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

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

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Choice of Dose Level for a Randomized Clinical Trial of Low-Dose Bevacizumab vs Laser for Type 1 Retinopathy of Prematurity

This study determines which of 8 doses of bevacizumab are effective in treating severe retinopathy of prematurity to carry forward to a large-scale randomized clinical trial

Retinal nerve fiber layer thickness in amblyopic eyes

To compare the peripapillary retinal nerve fiber layer (RNFL) thickness of amblyopic and fellow eyes. We hypothesized that the RNFL of the amblyopic eye may be thinner. Prospective, cross-sectional, observational case series. Optical coherence tomography of the peripapillary RNFL thickness of amblyopic and fellow eyes was performed in 37 patients 7 to 12 years of age (mean age +/- standard deviation, 9.2 +/- 1.5 years) with unilateral strabismic, anisometropic, or combined-mechanism amblyopia enrolled in a randomized treatment trial. Mean global RNFL thickness of the amblyopic and fellow eyes was 111.4 and 109.6 microm, respectively (mean difference, 1.8 microm thicker in the amblyopic eyes; 95% confidence interval, -0.6 to 4.3 microm). The amblyopic eye was 8 microm or more thicker than the fellow eye in 9 patients (24%); the fellow eye was 8 microm or more thicker than the amblyopic eye in 2 patients (5%); and the difference was within test-retest variability (7 microm) in 26 patients (70%). Our findings do not indicate that peripapillary RNFL thickness is thinner in eyes with moderate amblyopia compared with their fellow eyes

Tonic pupil after botulinum toxin-A injection for treatment of esotropia in children

A total of 27 children with esotropia (mean age, 3.9 years; range, 9 months to 13.8 years) were enrolled in a 9-month observational study following botulinum toxin A (BTX-A) injection of one (n = 7) or both (n = 20) medial rectus muscles. BTX-A dosage ranged from 3.0 to 6.0 units per muscle. Three participants developed tonic pupil, noted at the first follow-up visit, occurring 12-19 days after injection. All 3 cases occurred in the left eye of participants who underwent bilateral BTX-A injection by the same surgeon. Anisocoria diminished from a maximum of 4 mm at the 2-week visit to 1-2 mm in all patients over the 9-month postinjection data collection period. No adverse visual outcomes were noted. Tonic pupil is an infrequently reported complication of BTX-A injection for strabismus. The experience of our investigator group suggests the need for careful injection technique and thorough preinjection counseling

Visual Outcomes and Complications After Lensectomy for Traumatic Cataract in Children

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

Visual acuity through Bangerter filters in nonamblyopic eyes

To describe the amount of visual acuity degradation induced by Bangerter filters in the better seeing eye and to evaluate its stability over time in children with moderate amblyopia. Visual acuity with and without a Bangerter filter was measured in the nonamblyopic eye of 186 children with moderate amblyopia who were then treated with either patching or the Bangerter filters. A 0.2 filter was used for amblyopia of 20/80 and a 0.3 filter for amblyopia from 20/40 to 20/63. For the 89 children randomized to Bangerter filters, visual acuity was also measured in the nonamblyopic eye with and without the filters at both 6 weeks and 12 weeks after initiating treatment. Mean degradation in visual acuity of the nonamblyopic eye at baseline was 5.1 logMAR lines with the 0.2 filter and 4.8 logMAR lines with the 0.3 filter. The degradation with each filter did not always agree with the manufacturer's specifications. Over time, the amount of degradation with the filters decreased. The 0.2 and 0.3 Bangerter filters degrade nonamblyopic eye visual acuity sufficiently in amblyopic children. Because the amount of degradation decreases over time, it is recommended to periodically apply a new filter when using this type of amblyopia treatment

Assessment of Pediatric Optic Neuritis Visual Acuity Outcomes at 6 Months

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