POSTNATAL SERUM INSULIN-LIKE GROWTH FACTOR I AND RETINOPATHY OF PREMATURITY.

PURPOSE: Low serum IGF-1 has been associated with development of severe ROP, but no U.S. studies have been reported. We sought to determine the relationship between postnatal serum IGF-1 levels and severe ROP in a racially diverse U.S. cohort. METHODS: Prospective cohort study of 74 infants with birth weight <1,251 g and a known ROP outcome at 3 Philadelphia hospitals. Weekly postnatal filter paper blood spot IGF-1 assays were measured through 42 weeks postmenstrual age. RESULTS: The cohort included 20 white, 45 black, 2 Asian, and 9 other infants; median gestational age was 27.6 weeks (range 23-33 weeks), and median birth weight was 975 g (range 490-1,250 g). During postmenstrual age Weeks 28 to 33, mean IGF-1 was 20.0 ng/mL (standard error 0.52) for no ROP (n = 46), 18.0 (0.49) for Stage 1 or 2 (n = 23), and 17.0 (0.70) for Stage 3 (n = 5, 2 lasered) (P = 0.003). Adjustment for birth weight and gestational age showed similar results. CONCLUSION: The presence and timing of an association between low postnatal serum IGF and ROP in a racially diverse U.S. sample were found to be consistent with those of European cohorts. This association provides the pathophysiological basis for growth-based predictive models, which could improve efficiency of ROP screening.

Parvovirus B19 infection in the first trimester of pregnancy and risk of fetal loss: a population-based case-control study.

Because parvovirus B19 infection during pregnancy has been associated with increased risk of fetal loss in small or selected study populations, the authors evaluated the risk in a population-based study. A nested case-control study was conducted by using a population-based screening for syphilis in 3 regions in Denmark from 1992 to 1994. Cases of women with fetal loss were identified in the National Patient Register (n = 2,918), and control women with live-born children were identified in the Medical Birth Register (n = 8,429) by matching on age and sampling week. First-trimester serum samples were tested for parvovirus B19 immunoglobulin M positivity. Parvovirus B19 immunoglobulin M positivity was associated with a 71% increased risk of fetal loss (odds ratio = 1.71, 95% confidence interval: 1.02, 2.86). Adjustment for number of children or stratifying for gestational age at loss did not change the risk estimate. Assuming causality, only 0.1% of fetal losses were attributable to parvovirus B19 positivity, a proportion which could increase to approximately 1% during epidemic periods. In conclusion, acute parvovirus B19 infection during the first trimester of pregnancy was associated with an increased risk of fetal loss. However, the impact on the overall burden of fetal losses appeared small even during epidemics.

Autism Spectrum Disorder in Pediatric Idiopathic Intracranial Hypertension.

In recent years, the substantial burden of medical comorbidities in autism spectrum disorder (ASD) populations has been described. We report a retrospective observational case series of pediatric patients with suspected idiopathic intracranial hypertension (IIH) and concurrent ASD. Pediatric subjects with suspected IIH aged 2-18 years were identified by review of a pediatric neuro-ophthalmologist's database spanning from July 1993 to April 2013. ASD diagnoses were identified within this cohort by an ICD-9 diagnosis code search and database review. Three subjects had concurrent ASD diagnoses; all were non-obese males. Since the retrospective observational case series was performed in April 2013, we identified three additional IIH cases in boys with ASD. Our experience suggests that IIH may be a comorbidity of ASD, particularly in non-obese boys.

Symmetry of Disease in Retinopathy of Prematurity in the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study.

PURPOSE: To determine the symmetry of retinopathy of prematurity (ROP) between fellow eyes in a broad-risk cohort. METHODS: A retrospective cohort study, the Postnatal Growth and ROP (G-ROP) Study, of 7483 infants undergoing ROP examinations conducted at 29 hospitals in the United States and Canada from 2006 to 2012. The main outcomes were the symmetry for the highest stage and the most severe type (1, 2, not 1 or 2, no ROP) of ROP and disease course of the fellow eye when only one eye developed type 1. RESULTS: 93% of infants had eyes symmetric for the highest stage and 94% for type. Among 459 infants who developed type 1, 379 (82.6%) did so in both eyes simultaneously and were treated bilaterally; 44 (10%) were treated for type 1 in one eye and type 2 in the fellow eye; and 36 (8%) were treated unilaterally initially, of which 6 fellow eyes developed type 1 and were treated (4 within 2 weeks, all within 4 weeks); 5 developed type 2 and regressed; and 25 developed ROP less than type 1 or 2, which was treated in 13 cases and regressed spontaneously in 12 cases. CONCLUSIONS: ROP was highly symmetric between eyes with respect to the presence and severity of disease in a large, broad-risk cohort representative of infants undergoing ROP screening. When type 1 develops in one eye and type 2 in the fellow eye, the risk of progression to type 1 in the fellow eye appears very low if it has not occurred within 4 weeks.

Longitudinal study of the association between thrombocytopenia and retinopathy of prematurity.

BACKGROUND: An association between thrombocytopenia and retinopathy of prematurity (ROP) has been suggested but not been studied longitudinally. We sought to identify the time period in postnatal development during which thrombocytopenia and the subsequent development of severe ROP are associated. METHODS: This was a retrospective case-control study of 100 subjects who received laser photocoagulation for type 1 ROP between 2005 and 2009 and 100 controls with no ROP or only stage 1 ROP. The proportions of infants with thrombocytopenia, defined as a serum platelet level of <150,000/µL, among cases versus controls were compared on a weekly basis from birth through the time of laser during early (postmenstrual age [PMA] weeks 24-28), middle (PMA weeks 29-34), and late (PMA weeks 35-38) time periods. Main outcome measures were odds ratios for the association between thrombocytopenia and type 1 ROP from multivariate logistic regression models adjusted for gestational age, birth weight, culture-proven sepsis, and necrotizing enterocolitis. RESULTS: Thrombocytopenia was significantly associated with severe ROP during PMA weeks 24-28 (adjusted OR, 4.7; 95% CI, 2.0-1.1; P = 0.001) and 29-34 (adjusted OR, 2.8; 95% CI, 1.4-5.6; P = 0.006), but not during weeks 35-38 (adjusted OR, 2.0; 95% CI, 0.9-4.3; P = 0.10). CONCLUSIONS: Thrombocytopenia from birth through 34 weeks' PMA was associated with subsequent severe ROP. This time period corresponds to a period of poor retinal vascular growth, suggesting a possible proangiogenic effect of platelets in normal retinal vascular development in infants at risk for ROP.

Patterns of retinal hemorrhage associated with pediatric cerebral sinovenous thrombosis.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) has been proposed as an alternative cause of retinal hemorrhage (RH) in children being evaluated for abusive head trauma. This study investigated the prevalence and characteristics of RH in children with CSVT. METHODS: The medical records of children >6 weeks of age with newly diagnosed CSVT and fundus examination by an ophthalmologist were examined retrospectively. Primary outcomes were presence and patterns of RH. RESULTS: A total of 29 children (median age, 9 years; range, 7 weeks to 17 years) were studied. Of these, 5 (17%) had RH, in 4 of whom RH were peripapillary, superficial, intraretinal, and adjacent to a swollen optic disk. In the fifth child, who had meningitis, sepsis, and multiple cerebral infarcts, there were a moderate number of posterior pole intraretinal hemorrhages. Eighteen children (62%) had optic disk swelling. In 13 children, cerebrospinal fluid opening pressure was recorded (range, 27-59 cm H2O). CSVT risk factors included meningitis, mastoiditis, and hypercoagulability. CONCLUSIONS: RH in pediatric CSVT was uncommon. When RHs were present, the appearance matched RH patterns known to be caused by medical conditions, such as raised intracranial pressure and sepsis, also present in these children. These findings suggest that the RHs are due to these other causes and not directly to CSVT itself. In children with CSVT, if RHs are multilayered, extend beyond the peripapillary region into the rest of the posterior pole or retinal periphery, or occur in the absence of optic disk swelling, another etiology for the RH should be sought.

Confidence of ophthalmology residents in obtaining informed consent.

UNLABELLED: Ophthalmology residents often obtain informed consent for common procedures. In this study, we set out to determine the confidence levels among ophthalmology residents who obtain informed consent. An anonymous online survey was distributed to United States ophthalmology residents across the country. Ninety-five residents participated, evenly distributed geographically and by postgraduate year (PGY). Residents were frequently obtaining consent for procedures despite not being comfortable doing so. Only 18% of residents reported that they always felt comfortable with the informed consent process. Comfort level increased significantly with PGY (P < .001) and prior training in informed consent (P = .032). Of the residents surveyed, 76% indicated a desire for more formal training in the consent process. Most residents would welcome an informed-consent formal training curriculum, which would address 5 of the 6 Accreditation Council for Graduate Medical Education core competencies and meet resident milestones in the Next Accreditation System. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Filter paper-based insulin-like growth factor assay.

This study assessed validity, reliability, and feasibility of a filter paper blood spot insulin-like growth factor 1 (IGF-1) assay for retinopathy of prematurity (ROP) research. Blood samples were collected from 45 healthy children. Half of each sample was spun to obtain serum; half was applied to filter cards and stored for varying times and at different temperatures. IGF-1 assays were performed using a commercially available kit. Intraclass correlation between blood spot and serum IGF-1 values was high (0.97) for validity, and the mean differences were low for test-retest reliability. Time (up to 25 days) and temperature (4° C to 37° C) had no significant effect on sample stability. Feasibility was further assessed in a second cohort study of 74 premature infants being screened for ROP. A total of 817 filter card samples were successfully collected and transported to a central lab, where IGF-1 assays were successfully performed.

Widespread retinal hemorrhages after retinopathy of prematurity screening with scleral depression.

We report a case of extensive bilateral intraretinal hemorrhages in a premature infant with active retinopathy of prematurity (ROP) after an examination with scleral depression. In the only other previously reported case, the retinal hemorrhages were limited to the posterior pole of an eye with preexisting vitreous hemorrhage, and the child had a history of severe necrotizing enterocolitis that required surgery. Investigators have hypothesized that the combination of ocular manipulation, abrupt intraocular pressure change, and fragile immature retinal vasculature with poor autoregulation may contribute to the pathogenesis of retinal hemorrhages. Physicians performing ROP examinations should be aware of this possibility and judiciously use scleral depression; however, examination-induced retinal hemorrhages in children have never been reported in the absence of active ROP.

Thrombocytopenia and retinopathy of prematurity.

BACKGROUND: Platelets may act as vascular endothelial growth factor (VEGF) scavengers, possibly limiting neovascularization in retinopathy of prematurity (ROP). The purpose of this study was to investigate the association between thrombocytopenia (platelets <150,000/µL) and the development of type 1 ROP. METHODS: This was a retrospective 1:1 matched case-control study. Cases required laser; controls developed no or stage 1 ROP and were matched for birth weight within 100 g and gestational age within 1 week. Most recent platelet count prior to laser (case) and matched postmenstrual age (control) were abstracted. Conditional logistic regression was used. RESULTS: A total of 91 cases and 91 controls were reviewed. Of the cases, 25% had thrombocytopenia; of controls, 13% (P = 0.034; OR = 2.38; 95% CI, 1.04-5.43). Birth weight, gestational age, postmenstrual age, and culture-proven sepsis were not confounders in multivariate analysis. The association was significant for zone 1 (n = 16; OR = 9.00; 95% CI, 1.14-71.0) but not for zone 2 (OR = 1.43; 95% CI, 0.54-3.75) cases and controls. CONCLUSIONS: Thrombocytopenia was associated with type 1 ROP, primarily among infants with zone 1 ROP. This effect may result from disease location or disease timing, as posterior disease occurs at an earlier postmenstrual age. Longitudinal studies are required to further examine the roles of cumulative platelet deficits, thresholds, or critical time windows in the observed association.