative probability of suboptimal surgical outcome by 3 years was 46% (43/101) in the BLRc group versus 37% (33/96) in the R&R group (treatment group difference of BLRc minus R&R, 9%; 95% confidence interval [CI], -6% to 23%). Reoperation by 3 years occurred in 9 participants (10%) in the BLRc group (8 of 9 met suboptimal surgical outcome criteria) and in 4 participants (5%) in the R&R group (3 of 4 met suboptimal surgical outcome criteria; treatment group difference of BLRc minus R&R, 5%; 95% CI, -2% to 13%). Among participants completing the 3-year visit, 29% (25 of 86) in the BLRc group and 17% (13 of 77) in the R&R group underwent reoperation or met suboptimal surgical outcome criteria at 3 years (treatment group difference of BLRc minus R&R, 12%; 95% CI, -1% to 25%). CONCLUSIONS: We did not find a statistically significant difference in suboptimal surgical outcome by 3 years between children with IXT treated with BLRc compared with those treated with R&R. Based on these findings, we are unable to recommend one surgical approach over the other for childhood IXT.

Three-Year Observation of Children 3 to 10 Years of Age with Untreated Intermittent Exotropia.

PURPOSE: To describe the course of intermittent exotropia (IXT) in children followed up without treatment for 3 years. DESIGN: Observation arm from randomized trial of short-term occlusion versus observation. PARTICIPANTS: One hundred eighty-three children 3 to 10 years of age with previously untreated IXT and 400 seconds of arc (arcsec) or better near stereoacuity. METHODS: Participants were to receive no treatment unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, or 6-month intervals thereafter for 3 years. MAIN OUTCOME MEASURES: The primary outcome was deterioration by 3 years, defined as meeting motor criterion (constant exotropia ≥10 prism diopters [Δ] at distance and near) or near stereoacuity criterion (≥2-octave decrease from best previous measure). For the primary analysis, participants also were considered to have deteriorated if treatment was prescribed without meeting either deterioration criterion. RESULTS: The cumulative probability of protocol-specified deterioration by 3 years was 15% (95% confidence interval, 10%-22%), but that was likely an overestimate, partly because of misclassification. Among 25 deteriorations, 2 met motor deterioration, 11 met stereoacuity deterioration, and 12 started treatment without meeting either criteria (7 for social concern, 1 for diplopia, 4 for other reasons). Among the 132 participants who completed the 3-year visit and had not been treated during the study, only 1 (<1%) met motor or stereoacuity deterioration criteria at 3 years. Of the 4 participants completing the 3-year visit who met deterioration criteria previously and had not started treatment, none still met deterioration criteria. Between the baseline and 3-year examination for these 132 patients, improvement occurred in distance and near stereoacuity (mean improvement, 0.14 and 0.14 logarithm of arcsec; P ≤ 0.001 and P ≤ 0.001, respectively), distance exotropia control (mean improvement, 0.6 points; P ≤ 0.001), and distance exodeviation magnitude (mean improvement, 2.2 Δ; P = 0.002). CONCLUSIONS: Among children 3 to 10 years of age with IXT for whom surgery was not considered to be the immediately necessary treatment, stereoacuity deterioration or progression to constant exotropia over 3 years was uncommon, and exotropia control, stereoacuity, and magnitude of deviation remained stable or improved slightly.

A Randomized Trial Evaluating Short-term Effectiveness of Overminus Lenses in Children 3 to 6 Years of Age with Intermittent Exotropia.

PURPOSE: To evaluate the short-term effectiveness of overminus spectacles in improving control of childhood intermittent exotropia (IXT). DESIGN: Randomized, clinical trial. PARTICIPANTS: A total of 58 children aged 3 to <7 years with IXT. Eligibility criteria included a distance control score of 2 or worse (mean of 3 measures during a single examination) on a scale of 0 (exophoria) to 5 (constant exotropia) and spherical equivalent refractive error between -6.00 diopters (D) and +1.00 D. METHODS: Children were randomly assigned to overminus spectacles (-2.50 D over cycloplegic refraction) or observation (non-overminus spectacles if needed or no spectacles) for 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was distance control score for each child (mean of 3 measures during a single examination) assessed by a masked examiner at 8 weeks. Outcome testing was conducted with children wearing their study spectacles or plano spectacles for the children in the observation group who did not need spectacles. The primary analysis compared mean 8-week distance control score between treatment groups using an analysis of covariance model that adjusted for baseline distance control, baseline near control, prestudy spectacle wear, and prior IXT treatment. Treatment side effects were evaluated using questionnaires completed by parents. RESULTS: At 8 weeks, mean distance control was better in the 27 children treated with overminus spectacles than in the 31 children who were observed without treatment (2.0 vs. 2.8 points, adjusted difference = -0.75 points favoring the overminus group; 2-sided 95% confidence interval, -1.42 to -0.07 points). Side effects of headaches, eyestrain, avoidance of near activities, and blur appeared similar between treatment groups. CONCLUSIONS: In a pilot randomized clinical trial, overminus spectacles improved distance control at 8 weeks in children aged 3 to <7 years with IXT. A larger and longer randomized trial is warranted to assess the effectiveness of overminus spectacles in treating IXT, particularly the effect on control after overminus treatment has been discontinued.

A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months of Age.

PURPOSE: To determine the effectiveness of part-time patching for treating intermittent exotropia (IXT) in young children. DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: Two hundred one children 12 to 35 months of age with untreated IXT meeting the following criteria: (1) IXT at distance OR constant exotropia at distance and either IXT or exophoria at near, and (2) 15-prism diopter (Δ) or more exodeviation at distance or near by prism and alternate cover test (PACT) but at least 10 Δ exodeviation at distance by PACT. METHODS: Participants were assigned randomly to either observation (no treatment for 6 months) or patching prescribed for 3 hours daily for 5 months, followed by 1 month of no patching. MAIN OUTCOME MEASURES: The primary outcome was deterioration, defined as constant exotropia measuring at least 10 Δ at distance and near or receipt of nonprotocol treatment for IXT. RESULTS: Of the 177 participants (88%) completing the 6-month primary outcome examination, deterioration occurred in 4.6% (4 of 87) of the participants in the observation group and in 2.2% (2 of 90) of the participants in the patching group (difference, 2.4%; P = 0.27; 95% confidence interval, -3.8% to +9.4%). Motor deterioration occurred in 2.3% (2 of 87) of the observation group and in 2.2% (2 of 90) of the patching group (difference, 0.08%; P = 0.55; 95% confidence interval, -5.8% to +6.1%). For the observation and patching groups, respectively, 6-month mean PACT measurements were 27.9 Δ versus 24.9 Δ at distance (P = 0.02) and 19.3 Δ versus 17.0 Δ at near (P = 0.10); 6-month mean exotropia control scores were 2.8 versus 2.3 points at distance (P = 0.02) and 1.4 versus 1.1 points at near (P = 0.26). CONCLUSIONS: Among children 12 to 35 months of age with previously untreated IXT, deterioration over 6 months was uncommon, with or without patching treatment. There was insufficient evidence to recommend part-time patching for the treatment of IXT in children in this age group.

A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia.

OBJECTIVE: To determine the effectiveness of prescribed part-time patching for treatment of intermittent exotropia (IXT) in children. DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: Three hundred fifty-eight children 3 to <11 years of age with previously untreated (except for refractive correction) IXT and near stereoacuity of 400 seconds of arc or better were enrolled. Intermittent exotropia met the following criteria: (1) IXT at distance OR constant exotropia at distance and either IXT or exophoria at near; (2) exodeviation (tropia or phoria) of at least 15 prism diopters (PD) at distance or near by prism and alternate cover test (PACT); and (3) exodeviation of at least 10 PD at distance by PACT. METHODS: Participants were assigned randomly either to observation (no treatment for 6 months) or to patching for 3 hours daily for 5 months, with a 1-month washout period of no patching before the 6-month primary outcome examination. MAIN OUTCOME MEASURES: The primary outcome was deterioration at either the 3-month or the 6-month follow-up visit, defined as: (1) constant exotropia measuring at least 10 PD at distance and near by simultaneous prism and cover test, and/or (2) near stereoacuity decreased by at least 2 octaves from baseline, both assessed by a masked examiner and confirmed by a retest. Participants who were prescribed any nonrandomized treatment without first meeting either deterioration criteria also were counted as having deteriorated. RESULTS: Of the 324 participants (91%) completing the 6-month primary outcome examination, deterioration occurred in 10 of the 165 participants (6.1%) in the observation group (3 of these 10 started treatment without meeting deterioration criteria) and in 1 of the 159 participants (0.6%) in the part-time patching group (difference, 5.4%; lower limit of 1-sided exact 95% confidence interval, 2.0%; P = 0.004, 1-sided hypothesis test). CONCLUSIONS: Deterioration of previously untreated childhood IXT over a 6-month period is uncommon with or without patching treatment. Although there is a slightly lower deterioration rate with patching, both management approaches are reasonable for treating children 3 to 10 years of age with IXT.

The effects of environmental enrichment on depressive and anxiety-relevant behaviors in socially isolated prairie voles.

OBJECTIVES: Social isolation is associated with depression, anxiety, and negative health outcomes. Environmental enrichment, including environmental and cognitive stimulation with inanimate objects and opportunities for physical exercise, may be an effective strategy to include in treatment paradigms for affective disorders as a function of social isolation. In a rodent model-the socially monogamous prairie vole-we investigated the hypothesis that depression- and anxiety-related behaviors after social isolation would be prevented and remediated with environmental enrichment. METHODS: Experiment 1 investigated the preventive effects of environmental enrichment on negative affective behaviors when administered concurrently with social isolation. Experiment 2 investigated the remediating effects of enrichment on negative affective behaviors when administered after a period of isolation. Behaviors were measured in three operational tests: open field, forced swim test (FST), and elevated plus maze. RESULTS: In isolated prairie voles, enrichment prevented depression-relevant (immobility in FST, group × housing interaction, p = .049) and anxiety-relevant behaviors (exploration in open field, group × housing interaction, p = .036; exploration in elevated plus maze, group × housing interaction, p = .049). Delayed enrichment also remediated these behaviors in isolated animals (immobility in FST, main effect of housing, p = .001; exploration in open field, main effect of housing, p = .047; exploration in elevated plus maze, main effect of housing, p = .001) and was slightly more effective than physical exercise alone in remediating anxiety-relevant behaviors. CONCLUSIONS: These findings provide insight into the beneficial effects of an enriched environment on depression- and anxiety-relevant behaviors using a translational rodent model of social isolation.

Refractive Error Change and Overminus Lens Therapy for Childhood Intermittent Exotropia.

Importance: Increased myopic shift was found to be associated with 1 year of overminus spectacle treatment for children with intermittent exotropia (IXT). Persistence of myopic shift after discontinuing overminus spectacles is unknown. Objective: To compare refractive error change over 3 years in children with IXT originally treated with overminus vs nonoverminus spectacles. Design, Setting, and Participants: This study was an 18-month extension of the Trial of Overminus Spectacle Therapy for Intermittent Exotropia cohort, which previously randomized children aged 3 to 10 years with IXT and baseline spherical equivalent refractive error (SER) between -6.00 diopters (D) and 1.00 D to overminus spectacles (-2.50 D for 12 months, -1.25 D for 3 months, and nonoverminus for 3 months) or nonoverminus spectacles. Children were recruited from 56 sites from July 2010 to February 2022. Data were analyzed from February 2022 to January 2024. Interventions: After trial completion at 18 months, participants were followed up at 24 and 36 months. Treatment was at investigator discretion from 18 to 36 months. Main Outcomes and Measures: Change in SER (cycloplegic retinoscopy) from baseline to 36 months. Results: Of 386 children in the Trial of Overminus Spectacle Therapy for Intermittent Exotropia, 223 (57.8%) consented to 18 months of additional follow-up, including 124 of 196 (63.3%) in the overminus treatment group and 99 of 190 (52.1%) in the nonoverminus treatment group. Of 205 children who completed 36-month follow-up, 116 (56.6%) were female, and the mean (SD) age at randomization was 6.2 (2.1) years. Mean (SD) SER change from baseline to 36 months was greater in the overminus group (-0.74 [1.00] D) compared with the nonoverminus group (-0.44 [0.85] D; adjusted difference, -0.36 D; 95% CI, -0.59 to -0.12; P = .003), with 30 of 112 (26.8%) in the overminus group having more than 1 D of myopic shift compared with 14 of 91 (15%) in the nonoverminus group (risk ratio, 1.8; 95% CI, 1.0-3.0). From 12 to 36 months, mean (SD) myopic shift was -0.34 (0.67) D and -0.36 (0.66) D in the overminus and nonoverminus groups, respectively (adjusted difference, -0.001 D; 95% CI, -0.18 to 0.18; P = .99). Conclusions and Relevance: The greater myopic shift observed after 1 year of -2.50-D overminus lens treatment remained at 3 years. Both groups had similar myopic shift during the 2-year period after treatment weaning and cessation. The risk of myopic shift should be discussed with parents when considering overminus lens treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02807350.

Improved control of intermittent exotropia with part-time patching.

We evaluated the effect of part-time patching versus observation on distance exodeviation control in post hoc analyses of 3- to <11-year-olds with intermittent exotropia who were assigned to either patching 3 hours/day or observation in a previously reported randomized clinical trial. The present analysis was limited to a subgroup of 306 participants who at distance fixation spontaneously manifested either a constant or intermittent exotropia or had prolonged recovery after monocular occlusion (a distance control score of 2 or worse using the 0-5 Office Control Score scale) at baseline. We assessed change in control at distance and near fixation, from baseline to 3 months and baseline to 6 months (1 month after discontinuing patching). We found greater improvement in the distance control score with patching than with observation at 3 months (mean difference, 0.4 points; 95% CI, 0.1-0.7) and 6 months (mean difference, 0.3 points; 95% CI, 0.02-0.6). These analyses suggest that part-time patching may improve distance control in children with intermittent exotropia and a control score ≥ 2; however, because this conclusion is based on post hoc subgroup analyses, further studies are needed.

Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial.

Importance: Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia. Objective: To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children. Design, Setting, and Participants: This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]). Intervention: Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation. Main Outcome and Measures: Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo. Results: A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95% CI, -0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, -0.115 to 0.134 mm). Conclusions and Relevance: In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children. Trial Registration: ClinicalTrials.gov Identifier: NCT03334253.

The integration of depressive behaviors and cardiac dysfunction during an operational measure of depression: investigating the role of negative social experiences in an animal model.

OBJECTIVE: There is a bidirectional association between depression and cardiovascular disease. The neurobiological mechanisms underlying this association may involve an inability to cope with disrupted social bonds. This study investigated in an animal model the integration of depressive behaviors and cardiac dysfunction after a disrupted social bond and during an operational measure of depression, relative to the protective effects of intact social bonds. METHODS: Depressive behaviors in the forced swim test and continuous electrocardiographic parameters were measured in 14 adult, female socially monogamous prairie voles (rodents), after 4 weeks of social pairing or isolation. RESULTS: After social isolation, animals exhibited (all values are mean ± standard error of the mean; isolated versus paired, respectively) increased heart rate (416 ± 14 versus 370 ± 14 bpm, p < .05) and reduced heart rate variability (3.3 ± 0.2 versus 3.9 ± 0.2 ln(ms(2))). During the forced swim test, isolated animals exhibited greater helpless behavior (immobility = 106 ± 11 versus 63 ± 11 seconds, p < .05), increased heart rate (530 ± 22 versus 447 ± 15 bpm, p < .05), reduced heart rate variability (1.8 ± 0.4 versus 2.7 ± 0.2 ln(ms(2)), p < .05), and increased arrhythmias (arrhythmic burden score = 181 ± 46 versus 28 ± 12, p < .05). CONCLUSIONS: The display of depressive behaviors during an operational measure of depression is coupled with increased heart rate, reduced heart rate variability, and increased arrhythmias, indicative of dysfunctional behavioral and physiological stress coping abilities as a function of social isolation. In contrast, social pairing with a sibling is behaviorally protective and cardioprotective. The present results can provide insight into a possible social mechanism underlying the association between depression and cardiovascular disease in humans.

Testing depth of suppression in childhood intermittent exotropia.

A test of suppression was developed to provide a standardized approach to detecting and grading density of suppression in children with intermittent exotropia when manifestly exotropic. This new Office Suppression Test is a three-step procedure to grade suppression on a 4-point scale (from 0 for "negligible suppression" to 3 for "dense suppression"). The test was performed in 57 children 3-13 years of age with intermittent exotropia (distance angle of 16Δ-35Δ, with spontaneous tropia) during enrollment in a randomized trial. Of the 57 children, 51 could complete testing: 28 (55%) had dense suppression, 12 (24%) had moderate suppression, 5 (10%) had mild suppression, and 6 (12%) had negligible suppression. In a subgroup of 20 untreated children, suppression was evaluated again at 8 weeks. There was moderate agreement between suppression scores at baseline and at 8 weeks (weighted κ = 0.65 [95% CI, 0.45-0.84]).

24-hour autonomic dysfunction and depressive behaviors in an animal model of social isolation: implications for the study of depression and cardiovascular disease.

OBJECTIVE: To investigate the hypothesis that long-term social isolation in an animal model would produce depression-relevant behaviors and disruptions in the 24-hour autonomic and activity parameters, and to further demonstrate the utility and validity of an animal model for the study of social environment, behavior, and autonomic function. Converging evidence from both experimental and epidemiological studies indicates that there is a bidirectional association between depression and cardiovascular disease; however, the precise neurobiological mechanisms underlying this relationship are not well understood. Disruptions in the social environment may influence this relationship. METHODS: Depression-relevant behaviors and ambulatory electrocardiographic and activity data were measured in 12 adult, socially monogamous prairie voles (rodents) during a period of chronic social isolation or social pairing (control conditions). RESULTS: Prairie voles exposed to 4 weeks of social isolation versus control conditions (social pairing) exhibited anhedonia, increased 24-hour heart rate, reduced 24-hour heart rate variability, and predictable correlations between the behavioral measure (anhedonia) and the autonomic measures. CONCLUSIONS: Social isolation is associated with depressive behaviors, 24-hour autonomic dysfunction, and predictable interrelationships between these variables in prairie voles but does not seem to be associated with rhythmicity changes in activity level or autonomic function. These findings have implications for understanding the role of the social environment in mediating the association of mood and cardiovascular disorders in humans.

Improvement in health-related quality of life following strabismus surgery for children with intermittent exotropia.

PURPOSE: To investigate health-related quality of life (HRQOL) after strabismus surgery in children with intermittent exotropia (IXT) and relationships between HRQOL and surgical success. METHODS: A total of 197 children with IXT aged 3-11 years (and 1 parent of each child) were enrolled in a previously reported randomized clinical trial comparing two surgical procedures. The Intermittent Exotropia Questionnaire (IXTQ) was administered before surgery (baseline), and again at 6 and 36 months following surgery. The child version of the IXTQ was only completed by children 5-11 years of age (n = 123). Outcomes were classified as "resolved" (exodeviation of <10Δ, no decreased stereoacuity, and no other nonsurgical treatment for IXT or reoperation), "suboptimal" (exotropia ≥10Δ by simultaneous prism and cover test or constant esotropia ≥6Δ or loss of ≥2 octaves of stereoacuity), or "intermediate." Mean changes in Rasch-calibrated IXTQ domain scores (Child, Proxy, Parent-psychosocial, Parent-function, and Parent-surgery; converted to a 0-100 scale) were compared. RESULTS: Overall, mean IXTQ domain scores improved for all domains from baseline to 36 months after surgery, ranging from 10.7 points (Child IXTQ; P < 0.0001) to 34.5 points (Parent-surgery IXTQ; P < 0.0001). At 36 months after surgery, 62 (39%) children had resolved IXT, whereas 38 (24%) had suboptimal outcome. Greater improvement was found in all mean domain scores with resolved IXT (range, 19.8-46.0 points) compared with suboptimal outcome (all comparisons P < 0.05). CONCLUSIONS: Successful surgery for childhood IXT results in measurable improvement in a child's quality of life, in parental assessment of the child's quality of life, and in quality of life for the parent.

Health-related quality of life in children with untreated intermittent exotropia and their parents.

PURPOSE: To determine whether health-related quality of life (HRQOL) scores improved or worsened over 3 years of observation in childhood intermittent exotropia without treatment. METHODS: A total of 111 children aged 3-11 years with intermittent exotropia were assigned to observation in a previously reported randomized trial comparing patching with observation. The intermittent exotropia questionnaire (IXTQ) was administered at baseline, 6 months, and 36 months. Rasch-calibrated IXTQ domain scores (Child, Proxy, Parent-psychosocial, Parent-function, and Parent-surgery) were compared between time points. The Child IXTQ was administered only to children ≥5 years of age (n = 78). RESULTS: Overall, Child IXTQ and Proxy IXTQ scores showed no significant change over 36 months (mean improvement from baseline to 36 months of 3.2 points [95% CI, -1.9 to 8.2] and -2.4 points [95% CI: -7.9 to 3.1], resp.). By contrast, Parent-psychosocial, Parent-function, and Parent-surgery domain scores all improved over 36 months (mean improvements of 12.8 points [95% CI, 5.9-19.6] and 14.2 points [95% CI, 8.0-20.3] and 18.5 points [95% CI, 9.7-27.3], resp.). CONCLUSIONS: HRQOL of children with intermittent exotropia remains stable with observation over 3 years (by both child and proxy report), whereas parental HRQOL improves.