Serologic Evaluations in the Distinction Between Sinusitis-Related Orbital Cellulitis and Periorbital Necrotizing Fasciitis.

PURPOSE: While sinusitis-related orbital cellulitis (SROC) and periorbital necrotizing fasciitis (PNF) share similar clinical presentations, they are managed differently, making rapid recognition of the appropriate clinical entity critical to optimal outcomes. This study was performed to assess whether serologic testing might help clinicians to distinguish between SROC and PNF. METHODS: A retrospective review analysis was used to compare initial complete blood counts and comprehensive metabolic panels among adult patients with SROC and PNF. Statistical evaluations were used to determine the significance of differences between the groups. RESULTS: Thirteen patients with PNF and 14 patients with SROC were identified. The 2 groups were similar in age, gender, and likelihood of immunosuppression ( p > 0.05 for each metric). Mean leukocyte counts were 18.52 (standard deviation = 7.02) and 10.31 (standard deviation = 5.77) for PNF and SROC, respectively ( p = 0.0057). White blood cell levels were above normal limits for 12 patients with PNF (92.3%) and 7 patients with SROC (50%) ( p = 0.017). No other laboratory test was significantly different between the 2 groups. CONCLUSIONS: While the majority of serologic testing was quite similar in patients with either SROC or PNF, leukocyte levels may represent an important clue to distinguish between the two diseases. Clinical evaluation remains the gold standard to make the proper diagnosis, but markedly elevated white blood cell counts should prompt clinicians to at least consider a diagnosis of PNF.

Association of Cardiovascular Disease with Retinopathy of Prematurity.

PURPOSE: To determine the associations of presence and types of cardiovascular diseases (CVDs) with development of retinopathy of prematurity (ROP) in premature infants undergoing ROP examinations. STUDY DESIGN: We performed secondary analyses of data from the multi-center Postnatal Growth and ROP Validation Study (GROP-2). CVD was categorized based on pulmonary blood flow (PBF), systemic blood flow (SBF), pulmonary hypertension (PPHN), or dysrhythmia. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated from multivariable logistic regression models that included any ROP or severe ROP as outcome variable and any CVD or type of CVD as independent variable, with adjustment of covariates including birth weight (BW), gestational age (GA), and days on supplemental oxygen in the first month of postnatal life. RESULT: Among 3980 infants, 528 (13.3%) had CVD (304 had increased PBF, 101 had decreased PBF, and 49 had PPHN), 1643 (40.4%) developed ROP, and 503 (12.6%) developed severe ROP. In multivariable analyses, presence of CVD was not significantly associated with increased risk of any ROP (aOR = 1.15, 95% CI: 0.90-1.46, p = .26) or severe ROP (aOR = 0.98, 95% CI: 0.72-1.34, p = .92). However, there were trends associating CVD resulting in increased PBF with a higher risk of ROP (aOR = 1.32, 95% CI: 0.97-1.80, p = .08) and PPHN with a higher risk of severe ROP (aOR = 2.04, 95% CI: 0.96-4.35, p = .07). When adjusting only for BW and GA, these associations were significant (aOR = 1.47, 95% CI: 1.09-1.99, and aOR = 2.35, 95% CI: 1.19-4.65, respectively). CONCLUSION: CVD with increased PBF likely increases the risk of ROP. PPHN likely increases the risk of severe ROP.

Daily Oxygen Supplementation and Risk of Retinopathy of Prematurity.

PURPOSE: Excessive oxygen supplementation increases risk of retinopathy of prematurity (ROP). While numerous oxygen parameters could be considered when predicting ROP (saturation targets, actual saturation, fraction of inspired oxygen, etc.), complicated measures are impractical as screening criteria. We sought to develop a simple, clinically useful measure of daily oxygen supplementation during ages 0-28 days to improve prediction of ROP. METHODS: Secondary analysis of two Postnatal Growth and ROP (G-ROP) Study cohorts (G-ROP-1 and G-ROP-2) at 45 hospitals. Infants with a known ROP outcome and complete oxygen data were included. Associations between severe ROP and days on supplemental oxygen (FiO2 > 21%), during ages 0-28 days (DSO28) were assessed, controlling for birth weight (BW) and gestational age (GA). New screening criteria incorporating DSO were developed and compared to current guidelines. RESULTS: Among 8,949 studied infants, 459 (5.1%) developed type 1 ROP. DSO28 was associated with severe ROP (adjusted-OR 1.05 per day supplemental oxygen, 95%CI 1.03-1.07, p < .0001). The following criteria had 100% sensitivity for type 1 ROP and higher specificity than current guidelines: new BW/GA criteria with DSO (BW<901 g, GA<26 weeks, or DSO >3), 23.4% fewer infants examined; modified G-ROP criteria including DSO, 29.0% fewer infants; original G-ROP criteria, 31.8% fewer infants. CONCLUSION: In high-level neonatal-care settings, incorporating DSO (a simple measure of oxygen supplementation) into screening criteria improves sensitivity and specificity for type 1 ROP over current BW-GA criteria, but does not perform as well as the validated G-ROP criteria.

Pediatric glaucoma suspects: characteristics and outcomes.

PURPOSE: To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma. METHODS: This was a retrospective sequential cohort study of children <18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma. RESULTS: A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar. CONCLUSIONS: Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP >24 and presence of a periocular lesion carry higher risk.

Changes in institutional oxygen saturation targets are associated with an increased rate of severe retinopathy of prematurity.

PURPOSE: To evaluate the effect of changes in institutional peripheral oxygen saturation (SpO2) targets, made in response to recent randomized trials, on risk of developing severe retinopathy of prematurity (ROP). METHODS: This study was a secondary analysis of data from 21 North American hospitals during the periods 2006-2012 and 2015-2017. Hospitals were categorized based on whether or not SpO2 targets were increased between the two study periods. Severe ROP (type 1, type 2, or zone III stage 3+) rates were compared within and between groups. Generalized mixed effect models with random intercepts were used to account for within-center clustering and to calculate odds ratios (aOR) adjusted by birth weight (BW) and gestational age (GA), using patient-level data. RESULTS: A total of 8,142 infants underwent ROP examinations at 21 hospitals during the two study periods: 5,716 in 2006-2012 (mean BW, 1109 ± 369 g; GA, 28.0 ± 2.6; 11.6% severe ROP); 2,426 in 2015-2017 (mean BW, 1086 ± 347 g; GA, 28.0 ± 2.8; 12.8% severe ROP). Fourteen hospitals increased SpO2 targets, and 7 hospitals did not. Hospitals that increased targets had a 3% increase in severe ROP (from 12% to 15%; aOR = 1.25; 95% CI, 1.01-1.55; P = 0.044); hospitals without SpO2 changes had a 2% decrease (from 11% to 9%; aOR = 0.72; 95% CI, 0.52-1.00; P = 0.049). The difference in change of severe ROP between groups of hospitals was significant (P = 0.005). CONCLUSIONS: Increases in institutional SpO2 targets in response to recent randomized trials were associated with increased severe ROP. Hospitals considering increasing their SpO2 targets should anticipate increases in rates of severe ROP and manage screening and treatment resources accordingly.

Recovery of Vision after Optic Nerve Sheath Fenestration in Children and Adolescents with Elevated Intracranial Pressure.

PURPOSE: To evaluate the effect of optic nerve sheath fenestration (ONSF) on the recovery of visual function in pediatric patients with optic disc swelling owing to increased intracranial pressure. DESIGN: Retrospective case series. METHODS: Medical chart review of all pediatric patients who underwent ONSF between 2009 and 2020 at the Children's Hospital of Philadelphia. Visual function was assessed at pre and postoperative visits. The main outcome measures were visual acuity, color vision, extraocular motility, visual field mean deviation, retinal nerve fiber layer thickness measured by optical coherence tomography. RESULTS: Fourteen pediatric patients (10 females; mean ± SD age of 14 ± 2.6 years; range, 8.5-17.5 years) were included. Five patients underwent bilateral surgeries. Ten patients were diagnosed with idiopathic intracranial hypertension. Of the 10 idiopathic intracranial hypertension patients, 3 had a previous history of weight gain and 2 of systemic steroid treatment; these can be referred to as pseudotumor cerebri. The mean ± SD follow-up length was 16.4 ± 12.3 months. VA improved from 20/138 to 20/68 in the operated eye (P = .0003) and from 20/78 to 20/32 in the nonoperated eye (P = .02). Color vision improved in the operated eye (P = .04), extraocular motility improved in the operated and nonoperated eye (P = .002 and P = .04 respectively). Visual field mean deviation improved in the operated (-23.4 dB to -11.5 dB, P < .0001) and nonoperated eye (-19.8 dB to -6.8 dB, P = .02). Retinal nerve fiber layer thickness improved in the operated eye (349.1 to 66.2 µm; P < .0001). The postoperative improvement was observed as early as the postoperative day 1. CONCLUSIONS: ONSF produces a rapid and persistent vision improvement in both the operated eye and the nonoperated eye. In children and young adults with papilledema and elevated intracranial pressure causing vision loss that is severe at presentation or refractory to standard medical management, ONSF should be considered.

Retinal Detachment after Treatment of Retinopathy of Prematurity with Laser versus Intravitreal Anti-Vascular Endothelial Growth Factor.

PURPOSE: To compare rates of short-term retinal detachment (RD) of infants treated for type 1 retinopathy of prematurity (ROP) with intravitreal anti-vascular endothelial growth factor (VEGF) therapy with infants treated with laser therapy. The choice between these 2 treatments remains controversial. Comparative data are limited and describe re-treatment rates rather than retinal structural outcomes predictive of long-term vision. Anti-vascular endothelial growth factor acts faster than laser therapy, which may be beneficial for more aggressive ROP. DESIGN: Nonrandomized, comparative cohort study. PARTICIPANTS: The study included 1167 eyes of 640 infants treated for type 1 ROP. Among these, 164 eyes received anti-VEGF therapy and 1003 eyes received laser therapy. METHODS: Pretreatment and posttreatment examinations and treatments were completed by ophthalmologists with expertise in ROP. The study was a secondary analysis of data from the retrospective Postnatal Growth and Retinopathy of Prematurity Study (G-ROP) 1 study (2006-2012) and the prospective G-ROP 2 study (2015-2017). MAIN OUTCOME MEASURES: Rate of RD (ROP stages 4A, 4B, or 5) within 8 weeks of initial treatment, an end point predictive of poor long-term vision. The results were stratified by postmenstrual age (PMA) at treatment as occurring before versus at or after 36 weeks and 0 days, because earlier disease may be considered more aggressive. RESULTS: Among 458 eyes treated before PMA 36 weeks and 0 days, the short-term RD rate was higher after laser therapy (29/368 eyes [7.9%]) than after anti-VEGF therapy (0/90 eyes [0%]; P < 0.001). Of 709 eyes treated at or after PMA 36 weeks and 0 days, short-term RD risk did not differ between groups (laser [20/635 eyes], 3.1%; anti-VEGF [1/74 eyes], 1.4%; P = 0.27). CONCLUSIONS: Anti-vascular endothelial growth factor therapy results in better short-term structural outcomes than laser therapy when type 1 ROP is treated before 36 weeks' PMA. After this age, both treatments have very low rates of short-term RD. The faster action of anti-VEGF agents likely is responsible for these findings.

Poor postnatal weight growth is a late finding after sepsis in very preterm infants.

OBJECTIVE: To characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth. DESIGN: Retrospective matched cohort study using data from the Postnatal Growth and Retinopathy of Prematurity study. Participants were born with birth weights of <1500 g or gestational ages of <32 weeks between 2006 and 2011 at 29 neonatal centres in the USA and Canada. Sepsis was defined as a culture-confirmed bacterial or fungal infection of the blood or cerebrospinal fluid before 36 weeks' postmenstrual age (PMA). Growth was assessed as the change in weight z-score between birth and 36 weeks' PMA. RESULTS: Of 4785 eligible infants, 813 (17%) developed sepsis and 693 (85%) were matched 1:1 to controls. Sepsis was associated with a greater decline in weight z-score (mean difference -0.09, 95% CI -0.14 to -0.03). Postnatal weight growth failure (decline in weight z- score>1) was present in 237 (34%) infants with sepsis and 179 (26%) controls (adjusted OR 1.49, 95% CI 1.12 to 1.97). Longitudinal growth trajectories showed similar initial changes in weight z-scores between infants with and without sepsis. By 3 weeks after sepsis onset, there was a greater decline in weight z-scores relative to birth values in those with sepsis than without sepsis (delta z-score -0.89 vs -0.77; mean difference -0.12, 95% CI -0.18 to -0.05). This significant difference persisted until 36 weeks or discharge. CONCLUSION: Infants with sepsis had similar early weight growth trajectories as infants without sepsis but developed significant deficits in weight that were not apparent until several weeks after the onset of sepsis.

Incidence, timing and risk factors of type 1 retinopathy of prematurity in a North American cohort.

BACKGROUND/AIMS: Early detection and timely treatment of type 1 retinopathy of prematurity (ROP) can reduce the risk of blindness. To evaluate the incidence, timing and risk factors of type 1 ROP in a large, broad-risk cohort of premature infants. METHODS: Secondary analysis of data from the two Postnatal Growth and Retinopathy of Prematurity studies. Main outcomes are the incidence and timing of type 1 ROP. RESULTS: Among 11 463 infants (mean birth weight (BW), 1095 g; mean gestational age (GA), 28 weeks), 677 (5.9%, 95% CI 5.5% to 6.3%) developed type 1 ROP. Rate of type 1 ROP decreased with larger GA (28.8% for GA ≤23 weeks, 0.2% for GA of 31-32 weeks) and no infants with GA >32 weeks developed type 1 ROP. Type 1 ROP was first diagnosed at a median postmenstrual age (PMA) of 36 weeks (range 30-46 weeks) or postnatal age (PNA) of 11 weeks (range 5-21 weeks). The mean PMA at diagnosis of type 1 ROP increased with GA (35 weeks for GA of 22-24 weeks, 41 weeks for GA of 29-30 weeks), but the mean PNA at diagnosis of type 1 ROP was similar (11-13 weeks) across GA of 22-29 weeks. GA and BW dominate the association (area under the receiver operating characteristic curve=0.87, 95% CI 0.86 to 0.88). CONCLUSIONS: Type 1 ROP developed in about 6% of premature infants over wide time windows in terms of both PMA and PNA. BW and GA are the dominant risk factors for type 1 ROP, while other prenatal factors add minimal predictive power for type 1 ROP.

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.

Evaluation of the economic impact of modified screening criteria for retinopathy of prematurity from the Postnatal Growth and ROP (G-ROP) study.

IMPORTANCE: The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that the addition of postnatal weight gain to birth weight and gestational age detects similar numbers of infants with ROP, but requires examination of fewer infants. OBJECTIVE: To determine the incremental cost-effectiveness of screening with G-ROP compared with conventional screening. DESIGN, SETTING AND PARTICIPANTS: We built a microsimulation model of a 1-year US birth cohort <32 weeks gestation, using data from the G-ROP study. We obtained resource utilization estimates from the G-ROP dataset and from secondary sources, and test characteristics from the G-ROP cohort. RESULTS: Among 78,281 infants nationally, screening with G-ROP detected ~25 additional infants with Type 1 ROP. This was accomplished with 36,233 fewer examinations, in 14,073 fewer infants, with annual cost savings of approximately US$2,931,980 through hospital discharge. CONCLUSIONS: Screening with G-ROP reduced costs while increasing the detection of ROP compared with current screening guidelines.

Validation of the Postnatal Growth and Retinopathy of Prematurity Screening Criteria.

Importance: The first Postnatal Growth and Retinopathy of Prematurity Study (G-ROP-1) developed new screening criteria with 100% sensitivity for type 1 retinopathy of prematurity (ROP) and 30% reduction of infants requiring examinations in a retrospective development cohort of 7483 infants from 29 North American hospitals in 2006-2012. Infants meeting 1 or more of the following criteria undergo examinations: gestational age less than 28 weeks or birth weight less than 1051 g; weight gain less than 120 g during age 10 to 19 days, weight gain less than 180 g during age 20 to 29 days, or weight gain less than 170 g during age 30 to 39 days; or hydrocephalus. Objective: To evaluate the generalizability of the G-ROP screening criteria in a new cohort of at-risk infants. Design, Setting, and Participants: This prospective validation cohort study (G-ROP-2) was conducted at 41 hospitals in the United States and Canada (25 G-ROP-1 hospitals and 16 new hospitals) from September 8, 2015, to June 13, 2017, among 3981 premature infants at risk for ROP and with known ROP outcomes. Main Outcomes and Measures: Sensitivity for Early Treatment for Retinopathy of Prematurity Study type 1 ROP and potential reduction in infants receiving examinations. Results: Among the 3981 infants in the study (1878 girls and 2103 boys; median gestational age, 28 weeks [range, 22-35 weeks]; median birth weight, 1072 g [range, 350-4080 g]; 1966 white; 942 black; 321 Latino; 120 Asian; 22 Native Hawaian or Pacific Islander; and 25 American Indian or Alaskan Native), the G-ROP criteria correctly predicted 219 of 219 cases of type 1 ROP (sensitivity, 100%; 95% CI, 98.3%-100%), while reducing the number of infants undergoing examinations by 35.6% (n = 1418). In a combined G-ROP-1 and G-ROP-2 cohort of 11 463 infants, the G-ROP criteria predicted 677 of 677 cases of type 1 ROP (sensitivity, 100%; 95% CI, 99.4%-100%), reducing the number of infants receiving examinations by 32.5% (n = 3730), while current criteria (birth weight <1501 g or gestational age ≤30 weeks 0 days) predicted 674 of 677 type 1 cases (sensitivity, 99.6%; 95% CI, 98.7%-99.8%). Conclusions and Relevance: This study found that the G-ROP screening criteria were generalizable on validation and, if used clinically in the United States and Canada, could reduce the number of infants receiving examinations. The large G-ROP cohorts provide evidence-based screening criteria that have higher sensitivity and higher specificity (fewer infants receiving examinations) for type 1 ROP than currently recommended guidelines.

Treatment of non-type 1 retinopathy of prematurity in the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study.

PURPOSE: To determine the prevalence and characteristics of eyes treated for retinopathy of prematurity (ROP) not meeting currently recommended early treatment (type 1) criteria. METHODS: This was a secondary analysis of data from the Postnatal Growth and ROP (G-ROP) study, a retrospective cohort study of 7,483 infants undergoing ROP examinations and treatment at 29 North American hospitals between January 2006 and June 2012. Medical records were reviewed to determine the prevalence and characteristics of eyes treated for ROP less severe than type 1 ROP. RESULTS: Of 1,004 eyes that received ROP treatment, 126 eyes of 91 infants (0.8% of all eyes; 12.5% of treated eyes) underwent treatment for ROP less severe than type 1. Mean age at treatment was 38 weeks' post-menstrual age (range, 32-49 weeks). Reasons for treatment included type 1 ROP in the fellow eye (43%), stage 3 ROP with pre-plus in the treated eye (30%), concerning structural changes in the retina (7%), persistent stage 3 ROP for ≥6 weeks without regression (6%), stage 3 ROP with no plus disease in the treated eye (5%), stage 3, zone III ROP with plus disease (3%), logistical considerations (3%), or stage 2 disease in the treated eye (2%). CONCLUSIONS: Of all eyes treated for ROP, 1/8 were treated for disease less severe than currently recommended type 1 criteria. Clinician judgment of risk for permanent vision impairment superseded recommended treatment criteria and was usually related to type 1 disease in the fellow eye or pre-plus vascular changes in one or both eyes.

Perinatal Risk Factors for the Retinopathy of Prematurity in Postnatal Growth and Rop Study.

Objective: To evaluate perinatal risk factors for retinopathy of prematurity (ROP), in a large, broad-risk cohort of premature infants. Study design: Secondary analysis of data from the Postnatal Growth and ROP (G-ROP) Study, a retrospective cohort study of infants undergoing ROP examinations at 29 North American hospitals in 2006-2012. Results: Among 7483 infants, 3224 (43.1%) had any ROP and 931 (12.4%) had severe ROP (Type 1 or 2 ROP). In multivariable logistic regression analysis, significant risk factors for any ROP were lower birth weight (BW, odds ratio (OR) = 5.2, <501 g vs. >1250 g), younger gestational age (GA, OR = 32, <25 vs. >29 weeks), 1-min Apgar score <4 (OR = 1.2), race (OR = 1.6, White vs. Black), outborn (OR = 1.5), and delivery room intubation (OR = 1.3); and for severe ROP were lower BW (OR = 20, <501 g vs. >1250 g), younger GA (OR = 30, <25 vs. >29 weeks), male (OR = 1.5), Hispanic ethnicity (OR = 1.8), race (OR = 1.6, White vs. Black), outborn (OR = 1.6), and delivery room intubation (OR = 1.6). Together, these factors predicted well for any ROP (area under ROC curve (AUC) = 0.87) and severe ROP (AUC = 0.89), but BW and GA were the dominant factors for ROP (AUC = 0.86) and severe ROP (AUC = 0.88). Conclusions: Based on the largest report to date with detailed ROP data from infants meeting current screening guidelines, ROP risk is predominantly determined by the degree of prematurity at birth, with other perinatal factors contributing minimally.

Incidence and Early Course of Retinopathy of Prematurity: Secondary Analysis of the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study.

Importance: The current guidelines for retinopathy of prematurity (ROP) detection programs in the United States include a range of birth weights (BWs) and gestational ages and likely require examinations of many premature infants who are at low risk for developing serious retinopathy. Objective: To determine the incidence, onset, and early course of ROP in what to our knowledge is the largest cohort to date that is representative of infants who are undergoing ROP screening. Design, Setting, and Participants: This secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) retrospective cohort study was conducted in 29 hospitals in the United States and Canada between January 2006 and December 2011 and included 7483 infants who underwent serial ROP examinations. Main Outcomes and Measures: Most severe ROP in either eye, classified as no ROP, mild ROP, type 2 ROP, or type 1 ROP (per Early Treatment for ROP Study criteria). Onset at postmenstrual age for zone I disease and stage of ROP, plus disease, and treatment. Results: This study included 7483 infants with a mean (SD) BW of 1099 (259) g and a mean (SD) gestational age of 28 (3) weeks who underwent ROP examinations. Of these, 3224 infants (43.1%) developed ROP, 459 (6.1%) developed type 1 and 472 (6.3%) type 2 ROP, 514 (6.9%) underwent treatment in 1 or both eyes, and 147 (2%) had zone I disease. Additionally, 98.1% of type 1 or 2 ROP cases occurred in infants with a BW of less than 1251 g. Only about half of the eyes (49.4%) were vascularized into zone III by 37 weeks postmenstrual age. Conclusions and Relevance: These findings add to our knowledge of ROP screening as they include all eligible infants, not just high-risk infants as in previous studies. More than 40% of at-risk premature infants develop some stage of ROP, and most retinopathy regresses without treatment. However, approximately 12.5% develop severe ROP, which occurs almost exclusively among infants with a BW of less than 1251 g.

Development of Modified Screening Criteria for Retinopathy of Prematurity: Primary Results From the Postnatal Growth and Retinopathy of Prematurity Study.

Importance: Current retinopathy of prematurity (ROP) guidelines, which are based on studies of high-risk infants and expert opinion, have low specificity for disease requiring treatment. Postnatal weight gain-based models improve specificity but have been limited by complexity and small development cohorts, which results in model overfitting and resultant decreased sensitivity in validation studies. Objective: To develop a birth weight (BW), gestational age (GA), and weight gain (WG) prediction model using data from a broad-risk cohort of premature infants. Design, Setting, and Participants: The Postnatal Growth and ROP Study was a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada from 2006 to 2012 that included 7483 premature infants at risk for ROP with a known ROP outcome. A hybrid modeling approach was used that combined BW/GA criteria, weight comparison with expected growth from infants without ROP, multiple growth-interval assessments, consideration of nonphysiological WG, and user-friendly screening criteria. Numerous BW/GA levels, postnatal age periods, time intervals, and WG percentile thresholds were evaluated to identify the most robust parameters. Main Outcome and Measures: Sensitivity for Early Treatment of ROP Study type 1 ROP and potential reduction in infants who require examinations. Results: Of 7483 infants, the median (SD) BW was 1099 (359) g, the median GA was 28 weeks (range, 22-35), 3575 (47.8%) were female, 3615 (48.4%) were white, 2310 (30.9%) were black, 233 (3.1%) were Asian, 93 (1.2%) were Pacific Islander, and 40 (0.5%) were American Indian/Alaskan Native. Infants who met any of 6 criteria would undergo examinations: (1) a GA of younger than 28 weeks; (2) a BW of less than 1051 g; a WG of less than 120 g, 180 g, or 170 g during ages 10 to 19, 20 to 29, or 30 to 39 days, respectively; or hydrocephalus. These criteria predicted 459 of 459 (100%) type 1 (sensitivity, 100%; 95% CI, 99.2%-100%), 524 of 524 (100%) treated, and 466 of 472 (98.7%) type 2 cases while reducing the number of infants who required examinations by 2269 (30.3%). Conclusions and Relevance: This cohort study, broadly representative of infants who are undergoing ROP examinations, provides evidence-based screening criteria. With validation, the Postnatal Growth and ROP Study criteria could be incorporated into ROP screening guidelines to reduce the number of infants who require examinations in North America.

Pediatric Thyroid Eye Disease: Clinical Characteristics and Orbital Decompression Outcomes.

PURPOSE: To review the clinical presentation, disease severity, and surgical interventions of children with thyroid eye disease (TED) at a single institution over a 7-year period. METHODS: Retrospective cohort study of children 0 to 18 years of age with a diagnosis of TED, seen at the Children's Hospital of Philadelphia from 2009 to 2016. Ophthalmic examination findings, neuroimaging study results, and ophthalmological management were recorded. t-Tests were used to test for statistical significance. Institutional Review Board approval was obtained for the study. RESULTS: Sixty-seven subjects with pediatric TED were studied: 59 female and 8 male. The mean age at diagnosis was 11.6 years (SD 4.2, range 2.3-17.9). All subjects had proptosis (67, 100%). Other clinical findings were eyelid retraction in 46 (69%), chemosis in 7 (10%), punctate epithelial erosions in 8 (12%), and strabismus in 1 (1.5%). No subjects had evidence of optic neuropathy. Five subjects with static-phase TED received orbital decompression surgery for exposure keratopathy and disfigurement. All had significant cosmetic improvement and resolution of exposure keratopathy. DISCUSSION: In this series, children with TED generally exhibit mild ocular signs, which is in agreement with past studies. Our study presented a high incidence of proptosis compared with other studies; however, this may represent a referral bias to our quaternary care center. CONCLUSION: Pediatric TED patients exhibit mild symptoms, such as proptosis and eyelid retraction without strabismus, vision loss, or optic neuropathy. Some children with TED have severe disfigurement and corneal exposure due to the disease and benefit from orbital decompression.

Validation of the Colorado Retinopathy of Prematurity Screening Model.

Importance: The Colorado Retinopathy of Prematurity (CO-ROP) model uses birth weight, gestational age, and weight gain at the first month of life (WG-28) to predict risk of severe retinopathy of prematurity (ROP). In previous validation studies, the model performed very well, predicting virtually all cases of severe ROP and potentially reducing the number of infants who need ROP examinations, warranting validation in a larger, more diverse population. Objective: To validate the performance of the CO-ROP model in a large multicenter cohort. Design, Setting, Participants: This study is a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study, a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada between January 2006 and June 2012 of 6351 premature infants who received ROP examinations. Main Outcomes and Measures: Sensitivity and specificity for severe (early treatment of ROP [ETROP] type 1 or 2) ROP, and reduction in infants receiving examinations. The CO-ROP model was applied to the infants in the G-ROP data set with all 3 data points (infants would have received examinations if they met all 3 criteria: birth weight, <1501 g; gestational age, <30 weeks; and WG-28, <650 g). Infants missing WG-28 information were included in a secondary analysis in which WG-28 was considered fewer than 650 g. Results: Of 7438 infants in the G-ROP study, 3575 (48.1%) were girls, and maternal race/ethnicity was 2310 (31.1%) African American, 3615 (48.6%) white, 233 (3.1%) Asian, 40 (0.52%) American Indian/Alaskan Native, and 93 (1.3%) Pacific Islander. In the study cohort, 747 infants (11.8%) had type 1 or 2 ROP, 2068 (32.6%) had lower-grade ROP, and 3536 (55.6%) had no ROP. The CO-ROP model had a sensitivity of 96.9% (95% CI, 95.4%-97.9%) and a specificity of 40.9% (95% CI, 39.3%-42.5%). It missed 23 (3.1%) infants who developed severe ROP. The CO-ROP model would have reduced the number of infants who received examinations by 26.1% (95% CI, 25.0%-27.2%). Conclusions and Relevance: The CO-ROP model demonstrated high but not 100% sensitivity for severe ROP and missed infants who might require treatment in this large validation cohort. The model requires all 3 criteria to be met to signal a need for examinations, but some infants with a birth weight or gestational age above the thresholds developed severe ROP. Most of these infants who were not detected by the CO-ROP model had obvious deviation in expected weight trajectories or nonphysiologic weight gain. These findings suggest that the CO-ROP model needs to be revised before considering implementation into clinical practice.

Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.

Importance: The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. Objective: To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP. Design, Setting, and Participants: This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Main Outcomes and Measures: Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Results: Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks' postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%. Conclusion and Relevance: The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.

A Tiered Approach to Retinopathy of Prematurity Screening (TARP) Using a Weight Gain Predictive Model and a Telemedicine System.

IMPORTANCE: The Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study telemedicine system of remote fundus image grading and The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP-ROP) postnatal weight gain predictive model are 2 approaches for improving ROP screening efficiency. Current screening has low specificity for severe ROP. OBJECTIVE: To describe a tiered approach to ROP screening (TARP) for identifying children who develop severe ROP using telemedicine and a predictive model synergistically. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a post hoc analysis of a cohort in the e-ROP Study (a multicenter prospective telemedicine study) and the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study (a multicenter retrospective cohort study). The setting was neonatal intensive care units at The Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants in the e-ROP Study were premature infants with a birth weight less than 1251 g and a known ROP outcome enrolled between May 25, 2011, and October 31, 2013. The G-ROP Study enrolled all infants undergoing ROP examinations with a known ROP outcome who were born between January 1, 2006, and December 31, 2011. MAIN OUTCOMES AND MEASURES: The mean outcomes were the sensitivity for type 1 ROP, reductions in infants requiring imaging or examinations, numbers of imaging sessions and examinations, and total clinical encounters (imaging sessions and examinations combined). The following 4 screening approaches were evaluated: ROUTINE (only diagnostic examinations by an ophthalmologist), CHOP-ROP (birth weight and gestational age, with weekly weight gain initiating examinations when the risk cut point is surpassed), e-ROP IMAGING (trained reader grading of type 1 or 2 ROP initiates diagnostic examinations), and TARP (CHOP-ROP alarm initiates imaging, and imaging finding of severe ROP initiates diagnostic examinations). RESULTS: A total of 242 infants were included in the study, with a median birth weight of 858 g (range, 690-1035 g). The median gestational age was 27 weeks (range, 25-29 weeks). Fifty-one percent (124 of 242) were female, and 49% (118 of 242) were male. The race/ethnicity was 27.3% (66 of 242) white, 56.2% (136 of 242) black, 2.1% (5 of 242) Native American, 1.7% (4 of 242) Asian, and 12.8% (31 of 242) other. The sensitivity for detecting type 1 ROP (32 infants) was 100% (95% CI, 89.3%-100%) with each approach. With ROUTINE, 242 infants had 877 examinations; with CHOP-ROP, 184 infants had 730 examinations; with e-ROP IMAGING, 242 infants had 532 imaging sessions, and 94 infants had 345 examinations (877 patient encounters); and with TARP, 182 infants had 412 imaging sessions, and 87 infants had 322 examinations (734 patient encounters). CONCLUSIONS AND RELEVANCE: The tiered approach to ROP screening was associated with a reduced number of examinations and imaging sessions compared with the other approaches. Applying a postnatal growth model and telemedicine system in a tiered approach may reduce the number of clinical ROP interventions more than either approach alone.