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

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

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.

Visual Acuity and Ophthalmic Outcomes 5 Years After Cataract Surgery Among Children Younger Than 13 Years.

IMPORTANCE: Cataract is an important cause of visual impairment in children. Data from a large pediatric cataract surgery registry can provide real-world estimates of visual outcomes and the 5-year cumulative incidence of adverse events. OBJECTIVE: To assess visual acuity (VA), incidence of complications and additional eye operations, and refractive error outcomes 5 years after pediatric lensectomy among children younger than 13 years. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the Pediatric Eye Disease Investigator Group clinical research registry. From June 2012 to July 2015, 61 eye care practices in the US, Canada, and the UK enrolled children from birth to less than 13 years of age who had undergone lensectomy for any reason during the preceding 45 days. Data were collected from medical record reviews annually thereafter for 5 years until September 28, 2020. EXPOSURES: Lensectomy with or without implantation of an intraocular lens (IOL). MAIN OUTCOMES AND MEASURES: Best-corrected VA and refractive error were measured from 4 to 6 years after the initial lensectomy. Cox proportional hazards regression was used to assess the 5-year incidence of glaucoma or glaucoma suspect and additional eye operations. Factors were evaluated separately for unilateral and bilateral aphakia and pseudophakia. RESULTS: A total of 994 children (1268 eyes) undergoing bilateral or unilateral lensectomy were included (504 [51%] male; median age, 3.6 years; range, 2 weeks to 12.9 years). Five years after the initial lensectomy, the median VA among 701 eyes with available VA data (55%) was 20/63 (range, 20/40 to 20/100) in 182 of 316 bilateral aphakic eyes (58%), 20/32 (range, 20/25 to 20/50) in 209 of 386 bilateral pseudophakic eyes (54%), 20/200 (range, 20/50 to 20/618) in 124 of 202 unilateral aphakic eyes (61%), and 20/65 (range, 20/32 to 20/230) in 186 of 364 unilateral pseudophakic eyes (51%). The 5-year cumulative incidence of glaucoma or glaucoma suspect was 46% (95% CI, 28%-59%) in participants with bilateral aphakia, 7% (95% CI, 1%-12%) in those with bilateral pseudophakia, 25% (95% CI, 15%-34%) in those with unilateral aphakia, and 17% (95% CI, 5%-28%) in those with unilateral pseudophakia. The most common additional eye surgery was clearing the visual axis, with a 5-year cumulative incidence of 13% (95% CI, 8%-17%) in participants with bilateral aphakia, 33% (95% CI, 26%-39%) in those with bilateral pseudophakia, 11% (95% CI, 6%-15%) in those with unilateral aphakia, and 34% (95% CI, 28%-39%) in those with unilateral pseudophakia. The median 5-year change in spherical equivalent refractive error was -8.38 D (IQR, -11.38 D to -2.75 D) among 89 bilateral aphakic eyes, -1.63 D (IQR, -3.13 D to -0.25 D) among 130 bilateral pseudophakic eyes, -10.75 D (IQR, -20.50 D to -4.50 D) among 43 unilateral aphakic eyes, and -1.94 D (IQR, -3.25 D to -0.69 D) among 112 unilateral pseudophakic eyes. CONCLUSIONS AND RELEVANCE: In this cohort study, development of glaucoma or glaucoma suspect was common in children 5 years after lensectomy. Myopic shift was modest during the 5 years after placement of an intraocular lens, which should be factored into implant power selection. These results support frequent monitoring after pediatric cataract surgery to detect glaucoma, visual axis obscuration causing reduced vision, and refractive error.

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.

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.

Improvement in health-related quality of life following strabismus surgery for children with intermittent exotropia.

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 <10Δ, no decreased stereoacuity, and no other nonsurgical treatment for IXT or reoperation), "suboptimal" (exotropia ≥10Δ by simultaneous prism and cover test or constant esotropia ≥6Δ 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.

Health-related quality of life in children with untreated intermittent exotropia and their parents.

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.

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

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

A Randomized Clinical Trial of Immediate Versus Delayed Glasses for Moderate Hyperopia in Children 3 to 5 Years of Age.

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.

Visual Acuity and Ophthalmic Outcomes in the Year After Cataract Surgery Among Children Younger Than 13 Years.

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.

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

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

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments.

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.

Relationship among clinical factors in childhood intermittent exotropia.

PURPOSE: To determine the relationships between stereoacuity, control of exotropia, and angle of deviation in children with intermittent exotropia (IXT). METHODS: Data collected for 652 participants 3 to <11 years of age with IXT meeting eligibility criteria for enrollment into one of two multicenter, randomized clinical trials were used to evaluate relationships between stereoacuity, control, and angle of deviation at enrollment. RESULTS: Any level of stereoacuity and angle of deviation could be accompanied by any level of control. Worse distance exotropia control was weakly associated with poorer distance stereoacuity (R = 0.26; 99% CI, 0.17-0.36) and larger angles of deviation at distance (R = 0.27; 99% CI, 0.17-0.36). Worse near exotropia control was weakly associated with poorer near stereoacuity (R = 0.17; 99% CI, 0.07-0.27) and moderately associated with larger angles of deviation at near (R = 0.37; 99% CI, 0.28-0.45). There was no association between stereoacuity and angle of deviation at distance (R = 0.07; 99% CI, -0.03 to 0.17) or at near (R = 0.02; 99% CI, -0.08 to 0.12). CONCLUSIONS: Although weak and moderate associations were found between stereoacuity, control, and angle of deviation, a child may exhibit any combination of stereoacuity, control, and angle of deviation. The specific roles of control, stereoacuity, and angle of deviation in the diagnosis, management, and pathogenesis of IXT are unclear, and each appears to yield somewhat independent information.

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

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

Cataract Surgery in Children from Birth to Less than 13 Years of Age: Baseline Characteristics of the Cohort.

OBJECTIVE: To describe baseline characteristics, initial postoperative refractive errors, operative complications, and magnitude of the intraocular lens (IOL) prediction error for refractive outcome in children undergoing lensectomy largely in North America. DESIGN: Prospective registry study of children from birth to <13 years of age who underwent lensectomy for any reason within 45 days preceding enrollment. PARTICIPANTS: Total of 1266 eyes of 994 children; 49% female and 59% white. METHODS: Measurement of refractive error, axial length, and complete ophthalmic examination. MAIN OUTCOME MEASURES: Eye and systemic associated conditions, IOL style, refractive error, pseudophakic refraction prediction error, operative and perioperative complications. RESULTS: Mean age at first eligible lens surgery was 4.2 years; 337 (34%) were <1 year of age. Unilateral surgery was performed in 584 children (59%). Additional ocular abnormalities were noted in 301 eyes (24%). An IOL was placed in 35 of 460 eyes (8%) when surgery was performed before 1 year of age, in 70 of 90 eyes (78%) from 1 to <2 years of age, and in 645 of 716 eyes (90%) from 2 to <13 years of age. The odds of IOL implantation were greater in children ≥2 years of age than in those <2 years of age (odds ratio = 29.1; P < 0.001; 95% confidence interval: 19.6-43.3). Intraoperative complications were reported for 69 eyes (5%), with the most common being unplanned posterior capsule rupture in 14 eyes, 10 of which had an IOL placed. Prediction error of the implanted IOL was <1.00 diopter in 54% of eyes, but >2.00 diopters in 15% of eyes. CONCLUSIONS: Lensectomy surgery was performed throughout childhood, with about two-thirds of cases performed after 1 year of age. Initial surgery seemed safe, with a low complication rate. IOL placement was nearly universal in children 2 years of age and older. The immediate postoperative refraction was within 1 diopter of the target for about one-half of eyes.

Pharmacy Intervention to Improve HIV Testing Uptake Using a Comprehensive Health Screening Approach.

OBJECTIVE: HIV testing is increasingly available, yet barriers to HIV testing persist for low-income black and Latino people, especially those who use illicit drugs. HIV exceptionalism, or the idea that a positive HIV diagnosis is drastically different from a diagnosis for any other disease, may influence HIV testing-related stigma, resulting in reduced willingness to undergo HIV testing. This pharmacy-based intervention combined HIV testing with less stigmatized chronic disease screening tests (e.g., blood pressure, glucose, and cholesterol) to equate the concept of an HIV diagnosis with other diagnoses. METHODS: Three pharmacies located in low-income, minority neighborhoods in New York City were enrolled in an intervention to provide (1) HIV testing, chronic disease screening, and a healthy lifestyles video that normalized all screening tests and destigmatized HIV as a fatal disease (comprehensive arm); (2) HIV testing and the video (video arm); and (3) HIV testing only (control arm). Injection drug users (IDUs) and pharmacy staff recruited un- and underinsured pharmacy customers, IDUs, and IDU peers from 2010 to 2012. Participants in the control group were compared with those in the comprehensive and video intervention groups. RESULTS: Participants in the comprehensive arm (prevalence ratio [PR] = 1.61, 95% confidence interval [CI] 1.03, 2.49, p=0.08) and the video arm (PR=1.59, 95% CI 1.00, 2.53, p=0.09) were marginally significantly more likely to receive an HIV test in the pharmacy compared with those in the control arm after adjustment. CONCLUSIONS: These findings suggest that adoption of strategies that destigmatize and normalize HIV testing can improve uptake. Implementation of this strategy in low-access, minority communities with high HIV prevalence and among high-risk populations may help reduce racial/ethnic disparities in HIV.

A randomized trial of levodopa as treatment for residual amblyopia in older children.

OBJECTIVE: To assess the efficacy and short-term safety of levodopa as adjunctive treatment to patching for amblyopia. DESIGN: Randomized, placebo-controlled trial. PARTICIPANTS: One hundred thirty-nine children 7 to 12 years of age with residual amblyopia resulting from strabismus, anisometropia, or both combined (visual acuity [VA], 20/50-20/400) after patching. METHODS: Sixteen weeks of oral levodopa or placebo administered 3 times daily while patching the fellow eye 2 hours daily. MAIN OUTCOME MEASURES: Mean change in best-corrected amblyopic-eye VA at 18 weeks. RESULTS: At 18 weeks, amblyopic-eye VA improved from randomization by an average of 5.2 letters in the levodopa group and by 3.8 letters in the placebo group (difference adjusted for baseline VA, +1.4 letters; 1-sided P=0.06; 2-sided 95% confidence interval, -0.4 to 3.3 letters). No serious adverse effects from levodopa were reported during treatment. CONCLUSIONS: For children 7 to 12 years of age with residual amblyopia after patching therapy, oral levodopa while continuing to patch 2 hours daily does not produce a clinically or statistically meaningful improvement in VA compared with placebo and patching.