A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity.

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Quality of Life in Children: A Systematic Review.

TOPIC: This review summarizes existing evidence of the impact of vision impairment and ocular morbidity and their treatment on children's quality of life (QoL). CLINICAL RELEVANCE: Myopia and strabismus are associated with reduced QoL among children. Surgical treatment of strabismus significantly improves affected children's QoL. METHODS: We conducted a systematic review and meta-analysis by screening articles in any language in 9 databases published from inception through August 22, 2022, addressing the impact of vision impairment, ocular morbidity, and their treatment on QoL in children. We reported pooled standardized mean differences (SMDs) using random-effects meta-analysis models. Quality appraisal was performed using Joanna Briggs Institute and National Institutes of Health tools. This study was registered with the International Prospective Register of Systematic Reviews (identifier, CRD42021233323). RESULTS: Our search identified 29 118 articles, 44 studies (0.15%) of which were included for analysis that included 32 318 participants from 14 countries between 2005 and 2022. Seventeen observational and 4 interventional studies concerned vision impairment, whereas 10 observational and 13 interventional studies described strabismus and other ocular morbidities. Twenty-one studies were included in the meta-analysis. The QoL scores did not differ between children with and without vision impairment (SMD, -1.04; 95% confidence interval [CI], -2.11 to 0.03; P = 0.06; 9 studies). Myopic children demonstrated significantly lower QoL scores than those with normal vision (SMD, -0.60; 95% CI, -1.09 to -0.11; P = 0.02; 7 studies). Children with strabismus showed a significantly lower QoL score compared with those without (SMD, -1.19; 95% CI, -1.66 to -0.73; P < 0.001; 7 studies). Strabismus surgery significantly improved QoL in children (SMD, 1.36; 95% CI, 0.48-2.23; P < 0.001; 7 studies). No randomized controlled trials (RCTs) concerning refractive error and QoL were identified. Among all included studies, 35 (79.5%) were scored as low to moderate quality; the remaining met all quality appraisal tools criteria. DISCUSSION: Reduced QoL was identified in children with myopia and strabismus. Surgical correction of strabismus improves the QoL of affected children, which supports insurance coverage of strabismus surgery. Further studies, especially RCTs, investigating the impact of correction of myopia on QoL are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants.

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Refractive Accuracy and Visual Outcome by Self-Refraction Using Adjustable-Focus Spectacles in Young Children: A Randomized Clinical Trial.

Importance: Uncorrected refractive error is the most common cause of vision impairment in children. Most children 12 years or older can achieve visual acuity (VA) of 20/25 or better by self-refraction using adjustable-focus spectacles, but data on younger children are lacking. Objective: To assess refractive accuracy, corrected VA, and factors associated with not achieving VA of 20/25 or better among children aged 5 to 11 years performing self-refraction with Adspecs adjustable-focus spectacles (Adaptive Eyecare), compared with noncycloplegic autorefraction and cycloplegic refraction. Design, Setting, and Participants: This was a cross-sectional noninferiority trial conducted from September 2, 2015, to December 14, 2017. The study setting was an academic pediatric eye clinic. Children aged 5 to 11 years with uncorrected VA of 20/40 or worse in 1 or both eyes and without systemic or ocular conditions preventing best-corrected VA of 20/25 or better were enrolled. Children who had best-corrected VA worse than 20/25 were excluded. Study data were analyzed from September 2017 to June 2023. Exposures: Children were taught to self-refract with adjustable-focus spectacles. Main Outcomes and Measures: Spherical equivalent refractive error (using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) and VA (uncorrected and using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) for study eyes were evaluated. Potential predictors of failure to achieve VA of 20/25 or better with self-refraction were assessed using logistic regression. Results: A total of 127 consecutive children were enrolled. After exclusions, 112 children (median [IQR] age, 9.0 [8.0-10.3] years; 52 boys [46.4%]) were included in the study. Mean (SD) spherical equivalent refractive power was -2.00 (1.52) diopters (D) for self-refraction, -2.32 (1.43) D for noncycloplegic autorefraction, and -1.67 (1.49) D for cycloplegic refraction. Mean (SD) difference in refractive power between self-refraction and noncycloplegic autorefraction was 0.32 (1.11) D (97.5% 1-sided CI, 0.11 to ∞ D; P < .001) and between self-refraction and cycloplegic refraction was -0.33 (1.15) D (97.5% 1-sided CI, -0.54 to ∞ D; P = .77). The proportion of children with corrected VA of 20/25 or better was 79.5% (89 of 112) with self-refraction, 85.7% (96 of 112) with noncycloplegic autorefraction, and 79.5% (89 of 112) with cycloplegic refraction (self-refraction vs noncycloplegic autorefraction: McNemar P value = .27; self-refraction vs cycloplegic refraction: McNemar P value > .99). Those failing to achieve best-corrected VA of 20/25 or better with self-refraction had higher astigmatism (odds ratio [OR], 10.6; 95% CI, 3.1-36.4; P < .001) and younger age (OR, 1.5; 95% CI, 1.1-2.2; P = .02). Conclusions and Relevance: Self-refraction among children aged 5 to 11 years may result in more myopic power than cycloplegic refraction but not necessarily to a clinically relevant degree. Although the proportion of children achieving VA of 20/25 or better with self-refraction using adjustable-focus spectacles did not differ from cycloplegic refraction, it was less likely among younger children and those with higher astigmatism.

Ocular Pigmentation Impact on Retinal Versus Choroidal Optical Coherence Tomography Imaging in Preterm Infants.

Purpose: To evaluate the association of fundus pigmentation with the visibility of retinal versus choroidal layers on optical coherence tomography (OCT) in preterm infants. Methods: For infants enrolled in BabySTEPS, ophthalmologists recorded fundus pigmentation (blond, medium, or dark) at the first retinopathy of prematurity (ROP) examination. Bedside OCT imaging was performed at each examination, and a masked grader evaluated all OCT scans from both eyes of each infant for visibility (yes/no) of all retinal layers and of the chorio-scleral junction (CSJ). Multivariable logistic regression was used to assess associations between fundus pigmentation and visibility of all retinal layers and CSJ, controlling for potential confounders (i.e., birth weight, gestational age, sex, OCT system, pupil size, and postmenstrual age at imaging). Results: Among 114 infants (mean birth weight, 943 grams; mean gestational age, 27.6 weeks), 43 infants (38%) had blond, 56 infants (49%) had medium, and 15 infants (13%) had dark fundus pigmentation. Of 1042 scans, all retinal layers were visible in 977 (94%) and CSJ in 895 (86%). Pigmentation was not associated with retinal layer visibility (P = 0.49), but medium and dark pigmentation were associated with decreased CSJ visibility (medium: odds ratio [OR] = 0.34, P = 0.001; dark: OR = 0.24, P = 0.009). For infants with dark pigmentation, retinal layer visibility increased (OR = 1.87 per week; P ≤ 0.001) and CSJ visibility decreased (OR = 0.78 per week; P = 0.01) with increasing age. Conclusions: Although fundus pigmentation was not associated with the visibility of all retinal layers on OCT, darker pigmentation decreased CSJ visibility, and this effect increased with age. Translational Relevance: The ability of bedside OCT to capture retinal layer microanatomy in preterm infants, regardless of fundus pigmentation, may represent an advantage over fundus photography for ROP telemedicine.

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants.

This retrospective study of 68 premature infants examined whether there was a difference between male and female mixed-sex multiple gestation infants with regard to stage of retinopathy of prematurity (ROP) developed or need for ROP treatment. We found that among mixed-sex twin infants there was no statistically significant difference between sexes in most severe ROP stage developed or need for ROP treatment, but males were treated at an earlier postmenstrual age (PMA) than females, despite females having a lower mean birthweight and slower mean growth velocity compared to males.

Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).

Safety and efficacy of avalglucosidase alfa in individuals with infantile-onset Pompe disease enrolled in the phase 2, open-label Mini-COMET study: The 6-month primary analysis report.

PURPOSE: Mini-COMET (NCT03019406; Sanofi) is a phase 2, open-label, ascending-dose, 3-cohort study, evaluating avalglucosidase alfa safety, pharmacokinetics, and efficacy in individuals with infantile-onset Pompe disease aged <18 years who previously received alglucosidase alfa and showed clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3). METHODS: During a 25-week primary analysis period, cohorts 1 and 2 received avalglucosidase alfa 20 and 40 mg/kg every other week, respectively, for 6 months, whereas cohort 3 individuals were randomized (1:1) to receive avalglucosidase alfa 40 mg/kg every other week or alglucosidase alfa (current stable dose) for 6 months. RESULTS: In total, 22 individuals were enrolled (cohort 1 [n = 6], cohort 2 [n = 5], cohort 3-avalglucosidase alfa [n = 5], and cohort 3-alglucosidase alfa [n = 6]). Median treatment compliance was 100%. None of the individuals discontinued treatment or died. Percentages of individuals with treatment-emergent adverse events were similar across dose and treatment groups. No serious or severe treatment-related treatment-emergent adverse events occurred. Trends for better motor function from baseline to week 25 were observed for 40 mg/kg every other week avalglucosidase alfa compared with either 20 mg/kg every other week avalglucosidase alfa or alglucosidase alfa up to 40 mg/kg weekly. CONCLUSION: These data support the positive clinical effect of avalglucosidase alfa in patients with infantile-onset Pompe disease previously declining on alglucosidase alfa.

2021 U.S. Virgin Islands Zika health brigade: Providing recommended pediatric health screenings for children born to mothers with laboratory evidence of possible Zika virus infection during pregnancy.

BACKGROUND: The United States Virgin Islands (USVI) Department of Health (DOH) conducted a second Zika health brigade (ZHB) in 2021 to provide recommended Zika-related pediatric health screenings, including vision, hearing, neurologic, and developmental screenings, for children in the USVI. This was replicated after the success of the first ZHB in 2018, which provided recommended Zika-related pediatric health screenings to 88 infants and children exposed to Zika virus (ZIKV) during pregnancy. METHODS: Ten specialty pediatric care providers were recruited and traveled to the USVI to conduct the screenings. USVI DOH scheduled appointments for children included in CDC's U.S. Zika Pregnancy and Infant Registry (USZPIR). During the ZHB, participants were examined by pediatric ophthalmologists, pediatric audiologists, and pediatric neurologists. We report the percentage of participants who were referred for additional follow-up care or given follow-up recommendations in the 2021 ZHB and compare these referrals and recommendations to those given in the 2018 ZHB. RESULTS: Thirty-three children born to mothers with laboratory evidence of ZIKV infection during pregnancy completed screenings at the 2021 ZHB, of which 15 (45%) children were referred for additional follow-up care. Ophthalmological screenings resulted in the highest number of new referrals for a specialty provider among ZHB participants, with 6 (18%) children receiving referrals for that specialty. Speech therapy was the most common therapy referral, with 10 (30%) children referred, of which 9 (90%) were among those who attended the 2018 ZHB. CONCLUSIONS: Thirty-three children in a jurisdiction with reduced access to healthcare specialists received recommended Zika-related pediatric health screenings at the ZHB. New and continuing medical and developmental concerns were identified and appropriate referrals for follow-up care and services were provided. The ZHB model was successful in creating connections to health services not previously received by the participants.

Quantitative comparison of blood vessel changes after treatment of retinopathy of prematurity with laser versus bevacizumab.

Current therapies for treatment-indicated (type 1) retinopathy of prematurity mainly consist of laser photocoagulation and intravitreal anti-vascular endothelial growth factor (eg, bevacizumab) injection. The first visible signs of acute-phase regression are typically vascular, including decreased plus disease. Using a semiautomated computer program, we quantitatively compared posterior pole vascular changes following treatment with laser versus bevacizumab and found that in the first month following treatment, vascular dilation and tortuosity significantly decreased following either treatment modality, but tortuosity decreased earlier and faster after bevacizumab.

Association Between Retinal Microanatomy in Preterm Infants and 9-Month Visual Acuity.

Importance: Preterm infants are at risk for poor visual acuity (VA) outcomes, even without retinal problems on ophthalmoscopy. Infant retinal microanatomy may provide insight as to potential causes. Objective: To evaluate the association between preterm infant retinal microanatomy and VA at 9 months' corrected age. Design, Setting, and Participants: This prospective observational study took place from November 2016 and December 2019 at a single academic medical center and included preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS). Infants were eligible for enrollment in BabySTEPS if they met criteria for retinopathy of prematurity (ROP) screening, were 35 weeks' postmenstrual age or older at the time of first OCT imaging, and a parent or guardian provided written informed consent. Of 118 infants enrolled in BabySTEPS, 61 were included in this analysis. Data were analyzed from March to April 2021. Exposures: Bedside optical coherence tomography (OCT) imaging at a mean (SD) 39.85 (0.79) weeks' postmenstrual age and monocular grating VA measurement at 9 months' corrected age. Main Outcomes and Measures: Presence and severity of macular edema and presence of ellipsoid zone at the fovea measured by extracting semiautomated thicknesses of inner nuclear layer, inner retina, and total retina at the foveal center; choroid across foveal 1 mm; and retinal nerve fiber layer (RNFL) across the papillomacular bundle (PMB). Pearson correlation coefficients were calculated and 95% CIs were bootstrapped for the association between retinal layer thicknesses and continuous logMAR VA. Associations were analyzed between retinal microanatomy and normal (3.70 cycles/degree or greater) vs subnormal grating VA at 9 months' corrected age using logistic regression and with logMAR VA using linear regression, adjusting for birth weight, gestational age, and ROP severity at the time of OCT imaging and accounting for intereye correlation using generalized estimating equations. Results: The mean (SD; range) gestational age of included infants was 27.6 (2.8; 23.0-34.6) weeks, and mean (SD; range) birth weight was 958.2 (293.7; 480-1580) g. In 122 eyes of 61 infants, the correlations between retinal layer thicknesses and logMAR VA were as follows: r, 0.01 (95% CI, -0.07 to -0.27) for inner nuclear layer; r, 0.19 (95% CI, 0.01 to 0.35) for inner retina; r, 0.15 (95% CI, -0.02 to 0.31) for total retina; r, -0.22 (95% CI, -0.38 to -0.03) for choroid; and r, -0.27 (95% CI, -0.45 to 0.10) for RNFL across the PMB. In multivariable analysis, thinner RNFL across the PMB (regression coefficient, -0.05 per 10-µm increase in RNFL thickness; 95% CI, -0.10 to -0.01; P = .046) and prior ROP treatment (regression coefficient, 0.33 for ROP treatment; 95% CI, 0.11 to 0.56; P = .003) were independently associated with poorer 9-month logMAR VA. Conclusions and Relevance: In preterm infants, RNFL thinning across the PMB was associated with poorer 9-month VA, independent of birth weight, gestational age, need for ROP treatment, and macular microanatomy. Evaluation of RNFL thickness using OCT may help identify preterm infants at risk for poor vision outcomes.

Semi-automated vessel analysis of en face posterior pole vessel maps generated from optical coherence tomography for diagnosis of plus or pre-plus disease.

En face retinal vessel maps generated from bedside optical coherence tomography (OCT) can show posterior pole vascular tortuosity and dilation (ie, plus/pre-plus disease). In this proof-of-concept study, we found that ROPtool could trace OCT-generated retinal vessel maps with high reliability and accuracy for detecting plus or pre-plus disease.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Depression and Anxiety in Children: A Systematic Review.

TOPIC: This systematic review and meta-analysis summarizes existing evidence to establish whether vision impairment, ocular morbidity, and their treatment are associated with depression and anxiety in children. CLINICAL RELEVANCE: Understanding and quantifying these associations support early detection and management of mental health symptoms in children with vision impairment and ocular morbidity. Additionally, this review provides evidence in favor of insurance coverage for timely strabismus surgery. METHODS: We searched 9 electronic databases from inception through February 18, 2021, including observational and interventional studies assessing whether vision impairment, ocular morbidity, or both and their treatment are associated with depression, anxiety, or both in children. We used narrative synthesis and meta-analysis with the residual maximum likelihood method. A protocol was registered and published on The International Prospective Register of Systematic Reviews (identifier: CRD42021233323). RESULTS: Among 28 992 studies, 28 956 studies (99.9%) were excluded as duplicates or unrelated content. Among 36 remaining studies, 21 studies (58.3%) were observational studies concerning vision impairment, 8 studies (22.2%) were observational studies concerning strabismus, and 7 studies (19.4%) were interventional studies. Vision impaired children demonstrated significantly higher scores of depression (standard mean difference [SMD], 0.57; 95% confidence interval [CI], 0.26-0.89; 11 studies) and anxiety (SMD, 0.62; 95% CI, 0.40-0.83; 14 studies) than normally sighted children. In particular, children with myopia demonstrated higher scores of depression (SMD, 0.58; 95% CI, 0.36-0.81; 6 studies) than normally sighted children. Strabismus surgery significantly improved symptoms of depression (SMD, 0.59; 95% CI, 0.12-1.06; 3 studies) and anxiety (SMD, 0.69; 95% CI, 0.25-1.14; 4 studies) in children. CONCLUSION: Among children, vision impairment is associated with greater symptoms of depression and anxiety. Surgical treatment of strabismus improved these symptoms. Further randomized controlled trials exploring the impact of public health measures for myopia correction on mental health in children are needed. Scaling up access to strabismus surgery could improve the mental health of affected children.

Integrated Visualization Highlighting Retinal Changes in Retinopathy of Prematurity From 3-Dimensional Optical Coherence Tomography Data.

Importance: Early diagnosis of plus disease is critical in the management of retinopathy of prematurity (ROP). However, there is substantial interexpert disagreement in the diagnosis of plus disease based on vascular changes alone. Information derived from optical coherence tomography (OCT) may help characterize the severity of vascular and structural abnormalities in ROP. Objective: To describe integrated visualization of 3-dimensional (3-D) data from investigational swept-source OCT optimized to delineate retinal vascular and microanatomical features in eyes with and without ROP. Design, Setting, and Participants: This cross-sectional, observational report of OCT was captured in the prospective Study of Eye Imaging in Preterm Infants (BabySTEPS) designed in July 2016 at the Duke Health Intensive Care Nursery. Between December 2018 and August 2019, 2 preterm infants born at 24 and 30 weeks' gestation were enrolled, underwent ROP screening, and were imaged at those screening visits. Data at 36 weeks' postmenstrual age were analyzed via this visualization developed between September 2020 and May 2021. Main Outcomes and Measures: Superimposed en face retinal vascular shadow view (RVSV) montages and thickness maps were used along with OCT B-scans to evaluate retinal vasculature and cross-section in eyes with and without ROP. Results: In the right eyes of 2 infants, 3-D data were integrated and visualized from investigational bedside OCT imaging at the posterior pole. In the infant who developed type 1 ROP, RVSV-OCT confirmed presence of dilated and tortuous posterior pole vessels, shunting, and incomplete perifoveal vascular development, resulting in a temporal notch of avascular retina in zone 1. The thickness map revealed irregular pockets of thickening and thinning, and integrated visualization outlined the demarcation between thicker vascularized retina and thinner avascular fovea and presence of extraretinal neovascularization overlying elevated vessels in the superior arcades. In the infant without ROP (stage 0), RVSV-OCT revealed no abnormal vascular findings at the posterior pole. The integrated visualization showed a dome-shaped retinal thickening at the fovea, which was confirmed as macular edema. Conclusions and Relevance: In 2 preterm infants in BabySTEPS, 3-D visualization of OCT findings during the ongoing ROP disease process demonstrated supplemental information about the retinal vasculature and microanatomy that can be useful to clinicians. These additional details provided by OCT could be integrated into future ROP screening methods with artificial intelligence-based analytics.

Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.

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.

Cost comparison of using reusable versus disposable equipment for retinopathy of prematurity screening rounds.

Retinopathy of prematurity (ROP) screening rounds have been linked to pathogen transmission and serious adverse outcomes in neonatal intensive care units (NICUs). Using Monte Carlo simulations, we found that it is more likely less expensive to use reusable than disposable equipment in NICUs of all levels for maintaining sterile equipment on ROP screening rounds.

Photographic assessment of eyelid position using a simple measurement tool paired with cell phone photography in a pediatric population.

PURPOSE: This proof-of-concept study evaluates the ability to assess eyelid measurements and the reproducibility of eyelid measurements using a simple measurement tool paired with digital cell phone photography in children. METHODS: Seventy consecutive patients and their siblings, 2-19 years of age, were prospectively enrolled. Participants underwent clinical examination and cell phone photography with a simple measurement tool. An ophthalmologist and nonophthalmologist assessed photographs for interpalpebral fissure distance (IPFD), margin reflex distance-1 (MRD1), and levator function (LF). Clinical examinations and photographs were repeated on the same day in a random sample (n = 20). The agreement of grading photographs compared to clinical examination was assessed using Bland-Altman plots. Intra-grader repeatability of the clinical examination, repeatability of photographic technique, and interobserver reproducibility of photographic assessment was evaluated with intraclass correlation coefficients (ICC). RESULTS: Of photographs acquired, both graders considered quality good/fair in 100% to assess IPFD and MRD1, and 70% to assess LF. The mean difference (limits of agreement) in mm between clinical examination and photographic assessment was 1.1 (-1.5 to 3.8) for IPFD, 0.7 (-1.8 to 3.1) for MRD1, and 1.1 (-3.5 to 5.7) for LF. Intraobserver repeatability on clinical examination was excellent for IPFD (ICC = 0.81), MRD1 (ICC = 0.88), and LF (ICC = 0.94). Repeatability of photographic technique was fair for IPFD (ICC = 0.44) and good for MRD1 (ICC = 0.74) and LF (ICC = 0.77). Interobserver photographic assessment repeatability was excellent for IPFD (ICC = 0.94), MRD1 (ICC = 0.96), and LF (ICC = 0.92). CONCLUSIONS: Photographic assessment of eyelid measurements in children is possible, highly reproducible between graders, and enables documentation for future comparison.

Prophylactic laser versus continued surveillance after initial bevacizumab treatment for retinopathy of prematurity.

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.

Trends in Retinopathy of Prematurity Screening and Treatment: 2008-2018.

BACKGROUND AND OBJECTIVES: Retinopathy of prematurity (ROP) is the leading avoidable and treatable cause of childhood blindness in the United States. The objective of this study was to evaluate trends of ROP screening, incidence, and treatment in US NICUs over the last 11 years. METHODS: Using standardized data submitted by NICUs from US Vermont Oxford Network member hospitals from 2008 to 2018 on very low birth weight infants hospitalized at the recommended age for ROP screening, we assessed trends in the proportion of eligible infants who received ROP screening, incidence, and treatment of ROP using logistic regression models. RESULTS: This study included 381 065 very low birth weight infants at 819 US NICUs participating in Vermont Oxford Network. Over time, more eligible infants received ROP screening (89% in 2008 to 91% in 2018, trend P < .001). Among those screened, overall ROP (stages 1-5, 37% in 2008 to 32% in 2018), severe ROP (stages 3-5, 8% in 2008 to 6% in 2018), and retinal ablation (6% in 2008 to 2% in 2018) declined and anti-vascular endothelial growth factor injections (1% in 2012 to 2% in 2018) increased (all trend P < .001). CONCLUSIONS: Among US hospitals from 2008 to 2018, the proportion of ROP screening among infants hospitalized at the recommended age increased, less overall and severe ROP were reported, less retinal ablation was performed, and more anti-vascular endothelial growth factor treatment was used. Despite increased ROP screening over time, 10% of infants were not screened, representing an opportunity for improvement in health care delivery.