Association between per- and polyfluoroalkyl substances exposure and prevalence of chronic obstructive pulmonary disease: The mediating role of serum albumin.

BACKGROUND: No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship. METHODS: This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin. RESULTS: Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR males: 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR females: 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR males: 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR females: 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P interaction: <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P nonlinear:0.001), ln-PFNA (P nonlinear:0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %). CONCLUSION: This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms.

Keypoint regression strategy and angle loss based YOLO for object detection.

The YOLOv4 approach has gained significant popularity in industrial object detection due to its impressive real-time processing speed and relatively favorable accuracy. However, it has been observed that YOLOv4 faces challenges in accurately detecting small objects. Its bounding box regression strategy is rigid and fails to effectively leverage the asymmetric characteristics of objects, limiting its ability to enhance object detection accuracy. This paper proposes an enhanced version of YOLOv4 called KR-AL-YOLO (keypoint regression strategy and angle loss based YOLOv4). The KR-AL-YOLO approach introduces two customized modules: an keypoint regression strategy and an angle-loss function. These modules contribute to improving the algorithm's detection accuracy by enabling more precise localization of objects. Additionally, KR-AL-YOLO adopts an improved feature fusion technique, which facilitates enhanced information flow within the network, thereby further enhancing accuracy performance. Experimental evaluations conducted on the COCO2017 dataset demonstrate the effectiveness of the proposed method. KR-AL-YOLO achieves an average precision of 45.6%, surpassing both YOLOv4 and certain previously developed one-stage detectors. The utilization of keypoint regression strategy and the incorporation of robust feature fusion contribute to superior object detection accuracy in KR-AL-YOLO compared to YOLOv4.

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.

A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 4 to 6 Years.

SIGNIFICANCE: Binocular treatment for unilateral amblyopia is an emerging treatment that requires evaluation through a randomized clinical trial. PURPOSE: This study aimed to compare change in amblyopic-eye visual acuity (VA) in children aged 4 to 6 years treated with the dichoptic binocular iPad (Apple, Cupertino, CA) game, Dig Rush (not yet commercially available; Ubisoft, Montreal, Canada), plus continued spectacle correction versus continued spectacle correction alone. METHODS: Children (mean age, 5.7 years) were randomly assigned to home treatment for 8 weeks with the iPad game (prescribed 1 h/d, 5 d/wk [n = 92], or continued spectacle correction alone [n = 90]) in a multicenter randomized clinical trial. Before enrollment, children wearing spectacles were required to have at least 16 weeks of wear or no improvement in amblyopic-eye VA (<0.1 logMAR) for at least 8 weeks. Outcome was change in amblyopic-eye VA from baseline to 4 weeks (primary) and 8 weeks (secondary) assessed by masked examiner. RESULTS: A total of 182 children with anisometropic (63%), strabismic (16%; <5∆ near, simultaneous prism and cover test), or combined-mechanism (20%) amblyopia (20/40 to 20/200; mean, 20/63) were enrolled. After 4 weeks, mean amblyopic VA improved by 1.1 logMAR lines with binocular treatment and 0.6 logMAR lines with spectacles alone (adjusted difference, 0.5 lines; 95.1% confidence interval [CI], 0.1 to 0.9). After 8 weeks, results (binocular treatment: mean amblyopic-eye VA improvement, 1.3 vs. 1.0 logMAR lines with spectacles alone; adjusted difference, 0.3 lines; 98.4% CI, -0.2 to 0.8 lines) were inconclusive because the CI included both zero and the pre-defined difference in mean VA change of 0.75 logMAR lines. CONCLUSIONS: In 4- to 6-year-old children with amblyopia, binocular Dig Rush treatment resulted in greater improvement in amblyopic-eye VA for 4 weeks but not 8 weeks. Future work is required to determine if modifications to the contrast increment algorithm or other aspects of the game or its implementation could enhance the treatment effect.

Developmental Improvement in Children With Intellectual Disability After Photorefractive Keratectomy for Severe Isoametropia.

PURPOSE: To assess the impact of refractive error correction from photorefractive keratectomy on development in children with severe isoametropia, subnormal visual acuity, and intellectual disability unable to use refraction correction. DESIGN: Prospective noncomparative interventional case series. METHODS: Before and after photorefractive keratometry (PRK), subjects who had plateaued developmentally for 18 or more months were assessed using a battery of developmental tests. The primary outcome measure was the change in the developmental quotient (DQ) 6 months after PRK. Secondary outcomes were the change in the DQ, uncorrected visual acuity, cycloplegic refraction, and corneal status 12, 24, and 36 months after PRK. RESULTS: Sixteen subjects aged 2 to 8 years were included. Twelve were highly myopic (mean, -9.69 ± 3.82 diopters [D]), 3 highly hyperopic (mean, +5.75 ± 0.59 D) and 1 highly astigmatic (mean, +3.50 D). Six months after PRK, the DQ significantly improved for expressive communication (mean, 4.51 ± 2.27 months; P = .04), interpersonal relationships (mean, 9.45 ± 4.18 months; P = .02) and coping (mean, 6.44 ± 2.10 months; P = .05). Twelve months after PRK, the DQ significantly improved for receptive communication (8.04 ± 1.80 months; P < .001), expressive communication (6.99 ± 2.27 months; P < .05), written communication (9.28 ± 3.72 months; P < .04), domestic skills (6.50 ± 2.43 months; P < .03), interpersonal relationships (10.57 ± 4.17 months; P < .02), and coping (8.41 ± 3.25 months; P < .5). CONCLUSIONS: PRK significantly improves developmental abilities of children with intellectual disability, severe isoametropia, and previously plateaued development, in addition to improving visual acuity and refractive error.

Overminus Lens Therapy for Children 3 to 10 Years of Age With Intermittent Exotropia: A Randomized Clinical Trial.

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 PARTICIPANTS: This 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 MEASURES: Primary 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. RESULTS: The 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02807350.

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.

Corneal indices following photorefractive keratectomy in children at least 5 years after surgery.

PURPOSE: To evaluate long-term corneal outcomes in pediatric patients who underwent photorefractive keratotomy (PRK) for the treatment of refractive amblyopia. METHODS: In this prospective interventional case series, children with refractive amblyopia underwent PRK between January 1, 2007, and December 31, 2011, at Texas Children's Hospital's Department of Ophthalmology, a single tertiary eye center, and were followed for at least 5 years after surgery. Main outcome measures were 5+ years postoperative indices of corneal thickness, keratometry, degree of corneal haze, and presence or absence of keratectasia. RESULTS: Twelve eyes of 8 subjects aged 3-9 years who underwent PRK and were followed for at least 5 years were included. The mean PRK treatment dose was 8.46 D for the myopic cohort and 4.49 D for the hyperopic cohort, which removed an average of 72 µm of corneal stromal tissue in addition to the 50 µm of corneal epithelium that was removed prior to laser ablation. The mean corneal thickness was 563 µm preoperatively, which decreased to 441 µm immediately following the PRK. The mean corneal thickness 5+ years after PRK was stable, at 498 µm, because of epithelial regrowth. None of the subjects developed visually significant corneal haze or topographic evidence of keratectasia. CONCLUSIONS: In this study cohort, there were no topographic signs of keratectasia or corneal haze in children treated with PRK for high refractive error 5 years or more after surgery.

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.

Visual outcomes of patients presenting with bilateral infantile cataracts and nystagmus.

OBJECTIVE: To evaluate the outcomes of cataract surgery in pediatric patients presenting with bilateral infantile cataracts and nystagmus. DESIGN: Retrospective case study. PARTICIPANTS: Thirteen pediatric patients who presented between September 2002 and February 2014 at a single tertiary care institution. METHODS: Patients were included if they presented with bilateral visually significant cataracts and preoperative manifest nystagmus and had no other systemic or ocular condition that could explain the presence of the nystagmus. Data collected included best-corrected visual acuity (BCVA), etiology of cataracts, associated systemic/ocular conditions, status of strabismus, surgical complications, and presence of nystagmus. RESULTS: Mean age at diagnosis of the cataracts was 8.1 ± 10.6 months. Mean age at surgery was 8.4 ± 10.5 months. Average length of follow-up was 54.3 ± 32.6 months. Twelve patients were left aphakic bilaterally; 1 patient received primary intraocular lenses bilaterally. Ten patients were able to perform visual acuity at the most recent visit, with 5 out of 10 having BCVA ≥20/40 in the better-seeing eye. Two patients had no visible nystagmus and 3 patients had latent nystagmus only at the most recent visit. CONCLUSIONS: The presence of preoperative nystagmus does not preclude good visual outcomes in pediatric patients with cataracts.

Long-term Outcomes of Primary Intraocular Lens Implantation in Patients Aged 7 to 24 Months.

PURPOSE: To report long-term outcomes of primary intraocular lens (IOL) placement in patients aged 7 to 24 months. METHODS: This was a retrospective study of 27 consecutive patients (28 eyes) aged 7 to 24 months who underwent cataract surgery with primary IOL placement. RESULTS: Average follow-up was 62.7 ± 41.7 months and the mean age of surgery was 14.4 ± 5.6 months. Mean final visual acuity was 1.02 ± 0.72 logMAR (20/209). Adverse events occurred in 7 eyes (25%) and included visual axis opacification in 6 eyes and pupillary block glaucoma in 1 eye. Seven patients (25.9%) required additional intraocular surgery. Strabismus was present in 19 patients (70.4%). Better stereopsis was correlated with better final acuity. CONCLUSIONS: Cataract surgery with IOL placement in patients aged 7 to 24 months is associated with few complications. Visual axis opacification is the most frequent adverse event. [J Pediatr Ophthalmol Strabismus. 2017;54(3):149-155.].

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.

Colorado retinopathy of prematurity model: a multi-institutional validation study.

PURPOSE: The Colorado retinopathy of prematurity (ROP) prediction model (CO-ROP), developed using a cohort of infants from Colorado, calls for ROP examination of infants meeting all of the following criteria: gestational age of ≤30 weeks, birth weight of ≤1500 g, and a net weight gain of ≤650 g between birth and 4 weeks of age. The purpose of this study was to perform an external validation to assess the sensitivity and specificity of the CO-ROP model in a larger cohort of babies screened for ROP from four academic institutions in the United States. METHODS: The medical records of neonates screened for ROP according current national guidelines was conducted at 4 US academic centers were retrospectively reviewed. Sensitivity, specificity, and respective 95% confidence intervals in detecting ROP using CO-ROP were calculated for type 1, type 2, and any grade of ROP. RESULTS: A total of 858 cases were included. The CO-ROP algorithm had a sensitivity of 98.1% (95% CI, 93.3%-99.8%) for type 1 ROP, 95.6% (95% CI 78.0-99.9%) for type 2 ROP, and 95.0% (95% CI, 93.1-97.4%) for all grades of ROP. The CO-ROP model would have reduced the total number of infants screened by 23.9% compared to current 2013 screening guidelines. CONCLUSIONS: CO-ROP demonstrated high sensitivity in predicting ROP and would have greatly reduced the number of infants needing examination.

Assessment of Plasma Cytokine Profile Changes in Bevacizumab-Treated Retinopathy of Prematurity Infants.

PURPOSE: We compared changes of plasma angiogenesis cytokine profiles in infants who were treated with intravitreal injection of bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) with age-matched preterm non-ROP infants. METHODS: Thirteen infants with type 1 ROP and 13 age-matched preterm non-ROP infants were included. Blood samples were collected prior to treatment (time 0) and 6 weeks after the treatment (time 42). Plasma levels of nine cytokines from the angiogenesis growth factor panel and seven soluble cytokine receptors were measured using a magnetic multiplex assay. RESULTS: Plasma cytokine profiles changed from time 0 to time 42 in both groups. In bevacizumab-treated ROP infants, the following plasma angiogenesis growth factor and soluble cytokine receptor levels decreased significantly: soluble VEGF-A (sVEGF-A; P = 0.0001), sVEGF-D (P = 0.04), angiopoietin-2 (Ang-2; P = 0.002), sVEGF receptor 1 (R1) and R2 (P = 0.005), soluble IL-6 receptor (sIL-6R; P = 0.002), soluble glycoprotein 130 (spg130; P = 0.0001), and soluble TNF receptor (sTNFR) I and II (P = 0.0001). The following factors and receptors increased significantly: sVEGF-C (P = 0.05), placental growth factor (PlGF; P = 0.02), endothelin-1 (ET-1; P = 0.0001), and FGF-1 (P = 0.02). At time 42, sVEGF-A, sgp130, sIL-6R, sTNFR I, and sTNFR II were lower, and ET-1 level was higher, in bevacizumab-treated ROP infants compared to age-matched non-ROP infants. CONCLUSIONS: The results suggest that bevacizumab treatment resulted in significant angiogenic cytokine profile changes in infants with severe ROP. The long-term clinical impact of these changes should be studied carefully.

Evaluation of structural contributors in myopic eyes of preterm and full-term children.

PURPOSE: We conducted a cross-sectional study to test the hypothesis that the structural contributions to myopia in preterm and full-term born children are different. METHODS: In this study, 93 children ranging from ages 2 to 13 who had myopia ≥ -3 diopters in at least one eye were examined with A-scans. The following data was collected and analyzed: history of birth, refractive error (RE), cornea thickness (CT) and average corneal curvature (AVK), depth of anterior chamber (ACD), lens thickness (LT), and axial length (AL) of the eye. RESULTS: Eyes were tested and categorized into four groups: myopic eyes in full-term children (group 1), myopic eyes in premature children (group 2), non-myopic eyes in full-term children (group 3), and non-myopic eyes in preterm children (group 4). The RE were similar between group 1 and group2, and between group 3 and group 4. Myopic eyes in group 2 had higher AVK as compared to group 3; 45.4 ± 0.4 D vs. 43.5 ± 0.7 D, p = 0.008. The ACD in group 2 was shallower than that in group 1 (2.5 ± 0.5 vs. 3.2 ± 0.3, p = 0.01). The LT measurements in group 2 were thicker than those in group 1 (mean LT = 4.9 ± 1.0 vs 4.1 ± 0.3 mm, p = 0.001, respectively). Finally, AL of myopic eyes in group 1 was longer than that of group 2, p = 0.01. CONCLUSION: These results suggest that increased axial length plays an important role in myopia in full-term children, whereas corneal curvature and lens thickness are major contributors to myopia in preterm children.

Long-Term Outcomes of Iris-sutured Posterior Chamber Intraocular Lenses in Children.

PURPOSE: To report the long-term outcomes and complications of iris-sutured posterior chamber intraocular lenses (PCIOLs) in the pediatric population. DESIGN: Retrospective interventional case study. METHODS: This study involved 12 consecutive pediatric patients (17 eyes) who underwent placement of foldable iris-sutured PCIOLs between September 2004 and September 2007. Outcome measures included change in visual acuity and complications. RESULTS: Of the 17 eyes were reviewed, 6 (35%) had hereditary or idiopathic ectopia lentis, 5 (29%) had Marfan syndrome, 2 (12%) were aphakic after pars plana vitrectomy and 4 (24%) were aphakic after surgical intervention for trauma. Average follow-up was 4.69 ± 3.21 years and mean age of surgery was 7.21 ± 3.78 years. Seven eyes suffered dislocation of the PCIOL an average of 12.11 ± 11.97 months after surgery, with 2 patients undergoing dislocation a second time. There was a higher rate of dislocation in patients with a history of ectopia lentis due to Marfan syndrome, idiopathic causes, or hereditary causes than in patients being treated for aphakia resulting from other causes (71% vs 29%). Mean visual acuity improved in 12 of 17 patients (71%), from 0.80 ± 0.6 logMAR preoperatively to 0.35 ± 0.5 logMAR at most recent visit, P = .009. One eye of a Marfan patient sustained a retinal detachment 8 months after dislocation of the PCIOL, and 1 patient experienced iris capture of the PCIOL after surgery. CONCLUSIONS: Iris-sutured intraocular lenses have been used as an alternative to transsclerally sutured intraocular lenses to correct aphakia in pediatric patients. Dislocation of the intraocular lenses can occur frequently, however. The procedure should be considered with caution in pediatric patients.

Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity.

PURPOSE: To measure serum levels of bevacizumab and to compare serum levels of free vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in infants who were treated with either intravitreal injection of bevacizumab (IVB) or laser for type 1 retinopathy of prematurity (ROP). METHODS: Twenty-four infants with type 1 ROP were randomized into three treatment groups: IVB at 0.625 mg per eye per dose, IVB at 0.25 mg per eye per dose, and laser. Blood samples were collected prior to treatment and on posttreatment days 2, 14, 42, and 60. Weekly body weights were documented from birth until 60 days post treatment. Serum levels of bevacizumab, free VEGF, and IGF-1 were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum bevacizumab was detected 2 days after the injection, peaked at 14 days, and persisted for up to 60 days with half-life of 21 days. Area under the curve (AUC) analysis showed that systemic exposure to bevacizumab was variable among the subjects and was dose dependent. Serum free VEGF levels decreased in all three subgroups 2 days post treatment, with more significant reductions found in both IVB-treated groups, P = 0.0001. Serum IGF-1 levels were lower in both IVB-treated groups. CONCLUSIONS: 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.

Evaluating the association of autonomic drug use to the development and severity of retinopathy of prematurity.

PURPOSE: To explore the association of autonomic agents with the development and severity of retinopathy of prematurity (ROP). METHODS: The medical records of all preterm infants screened for ROP were retrospective reviewed. The association between development and severity of ROP and the use and dose(s) of autonomic agents was analyzed, after adjustment for the covariates gestational age, weight, development of septicemia, intraventricular hemorrhage, and respiratory distress syndrome. RESULTS: A total of 350 infants were screened. Caffeine was used in 338 infants; dopamine in 98 infants. There was a significant association between the use of dopamine and development of ROP (P < 0.001; relative risk [RR] = 1.6 [95% CI, 1.23-2.06]) and the need for ROP treatment (P = 0.001; RR = 4.63 [95% CI, 1.82-11.79]). The number of dopamine doses was significantly associated with the development of any ROP (P < 0.001; RR = 1.07 [95% CI, 1.03-1.1]), the severity of ROP (P < 0.001; RR = 1.09 [95% CI, 1.05-1.14]), and the need for treatment (P < 0.001; RR = 1.09 [95% CI, 1.05-1.14]). The total dose of caffeine was significantly associated with the development of any ROP (P = 0.003; RR = 1.03 [95% CI, 1.01-1.05]) and the need for treatment (P = 0.006, RR = 1.073 [95% CI; 1.021-1.13]). CONCLUSIONS: Although a causal relationship was not identified, the use of the autonomic agents caffeine and dopamine was associated with the development and severity of retinopathy of prematurity in this cohort.

Scleral-fixated capsular tension rings and segments for ectopia lentis in children.

PURPOSE: To report the short-term outcomes and complications of implantation of scleral-fixated capsular tension rings and/or capsular tension segments with intraocular lenses (IOL) in pediatric patients with ectopia lentis. DESIGN: Retrospective, observational case series. METHODS: Thirteen consecutive pediatric patients (19 eyes) underwent placement of in-the-bag IOL with either a Cionni modified capsular tension ring or a capsular tension segment in conjunction with a conventional capsular tension ring between January 1, 2009 and March 30, 2013 by 3 anterior segment surgeons at a single academic center. The scleral fixation suture was 9-0 polypropylene in 16 eyes and CV-8 Gore-Tex (expanded polytetrafluoroethylene) in 3 eyes. Outcome measures included change in corrected distance visual acuity (CDVA) and complications. RESULTS: The mean age was 10.2 years ± 4.8 (SD) and the median follow-up, 23.4 months. A Cionni modified capsular tension ring was implanted in 5 eyes and a capsular tension segment with an unsutured capsular tension ring was implanted in 12 eyes. In 2 eyes, capsular tension segment alone was placed. The mean CDVA at the final follow-up (0.10 ± 0.11 logMAR, 18 eyes) was significantly better than preoperatively (0.58 ± 0.26 logMAR, 15 eyes) (P < .001). The CDVA at the final follow-up was 20/40 or better in 18 eyes (94.7%). All IOLs were well centered. Posterior capsule opacification developed in 11 eyes (57.9%), 9 eyes (47.4%) required neodymium-yttrium-aluminum-garnet capsulotomy, and 3 eyes (15.8%) required pars plana vitrectomy and posterior capsulotomy. Other complications included broken suture (5.3%) (9-0 polypropylene at CTR eyelet, repaired with CV-8 Gore-Tex), conjunctival dehiscence (5.3%), suture exposure (5.3%) (trans-scleral 9-0 polypropylene), and vitreous strand at inferior paracentesis (5.3%). CONCLUSIONS: Implantation of in-the-bag IOL with either a Cionni modified capsular tension ring or a capsular tension segment in conjunction with a conventional capsular tension ring appears to be a safe and effective technique for visual rehabilitation in pediatric ectopia lentis.