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.

Complications, Visual Acuity, and Refractive Error Three Years After Secondary Intraocular Lens implantation for Pediatric Aphakia.

OBJECTIVE: To report the cumulative incidence of complications and describe refractive error and visual acuity (VA) outcomes in children undergoing secondary intraocular lens (IOL) implantation following previous surgery for non-traumatic cataract. DESIGN: Pediatric cataract registry. PARTICIPANTS: 80 children (108 eyes: 60 bilateral, 48 unilateral) undergoing lensectomy at <13 years of age, followed by secondary IOL implantation at median age (range) of 2.7 (0.6 to 5.0) years for bilateral and 2.1 (0.5 to 6.4) for unilateral cases. METHODS: Annual data collection from medical record review through 5 years following lensectomy. MAIN OUTCOME MEASURES: Cumulative incidence of newly emergent complications following secondary IOL implantation; refractive error and VA by 5 years after lensectomy. RESULTS: Median (interquartile range [IQR]) follow-up following secondary IOL implantation was 2.5 years (0.8 to 3.3 years). A common complication following secondary IOL implantation was a glaucoma-related adverse event (GRAE: glaucoma or glaucoma suspect); the cumulative incidence was 17% (95% CI: 3%-29%) in bilateral and 12% (95% CI: 0%-23%) in unilateral cases. The cumulative incidence of surgery for visual axis opacification was 2% (95% CI: 0%-7%) for bilateral and 4% (95% CI: 0%-10%) for unilateral cases. Median prediction error (IQR) within 90 days of implantation was 0.88 D (-0.50 D to +3.00 D) less hyperopic than intended among 21 eyes for bilateral cases and 1.50 D (-0.25 D to +2.38 D) less among 19 unilateral cases. Median (IQR) spherical equivalent refractive error at 5 years (median 5.1 years of age) in eyes receiving a secondary IOL was +0.50 D (-2.38 D to +2.94 D) for 48 bilateral and +0.06 D (-2.25 D to +0.75 D) for 22 unilateral cases. Median (IQR) monocular VA at 5 years was 20/63 (20/50-20/100) for bilateral (n=42) and 20/400 (20/160-20/800) for unilateral (n=33) cases. CONCLUSIONS: Eyes with secondary IOL implantation have an ongoing risk of new glaucoma-related adverse events. Five years after lensectomy (approximately 2.5 years after secondary IOL implantation), average refractive error was less hyperopic than desired given the anticipated further myopic shift before refraction stabilizes.

Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

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.

Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes.

PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results.

PURPOSE: Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. DESIGN: Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. PARTICIPANTS: A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3-<16 years) who completed their 2-year study visit. METHODS: Participants were treated at the investigator's discretion. MAIN OUTCOMES MEASURES: Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. RESULTS: A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein-associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, -0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60-90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48-0.88 [20/50+1-20/150-1]). CONCLUSIONS: Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).

A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 4 to 6 Years.

SIGNIFICANCE: Binocular treatment for unilateral amblyopia is an emerging treatment that requires evaluation through a randomized clinical trial. PURPOSE: This study aimed to compare change in amblyopic-eye visual acuity (VA) in children aged 4 to 6 years treated with the dichoptic binocular iPad (Apple, Cupertino, CA) game, Dig Rush (not yet commercially available; Ubisoft, Montreal, Canada), plus continued spectacle correction versus continued spectacle correction alone. METHODS: Children (mean age, 5.7 years) were randomly assigned to home treatment for 8 weeks with the iPad game (prescribed 1 h/d, 5 d/wk [n = 92], or continued spectacle correction alone [n = 90]) in a multicenter randomized clinical trial. Before enrollment, children wearing spectacles were required to have at least 16 weeks of wear or no improvement in amblyopic-eye VA (<0.1 logMAR) for at least 8 weeks. Outcome was change in amblyopic-eye VA from baseline to 4 weeks (primary) and 8 weeks (secondary) assessed by masked examiner. RESULTS: A total of 182 children with anisometropic (63%), strabismic (16%; <5∆ near, simultaneous prism and cover test), or combined-mechanism (20%) amblyopia (20/40 to 20/200; mean, 20/63) were enrolled. After 4 weeks, mean amblyopic VA improved by 1.1 logMAR lines with binocular treatment and 0.6 logMAR lines with spectacles alone (adjusted difference, 0.5 lines; 95.1% confidence interval [CI], 0.1 to 0.9). After 8 weeks, results (binocular treatment: mean amblyopic-eye VA improvement, 1.3 vs. 1.0 logMAR lines with spectacles alone; adjusted difference, 0.3 lines; 98.4% CI, -0.2 to 0.8 lines) were inconclusive because the CI included both zero and the pre-defined difference in mean VA change of 0.75 logMAR lines. CONCLUSIONS: In 4- to 6-year-old children with amblyopia, binocular Dig Rush treatment resulted in greater improvement in amblyopic-eye VA for 4 weeks but not 8 weeks. Future work is required to determine if modifications to the contrast increment algorithm or other aspects of the game or its implementation could enhance the treatment effect.

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.

Relationships among Clinical Factors and Patient-reported Outcome Measures in Adults with Convergence Insufficiency.

SIGNIFICANCE: When exploring relationships among clinical measures and patient-reported outcome measures in adults with convergence insufficiency, worse symptoms (Convergence Insufficiency Symptom Survey [CISS] score) seemed to be correlated with worse reading function domain score (Adult Strabismus-20 quality-of-life questionnaire). After treatment, improved symptoms were associated with improved reading function quality of life. PURPOSE: This study aimed to explore relationships between clinical measures and patient-reported outcome measures in adults undergoing treatment for symptomatic convergence insufficiency. METHODS: In a prospective multicenter observational study, we evaluated adults with symptomatic convergence insufficiency (i.e., clinical measures of near exodeviation, receded near point of convergence, reduced near positive fusional vergence; CISS score ≥21). Fifty-seven participants treated with vision therapy/exercises (n = 35) or base-in prism (n = 22) were analyzed. Spearman correlation coefficients ( R ) were used to assess associations among the three clinical measures and patient-reported outcome measures (CISS, Diplopia Questionnaire, four Adult Strabismus-20 quality-of-life domains) before treatment (baseline) and after 10 weeks and 1 year. Associations were interpreted to be present when the lower limit of the 95% confidence interval (CI) was moderate to strong ( R ≥ 0.4). RESULTS: Among multiple exploratory analyses, the only moderate to strong baseline correlation was between worse CISS and worse Adult Strabismus-20 reading function scores ( R = 0.62; 95% CI, 0.43 to 0.76). Regarding change in measures with treatment, the only moderate to strong correlations were between improved CISS and improved Adult Strabismus-20 reading function scores for prism at 10 weeks ( R = 0.78; 95% CI, 0.52 to 0.91) and 1 year ( R = 0.85; 95% CI, 0.65 to 0.94) and for vision therapy/exercises at 1 year ( R = 0.78; 95% CI, 0.57 to 0.89). CONCLUSIONS: In exploratory analyses, we found positive correlations between CISS symptom scores and reading function quality-of-life scores. The absence of correlations between symptoms and individual clinical measures is consistent with clinical experience that, in convergence insufficiency, symptoms and clinical findings can be discordant.

Does coexisting accommodative dysfunction impact clinical convergence measures, symptoms and treatment success for symptomatic convergence insufficiency in children?

PURPOSE: To determine whether coexisting accommodative dysfunction in children with symptomatic convergence insufficiency (CI) impacts presenting clinical convergence measures, symptoms and treatment success for CI. METHODS: Secondary data analyses of monocular accommodative amplitude (AA; push-up method), monocular accommodative facility (AF; ±2.00 D lens flippers) and symptoms (CI Symptom Survey [CISS]) in children with symptomatic CI from the Convergence Insufficiency Treatment Trial (N = 218) and CITT-Attention and Reading Trial (N = 302) were conducted. Decreased AA was defined as more than 2D below the minimum expected amplitude for age (15 - » age); those with AA < 5 D were excluded. Decreased AF was defined as <6 cycles per minute. Mean near point of convergence (NPC), near positive fusional vergence (PFV) and symptoms (CISS) were compared between those with and without accommodative dysfunction using analysis of variance and independent samples t-testing. Logistic regression was used to compare the effect of baseline accommodative function on treatment success [defined using a composite of improvements in: (1) clinical convergence measures and symptoms (NPC, PFV and CISS scores) or (2) solely convergence measures (NPC and PFV)]. RESULTS: Accommodative dysfunction was common in children with symptomatic CI (55% had decreased AA; 34% had decreased AF). NPC was significantly worse in those with decreased AA (mean difference = 6.1 cm; p < 0.001). Mean baseline CISS scores were slightly worse in children with coexisting accommodative dysfunction (decreased AA or AF) (30.2 points) than those with normal accommodation (26.9 points) (mean difference = 3.3 points; p < 0.001). Neither baseline accommodative function (p ≥ 0.12 for all) nor interaction of baseline accommodative function and treatment (p ≥ 0.50) were related to treatment success based on the two composite outcomes. CONCLUSIONS: A coexisting accommodative dysfunction in children with symptomatic CI is associated with worse NPC, but it does not impact the severity of symptoms in a clinically meaningful way. Concurrent accommodative dysfunction does not impact treatment response for CI.

Negative Fusional Vergence Is Abnormal in Children with Symptomatic Convergence Insufficiency.

SIGNIFICANCE: Deficits of disparity divergence found with objective eye movement recordings may not be apparent with standard clinical measures of negative fusional vergence (NFV) in children with symptomatic convergence insufficiency. PURPOSE: This study aimed to determine whether NFV is normal in untreated children with symptomatic convergence insufficiency and whether NFV improves after vergence/accommodative therapy. METHODS: This secondary analysis of NFV measures before and after office-based vergence/accommodative therapy reports changes in (1) objective eye movement recording responses to 4° disparity divergence step stimuli from 12 children with symptomatic convergence insufficiency compared with 10 children with normal binocular vision (NBV) and (2) clinical NFV measures in 580 children successfully treated in three Convergence Insufficiency Treatment Trial studies. RESULTS: At baseline, the Convergence Insufficiency Treatment Trial cohort's mean NFV break (14.6 ± 4.8Δ) and recovery (10.6 ± 4.2Δ) values were significantly greater (P < .001) than normative values. The post-therapy mean improvements for blur, break, and recovery of 5.2, 7.2, and 1.3Δ, respectively, were statistically significant (P < .0001). Mean pre-therapy responses to 4° disparity divergence step stimuli were worse in the convergence insufficiency group compared with the NBV group for peak velocity (P < .001), time to peak velocity (P = .01), and response amplitude (P < .001). After therapy, the convergence insufficiency group showed statistically significant improvements in mean peak velocity (11.63°/s; 95% confidence interval [CI], 6.6 to 16.62°/s), time to peak velocity (-0.12 seconds; 95% CI, -0.19 to -0.05 seconds), and response amplitude (1.47°; 95% CI, 0.83 to 2.11°), with measures no longer statistically different from the NBV cohort (P > .05). CONCLUSIONS: Despite clinical NFV measurements that seem greater than normal, children with symptomatic convergence insufficiency may have deficient NFV when measured with objective eye movement recordings. Both objective and clinical measures of NFV can be improved with vergence/accommodative therapy.

Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years.

SIGNIFICANCE: This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction. PURPOSE: This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children. METHODS: Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves. RESULTS: Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors. CONCLUSIONS: Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.

Effectiveness of vergence/accommodative therapy for accommodative dysfunction in children with convergence insufficiency.

PURPOSE: To determine the effectiveness of office-based vergence/accommodative therapy for improving accommodative amplitude and accommodative facility in children with symptomatic convergence insufficiency and accommodative dysfunction. METHODS: We report changes in accommodative function following therapy among participants in the Convergence Insufficiency Treatment Trial - Attention and Reading Trial with decreased accommodative amplitude (115 participants in vergence/accommodative therapy; 65 in placebo therapy) or decreased accommodative facility (71 participants in vergence/accommodative therapy; 37 in placebo therapy) at baseline. The primary analysis compared mean change in amplitude and facility between the vergence/accommodative and placebo therapy groups using analyses of variance models after 4, 8, 12 and 16 weeks of treatment. The proportions of participants with normal amplitude and facility at each time point were calculated. The average rate of change in amplitude and facility from baseline to week 4, and from weeks 4 to 16, were determined in the vergence/accommodative therapy group. RESULTS: From baseline to 16 weeks, the mean improvement in amplitude was 8.6 dioptres (D) and 5.2 D in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 3.5 D, 95% confidence interval (CI): 1.5 to 5.5 D; p = 0.01). The mean improvement in facility was 13.5 cycles per minute (cpm) and 7.6 cpm in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 5.8 cpm, 95% CI: 3.8 to 7.9 cpm; p < 0.0001). Significantly greater proportions of participants treated with vergence/accommodative therapy achieved a normal amplitude (69% vs. 32%, difference = 37%, 95% CI: 22 to 51%; p < 0.0001) and facility (85% vs. 49%, difference = 36%, 95% CI: 18 to 55%; p < 0.0001) than those who received placebo therapy. In the vergence/accommodative therapy group, amplitude increased at an average rate of 1.5 D per week during the first 4 weeks (p < 0.0001), then slowed to 0.2 D per week (p = 0.002) from weeks 4 to 16. Similarly, facility increased at an average rate of 1.5 cpm per week during the first 4 weeks (p < 0.0001), then slowed to 0.6 cpm per week from weeks 4 to 16 (p < 0.0001). CONCLUSION: Office-based vergence/accommodative therapy is effective for improving accommodative function in children with symptomatic convergence insufficiency and coexisting accommodative dysfunction.

Interventions for convergence insufficiency: a network meta-analysis.

BACKGROUND: Convergence insufficiency is a common binocular vision disorder in which the eyes have a strong tendency to drift outward (exophoria) with difficulty turning the eyes inward when reading or doing close work. OBJECTIVES: To assess the comparative effectiveness and relative ranking of non-surgical interventions for convergence insufficiency through a systematic review and network meta-analysis (NMA). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed and three trials registers up to 20 September 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) examining any form of non-surgical intervention versus placebo, no treatment, sham treatment, or other non-surgical interventions. Participants were children and adults with symptomatic convergence insufficiency. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. We performed NMAs separately for children and adults. MAIN RESULTS: We included 12 trials (six in children and six in adults) with a total of 1289 participants. Trials evaluated seven interventions: 1) office-based vergence/accommodative therapy with home reinforcement; 2) home-based pencil/target push-ups; 3) home-based computer vergence/accommodative therapy; 4) office-based vergence/accommodative therapy alone; 5) placebo vergence/accommodative therapy or other placebo intervention; 6) prism reading glasses; and 7) placebo reading glasses. Six RCTs in the pediatric population randomized 968 participants. Of these, the Convergence Insufficiency Treatment Trial (CITT) Investigator Group completed four RCTs with 737 participants. All four CITT RCTs were rated at low risk of bias. Diagnostic criteria and outcome measures were identical or similar among these trials. The four CITT RCTs contributed data to the pediatric NMA, incorporating interventions 1, 2, 3 and 5. When treatment success was defined by a composite outcome requiring both clinical measures of convergence to be normal, and also show a pre-specified magnitude of improvement, we found high-certainty evidence that office-based vergence/accommodative therapy with home reinforcement increases the chance of a successful outcome, compared with home-based computer vergence/accommodative therapy (risk ratio (RR) 1.96, 95% confidence interval (CI) 1.32 to 2.94), home-based pencil/target push-ups (RR 2.86, 95% CI 1.82 to 4.35); and placebo (RR 3.04, 95% CI 2.32 to 3.98). However, there may be no evidence of any treatment difference between home-based computer vergence/accommodative therapy and home-based pencil/target push-ups (RR 1.44, 95% CI 0.93 to 2.24; low-certainty evidence), or between either of the two home-based therapies and placebo therapy, for the outcome of treatment success. When treatment success was defined as the composite convergence and symptom success outcome, we found moderate-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement were 5.12 (95% CI 2.01 to 13.07) times more likely to achieve treatment success than those who received placebo therapy. We found low-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement might be 4.41 (95% CI 1.26 to 15.38) times more likely to achieve treatment success than those who received home-based pencil push-ups, and 4.65 (95% CI 1.23 to 17.54) times more likely than those who received home-based computer vergence/accommodative therapy. There was no evidence of any treatment difference between home-based pencil push-ups and home-based computer vergence/accommodative therapy, or between either of the two home-based therapies and placebo therapy. One RCT evaluated the effectiveness of base-in prism reading glasses in children. When base-in prism reading glasses were compared with placebo reading glasses, investigators found no evidence of a difference in the three outcome measures of near point convergence (NPC), positive fusional vergence (PFV), or symptom scores measured by the Convergence Insufficiency Symptom Survey (CISS). Six RCTs in the adult population randomized 321 participants. We rated only one RCT at low risk of bias. Because not all studies of adults included composite success data, we could not conduct NMAs for treatment success. We thus were limited to comparing the mean difference (MD) between interventions for improving NPC, PFV, and CISS scores individually using data from three RCTs (107 participants; interventions 1, 2, 4 and 5). Compared with placebo treatment, office-based vergence accommodative therapy was relatively more effective in improving PFV (MD 16.73, 95% CI 6.96 to 26.60), but there was no evidence of a difference for NPC or the CISS score. There was no evidence of difference for any other comparisons for any outcomes. One trial evaluated base-in prism glasses prescribed for near-work activities and found that the prism glasses group had fewer symptoms compared with the placebo glasses group at three months (MD -8.9, 95% CI -11.6 to -6.3). The trial found no evidence of a difference with this intervention in NPC or PFV. No adverse effects related to study treatments were reported for any of the included studies. Excellent adherence was reported for office-based vergence/accommodative therapy (96.6% or higher) in two trials. Reported adherence with home-based therapy was less consistent, with one study reporting decreasing adherence over time (weeks 7 to 12) and lower completion rates with home-based pencil/target push-ups. AUTHORS' CONCLUSIONS: Current research suggests that office-based vergence/accommodative therapy with home reinforcement is more effective than home-based pencil/target push-ups or home-based computer vergence/accommodative therapy for children. In adults, evidence of the effectiveness of various non-surgical interventions is less clear.

Interventions to slow progression of myopia in children.

BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents. OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children. SEARCH METHODS: We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25 diopters (D) spherical equivalent myopia. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: We included 41 studies (6772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15 D (95% confidence interval [CI] -0.29 to 0.00; n = 142; low-certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95% CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95% CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95% CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95% CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95% CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95% CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95% CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95% CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and sperical aberration SCLs.

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.

Prevalence, Characteristics, and Risk Factors of Moderate or High Hyperopia among Multiethnic Children 6 to 72 Months of Age: A Pooled Analysis of Individual Participant Data.

PURPOSE: To describe the prevalence, ocular characteristics, and associated risk factors of moderate to high hyperopia in early childhood. DESIGN: Pooled analysis of individual participant data from population-based studies. PARTICIPANTS: Six- to 72-month-old multiethnic children who participated in 4 population-based studies of pediatric eye diseases. METHODS: The pooled studies conducted comparable parental interviews and ocular examinations including cycloplegic autorefraction. Presence of hyperopia was defined based on cycloplegic refractive error in the worse eye. Multivariate analyses were performed to evaluate the association of potential risk factors with hyperopia risk. MAIN OUTCOME MEASURES: Prevalence and odds ratios of moderate to high hyperopia (≥4.0 diopters [D]). RESULTS: Cycloplegic refraction was completed in 15 051 children 6 to 72 months of age. Among these children, the overall prevalence of moderate to high hyperopia (≥4.0 D) in the worse eye was 3.2% (95% confidence interval, 2.9%-3.5%), accounting for 15.6% of all hyperopia (≥2.0 D). Among children with moderate to high hyperopia, both eyes were affected in 64.4%, 28.9% showed spherical anisometropia of 1.0 D or more, and 19.5% showed astigmatism of 1.5 D or more. Among 36- to 72-month-old children with moderate to high hyperopia, 17.6% wore glasses. Prevalence of moderate to high hyperopia was slightly less in 12- to 23-month-old children and was relatively stable in children 24 months of age and older. Non-Hispanic and Hispanic white race and ethnicity, family history of strabismus, maternal smoking during pregnancy, and being a participant in the United States studies were associated with a higher risk of moderate to high hyperopia (P < 0.05). CONCLUSIONS: By assembling similarly designed studies, our consortium provided robust estimates of the prevalence of moderate to high hyperopia in the general population and showed that in 6- to 72-month-old children, moderate to high hyperopia is not uncommon and its prevalence does not decrease with age. Risk factors for moderate to high hyperopia differ from those for low to moderate hyperopia (2.0-<4.0 D) in preschool children, with family history of strabismus and maternal smoking during pregnancy more strongly associated with moderate to high hyperopia than low to moderate hyperopia.

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 Clinical Trial of Immediate versus Delayed Glasses for Moderate Hyperopia in 1- and 2-Year-Olds.

PURPOSE: Two strategies were compared for managing moderate hyperopia without manifest strabismus among 1- and 2-year-old children: (1) immediate prescription of glasses versus (2) observation without glasses unless reduced distance visual acuity (VA), reduced stereoacuity, or manifest strabismus. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: A total of 130 children aged 1 to 2 years with hyperopia between +3.00 diopters (D) and +6.00 D spherical equivalent (SE) in at least 1 eye, anisometropia ≤1.50 D SE, and astigmatism ≤1.50 D based on cycloplegic refraction and no manifest strabismus. METHODS: Participants were randomly assigned to glasses (1.00 D less than full cycloplegic hyperopia) versus observation and followed every 6 months for 3 years. Glasses were prescribed to those assigned to observation if they met prespecified deterioration criteria of distance VA or near stereoacuity below age norms, or development of manifest strabismus. MAIN OUTCOME MEASURES: At the 3-year primary outcome examination, participants were classified as failing the randomized management regimen if distance VA or stereoacuity was below age norms or manifest strabismus was observed (each with and without correction in trial frames, confirmed by masked retest, irrespective of whether deterioration had occurred previously), or if strabismus surgery had been performed. RESULTS: Of the 106 participants (82%) completing the 3-year primary outcome examination, failure occurred in 11 (21%) of 53 in the glasses group and 18 (34%) of 53 in the observation group (difference = -13%; 95% confidence interval [CI], -31 to 4; P = 0.14). Sixty-two percent (95% CI, 49-74) in the observation group and 34% (95% CI, 23-48) in the glasses group met deterioration criteria (requiring glasses if not wearing). CONCLUSIONS: For 1- and 2-year-olds with uncorrected moderate hyperopia (+3.00 D to +6.00 D SE), our estimates of failure, after 3 years of 6-month follow-ups, are inconclusive and consistent with a small to moderate benefit or no benefit of immediate prescription of glasses compared with careful observation (with glasses only if deteriorated).