Clearance of bevacizumab from the bloodstream in premature infants takes at least 2 months. Although serum free VEGF levels decreased following either laser or bevacizumab treatment, the reductions were more significant in the IVB-treated groups. Potential long-term effects of systemic exposure to bevacizumab in infants need to be studied further.

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.

IMPORTANCE This is the first large-scale randomized clinical trial evaluating the effectiveness and safety of overminus spectacle therapy for treatment of intermittent exotropia (IXT).OBJECTIVE To evaluate the effectiveness of overminus spectacles to improve distance IXT control. DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial conducted at 56 clinical sites between January 2017 and January 2019 associated with the Pediatric Eye Disease Investigator Group enrolled 386 children aged 3 to 10 years with IXT, a mean distance control score of 2 or worse, and a refractive error between 1.00 and −6.00 diopters (D). Data analysis was performed from February to December 2020.INTERVENTIONS Participants were randomly assigned to overminus spectacle therapy (−2.50 D for 12 months, then −1.25 D for 3 months, followed by nonoverminus spectacles for 3 months) or to nonoverminus spectacle use. MAIN OUTCOMES AND MEASURESPrimary and secondary outcomes were the mean distance IXT control scores of participants examined after 12 months of treatment (primary outcome) and at 18 months (3 months after treatment ended) assessed by an examiner masked to treatment group. Change in refractive error from baseline to 12 months was compared between groups. Analyses were performed using the intention-to-treat population. RESULTSThe mean (SD) age of 196 participants randomized to overminus therapy and 190 participants randomized to nonoverminus treatment was 6.3 (2.1) years, and 226 (59%) were female. Mean distance control at 12 months was better in participants treated with overminus spectacles than with nonoverminus spectacles (1.8 vs 2.8 points; adjusted difference, −0.8; 95% CI, −1.0 to −0.5; P < .001). At 18 months, there was little or no difference in mean distance control between overminus and nonoverminus groups (2.4 vs 2.7 points; adjusted difference, −0.2; 95% CI, −0.5 to 0.04; P = .09). Myopic shift from baseline to 12 months was greater in the overminus than the nonoverminus group (−0.42 D vs −0.04 D; adjusted difference, −0.37 D; 95% CI, −0.49 to −0.26 D; P < .001), with 33 of 189 children (17%) in the overminus group vs 2 of 169 (1%) in the nonoverminus group having a shift higher than 1.00 D.CONCLUSIONS AND RELEVANCE Children 3 to 10 years of age had improved distance exotropia control when assessed wearing overminus spectacles after 12 months of overminus treatment; however, this treatment was associated with increased myopic shift. The beneficial effect of overminus lens therapy on distance exotropia control was not maintained after treatment was tapered off for 3 months and children were examined 3 months later.

IMPORTANCEIntravitreous 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. INTERVENTIONSBevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. MAIN OUTCOMES AND MEASURESSuccess was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks.RESULTS Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg.CONCLUSIONS AND RELEVANCE These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.

Background Cytomegalovirus (CMV) is the most common congenital viral infection in the United States. Visual and ocular sequelae in adolescents and adults who are congenitally infected with CMV have not been well studied. Better understanding of the long-term visual and ocular sequelae can help with early detection, intervention, and appropriate educational accommodations. Methods This study evaluated 237 (77 symptomatic, 109 asymptomatic, and 51 control) patients who underwent a series of age-appropriate ophthalmologic, audiologic, and neurodevelopmental examinations from 1982 to 2013. The frequency and etiology of visual impairment and other non-ophthalmologic findings were recorded for each patient. Ophthalmologic findings were tabulated and risk factors for abnormalities were analyzed. Results Fourteen of the 77 (18.2%) symptomatic and none of the asymptomatic and control subjects had severe visual impairments (p ≤ 0.006). Moderate visual impairment did not differ between symptomatic and asymptomatic subjects. Three asymptomatic subjects had retinal scars. The most common visual or ocular sequelae in the symptomatic group were strabismus (23.4%), chorioretinal scars (19.5%), cortical visual impairment (14.3%), nystagmus (14.3%), and optic nerve atrophy (11.7%). Three symptomatic patients had delayed visual deterioration due to later occurring retinal disorders: peripheral retinal scar, rhegmatogenous retinal detachment, and Coats’ disease. Conclusion Symptomatic CMV patients experienced more ophthalmologic sequelae and significantly worse visual outcomes than asymptomatic CMV and control patients. Later occurring retinal disorders were found in symptomatic patients, and there is no clear evidence that CMV can reactivate in the retinas of children who were congenitally infected. Major risk factors for severe visual impairment included symptomatic status, optic nerve atrophy, chorioretinitis, cortical visual impairment, and sensorineural hearing loss.