Deborah K. VanderVeen

The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment

OBJECTIVE To compare the use of contact lenses and intraocular lenses (IOLs) for the optical correction of unilateral aphakia during infancy. METHODS In a randomized, multicenter (12 sites) clinical trial, 114 infants with unilateral congenital cataracts were assigned to undergo cataract surgery with or without IOL implantation. Children randomized to IOL treatment had their residual refractive error corrected with spectacles. Children randomized to no IOL treatment had their aphakia treated with a contact lens. MAIN OUTCOME MEASURES Grating acuity at 12 months of age and HOTV visual acuity at 4 1/2 years of age. APPLICATION TO CLINICAL PRACTICE This study should determine whether either treatment for an infant with a visually significant unilateral congenital cataract results in a better visual outcome. RESULTS Enrollment began December 23, 2004, and was completed January 16, 2009. The median age at the time of cataract surgery was 1.8 months. Fifty patients were 4 to 6 weeks of age at the time of enrollment; 32, 7 weeks to 3 months of age; and the remaining 32, more than 3 to less than 7 months of age. Fifty-seven children were randomized to each treatment group. Eyes with cataracts had shorter axial lengths and steeper corneas on average than the fellow eyes. CONCLUSIONS The optimal optical treatment of aphakia in infants is unknown. However, the Infant Aphakia Treatment Study was designed to provide empirical evidence of whether optical treatment with an IOL or a contact lens after unilateral cataract surgery during infancy is associated with a better visual outcome.

Longitudinal postnatal weight measurements for the prediction of retinopathy of prematurity.

OBJECTIVE To validate longitudinal postnatal weight gain as a method for predicting severe retinopathy of prematurity (ROP) in a US cohort. METHODS Both ROP evaluations and weekly weight measurements from birth to postmenstrual week 36 for 318 infants were entered into a computer-based surveillance system, WINROP. This system signaled an alarm when the rate of weight gain decreased compared with control subjects. Infants were classified into 3 groups: (1) no alarm, (2) low-risk alarm, or (3) high-risk alarm. Maximum ROP for each infant was categorized as (1) no ROP (immature or mature vascularization), (2) mild ROP (stage 1 or 2 ROP in zone II or III, without plus disease), or (3) severe ROP (any prethreshold, any stage 3, or threshold ROP). A high-risk alarm identified infants at risk for developing severe ROP. RESULTS A high-risk alarm occurred in 81 infants (25.5%) and detected all infants who developed severe ROP a median of 9 weeks before diagnosis. The remaining infants received no alarm or a low-risk alarm. None of these infants developed more than mild ROP. CONCLUSIONS Longitudinal postnatal weight gain may help predict ROP. In a US cohort, the WINROP system had a sensitivity of 100% and identified infants early who developed severe ROP. With further validation, WINROP has the potential to safely reduce the number of ROP examinations.

Retinopathy of Prematurity: Current Concepts in Molecular Pathogenesis

Retinopathy of prematurity is marked by the proliferative vascularization of the retina in preterm babies. An understanding of the molecular pathogenesis of ROP provides the basis for identifying novel therapeutic targets for treatment. Using the mouse model of oxygen-induced retinopathy, the roles of the hypoxia induced factors vascular endothelial growth factor and erythropoietin as well as the maternally derived factors insulin-like growth factor-1 and omega-3 polyunsaturated fatty acids have begun to be elucidated. Understanding the phase specific effects of these factors will serve to guide the development of non destructive treatments for ROP and for other ischemic retinopathies including diabetic retinopathy and neovascular age-related macular degeneration.

Presentation and Management of Congenital Dacryocystocele

OBJECTIVE. Our goal was to report the presentation, complications, and treatment strategies for infants with congenital dacryocystocele. PATIENTS AND METHODS. We performed a retrospective chart review of all patients presenting with dacryocystoceles to Childrens Hospital Boston between the years of 1997 and 2006. This study was approved by the institutional review board. RESULTS. Forty-two patients (46 eyes) were identified (18 male, 24 female), presenting at a median age of 7 days of life. Twenty-eight (65%) patients presented with cellulitis or dacryocystitis and required systemic antibiotics. Four (9.5%) patients presented with respiratory compromise. Resolution occurred with conservative treatment for 10 eyes, but 36 (78%) required surgical intervention. Seventeen (37%) eyes received probing in the office or nursery, and 13 (76%) were successful. Probing in the operating room was required for 21 patients, 8 of whom required marsupialization of an intranasal cyst. CONCLUSIONS. Although congenital dacryocystoceles may resolve with conservative measures, many become infected and require systemic antibiotic treatment, and most require surgical intervention. Referral in the early neonatal period can aid in timely intervention before complications such as infection occur.

Comparison of intraocular lens power calculation formulae in pediatric eyes.

PURPOSE To evaluate accuracy of intraocular lens (IOL) power calculation formulae (SRK II, SRK/T, Holladay 1, Hoffer Q) in pediatric eyes. DESIGN Retrospective case series. PARTICIPANTS One hundred thirty-five eyes of 96 children with congenital, developmental, or acquired cataracts who underwent uncomplicated cataract surgery and IOL implantation by a single surgeon over a 10-year period. METHODS Axial length (AL), keratometry (K), and manufacturers A constant were employed in 4 common IOL power calculation formulae to predict the refractive outcome. Retinoscopy was measured at 4 to 8 weeks postoperatively and converted to spherical equivalent. For analysis, eyes were grouped by age at surgery, AL, and mean K. MAIN OUTCOME MEASURES We determined the prediction error (PE) = predicted refraction - actual refraction and the absolute PE = |predicted refraction - actual refraction|. The formula that gave the best prediction (minimum PE) was determined. RESULTS The mean age at surgery was 6.4 years. Mean absolute PE was 1.11 for the SRK II, 0.84 for SRK/T, 0.76 for Holladay, and 0.76 for Hoffer Q formulae. There was a trend toward greater PE in eyes of younger children (< or =2 years), shorter AL (AL < or = 22 mm) and steeper corneas (mean K > 43.5 diopters [D]). On comparing absolute PE obtained with 4 formulae in each patient, Hoffer Q gave the minimum PE in 46% of eyes compared with 23% with SRK II, 18.5% with SRK/T, and 12.5% with Holladay 1. The SRK/T, Holladay 1, and Hoffer Q were similar in accurately predicting refractive error within +/-0.5 D in about 43% eyes. When clinically significant deviation in PE occurred (>0.5 D), there was usually an undercorrection (72%), except for Hoffer Q, which was almost as likely to overcorrect as undercorrect (44% vs 56%). The PE was lower with office measurements when compared with anesthesia measurements, owing probably to better fixation in older children with higher ALs. CONCLUSION The PE was insignificant (PE < or = 0.5 D) in 43% eyes, and similar for all formulae. However, the Hoffer Q was predictable for the highest number of eyes. When the PE was >0.5 D, most formulae gave an undercorrection, except for the Hoffer Q, which the surgeon may want to consider when targeting postoperative refractions.

Blood Gases and Retinopathy of Prematurity: The ELGAN Study

Objective: This study tested the hypothesis that preterm infants who had a blood gas derangement on at least 2 of the first 3 postnatal days are at increased risk for more severe retinopathy of prematurity (ROP). Method: 1,042 infants born before 28 weeks’ gestational age (GA) were included. An infant was considered to be exposed if his/her blood gas measure was in the highest or lowest quartile for GA on at least 2 of the first 3 postnatal days. Results: Multivariable models adjusting for confounders indicate that exposure to a PCO2 in the highest quartile predicts ROP (stage 3, 4 or 5: OR = 1.6, 95% CI = 1.1–2.3); zone 1: 2.0, 1.1–3.6; prethreshold/threshold: 1.9, 1.2–3.0; plus disease: 1.8, 1.1–2.9). Estimates are similar for a low pH for zone 1 (2.1, 1.2–3.8), prethreshold/threshold (1.8, 1.1–2.8), but did not quite achieve statistical significance for ROP stage 3, 4, or 5 (1.4, 0.9–2.0) and plus disease (1.5, 0.9–2.4). A PaO2 in the highest quartile for GA on at least 2 of the first 3 postnatal days was associated with a doubling of the risk of ROP in zone 1 (2.5, 1.4–4.4) and of prethreshold/threshold disease (2.1, 1.4–3.3), a 70% risk increase for plus disease (1.7, 1.04–2.8), while a 40% risk increase for ROP stage 3 or higher did not achieve statistical significance (1.4, 0.96–2.0). Conclusion: Infants exposed to high PCO2, low pH and high PaO2 appear to be at increased risk of more severe ROP.

Placenta Microbiology and Histology and the Risk for Severe Retinopathy of Prematurity

PURPOSE To test the hypothesis that the presence of bacteria and/or histologic inflammation in the placenta of infants born preterm is associated with an increased risk for severe retinopathy of prematurity (ROP). METHODS This was a prospective cohort study. Exploratory and multivariable data analyses were used, including logistic regression models with interaction terms. Main outcomes were four definitions of severe ROP: stage 3 or higher, any ROP in zone I, prethreshold/threshold, and plus disease. RESULTS Individually, placenta bacteria and histologic inflammation were not associated with severe ROP in univariable analyses among 1064 infants with gestational age <28 weeks or among 715 infants with gestational age <27 weeks (we excluded infants with a gestational age of 27 weeks because of the very small number of ROP cases). However, the co-occurrence of bacteria and inflammation was associated with an increased risk for ROP in zone I (odds ratio, 3.1; 95% confidence interval, 1.02-9.5). Among 339 infants with any placental bacteria, the co-occurrence of (1) inflammation and a gestational age of 23 to 24 weeks and (2) inflammation and hyperoxia were associated with prominent increases in risk for all definitions of severe ROP. CONCLUSIONS While antenatal exposure to infection or inflammation alone does not appear to convey risk information for severe ROP, their co-occurrence does. This finding supports the hypothesis that a fetal inflammatory response to antenatal infection might be part of the etiology of severe ROP.

Acute Periorbital Infections: Who Needs Emergent Imaging?

OBJECTIVES: Computed tomography (CT) is used often in the evaluation of orbital infections to identify children who are most likely to benefit from surgical intervention. Our objective was to identify predictors for intraorbital or intracranial abscess among children who present with signs or symptoms of periorbital infection. These predictors could be used to better target patients for emergent CT. METHODS: This was a retrospective cohort study of all patients admitted to an urban pediatric tertiary care emergency department between 1995 and 2008. We included otherwise healthy patients with suspected acute clinical periorbital or orbital cellulitis without a history of craniofacial surgery, trauma, or external source of infection. Immunocompromised patients and patients with noninfectious causes of periorbital swelling were excluded. Variables analyzed included age, duration of symptoms, highest recorded temperature, previous antibiotic therapy, physical examination findings, laboratory results, and interpretation of imaging. CT scans of the orbit were reread by a neuroradiologist. RESULTS: Nine hundred eighteen patients were included; 298 underwent a CT scan, and of those, 111 were shown to have an abscess. Although proptosis, pain with external ocular movement, and ophthalmoplegia were associated with presence of an abscess, 56 (50.5%) patients with abscess did not experience these symptoms. Other variables associated with the presence of an abscess in multivariate analysis were a peripheral blood neutrophil count greater than 10 000/μL, absence of infectious conjunctivitis, periorbital edema, age greater than 3 years, and previous antibiotic therapy (P < .05 for all). Our recursive partitioning model identified all high-risk (44%) patients as well as a low-risk (0.4%–2%) group (Rsq = 0.27). CONCLUSIONS: We confirmed that patients with proptosis and/or pain or limitation of extraocular movements are at high risk for intraorbital abscess, yet many do not have these predictors. Other features can identify patients who do not have such obvious predictors but do have significant risk of disease. A recursive partitioning model is presented.

Prevalence and course of strabismus through age 6 years in participants of the Early Treatment for Retinopathy of Prematurity randomized trial

PURPOSE To present strabismus data for children who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. METHODS The prevalence of strabismus, categorized as present or absent, was tabulated for all children with history of high-risk prethreshold retinopathy of prematurity (ROP) who participated in the ETROP randomized trial and were examined at 9 months to 6 years of age. Relationships among strabismus and demographic measures, eye characteristics, and neurodevelopmental factors were analyzed. RESULTS Among the 342 children evaluated at 6 years, the prevalence of strabismus was 42.2%. Even with favorable acuity scores in both eyes, the prevalence of strabismus was 25.4%, and with favorable structural outcomes in both eyes the prevalence of strabismus was 34.2%. Of children categorized as visually impaired as the result of either ocular or cerebral causes, 80% were strabismic at the 6-year examination. Of 103 study participants who were strabismic at 9 months, 77 (74.8%) remained so at 6 years. Most strabismus was constant at both the 9-month (62.7%) and the 6-year examination (72.3%). After multiple logistic regression analysis, risk factors for strabismus were abnormal fixation behavior in one or both eyes (P < 0.001), history of amblyopia (P < 0.003), unfavorable structural outcome in one or both eyes (P = 0.025), and history of anisometropia (P = 0.04). Strabismus surgery was performed for 53 children. By 6 years, the cumulative prevalence of strabismus was 59.4%. CONCLUSIONS Most children with a history of high-risk prethreshold ROP develop strabismus at some time during the first 6 years of life.

Emerging Treatments for Retinopathy of Prematurity

Retinopathy or prematurity (ROP) is a leading cause of potentially preventable blindness in children. With increased survival of infants born at earlier gestational ages the number of infants at risk from vision loss from ROP has increased. Current treatments consist of close monitoring of oxygen saturation levels, peripheral retinal ablation by cryotherapy or laser photocoagulation, and vitreoretinal surgery. Research in the area of angiogenesis has lead to numerous breakthroughs. Emerging treatments for ROP are targeting the Vascular Endothelial Growth Factor (VEGF) and Insulin-Like Growth Factor 1 (IGF-1) pathways, as well as dietary supplementation with omega-3-polyunsaturated fatty acids.