Objective: To evaluate the impact on visual acuity of reducing or abandoning patching therapy during the first six years of life after early unilateral cataract surgery. Methods: We reviewed the medical records of nine children with unilateral congenital cataracts who underwent cataract surgery when ≤6 weeks of age. All had good compliance with optical correction until 6 years of age and patching therapy until at least 12 months of age. Results: The children underwent cataract surgery at a mean age of 21.7 ± 9.5 days. At 12 months of age the children were patched a mean of 6.7 ± 2.4 hours/day. Patching compliance declined steadily thereafter. By 6 years of age, they were only being patched a mean of 1.7 ± 2.0 hours/day. Four children abandoned patching prior to the 6 year exam; the acuities improved or remained the same for three of these children, but worsened for one child by two lines. Conclusion: Visual acuity remained relatively stable even when patching therapy was reduced or abandoned by children ≤ 6 years of age provided cataract surgery was performed during early infancy, an optical correction was consistently worn and there was good compliance with patching therapy during early childhood.

IMPORTANCE: Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described. OBJECTIVE: To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study. DESIGN, SETTING, AND PARTICIPANTS: Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director. EXPOSURE Digital retinal images. MAIN OUTCOMES AND MEASURES: Intragrader and intergrader variability and monitoring for temporal drift. RESULTS: Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5%requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9%for plus disease, 12.4% for zone I ROP, and 16.9%for stage 3 or worse ROP. The weighted κ for intergrader agreement (n = 80 image sets) was 0.72 (95%CI, 0.52-0.93) for RW-ROP, 0.57 (95%CI, 0.37-0.77) for plus disease, 0.43 (95%CI, 0.24-0.63) for zone I ROP, and 0.67 (95%CI, 0.47-0.88) for stage 3 or worse ROP. The weighted κ for grade-regrade agreement was 0.77 (95%CI, 0.57-0.97) for RW-ROP, 0.87 (95%CI, 0.67-1.00) for plus disease, 0.70 (95%CI, 0.51-0.90) for zone I ROP, and 0.77 (95%CI, 0.57-0.97) for stage 3 or worse ROP. CONCLUSIONS AND RELEVANCE: These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.

Objective: To evaluate the efficacy of subconjunctival nanoparticle carboplatin in the treatment of transgenic murine retinoblastoma. Methods: Dendrimeric nanoparticles loaded with carboplatin were prepared. Forty LHβ-Tag mice were randomly assigned into 4 groups, and treated at 10 weeks of age. Each mouse received a single subconjunctival injection in one eye, and the opposite eye was left untreated as a control. Group 1 (high-dose nanoparticle) received 37.5 mg/ml nanoparticle carboplatin; Group 2 (low-dose nanoparticle) received 10 mg/ml nanoparticle carboplatin; Group 3 (conventional carboplatin) received 10 mg/ml of carboplatin in aqueous solution, and group 4 (phosphate-buffered saline; PBS) received PBS. Mice were euthanized on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. Results: Mean tumor burden in the treated eyes was significantly smaller compared to the untreated eyes in the same mice in both nanoparticle carboplatin groups (Group 1, P=0.02; Group 2, P=0.02), to the treated eyes in conventional carboplatin group (Group 1 vs. 3, P<0.01; Group 2 vs. 3, P=0.01), and PBS group (Group 1 vs. 4, P<0.01; Group 2 vs. 4, P=0.01). The untreated eyes in high-dose nanoparticle carboplatin showed significantly smaller tumor mass compared to conventional carboplatin (P=0.03) and PBS group (P=0.04). No toxicity was observed in any of the groups. Conclusions and Clinical Relevance: A single injection of subconjunctival nanoparticle carboplatin was effective in the treatment of transgenic murine retinoblastoma with no associated toxicity. The higher dose of subconjunctival nanoparticle carboplatin decreased the tumor burden in the contralateral eye.

Importance: Metagenomic deep sequencing (MDS) demonstrates that persistent and active rubella virus (RV) infection is associated with Fuchs heterochromic iridocyclitis (FHI). Objective: To assess the utility of MDS in identifying RV infection in patients with uveitis. Design, Setting, and Participants: This case series assessed 6 patients diagnosed by MDS with RV-associated uveitis at a tertiary uveitis referral center in the United States. Exposures: Prior RV infection. Main Outcomes and Measures: Clinical examination findings, slitlamp photography, corneal confocal imaging, and infectious pathogen genome obtained from RNA sequencing. Results: Six white men (age range, 36-61 years) were diagnosed with RV-associated uveitis by MDS. Three patients exhibited iris heterochromia associated with their uveitis in classic FHI fashion. The other 3 patients had less classic FHI features and exhibited anterior vitritis. Three patients had in vivo corneal confocal microscopy, with 2 demonstrating stellate keratic precipitates in addition to endothelial infiltration, spotlike holes, and enlarged intercellular boundaries. Of these 3 patients, 1 patient exhibited polymorphism and polymegathism of the endothelial cells. Conclusions and Relevance: These findings suggest that persistent RV infection is associated with recurrent or chronic anterior or anterior-intermediate uveitis as well as corneal endothelial cell damage. Ophthalmologists should consider RV infection as a potential cause of hypertensive anterior and intermediate uveitis.

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 achievedin 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 aslow as 0.031 mgwas effectivein 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.