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

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

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

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

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.

Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes.

PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

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.

International Classification of Retinopathy of Prematurity, Third Edition.

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.

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.

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.

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.

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

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.