Doses of medial rectus muscle recessions for divergence insufficiency-type esotropia.

We evaluated whether doses of bilateral medial rectus recessions greater than Parks's tables yielded superior outcomes for adult-onset divergence insufficiency. Forty-two patients underwent bilateral medial rectus recessions. Dose was analyzed as the average total per muscle (surgery + suture adjustment if performed) and compared with the standard dose tables (based on preoperative distance esodeviation), as difference between dose performed and dose indicated by Parks's tables. Each participant was classified as having received either Parks's dose (within 0.5 mm) or a dose greater than Parks's dose. Success was defined as "rarely" or "never" diplopia in distance straight-ahead gaze and reading. For patients classified as success, the mean difference between actual surgical dose performed and Parks's dose was calculated. Success was 91% (29/32) in those receiving greater than Parks's dose versus 67% (6/9) with Parks's dose (difference = 24%; 95% CI, -5% to 60%). The mean surgical dose was 1.0 mm greater than Parks's tables for the 35 successes (at 10 weeks) versus 0.7 mm greater for the 6 failures (difference = 0.4 mm; 95% CI, -0.2 to 0.9). For medial rectus recessions in adult-onset divergence insufficiency-type esotropia, a surgical dose 1 mm greater than Parks's tables, for each muscle, is a reasonable strategy.

Ocular and developmental outcomes of a dosing study of bevacizumab for retinopathy of prematurity.

PURPOSE: To report 2-year ocular and developmental outcomes for infants receiving low doses of intravitreal bevacizumab for type 1 retinopathy of prematurity (ROP). METHODS: A total of 120 premature infants (mean birthweight, 687 g; mean gestational age, 24.8 weeks) with type 1 ROP were enrolled in a multicenter, phase 1 dose de-escalation study. One eye per infant received 0.25 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreal bevacizumab; fellow eyes when treated received one dosage level higher. At 2 years, 70 of 120 children (58%) underwent ocular examinations; 51 (43%) were assessed using the Bayley Scale of Infant and Toddler Development. RESULTS: Correlation coefficients for the association of total dosage of bevacizumab with Bayley subscales were -0.20 for cognitive (95% CI, -0.45 to 0.08), -0.15 for motor (95% CI, -0.41 to 0.14), and -0.19 for language (95% CI, -0.44 to 0.10). Fourteen children (21%) had myopia greater than -5.00 D in one or both eyes, 7 (10%) had optic nerve atrophy and/or cupping, 20 (29%) had strabismus, 8 (11%) had manifest nystagmus, and 9 (13%) had amblyopia. CONCLUSIONS: In this study cohort, there was no statistically significant correlation between dosage of bevacizumab and Bayley scores at 2 years. However, the sample size was small and the retention rate relatively low, limiting our conclusions. Rates of high myopia and ocular abnormalities do not differ from those reported after larger bevacizumab doses.

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.

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.

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.

A Survey of Pediatric Ophthalmologists to Assess Practice Patterns for Primary Surgical Management of Nasolacrimal Duct Obstruction.

PURPOSE: To survey current practice patterns of pediatric ophthalmologists regarding primary surgical management of infantile dacryostenosis. METHODS: Responses to a five-question survey were cross-tabulated to compare surgery preferences across patient age ranges and intubation method. Surveys were submitted to members of the American Association for Pediatric Ophthalmology and Strabismus following institutional review board approval. RESULTS: Results from 142 completed surveys were analyzed. A bimodal distribution of reported propensity to intubate the nasolacrimal duct during primary surgery for dacryostenosis was observed, with one group of ophthalmologists intubating frequently and a second group intubating rarely. For patients younger than 24 months, 33 of 142 surgeons (23%) preferred to intubate 91% or more of the time and 76 of 142 (54%) preferred to intubate 10% or less of the time. For patients older than 24 months, the overall preference for intubation increased compared to the younger patient age group (P < .0007). In older patients, 52 of 142 surgeons (37%) preferred to intubate 91% or more of the time and 45 of 142 surgeons (32%) preferred to intubate 10% or less of the time. The most common preferred intubation methods were self-threading monocanalicular stent (42%) and metal-swaged bicanalicular stent (21%). Surgeons who preferred self-threading monocanalicular stents more often also preferred intubation procedures. CONCLUSIONS: Best practice for infantile dacryostenosis remains a surgeon preference, with some surgeons performing intubation frequently and others performing it rarely. Overall estimated intubation rates for primary surgery increased from 36% in children younger than 24 months to 50% at age 24 months or older. [J Pediatr Ophthalmol Strabismus. 2022;59(1):35-40.].

A prospective study of treatments for adult-onset divergence insufficiency-type esotropia.

PURPOSE: To describe 10-week and 12-month outcomes following treatment for divergence insufficiency-type esotropia in adults. METHODS: In this prospective observational study, 110 adults with divergence insufficiency-type esotropia, with a distance esodeviation measuring 2Δ to 30Δ and at least 25% larger at distance than near, and binocular diplopia present at least "sometimes" at distance, were enrolled at 28 sites when initiating new treatment. Surgery, prism, or divergence exercises/therapy were chosen at the investigator's discretion. Diplopia was assessed at enrollment and at 10-week and 12-month outcome examinations using a standardized diplopia questionnaire (DQ). Success was defined as DQ responses of "rarely" or "never" when looking straight ahead in the distance, with no alternative treatment initiated. RESULTS: Of the 110 participants, 32 (29%) were prescribed base-out prism; none had received prior treatment for esotropia. Success criteria were met by 22 of 30 at 10 weeks (73%; 95% CI, 54%-88%) and by 16 of 26 at 12 months (62%; 95% CI, 41%-80%). For the 76 (68%) who underwent strabismus surgery (82% of whom had been previously treated with prism), success criteria were met by 69 of 74 at 10 weeks (93%; 95% CI, 85%-98%) and by 57 of 72 at 12 months (79%; 95% CI, 68%-88%). CONCLUSIONS: In this study cohort, both base-out prism as initial therapy and strabismus surgery (usually following prism) were successful in treating diplopia for most adults with divergence insufficiency-type esotropia when assessed during the first year of follow-up.

Digital therapeutic improves visual acuity and encourages high adherence in amblyopic children in open-label pilot study.

BACKGROUND: The effectiveness of amblyopia therapy can be limited by poor adherence. Dichoptic therapies are a new approach, but recent trials have demonstrated difficulty maintaining high adherence over extended periods of at-home treatment. We evaluated the efficacy and adherence of Luminopia One-a dichoptic treatment that applies therapeutic modifications to streaming content chosen by the patient. METHODS: This single-arm, multicenter prospective pilot study enrolled children aged 4-12 with anisometropic, strabismic, or mixed amblyopia at 10 pediatric ophthalmic and optometric practices across the United States. The therapeutic was prescribed for 1 hour/day, 6 days/week for 12 weeks of at-home use. The primary endpoint was best-corrected visual acuity (BCVA) at the 12-week follow-up visit. RESULTS: In total, 90 participants (mean age, 6.7 ± 2.0 years) were enrolled, and 73/90 participants (81%) had prior treatment beyond refractive correction. For those who completed the 12-week visit, mean amblyopic eye BCVA improved from 0.50 logMAR to 0.35 logMAR (1.5 logMAR lines; 95% CI, 1.2-1.8 lines; P < 0.0001). Mean stereoacuity improved by 0.28 log arcsec (95% CI, 0.14-0.42 log arcsec; P < 0.0001). Median adherence was 86% (interquartile range, 70%-97%). CONCLUSIONS: In our study cohort, adherence over the 12-week study period was high, and participants demonstrated clinically and statistically significant improvements in visual acuity and stereoacuity.

Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity.

Importance: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. Objective: To find the lowest dose of intravitreous bevacizumab effective for severe ROP. Design, Setting, and Participants: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. Interventions: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. Main Outcomes and Measures: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg. Conclusions and Relevance: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.

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.

Secondary 12-Month Ocular Outcomes of a Phase 1 Dosing Study of Bevacizumab for Retinopathy of Prematurity.

Importance: Lower bevacizumab dosages are being used for type 1 retinopathy of prematurity, but there are limited data on long-term ocular outcomes with lower doses. Objective: To evaluate ocular outcomes at 12 months' corrected age for eyes that received a dose of 0.625 mg, 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab for type 1 retinopathy of prematurity. Design, Setting, and Participants: This prospective cohort study used a masked, multicenter, phase 1 dose de-escalation study design and was conducted from April 2016 to October 2017. Study eyes were treated with a dose of 0.25, 0.125, 0.063, or 0.031 mg of bevacizumab; fellow eyes were treated with a dosage 1 level higher than the study eye. Additional treatment after 4 weeks was at investigator discretion. Data analysis occurred from November 2018 to March 2019. Interventions: Intravitreous bevacizumab injections of 0.625 mg to 0.031 mg. Main Outcomes and Measures: Visual fixation, amblyopia, alignment, nystagmus, cycloplegic refraction, and ocular examinations were assessed at 12 months' corrected age as preplanned secondary outcomes. The primary outcome 4 weeks after treatment and secondary outcomes after 6 months' corrected age have been previously reported. Results: Forty-six of 61 infants (75%) had a 12-month follow-up examination (46 study eyes and 43 fellow eyes; median [interquartile range] birth weight, 650 [590-760] g). Of 87 eyes with a cycloplegic refraction, 12 (14% [95% CI, 7%-27%]) had myopia of more than -5.00 D spherical equivalent; 2 (2%; [95% CI, 0%-8%]) had hyperopia greater than 5.00 D spherical equivalent; and 5 infants (11% [95% CI, 4%-24%]) had anisometropia greater than 1.50 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye (1% [95% CI, 0%-6%]), 3 eyes (3% [95% CI, 1%-10%]), and 3 eyes (3% [95% CI, 1%-10%]), respectively. Optic nerve atrophy was identified in 11 eyes (13% [95% CI, 6%-26%]), and 1 eye (1% [95% CI, 0%-6%]) had total retinal detachment. Strabismus was reported in 13 infants (30% [95% CI, 17%-45%]), manifest nystagmus in 7 infants (15% [95% CI, 6%-29%]), and amblyopia in 3 infants (7% [95% CI, 1%-18%]). Overall, 98% of infants had central fixation in each eye (44 of 45 eyes). Conclusions and Relevance: In this study of low-dose bevacizumab, the secondary outcomes of high myopia, strabismus, retinal detachment, nystagmus, and other ocular abnormalities at 1 year were consistent with rates reported in other studies with higher dosages. Trial Registration: ClinicalTrials.gov identifier: NCT02390531.

Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.

BACKGROUND: The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. RESULTS: Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the proband's phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. Zebrafish in vivo complementation studies of the latter transcript demonstrated a loss of function effect. Finally, we conducted post-hoc trio-based whole exome sequencing studies to (a) test the possibility of other causal loci in the proband and (b) explain the Mendelian error of segregation for the IFT140 mutation. We show that the proband harbors a chromosome 16 maternal heterodisomy, with segmental isodisomy at 16p13, likely due to a meiosis I error in the maternal gamete. CONCLUSIONS: Using clinical phenotyping combined with research-based genetic and functional studies, we have characterized a recurrent IFT140 mutation in the proband; together, these data are consistent with MZSDS. Additionally, we report a rare instance of a uniparental isodisomy unmasking a deleterious mutation to cause a ciliary disorder.

Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study.

Importance: Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. Objective: To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Design, Setting, and Participants: Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles. Interventions: Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Main Outcomes and Measures: Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. Conclusions and Relevance: A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.

Comparison of EX-PRESS Shunt and Trabeculectomy With Mitomycin-C in Congenital and Juvenile Glaucoma.

PURPOSE: To compare efficacy and safety of EX-PRESS mini glaucoma shunt (Alcon) and trabeculectomy with mitomycin-C (MMC) in the management of pediatric glaucoma. METHODS: The authors retrospectively reviewed patients from a single pediatric ophthalmology practice with either congenital or juvenile glaucoma who underwent surgical treatment with either trabeculectomy or EX-PRESS shunt insertion with MMC. Postoperative intraocular pressure at 6, 18, and 36 months, medication requirements, visual acuities, postoperative interventions, complications, and noncompliance with medications or follow-up was reviewed. RESULTS: A total of 42 cases of glaucoma with either trabeculectomy or EX-PRESS shunt were identified for review (n trabeculectomy=25, n EX-PRESS=17). At 6 months, 62.5% of trabeculectomies and 94.1% of EX-PRESS shunts met criteria for success (P=0.0281). At 18 months, 38.1% of trabeculectomies and 81.3% of EX-PRESS shunts met criteria for success (P=0.0178). At 36 months, trabeculectomies had a success rate of 33.3% versus 66.7% for EX-PRESS shunts (P=0.321). The average decrease in medications postoperatively was 0.375 and 1.63 for trabeculectomy and EX-PRESS shunt, respectively (P=0.06). Preoperative visual acuities compared with postoperative best-corrected visual acuities before additional surgery demonstrated a slight average worsening of 0.11 logMAR in trabeculectomy patients and an average improvement of 0.56 logMAR in EX-PRESS shunt patients (P=0.0037). CONCLUSIONS: In this review, patients with pediatric glaucoma managed with EX-PRESS shunt with MMC compared with trabeculectomy with MMC appear to have better intraocular pressure control, better visual acuities, and fewer complications and reoperations.

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.

Office probing for treatment of nasolacrimal duct obstruction in infants.

PURPOSE: To determine whether demographic or clinical factors are associated with the outcome of office-based nasolacrimal duct probing for the treatment of congenital nasolacrimal duct obstruction (NLDO). METHODS: In two multicenter prospective studies, 384 eyes of 304 children aged 6 to <15 months with NLDO underwent a nasolacrimal duct probing performed in the office using topical anesthesia. Treatment success, defined as no clinical signs of NLDO (epiphora, increased tear lake, or mucous discharge) and no reoperation, was assessed 1 month after probing in one study and 6 months after probing in the other study. Data from both studies were pooled to evaluate associations between baseline characteristics and treatment success. RESULTS: Office probing was successful in 75% of eyes overall (95% CI, 70%-80%). The procedure was less successful in eyes of children with bilateral NLDO compared with unilateral NLDO (63% vs 80%; relative risk = 0.78 [95% CI, 0.66-0.92]) and in eyes that had 2 or 3 clinical signs of NLDO compared with one (71% vs 83%; relative risk = 0.88 [95% CI, 0.81-0.96]). Treatment success did not appear to be related to age, specific clinical signs of NLDO, prior treatment, or research study. CONCLUSIONS: Performing nasolacrimal duct probing in the office successfully treats NLDO in the majority of cases in children aged 6 to <15 months. The success rate is lower with bilateral disease or when more than one clinical sign of NLDO is present.

Diurnal variation in nicotine sensitivity in mice: role of genetic background and melatonin.

Despite the evidence that there is a daily rhythm in smoking behavior and that the effects of drugs of abuse exhibit diurnal variations, very few studies have explored the extent to which sensitivity to the effects of nicotine vary over the course of the day. In the studies described in this report, the melatonin proficient mouse strain C3H/Ibg and the melatonin deficient mouse strains C57BL/6J and DBA/2J were assessed for diurnal variations in sensitivity to the effects of nicotine. Results indicated that there is significant variation in sensitivity to both activity and body temperature depressant effects of nicotine in the melatonin proficient C3H/Ibg strain with maximal sensitivity occurring during the latter third of the light period of the light cycle and minimal sensitivity taking place during the last third of the dark phase of the light cycle. The melatonin deficient strains did not exhibit diurnal differences in sensitivity to the effects of nicotine suggesting a potential role for melatonin in modulating the effects of nicotine. Experiments with knockout mice lacking both the Mtnr1a and Mtnr1b melatonin receptors confirmed that the reduced sensitivity observed during the dark phase is melatonin dependent. Diurnal variation in nicotinic receptor expression also was measured in cortex, hippocampus, hypothalamus and striatum using [(125)I]-α-bungarotoxin and [(125)I]-epibatidine. [(125)I]-α-bungarotoxin binding in hypothalamus of C3H mice exhibited a diurnal pattern with maximal binding observed in the latter third of the light portion of the light cycle. No other significant differences in binding were detected.

Optical treatment of strabismic and combined strabismic-anisometropic amblyopia.

OBJECTIVE: To determine visual acuity improvement in children with strabismic and combined strabismic-anisometropic (combined-mechanism) amblyopia treated with optical correction alone and to explore factors associated with improvement. DESIGN: Prospective, multicenter, cohort study. PARTICIPANTS: We included 146 children 3 to <7 years old with previously untreated strabismic amblyopia (n = 52) or combined-mechanism amblyopia (n = 94). METHODS: Optical treatment was provided as spectacles (prescription based on a cycloplegic refraction) that were worn for the first time at the baseline visit. Visual acuity with spectacles was measured using the Amblyopia Treatment Study HOTV visual acuity protocol at baseline and every 9 weeks thereafter until no further improvement in visual acuity. Ocular alignment was assessed at each visit. MAIN OUTCOME MEASURES: Visual acuity 18 weeks after baseline. RESULTS: Overall, amblyopic eye visual acuity improved a mean of 2.6 lines (95% confidence interval [CI], 2.3-3.0), with 75% of children improving ≥ 2 lines and 54% improving ≥ 3 lines. Resolution of amblyopia occurred in 32% (95% CI, 24%-41%) of the children. The treatment effect was greater for strabismic amblyopia than for combined-mechanism amblyopia (3.2 vs 2.3 lines; adjusted P = 0.003). Visual acuity improved regardless of whether eye alignment improved. CONCLUSIONS: Optical treatment alone of strabismic and combined-mechanism amblyopia results in clinically meaningful improvement in amblyopic eye visual acuity for most 3- to <7-year-old children, resolving in at least one quarter without the need for additional treatment. Consideration should be given to prescribing refractive correction as the sole initial treatment for children with strabismic or combined-mechanism amblyopia before initiating other therapies. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.