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Amphibians are experiencing declines globally, with emerging infectious diseases as one of the main causes. Haematological parameters present a useful method for determining the health status of animals and the effects of particular diseases, but the interpretation of differential cell counts relies on knowing the normal ranges for the species and factors that can affect these counts. However, there is very little data on either normal haematological parameters or guides for blood cell types for free-ranging frog species across the world. This study aims to 1) create a visual guide for three different Australian frog species: Litoria paraewingi , Limnodynastes dumerilii , and Crinia signifera , 2) determine the proportions of erythrocytes to leukocytes and 3) differential leukocytes within blood smears from these three species and 4) assess the association between parasites and differential counts. We collected blood samples from free-ranging frogs and analysed blood smears. We also looked for ectoparasites and tested for the fungal disease chytridiomycosis. Overall, we found that the differentials of erythrocytes to leukocytes were not affected by species, but the proportions of different leukocytes did vary across species. For example, while lymphocytes were the most common type of leukocyte across the three species, eosinophils were relatively common in Limnodynastes dumerilii but rarely present in the other two species. We noted chytridiomycosis infection as well as ectoparasites present in some individuals but found no effect of parasites on blood parameters. Our results add baseline haematological parameters for three Australian frog species and provide an example of how different frog species can vary in their differential blood cell counts. More information is needed on frog haematological data before these parameters can be used to determine the health status of wild or captive frogs., Competing Interests: Laura Brannelly is an Academic Editor at PeerJ., (© 2024 Jadwani-Bungar et al.)

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., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Amphibians are experiencing dramatic worldwide declines and many species are reliant on captive breeding programs to ensure continued survival. However, captive breeding in amphibians is not always successful because many species, especially ones in decline, have particular and specific breeding needs. The endangered alpine tree frog, Litoria verreauxii alpina , has never been bred in captivity before. Due to its dramatic declines across the Australian Alps caused by the global pandemic chytridiomycosis, the species is a potential candidate for captive assurance colonies, which rely on captive breeding. For this study we tested hormone induction using two hormones that have had some success in other amphibian species, to no avail. We then tried outdoor breeding mesocosms during the winter/spring at temperatures similar to their natural breeding season, which was successful. Sixty-five percent of the egg masses laid successfully hatched tadpoles. Females laid more than one clutch over the experiment indicating either a shorter than annual ovulation cycle, or that females are capable of partial ovulation during breeding events. Outdoor breeding mesocosms are a possibility outside the native climate of a species, provided that temperatures overlap with their natural environment. Here, we highlight that troubleshooting is essential before embarking on a captive breeding program of a species that has not been bred before. Hormonal induction of breeding is not always successful; therefore, outdoor mesocosms might be required to achieve healthy tadpoles., Competing Interests: Laura A Brannelly is an Academic Editor for PeerJ., (©2023 Brannelly et al.)

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., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant., Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP., Design, Setting, and Participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021., Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection., Main Outcomes and Measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels., Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection., Conclusions and Relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.

Purpose: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system., Design: Review of evidence-based literature, along with expert consensus opinion., Participants: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men., Methods: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification., Main Outcome Measures: Consensus statement., Results: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae., Conclusions: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care., (Published by Elsevier Inc.)

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 2 Δ to 30 Δ 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., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial., Study Design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed., Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40)., Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Guidelines on managing infants after initial anti-vascular endothelial growth factor (VEGF) treatment (eg, bevacizumab) for retinopathy of prematurity (ROP) are limited. We found that following initial bevacizumab treatment for ROP, prophylactically lasering infant eyes before hospital discharge reduced the number and duration of outpatient ROP screening examinations compared with following infants, per current United States (US) ROP screening guidelines., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Importance: The Pediatric Eye Disease Investigator Group Cataract Registry provides a multicenter assessment of visual outcomes and complications after lensectomy for traumatic pediatric cataract., Objective: To report visual acuity (VA) and the cumulative proportion with strabismus, glaucoma, and other ocular complications by 15 months after lensectomy for traumatic cataract among children younger than 13 years at the time of surgery., Design, Setting, and Participants: From June 18, 2012, to July 8, 2015, 1266 eyes of 994 children from 33 pediatric eye care practices seen within 45 days after lensectomy were enrolled in a multicenter, prospective observational registry. Of these, 74 eyes of 72 participants undergoing lensectomy for traumatic cataract were included in a cohort study. Follow-up was completed by November 2, 2015, and data were analyzed from March 20, 2018, to July 7, 2020., Exposures: Lensectomy after ocular trauma., Main Outcomes and Measures: Best-corrected VA from 9 to 15 months after lensectomy for traumatic cataract (for those 3 years or older) and the cumulative proportion with strabismus, glaucoma, and other ocular complications by 15 months., Results: Of 994 participants in the registry, 84 (8%) had traumatic cataract. The median age at lensectomy for 72 participants examined within 15 months after surgery was 7.3 (range, 0.1-12.6) years; 46 (64%) were boys. An intraocular lens was placed in 57 of 74 eyes (77%). In children 3 years or older at outcome, the median best-corrected VA was 20/250 (range, 20/20 to worse than 20/800) in 6 eyes with aphakia and 20/63 (range, 20/20 to 20/200) in 26 eyes with pseudophakia. Postoperative visual axis opacification was reported in 18 of 27 eyes with pseudophakia without primary posterior capsulotomy (15-month cumulative proportion, 77%; 95% CI, 58%-92%). The cumulative proportion with strabismus was 43% (95% CI, 31%-58%) in 64 participants with ocular alignment data; exotropia was present in 14 of 23 participants (61%). The cumulative proportion with glaucoma was 6% (95% CI, 2%-16%)., Conclusions and Relevance: Trauma was not a common cause of pediatric cataract requiring surgery. For children with traumatic cataract, substantial ocular morbidity including permanent vision loss was found, and long-term eye and vision monitoring are needed for glaucoma, strabismus, and capsular opacification.

Purpose: To compare objectively measured changes in plus disease after bevacizumab and laser for Type 1 retinopathy of prematurity., Methods: ROPtool (a computer program) analyzed fundus images at baseline, 1 week, and subsequent examinations., Results: Six infants (9 eyes) were treated with bevacizumab and 7 (12 eyes) with laser. One week after treatment, bevacizumab compared with laser resulted in a greater median percent change from pretreatment in tortuosity (-53.8 vs. -0.2%, P < 0.001) and overall plus disease (-20.1 vs. -3.1%, P < 0.001). Change in dilation did not differ (-3.5 vs. -5.5%, P = 0.48). After week 1, all median ROPtool parameters continued to decrease for both groups. At last follow-up (median 3, range: 2-10 weeks), both bevacizumab and laser significantly decreased tortuosity (-54.3 and -23.8%), dilation (-8.7 and -7.5%), and overall plus disease (-27.3 and -10.3%)., Conclusion: Improvement in plus disease, in particular tortuosity, likely occurs more quickly after bevacizumab compared with laser, particularly at 1 week after treatment. These results guide clinical expectations for plus disease resolution after both treatment modalities.

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., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

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 <10 Δ , no decreased stereoacuity, and no other nonsurgical treatment for IXT or reoperation), "suboptimal" (exotropia ≥10 Δ by simultaneous prism and cover test or constant esotropia ≥6 Δ 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., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images., Methods: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye)., Results: Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P ≤ 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P < 0.001)., Conclusions: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Importance: Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis., Objective: To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively., Design, Setting, and Participants: This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON., Main Outcomes and Measures: Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein., Results: A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA., Conclusions and Relevance: The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.

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.

Background: The presence of plus disease is important in determining when to treat retinopathy of prematurity (ROP), but the diagnosis of plus disease is subjective. Semiautomated computer programs (eg, ROPtool) can objectively measure retinal vascular characteristics in retinal images, but are limited by image quality. The purpose of this study was to evaluate whether ROPtool can accurately identify pre-plus and plus disease in narrow-field images of varying qualities using a new methodology that combines quadrant-level data from multiple images of a single retina., Methods: This was a cross-sectional study of previously collected narrow-field retinal images of infants screened for ROP. Using one imaging session per infant, we evaluated the ability of ROPtool to analyze images using our new methodology and the accuracy of ROPtool indices (tortuosity index [TI], maximum tortuosity [T max ], dilation index [DI], maximum dilation [D max ], sum of adjusted indices [SAI], and tortuosity-weighted plus [TWP]) to identify pre-plus and plus disease in images compared to clinical examination findings., Results: Of 198 eyes (from 99 infants) imaged, 769/792 quadrants (98%) were analyzable. Overall, 98% of eyes had 3-4 analyzable quadrants. For plus disease, area under the curves (AUCs) of receiver operating characteristic curves were: TWP (0.98) > TI (0.97) = T max (0.97) > SAI (0.96) > DI (0.88) > D max (0.84). For pre-plus or plus disease, AUCs were: TWP (0.95) > TI (0.94) = T max (0.94) = SAI (0.94) > DI (0.86) > D max (0.83)., Conclusions: Using a novel methodology combining quadrant-level data, ROPtool can analyze narrow-field images of varying quality to identify pre-plus and plus disease with high accuracy., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether age at surgery is associated with surgical outcome of intermittent exotropia (IXT) at 3 years., Design: Secondary analysis of pooled data from a randomized trial., Methods: A total of 197 children 3 to <11 years of age with basic-type IXT of 15-40 prism diopters (Δ) were randomly assigned to 1 of 2 surgical procedures for treatment of intermittent exotropia. Masked examinations were conducted every 6 months for 3 years. The primary outcome was suboptimal surgical outcome by 3 years, defined as constant or intermittent exotropia of ≥10 Δ at distance or near by simultaneous prism and cover test (SPCT); constant esotropia of ≥6 Δ at distance or near by SPCT; or decrease in near stereoacuity of ≥2 octaves, at any masked examination; or reoperation without meeting any of these criteria., Results: The cumulative probability of a suboptimal surgical outcome by 3 years was 28% (19 of 72) for children 3 to <5 years of age, compared with 50% (57 of 125) for children 5 to <11 years of age (adjusted hazard ratio = 2.05; 95% confidence interval = 1.16 to 3.60). No statistically significant associations were found between suboptimal outcome and other baseline factors (magnitude of deviation, control score, fixation preference, or near stereoacuity) (P values ≥ .20)., Conclusions: This analysis suggests that in children with IXT, younger age at surgery (3 to <5 years) is associated with better surgical outcomes; however, further evidence from a randomized trial comparing immediate with delayed surgery is needed for confirmation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© 2020 The Authors Ophthalmic & Physiological Optics © 2020 The College of Optometrists.)

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.

Importance: Glaucoma can occur following cataract removal in children, and determining the risk for and factors associated with glaucoma and glaucoma suspect in a large cohort of children after lensectomy can guide clinical practice., Objective: To estimate the incidence of glaucoma and glaucoma suspect and describe its management in the first year following lensectomy in children before 13 years of age., Design, Setting, and Participants: A multicenter clinical research registry containing data for 1361 eyes of 994 children who underwent unilateral or bilateral lensectomy between June 2012 and July 2015 at 1 of 61 sites in the United States (n = 57), Canada (n = 3), and the United Kingdom (n = 1). Patients were eligible for inclusion in the study if they were enrolled in the registry within 45 days after lensectomy and had at least 1 office visit between 6 and 18 months after lensectomy. Patient data were reviewed, and glaucoma and glaucoma suspect were diagnosed by investigators using standardized criteria. Statistical analysis was performed between June 2017 and August 2019., Exposures: Clinical care 6 to 18 months after lensectomy., Main Outcomes and Measures: Incidence risk using standardized definitions of glaucoma and glaucoma suspect after lensectomy., Results: Among 702 patients included in this cohort study, 353 (50.3%) were male and 427 (60.8%) were white; mean age at lensectomy was 3.4 years (range, 0.04-12.9 years). After lensectomy, glaucoma or glaucoma suspect was diagnosed in 66 of 970 eyes (adjusted overall incidence risk, 6.3%; 95% CI, 4.8%-8.3%). Glaucoma was diagnosed in 52 of the 66 eyes, and glaucoma suspect was diagnosed in the other 14 eyes. Mean age at lensectomy in these 66 eyes was 1.9 years (range, 0.07-11.2 years), and 40 of the 66 (60.6%) were eyes of female patients. Glaucoma surgery was performed in 23 of the 66 eyes (34.8%) at a median of 3.3 months (range, 0.9-14.8 months) after lensectomy. The incidence risk of glaucoma or glaucoma suspect was 15.7% (99% CI, 10.1%-24.5%) for 256 eyes of infants 3 months or younger at lensectomy vs 3.4% (99% CI, 1.9%-6.2%) for 714 eyes of infants older than 3 months (relative risk, 4.57; 99% CI, 2.19-9.57; P < .001) and 11.2% (99% CI, 7.6%-16.7%) for 438 aphakic eyes vs 2.6% (99% CI, 1.2%-5.6%) for 532 pseudophakic eyes (relative risk, 4.29; 99% CI, 1.84-10.01; P < .001). No association was observed between risk of developing glaucoma or glaucoma suspect and any of the following variables: sex, race/ethnicity, laterality of lensectomy, performance of anterior vitrectomy, prelensectomy presence of anterior segment abnormality, or intraoperative complications., Conclusions and Relevance: This study found that glaucoma or glaucoma suspect developed in a small number of eyes in the first year after lensectomy and may be associated with aphakia and younger age at lensectomy. Frequent monitoring for signs of glaucoma following lensectomy is warranted, especially in infants 3 months or younger at lensectomy and in children with aphakia after lensectomy.

Purpose: To compare visual acuity (VA) and binocularity outcomes in moderately hyperopic children with normal VA and binocularity assigned to glasses versus observation., Design: Prospective randomized clinical trial (RCT)., Methods: One hundred nineteen 3- to 5-year-old children with hyperopia between +3.00D and +6.00D spherical equivalent were randomly assigned to glasses versus observation (with glasses prescribed if deteriorated for subnormal distance VA or near stereoacuity, or manifest strabismus). Follow-up occurred every 6 months. At 3 years, the treatment strategy was classified as "failed" if any of the following were met, both with and without correction: subnormal distance VA or stereoacuity; manifest strabismus; or strabismus surgery during follow-up., Results: Of 84 (71%) children who completed the primary outcome examination, failure occurred in five (12%; 95% confidence interval [CI]: 4%-26%) of 41 assigned to glasses and four (9%; 95% CI: 3%-22%) of 43 assigned to observation (difference = 3%; 95% CI: -12%-18%; P = .72). Deterioration prior to 3 years (requiring glasses per protocol) occurred in 29% (95% CI: 19%-43%) assigned to glasses and 27% (95% CI: 17%-42%) assigned to observation., Conclusions: In an RCT comparing glasses to observation for moderately hyperopic 3- to 5-year-old children with normal VA and binocularity, failure for VA or binocularity was not common. With insufficient enrollment and retention, our study was unable to determine whether immediate glasses prescription reduces failure rate, but low failure rates suggest that immediate glasses prescription for these children may not be needed to prevent failure for VA and/or binocularity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Cataract is an important cause of visual impairment in children. Outcomes reported from a large clinical disease-specific registry can provide real-world estimates of visual outcomes and rates of adverse events in clinical practice., Objective: To describe visual acuity and refractive error outcomes, as well as rates of amblyopia, glaucoma, and additional eye surgery, during the first year after lensectomy in children., Design, Setting, and Participants: A prospective observational study was conducted from June 18, 2012, to July 8, 2015, at 61 pediatric eye care practices among 880 children younger than 13 years at the time of lensectomy in at least 1 eye with follow-up within 15 months after surgery. Statistical analysis was performed from December 12, 2016, to December 14, 2018., Exposures: Lensectomy with or without implantation of an intraocular lens., Main Outcomes and Measures: Visual acuity as well as rates of amblyopia, glaucoma, suspected glaucoma, and other intraocular surgery., Results: Among the 880 children (432 girls and 448 boys; mean [SD] age at annual follow-up, 4.9 [3.8] years) in the study, lens surgery was bilateral in 362 (41.1%; 95% CI, 37.9%-44.4%) children and unilateral in 518 (58.9%; 95% CI, 55.6%-62.1%). An intraocular lens was implanted in 654 of 1132 eyes (60.2%; 95% CI, 57.0%-63.4% [proportions reported for eye-level outcomes account for the potential correlation induced by enrolling both eyes of some individuals; for participants who received bilateral surgery, these numbers will differ from the quotient of the number of cases divided by the total sample size]). Amblyopia was identified in 449 children (51.0%; 95% CI, 47.7%-54.3%). In children age 3 years or older, mean visual acuity was 0.30 logMAR (about 20/40) in 153 bilateral pseudophakic eyes, 0.49 logMAR (about 20/63) in 141 unilateral pseudophakic eyes, 0.47 logMAR (about 20/63) in 21 bilateral aphakic eyes, and 0.61 logMAR (about 20/80) in 17 unilateral aphakic eyes. Mean visual acuity improved with older age at surgery in eyes with bilateral pseudophakia by 0.2 logMAR line (99% CI, 0.02-0.4; P = .005) and by 0.3 logMAR line (99% CI, 0.04-0.60; P = .004) in eyes with unilateral pseudophakia. A new diagnosis of glaucoma or suspected glaucoma was made in 67 of 1064 eyes that did not have glaucoma prior to lensectomy (5.9%; 95% CI, 4.6%-7.7%); 36 of 273 eyes with bilateral aphakia (13.2%; 95% CI, 9.0%-19.0%), 5 of 308 eyes with bilateral pseudophakia (1.5%; 95% CI, 0.6%-4.2%), 14 of 178 eyes with unilateral aphakia (7.9%; 95% CI, 4.7%-12.8%), and 12 of 305 eyes with unilateral pseudophakia (3.9%; 95% CI, 2.2%-6.8%). Additional intraocular surgery, most commonly vitrectomy or membranectomy to clear the visual axis, was performed in 189 of 1132 eyes (17.0%; 95% CI, 14.8%-19.6%)., Conclusions and Relevance: Amblyopia was frequently observed during the first year after lensectomy in this cohort of children younger than 13 years. For children age 2 years or older at surgery visual acuity was typically less than normal for age and was worse with unilateral cataract. Management of visual axis obscuration was the most common complication requiring surgical intervention during the first year after surgery.

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)., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare visual acuity (VA) improvement in children aged 7 to 12 years with amblyopia treated with a binocular iPad game plus continued spectacle correction vs. continued spectacle correction alone., Design: Multicenter randomized clinical trial., Participants: One hundred thirty-eight participants aged 7 to 12 years with amblyopia (33-72 letters, i.e., approximately 20/200 to 20/40) resulting from strabismus, anisometropia, or both. Participants were required to have at least 16 weeks of optical treatment in spectacles if needed or demonstrate no improvement in amblyopic-eye visual acuity (VA) for at least 8 weeks prior to enrollment., Methods: Eligible participants (mean age 9.6 years, mean baseline VA of 59.6 letters, history of prior amblyopia treatment other than spectacles in 96%) were randomly assigned to treatment for 8 weeks with the dichoptic binocular Dig Rush iPad game (prescribed for 1 hour per day 5 days per week) plus spectacle wear if needed (n = 69) or continued spectacle correction alone if needed (n = 69)., Main Outcome Measures: Change in amblyopic-eye VA from baseline to 4 weeks, assessed by a masked examiner., Results: At 4 weeks, mean amblyopic-eye VA letter score improved from baseline by 1.3 (2-sided 95% confidence interval [CI]: 0.1-2.6; 0.026 logMAR) with binocular treatment and by 1.7 (2-sided 95% CI: 0.4-3.0; 0.034 logMAR) with continued spectacle correction alone. After adjusment for baseline VA, the letter score difference between groups (binocular minus control) was -0.3 (95% CI: -2.2 to 1.5, P = 0.71, difference of -0.006 logMAR). No difference in letter scores was observed between groups when the analysis was repeated after 8 weeks of treatment (adjusted mean: -0.1, 98.3% CI: -2.4 to 2.1). For the binocular group, adherence data from the iPad indicated that slightly more than half of the participants (58% and 56%) completed >75% of prescribed treatment by the 4- and 8-week visits, respectively., Conclusions: In children aged 7 to 12 years who have received previous treatment for amblyopia other than spectacles, there was no benefit to VA or stereoacuity from 4 or 8 weeks of treatment with the dichoptic binocular Dig Rush iPad game., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify and analyze cases of postoperative infection following strabismus surgery at a large referral center and to report the incidence, risk factors, and outcomes., Methods: An electronic database search identified strabismus procedures at Duke Eye Center from July 1996 to October 2017. Diagnosis codes for periocular infections were used to further identify patients with possible infections following strabismus surgery., Results: Of 9,111 strabismus surgeries, 13 (0.14%) met criteria for probable infection, all occurring since October 2012 (0/6580 before vs 13/2531 [0.51%] after; P < 0.0001). Mean age of infection cases was 11.4 years; 11 patients (85%) were under 18 years of age. Associated previous diagnoses were genetic abnormalities with associated developmental delay (n = 5 [38%]), previous skin or ear infection (n = 4 [31%]), and acute or chronic rhinitis (n = 3 [23%]). Infection site cultures revealed methicillin-resistant Staphylococcus aureus (n = 3 [23%]), methicillin-sensitive S. aureus (n = 3 [23%]), and Streptococcus pyogenes/group-A Streptococcus (n = 2 [15%]). Only 1 case had bilateral infection. Infection remained extraocular in all cases, but one eye lost light perception secondary to optic atrophy. No common surgeon/procedure/preparation-related risks were identified., Conclusions: A unifying explanation for the increase in post-strabismus surgery infections at Duke Eye Center was not identified. Potential risk factors include age <18 years, developmental delay, immune compromise, preceding nonocular infection, and bacterial colonization., (Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments., Design: Masked, multicenter, dose de-escalation study., Participants: A total of 61 premature infants with type 1 ROP., Methods: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator., Main Outcome Measures: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months., Results: Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions., Conclusions: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety., Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age., Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group., Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks., Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP., Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%)., Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Objective: Most retinopathy of prematurity screening involves an ophthalmologist performing indirect ophthalmoscopy, which can be stressful to infants. The purpose of this study is to evaluate the safety profile (using cardiopulmonary events as an indicator) of imaging infants with a non-contact retinal camera compared to examining them using indirect ophthalmoscopy., Study Design: Prospective cohort study of 99 infants at a community hospital who were examined using indirect ophthalmoscopy and imaged using a non-contact retinal camera for retinopathy of prematurity. We evaluated the difference in the occurrence of safety events (i.e., clinically significant bradycardia, tachycardia, oxygen desaturation, or apnea) following the clinical examination versus retinal imaging., Result: Safety events occurred after 0.8% (n = 1) of imaging sessions and 5.8% (n = 18) of clinical examinations (mean difference = -0.055 (p = 0.015), favoring imaging)., Conclusion: Retinal imaging with a non-contact camera was well tolerated and less stressful to infants compared to indirect ophthalmoscopy by an ophthalmologist.

Purpose: Bedside examination of premature infants at risk for retinopathy of prematurity (ROP) is predominantly performed with ophthalmoscopic en face viewing of the retina. While postmortem retinal microstructures have been studied at the vascular-avascular junction, a critical location for pathogenesis of ROP, to date this has not been possible in vivo . Here we present bedside, non-sedated in vivo cross-sectional imaging and analysis of retinal microstructures at the vascular-avascular junction in infants with ROP using handheld spectral-domain optical coherence tomography (SDOCT)., Design: Prospective observational study., Participants: Eleven preterm infants consented for research imaging during ROP screening examinations., Methods: We imaged the vascular-avascular junction in the temporal retina using a SDOCT system (Envisu, Bioptigen Inc., NC) in 18 eyes from 11 preterm infants with zone I or II, stage 0 through 4 ROP. B-scan and en face images were analyzed and compared to historical light micrographs., Main Outcome Measures: SDOCT morphology at the vascular-avascular junction., Results: Multiple bedside SDOCT findings at the vascular-avascular junction were comparable to historic light micrographs: thickened inner retinal ridge structure in stage 2 ROP was comparable to thickened vanguard and rear guard cells in micrographs; vascular tufts on the posterior retinal surface in stage 2 ROP, broad arcs of neovascularization above the retina in stage 3 ROP, and splitting of inner retinal layers into clefts on either side of neovascularization mimicked findings of historic light micrographs. A unique findings was thickening of the avascular inner retinal band adjacent to neovascularization. On SDOCT imaging over several weeks, neovascularization and retinal clefts diminished after intravitreal bevacizumab therapy., Conclusions: Retinal morphology at the vascular-avascular junction imaged with handheld SDOCT is consistent with known histopathology, and provide the advantage of monitoring change in vivo over time. These unique findings provide new insights into preterm retinal neurovascular development in ROP., Competing Interests: Conflict of Interest: No other authors have financial disclosures. No authors have a proprietary interest in the current study.