Retrospective validation of the postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria in a Swiss cohort

Background Currently used screening criteria for retinopathy of prematurity (ROP) show high sensitivity for predicting treatment-requiring ROP but low specificity; over 90% of examined infants do not develop ROP that requires treatment (type 1 ROP). A novel weight gain-based prediction model was developed by the G-ROP study group to increase the specificity of the screening criteria and keep the number of ophthalmic examinations as low as possible. This retrospective cohort study aimed to externally validate the G-ROP screening criteria in a Swiss cohort. Methods Data from 645 preterm infants in ROP screening at Inselspital Bern between January 2015 and December 2019 were retrospectively retrieved from the screening log and analysed. The G-ROP screening criteria, consisting of 6 trigger parameters, were applied in infants with complete data. To determine the performance of the G-ROP prediction model for treatment-requiring ROP, sensitivity and specificity were calculated. Results Complete data were available for 322 infants who were included in the analysis. None of the excluded infants had developed type 1 ROP. By applying the 6 criteria in the G-ROP model, 214 infants were flagged to undergo screening: among these, 14 developed type 1 ROP, 9 developed type 2 ROP, and 43 developed milder stages of ROP. The sensitivity for predicting treatment-requiring ROP was 100% (CI, 0.79–1.00), and the specificity was 41% (CI, 0.35 –0.47). Implementing the novel G-ROP screening criteria would reduce the number of infants entering ROP screening by approximately one third. Conclusions The overall prevalence of treatment-requiring ROP was low (2.15%). Previously published performance parameters for the G-ROP algorithm were reproducible in this Swiss cohort. Importantly, all treatment-requiring infants were correctly identified. By using these novel criteria, the burden of screening examinations could be significantly reduced.

Prevalence and Risk Factors for Retinopathy of Prematurity in China: A Systematic Review and Meta-Analysis

Background The etiology of retinopathy of prematurity (ROP) is thought to be related to genetic susceptibility and environmental exposure factors. The purpose of this article was to estimate the prevalence of ROP in mainland China and to attempt to summarize the environmental risk factors for ROP in Chinese infants. Method We searched 9 databases for articles that were published before May 29, 2021, and studies describing the prevalence and risk factors for ROP in Chinese infants were included. The fixed-effects model and the random-effects model were applied to the effect sizes (ES) and their 95% confidence intervals (CIs) with I2≤50% and I2>50% in the heterogeneity tests, respectively. Results Twenty-two separate populations were included in the meta-analysis of the prevalence of ROP. The prevalence of ROP in mainland China was 9.284% (95% CI: 6.546-12.022%). It was negatively correlated with birth weight (BW) and gestational age (GA). Fifty independent meta-analyses were observed to be related to environmental exposure factors of ROP. Thirty of the 50 meta-analyses had results that were significant at p values less than 0.05. The first three risk factors with the largest combined effect size were GA≤34 w, bronchopulmonary dysplasia (BPD) and BW≤2,000 g. Conclusions Approximately one in ten immature infants suffered from ROP. More studies need to be included. Premature babies with diseases that cause hypoxia and irregular oxygen use should be paid more attention for ROP screening.

Effectiveness of Reverse Kangaroo Mother Care Position in Decreasing Adverse Physiological Events and Pain during Screening of Premature Infants for Retinopathy of Prematurity

Background. Retinopathy of prematurity (ROP) screening is uncomfortable and even painful in preterm infants. Objective. To determine the effectiveness of the Reverse-Kangaroo Mother Care (R-KMC) position compared with the conventional position in decreasing adverse physiological events and pain during ROP screening. Methods. This was a parallel randomized controlled trial with two arms- R-KMC position and conventional position (control). The primary outcomes included increased oxygen saturation, decreased heart and respiratory rates, and decreased pain intensity measured by Prematurity Infant Pain Profile (PIPP). Results. There were 100 preterm infants recruited. There were no differences in baseline characteristics, mean ROP screening duration, mean physiological parameters after the mydriatic application and during ROP screening between the two. Only the mean respiratory rates were significantly lower among the R-KMC group during the application of mydriatric agent. (50.26 ± 6.18 vs. 51.6 ± 8.35; p=0.0191). Relative risk (RR) in the control group is 37 to 84 versus 40 to 68 in the R-KMC group. The R-KMC group had a significantly lower mean PIPP score (6.5±2.06 vs. 8.8±2.80; p<0.0001) after mydriatic application and during ROP screening (7.6±2.05 vs. 9.8±2.90; p<0.0001) compared with control. No apnea was observed after mydriatic application, but one apneic episode was in control during ROP screening. 26% of the ROP screeners recommended the R-KMC position during ROP screening, while a majority (70%) was neutral. Conclusion. R-KMC position, a low-cost intervention, significantly reduces pain during ROP screening. It is recommended as a position of choice during ROP screening.

Cost–Utility Analysis of Wide-Field Imaging as an Auxiliary Technology for Retinopathy of Prematurity Care in Brazil

Purpose: To evaluate the cost–utility of wide-field imaging (WFI) as a complementary technology for retinopathy of prematurity (ROP) screening from the Brazilian Unified Health System's perspective.Introduction: ROP is one of the leading causes of avoidable childhood blindness worldwide, especially in middle-income countries. The current ROP screening involves indirect binocular ophthalmoscopy (IBO) by ROP expert ophthalmologists. However, there is still insufficient ROP screening coverage. An alternative screening strategy is the combination of WFI with IBO.Methods: A cost–utility analysis was performed using a deterministic decision-tree simulation model to estimate incremental cost–utility for ROP care. Two screening strategies were compared: (1) IBO and (2) combination of WFI of all eligible preterm infants and IBO for type 2 ROP or worse and for non-readable images. Eligible population included preterm infants &lt;32 weeks of gestational age or birth weight equal to or &lt;1,500 g. The temporal horizon was lifetime. Visual outcome data was converted to utility, and the health benefits were estimated on quality-adjusted life-years (QALY). Incremental cost per QALY gained was calculated from the health system perspective. Costs were estimated considering equipment, maintenance, consumables, and staff. A micro-costing approach was used for WFI. Two technician nurses were trained for imaging execution and had their time evaluated. Two ROP expert ophthalmologists had their time evaluated for imaging reading. One-way sensitivity analysis and probabilistic sensitivity analysis were performed.Results: Combined screening strategy resulted in a cost-effective program considering 90% ROP screening coverage. Costs per examination: (1) screening with IBO: US dollar (US $) 34.36; (2) screening with combination: US $58.20; (3) laser treatment: US $642.09; (4) long-term follow-up: ranged from US $69.33 to 286.91, based on the infant's visual function. Incremental cost per QALY gained was US $1,746.99/QALY per infant screened with the combination strategy. One-way sensitivity analysis resulted in cost-effectiveness for all parameters. Probabilistic sensitivity analyses yielded a 100% probability of combination being cost-effective in a willingness-to-pay threshold of US $1,800/QALY.Conclusion: The combined strategy for ROP screening was cost-effective. It enhances access for appropriate ROP care in middle-income countries and dminishes opportunity costs for ophthalmologists.

Nationwide inventory on retinopathy of prematurity screening in the Netherlands

PurposeProvide up-to-date insight in incidence of retinopathy of prematurity (ROP), logistics of screening and treatment in the Netherlands and influence of the new national ROP guideline in which more stringent screening criteria were implemented and the early treatment for ROP criteria (ETROP) were emphasised.MethodsMulticentre prospective nationwide study including all preterm infants, born in the Netherlands in 2017, and considered eligible for ROP screening. Anonymised data from ophthalmologists and paediatricians were merged. Outcome data were compared with the first national ROP inventory (NEDROP-1, 2009).ResultsIn 2017, 1492 infants were live born with gestational age (GA) <32 weeks (2009: 1662); 1287 infants were eligible for screening (2009: 2033). Ophthalmologists screened 1085 infants, versus 1688 in 2009, corrected with factor 1.114 for the difference in number of live births, a 28.4% (479/1688) decrease in screened infants was seen. Among surviving infants with GA <32 week, ROP was found in 305/1492 babies, 20.4% (2009: 324/1662, 19.5%) of which 49/1492 stage ≥3, 3.3% (2009: 30/1662, 1.8%). In all infants, report on presence or absence of plus disease was provided, according to the ETROP criteria. Treatment was performed in 39 infants. Of infants with ROP stage ≥3, 3/49 (6.1%) progressed to retinal detachment (2009: 6/30, 20.0%).ConclusionThe overall ROP incidence expressed as a percentage, remained stable but the number of infants that developed severe ROP nearly doubled. A near one-third reduction in screened infants shows satisfactory implementation of the new screening criteria. A notable decrease in retinal detachment delineates improved treatment outcome.

New method to measure interbreath intervals in infants for the assessment of apnoea and respiration

BackgroundRespiratory disorders, including apnoea, are common in preterm infants due to their immature respiratory control compared with term-born infants. However, our inability to accurately measure respiratory rate in hospitalised infants results in unreported episodes of apnoea and an incomplete picture of respiratory activity.MethodsWe develop, validate and use a novel algorithm to identify interbreath intervals (IBIs) and apnoeas in preterm infants. In 42 preterm infants (1600 hours of recordings), we assess IBIs from the chest electrical impedance pneumograph using an adaptive amplitude threshold for the detection of breaths. The algorithm is refined by comparing its accuracy with clinically observed breaths and pauses in breathing. We develop an automated classifier to differentiate periods of true apnoea from artefactually low amplitude signal. We assess the performance of this algorithm in the detection of morphine-induced respiratory depression. Finally, we use the algorithm to investigate whether retinopathy of prematurity (ROP) screening alters the IBI distribution.ResultsIndividual breaths were detected with a false-positive rate of 13% and a false-negative rate of 12%. The classifier identified true apnoeas with an accuracy of 93%. As expected, morphine caused a significant shift in the IBI distribution towards longer IBIs. Following ROP screening, there was a significant increase in pauses in breathing that lasted more than 10 s (t-statistic=1.82, p=0.023). This was not reflected by changes in the monitor-derived respiratory rate and no episodes of apnoea were recorded in the medical records.ConclusionsWe show that our algorithm offers an improved method for the identification of IBIs and apnoeas in preterm infants. Following ROP screening, increased respiratory instability can occur even in the absence of clinically significant apnoeas. Accurate assessment of infant respiratory activity is essential to inform clinical practice.

Role of studying the pathogenesis of retinopathy of prematurity in optimizing disease screening

Background: The efficiency of treatment and prevention of retinopathy of prematurity (ROP) has improved. In addition, the development of a disease screening system to reduce the incidence of disability resulting from this pathology is important. Aim: This study aimed to determine new laboratory criteria for screening and predicting the ROP course through in-depth investigation of the molecules participating in the pathogenesis of ROP. Material and methods: A comprehensive clinical and experimental study was performed to assess the local and systemic levels of 49 cytokines with various biological effects, four monoamines, and angiotensin-II (AT-II) at different stages of the pathological process. In the clinical analysis, 165 preterm infants at risk of ROP development were examined. For the experimental part, the disease course of 145 Wistar infant rats in the developed model of experimental ROP was analyzed. Results: Among cytokines, the seven most promising potential laboratory markers of ROP development and adverse course were as follows: MCP1 95 pg/mL, IGF-II 140 pg/mL, TGFbeta1 18000 pg/mL, and IGF-I 24 pg/mL in the blood serum of preterm infants before the first signs of ROP and VEGF-A 108 pg/mL, TGF-beta2 100 pg/mL, and PDGF-BB 1800 pg/mL at ROP manifestation. Among monoamines, serotonin (17.0 pg/mL) and L-DOPA indicated their prognostic value in the clinical and experimental settings. Moreover, a possible prognostic role of AT-II was found. Conclusion: In this study, methods to improve the ROP screening system are outlined, but further work is necessary to assess the possibility of implementing the results in clinical practice

Peripheral optical coherence tomography assisted by scleral depression in retinopathy of prematurity

Objective: To determine whether handheld widefield optical coherence tomography (OCT) can be used to document retinopathy of prematurity (ROP) stage while using scleral depression to improve peripheral views. Design: Prospective observational study. Participants: Consecutive neonates admitted to the neonatal intensive care unit (NICU) in a single academic medical center who also met criteria for ROP screening and consented for research imaging. Methods: Scleral depression was combined with widefield OCT using an investigational 400-kHz, 55-degree field of view handheld OCT during ROP screening from October 28, 2020 to March 03, 2021. Main Outcome Measures: Acquisition of en face and B-scan imaging of the peripheral retina to objectively assess early vitreoretinal pathology, including the demarcation between vascularized and anterior avascular retina, the presence of early ridge formation, and small neovascular tufts. Results: Various stages of ROP were detected using a rapid acquisition OCT system. In one neonate, serial OCT imaging over a five-week period demonstrated accumulation of neovascular tufts with progression to stage 3 ROP with extraretinal fibrovascular proliferation along the ridge. Videography of this technique is included in this report for instructional purposes. Conclusions: Serial examinations using widefield OCT and scleral depression may improve detection and documentation of ROP disease progression. Earlier detection of ROP-related proliferation may prevent vitreoretinal traction, retinal detachment, and blindness.

Retinopathy of prematurity in the period 2015-2019 in a tertiary referral centre in Slovenia

Background: Retinopathy of prematurity (ROP) is the leading cause of blindness among prematurely born children. The incidence of any stage of ROP in children born before the 31st gestational week in Europe and the USA is between 10-45%. The purpose of this study was to show characteristics of ROP between 2015 and 2019 at the Neonatal Intensive Care Unit of the University Medical Centre Ljubljana (NICU-Lj), which is the larger of the two tertiary referral centres in Slovenia and in which more than two thirds of Slovenian very low birth weight children are treated. Methods: All prematurely born children screened for ROP at NICU-Lj between 2015 and 2019 were included in the study. The following parameters were recorded: number of children screened, total number of exams, number of exams per child, number of children with ROP, ROP stages, number of children who needed ROP treatment and number of treatments per child treated. Results: Between 2015 and 2019, 82-130 prematurely born children fulfilled ROP screening criteria each year. A total of 1,412 exams were performed over the period of five years (range: 239-386 per year). Every child had one or more ROP screening exams (range: 1-10). Extremely preterm children born before the 27th week of gestation had more exams (average: 5 exams/child) compared to other prematurely born children (average: 1.5 exams/child). The number of prematurely born children with any stage of ROP ranged from 17 to 30 per year. ROP of any stage was present in 18.75% (2015), in 17.7% (2016), in 23% (2017), in 29.3% (2018), and in 24.1% (2019). More than 70% of all babies with ROP were born before the 27th gestational week. The most mature baby with ROP was born with 29 6/7 weeks of gestational age. Every year, 15-35% of babies with ROP received laser treatment. Conclusions: ROP is an important disease in prematurely born children. During the period 2015-2019, the incidence of any stage of ROP and of serious ROP requiring treatment was comparable. The screening and treatment of ROP requires intense cooperation between paediatric ophthalmologists and neonatologists in order to prevent blindness in prematurely born children.

Identification of treatment-warranted retinopathy of prematurity by neonatal nurse specialist

ObjectiveTo determine the accuracy in the identification of infants with treatment-warranted retinopathy of prematurity (ROP) by a trained and experienced ROP neonatal nurse specialist compared with skilled ophthalmologists.MethodsA single-centre, prospective, blinded, agreement study was performed on a cohort of infants undergoing ROP screening. An experienced ROP neonatal nurse specialist obtained retinal images using a wide field digital retinal imaging system (WFDRI) on 127 infants and identified those with treatment-warranted ROP. This interpretation was compared with the interpretation of the same images by skilled ophthalmologists. The accuracy of the ROP nurse specialist’s interpretation was assessed for sensitivity and specificity compared with the gold standard interpretation by the ophthalmologists.ResultsThe ROP nurse specialist performed 345 ROP screens on both eyes of 127 infants. The mean (SD) gestation age (weeks) and birth weight (g) of the infants screened was 26.8 (2.8) and 929 (327), respectively. The nurse specialist correctly identified all 8 infants with treatment-warranted ROP and 118/119 infants without. The sensitivity and specificity (95% CI) of ROP screening episodes were 100% (63% to 100%) and 99.7% (98.4% to 100.0%), respectively.ConclusionA trained and experienced ROP neonatal nurse specialist can correctly identify infants with treatment-warranted ROP using WFDRI. Further work is required to examine the generalisability of this finding and its impact on ROP screening services.