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Purpose: to assess the changes in the macular structure in children with history of prematurity and to find the relationship between retinopathy of prematurity (ROP) treatment and macular ultrastructural changes found in optical coherence tomography angiography study. Methods: a search for identifying relevant studies published in English using PubMed, Google Scholar, Scopus, and Web of Science databases from the date of inception to 21 October 2022 was conducted. Studies were included if their subjects were >5 years and used Optovue device for imaging. Twelve studies were included for final analysis. After extracting data, foveal avascular zone (FAZ), vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the foveal and parafoveal area, central foveal thickness (CFT), and visual acuity (VA) were compared between the study groups. Results: in individual who were born full term the FAZ was significantly larger. The SCP and DCP VD was significantly higher in children with history of ROP treatment. Superficial parafoveal VD was significantly lower in term children than both treated groups. The CFT was significantly higher in children with history of ROP (treated and untreated) than the terms. VA was lower in laser and IVI treated children than terms and it was related to the changes in CFT, foveal superficial and deep VD and FAZ area. Conclusions: Patients with a history of ROP treatment have a significantly greater CFT, higher VD of foveal SCP and DCP, and lower VA than the term-born children. Furthermore, the FAZ is negatively associated with VA and CFT. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo assess the efficacy of the DIGIROP-Birth algorithm in identifying infants at risk for developing retinopathy of prematurity (ROP).In a retrospective study, we included preterm infants over 11 years, 2010–2020, meeting the inclusion criteria for the DIGIROP-Birth calculator (24 + 0/7 to 30 + 6/7 weeks of gestational age). We assessed the validity of DIGIROP-Birth using receiver-operating characteristic (ROC) curves and calculated area-under-curve (AUC), sensitivity, specificity, and positive and negative predictive values.897 infants were included in the analysis. The median age of the first ophthalmological examination was 40 days (IQR 32–50), the median gestational age was 198 days (IQR 185–209; corresponding to 28 + 2/7 gestational weeks), median birth weight was 1000 g (IQR 790–1300). Of 897 screened children, 458 (51.1%) were diagnosed with ROP, and 34 of 897 (3.8%) required treatment.Analysis of ROP requiring treatment predicted by DIGIROP showed an AUC of 0.860 [95%-CI 0.795–0.925]. An equilibrium of sensitivity and specificity existed at a probability of 4.12%. The positive predictive value was 10.95%, and the negative predictive value was 99.36%. Independent significant peri- and postnatal risk factors were emergency cesarean section and mass blood transfusions.The DIGIROP-Birth calculator showed good predictive power in our studied population, with an incidence of 3.79% for therapy-requiring ROP. Peri- and postnatal risk factors should be included in ROP screening. [ABSTRACT FROM AUTHOR]

Objective: Infants who meet the screening guidelines for retinopathy of prematurity (ROP) based on birth weight and gestational age undergo serial ophthalmological examinations for its detection and treatment. However, <10% of patients require treatment, and less than half develop ROP. Poor postnatal weight gain has been reported to be a strong indicator of ROP development; however, the information regarding this is unclear. Therefore, this study aimed to determine the relationship between postnatal weight gain and ROP development in preterm infants. Methods: The data of 675 preterm infants with gestational age ≤32 weeks, who were hospitalized in our neonatal intensive care unit, were obtained retrospectively from file records. The infants' demographic characteristics, clinical findings, and weekly weight gain (g/kg/day) during the first 8 weeks were recorded. The univariate was used to examine the risk factors for ROP followed by multivariate regression. Results: The incidence of ROP in the infants included in the study was 41% (n = 278) and 13.3% (n = 37) of them required treatment. In the infants of the group that developed ROP, the mean birth weight and gestational age were significantly lower than those in the group that did not develop ROP (973 ± 288 and 1301 ± 349 g, p = 0.001 and 28.48 ± 1.95 and 30.08 ± 1.60 weeks, p = 0.001, respectively). As the gestational week and birth weight decreased, ROP development and the risk of ROP-requiring treatment increased. In the infants of the group that developed ROP, the mean weight gain in the postnatal third week was detected as significantly lower compared to those in the group that did not develop ROP (13.9 ± 8.2 and 15.4 ± 6.8 g, p = 0.034). On multiple logistic regression analysis, birth weight (<750 g) (odds ratio [OR], 8.67; 95% confidence interval [CI], 3.99–18.82, p = 0.001), blood transfusion (OR, 2.39; 95% CI, 1.34–4.24, p = 0.003), necrotizing enterocolitis (OR, 4.79; 95% CI, 1.05–26.85, p = 0.045), bronchopulmonary dysplasia (OR, 2.03; 95% CI, 1.22–3.36, p = 0.006), antenatal steroid therapy (OR, 1.60; 95% CI, 1.05–2.43, p = 0.028), surfactant administration (OR, 2.06; 95% CI, 1.32–3.2, p = 0.001) were independent risk factors for ROP development. Conclusion: Postnatal weight gain may not be an accurate predictor of ROP development after adjusting for confounding factors. However, the analysis of independent risk factors that influenced the development of ROP revealed a statistically significant effect in cases of low birth weight, blood transfusion, necrotizing enterocolitis, bronchopulmonary dysplasia, and antenatal steroid and surfactant therapies. These findings may help ophthalmologists and neonatologists to pay special attention to this patient group during ROP scanning. [ABSTRACT FROM AUTHOR]

Purpose: Melatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model. Methods: Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, β-actin, and Lamin B1. Results: Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2. Conclusion: Our study showed that melatonin could ameliorate H2O2-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration. [ABSTRACT FROM AUTHOR]

Control of blindness due to retinopathy of prematurity (ROP) requires timely screening and treatment within 48–72 h. Anticipating that the coronavirus disease 2019 (COVID-19) pandemic would disrupt ROP services, we devised strategies ''on-the''-go"" to ameliorate this possiblity. We describe the successful outcomes of this approach in preventing infant blindness during the pandemic. Data on the number of preemies recruited, screened and treated in the Karnataka Internet-assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program were collected in a retrospective (2019, interval 1) – prospective (2020, interval 2) manner. We summarize 10 key strategies that were developed as we faced logistic, operational and implementation challenges. These included pragmatic methods of enhancing enrolment, transporting for screening and ensuring timely treatment in the outreach. The total number of ROP screening sessions was 20,598 (7,197 new) and 14,371 (5,773 new) during interval 1 and 2 respectively. Of these, 166 (2.3%) and 157 (2.7%) infants required treatment during interval 1 and 2 respectively. All infants needing treatment during the COVID period, were treated on time which was possible due to successful implementation of the 'on-the-go' strategies throughout the state of Karnataka. The fiscal equivalent of the blindness prevented during this period is USD 15.6 million. The greater decline in the number of ROP screening episodes in neonatal units in government hospitals was because several were converted to 'COVID only" hospitals. KIDROP's multi-zonal, decentralized strategy, which uses non-physician-based imaging in a telemedicine network, ensured that essential ROP services continued even during the lockdown. [ABSTRACT FROM AUTHOR]

In recent decades, there have been significant advances in the field of Artificial intelligence (AI), retinal imaging, and therapeutics. The specialty of retina generates huge datasets, which are ideally suited to create robust AI models for early detection, diagnosis, classification, and treatment of retinal diseases. Basic aspects of AI algorithms, machine learning models, application of AI in diabetic retinopathy (DR), retinopathy of prematurity (ROP), retinal vascular occlusion (RVO) and age-related macular degeneration (AMD) have been described, highlighting findings from important studies. Comprehensive search of indexed medical literature on Medline/PubMed and Google Scholar databases. The search terms included artificial intelligence, deep learning, machine learning in DR, AMD, ROP, retinal vascular disease, and RVO. The manuscripts published in English literature in the last two decades were selected for this review. Several AI algorithms have been developed which are accurate and efficacious in screening, detecting, diagnosing, and aiding in managing patients with various retinal diseases. Proper external validation using large datasets and establishing their accuracy is central to increasing the confidence and acceptance of these algorithms. The application of AI to screening models can be a boon in many environments, but particularly resource-depleted settings. [ABSTRACT FROM AUTHOR]

This article discusses a case of a premature infant who was misdiagnosed with retinopathy of prematurity (ROP) but was later diagnosed with familial exudative vitreoretinopathy (FEVR). FEVR is a rare inherited disorder that affects the vitreous and retina, and it can be challenging to differentiate from ROP in premature infants. The case highlights the importance of monitoring changes in the ocular axis and refractive status in infancy and early childhood for FEVR patients, as well as monitoring the progression of their fundus lesions. The article also discusses the clinical characteristics, genetic testing, and management approaches for FEVR. [Extracted from the article]

To determine the retinal transcriptomic differences underlying the oxygen-induced retinopathy phenotypes between Sprague Dawley rat pups from two commonly used commercial vendors. This will allow us to discover genes and pathways that may be related to differences in disease severity in similarly aged premature babies and suggest possible new treatment approaches. We analyzed retinal vascular morphometry and transcriptomes from Sprague Dawley rat pups from Charles River Laboratories and Envigo (previously Harlan). Room air control and oxygen-induced retinopathy groups were compared. Oxygen-induced retinopathy was induced with the rat 50/10 model. Pups from Charles River Laboratories developed a more severe oxygen-induced retinopathy phenotype, with 3.6-fold larger percent avascular area at P15 and twofold larger % neovascular area at P20 than pups from Envigo. Changes in retinal transcriptomes of rat pups from both vendors were substantial at baseline and in response to oxygen-induced retinopathy. Baseline differences centered on activated pathways of neuronal development in Charles River Laboratories pups. In response to oxygen-induced retinopathy, during the neovascular phase, retinas from Charles River Laboratories pups exhibited activation of pathways regulating necrosis, neuroinflammation, and interferon signaling, supporting the observed increase of neovascularization. Conversely, retinas from Envigo pups showed decreased necrosis and increased focal adhesion kinase signaling, supporting more normal vascular development. Comparing oxygen-induced retinopathy transcriptomes at P15 to those at P20, canonical pathways such as phosphate and tensin homolog, interferon, and coordinated lysosomal expression and regulation element signaling were identified, highlighting potential novel mechanistic targets for future research. Transcriptomic profiles differ substantially between rat pup retinas from Charles River Laboratories and Envigo at baseline and in response to oxygen-induced retinopathy, providing insight into vascular morphologic differences. Comparing transcriptomes identified new pathways for further research in oxygen-induced retinopathy pathogenesis and increased scientific rigor of this model. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role of the brain-sparing effect (BSE) on retinopathy of prematurity (ROP) in fetal growth restriction (FGR). In this retrospective study, 127 pregnant women were divided into two groups considering the cerebroplacental ratio (CPR): FGR with abnormal CPR group (n = 74) and the appropriate for gestational age with normal Doppler group (n = 53). CPR was computed using the pulsatility index (PI) and resistance index (RI) to quantitate the waveforms [middle cerebral artery (MCA) PI/umbilical artery (UA) PI and MCA RI/UA RI: a result <1 was taken into account as abnormal]. ROP screening results of newborns were recorded from electronic files. After adjusting for co-variants, BSE was not related to ROP (adjusted odds ratio [aOR], 1.06; 95% confidence interval [CI], 0.23–4.95). Gestational age at delivery <30 weeks (aOR, 2.55; 95% CI, 1.04–6.93) and birth weight <1500 g (aOR, 5.15; 95% CI, 1.15–25.2) were independently associated with ROP. Preeclampsia, emergency cesarean section birth, or 48 h completion after the first steroid administration were not associated with ROP. Gestational age at delivery <30 weeks and birth weight <1500 g are independent risk factors for ROP in FGR whereas the BSE is not a risk factor. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate both dynamic thiol-disulfide homeostasis and oxidative stress (OS) levels in patients with retinopathy of prematurity (ROP). A total of 129 infants of <34 weeks gestational age were enrolled in the present study. The thiol-disulfide homeostasis was determined by using the new, cost-effective and fully automated colorimetric method. Total antioxidant status (TAS), Total oxidant status (TOS) and Oxidative stress index (OSI) levels were evaluated. We found serum TAS levels were lower while serum TOS and OSI levels were significantly higher in patients with ROP compare to the without ROP group (p <.05). However, native, total and disulfide values were not statistically significant between the groups (p >.05). In addition, we also evaluated the native, total and disulfide levels in patients with ROP according to grades and no statistically significant results were found (p >.05). Low birth weight (p =.001), gestational age (p =.001) and 5-min Apgar score were significantly lower in the ROP group. This study revealed that dynamic thiol-disulfide homeostasis was changed in patients with ROP. Increased TOS and decreased TAS levels may be associated with functional reduction of the antioxidant system due to increased OS. This indicate that ROP patients are highly sensitive to OS. The dynamic thiol-disulfide homeostasis may conduce to the pathophysiological mechanism and disease follow-up in patients with ROP. The results of this study show that ROP patients are highly sensitive to oxidative stress. [ABSTRACT FROM AUTHOR]

To delineate racial differences in the incidence and time course of ROP in a large cohort of premature infants. The secondary analysis of data from the two Postnatal Growth and ROP Studies (G-ROP-1 and G-ROP-2) that were collected in 41 hospitals in North America from 2006 to 2017. According to self-reported maternal race, premature infants were classified into 3 groups: White (N = 5580), Black (N = 3252), and Asian (N = 353). Incidence, severity, and time course of ROP; plus disease; and postnatal weight gain rate were compared among racial groups. Black infants had significantly smaller BW (mean 1035 vs. 1131 vs.1144 grams, P <.001) and lower GA (28.2 vs. 28.6, vs. 29.1 weeks, P <.001) than White and Asian infants. However, Black infants had lower incidences of severe ROP (11.1% vs. 12.4% vs. 11.9%), ROP (42.1% vs. 43.2% vs. 30.6%), and plus disease (3.6% vs. 6.3%, vs. 5.9%) than White and Asian infants (BW and GA adjusted risk ratio for Black vs. White 0.69 for severe ROP, 0.83 for ROP, 0.44 for plus disease, all P <.0001). Mean daily-weight-gain on days of life 11–20 and 21–30 were similar across groups (P >.05), but lower in Black and Asian infants on days 31–40 (P <.001). There were no differences in the timing of severe ROP and ROP across racial groups. Despite relatively lower GA, BW, and daily-weight-gain, Black preterm infants had lower incidences of ROP and plus disease than White preterm infants. The mechanisms for these differences require further investigation. [ABSTRACT FROM AUTHOR]

Aim: This study aims to show speech and language, sensory-motor, and emotional progress after one year of therapy according to the needs of and resources for a child with multiple disabilities and blindness due to retinopathy of prematurity (ROP). Methods: A 45-month-old boy was examined by a multidisciplinary team and assessed using the Sensory Profile 2, The Vineland Adaptive Behavior Scale II, The Communication Matrix, and The Scale for Evaluation of Psychophysiological Abilities of Children Aged 0–7. After a year of daily individually adopted speech and language therapy followed by supplementary therapeutics method, based on a multidisciplinary approach, the child was reassessed using the same battery of tests. Results: The obtained results might indicate the importance of factors such as a multidisciplinary approach, individualization, communication pathways, therapist's characteristics, and trust when working with children with multiple disabilities. Conclusion: Taking into account all the features of multiple disabilities during the treatment course, continuous monitoring, modification, and adaptation of applied therapy method proved successful in this case. [ABSTRACT FROM AUTHOR]

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 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. 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. 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. [ABSTRACT FROM AUTHOR]

Familial exudative vitreoretinopathy (FEVR) is a rare inherited disease characterized by abnormal retinal angiogenesis that leads to incomplete vascularization of the peripheral retina and ischemia. The disease demonstrates complex genetics and can be inherited in an autosomal recessive, autosomal dominant, or X-linked recessive fashion. All presently identified pathogenic genetic variants account for about 50% of all FEVR cases worldwide. Genetic testing can confirm the diagnosis. Case report A 7-year-old female who was born prematurely at 33 weeks gestation and was thought to have progression of bilateral retinopathy of prematurity (ROP) was referred to a pediatric-retina specialist for management. Upon initial examination under anesthesia with multimodal imaging, the diagnosis of FEVR was suspected. Genetic testing identified a FZD4 variant involving a novel complex interchromosomal rearrangement involving chromosomes 2 and 11 associated with microarray-defined deletion of 11q14. The patient was conceived via IVF and has a fraternal twin without FEVR. This is the first report of familial exudative vitreoretinopathy associated with this combination of genetic findings. Autosomal dominant FEVR involves abnormalities in several genes, including FZD4 at the chromosome 11q. We recommend that patients with microarray-defined deletions of 11q have careful review of the allelic deletions in Chromosome 11 to determine if FZD4 is included because a loss of function variant of a single copy of FZD4 is sufficient to cause the FEVR phenotype. It is essential to differentiate FEVR from other pediatric retinal diseases in children, including ROP, persistent fetal vasculature, and Coats disease. [ABSTRACT FROM AUTHOR]

Children with a history of regressed retinopathy of prematurity (ROP) are at increased risk of peripheral avascular retina. Wide-field digital retinal imaging and telemedicine is an effective tool for ROP screening. Ophthalmologists and Optometrists should have a high level of clinical suspicion for peripheral retinal changes in children screened for ROP. Retinopathy of prematurity, a vaso-proliferative disorder of the pre-term retina, is a preventable cause of childhood visual impairment. The Auckland Regional Telemedicine ROP (ART-ROP) network, established in 2006, utilises wide-field digital imaging and telemedicine to screen at-risk infants for ROP. This prospective observational study reports the long-term ocular outcomes of ART-ROP network infants. A comprehensive paediatric eye examination including cycloplegic autorefraction and wide-field retinal imaging was completed on all participants. Participants had been screened for ROP by the ART-ROP network between May 2008 and October 2011. A total of 69 children, with a mean age of 5 to 8 years old were assessed and divided into two groups: those with or without a history of ROP, 44 and 25 children, respectively. Infants with a history of ROP had significantly lower gestational age (26.6 ± 1.9 vs. 29.1 ± 1.6 weeks, p < 0.001) and birth weight (937 ± 237 vs. 1177 ± 311 grams, p = 0.001). No significant differences were detected between the two groups for visual acuity (p = 0.596), stereopsis (p = 0.219), refractive error (p = 0.472), or strabismus. Clinically significant refractive error was noted in 10 participants; none with moderate or high myopia. Retinal imaging exposed asymptomatic, persistent, peripheral avascular retina in four children, all of whom had a history of regressed ROP. Visual and ocular outcomes did not vary based on history of ROP, with no participant having reduced vision as a result of undetected or untreated ROP. Further research is required into the long-term implication of persistent avascular retina in regressed ROP. [ABSTRACT FROM AUTHOR]

A systematic literature review (SLR) of economic evaluations (EE) conducted for interventions to screen, treat, and manage retinopathy of prematurity (ROP) in the United States (US), United Kingdom (UK), and Canada was performed. The SLR accessed the MEDLINE, Embase, Cochrane, Web of Science, Health Business Elite, Econ. Lit, NHS EED, and Google Scholar databases over the period 1st January 2000 to 4th August 2021. The key Medical Subject Heading (MeSH) search terms used included: Retinopathy of prematurity, Cost-effectiveness analysis, Cost-utility analysis, Cost of illness, Cost-benefit analysis, Cost minimization analysis, Incremental cost-effectiveness ratio, Quality adjusted life years, return on investment, burden of illness, disability adjusted life years, and Economic evaluation. Screening was conducted using Covidence, and the risk of bias was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Data extraction was performed using MS Excel. 1,527 articles were examined with nine (9) papers identified, one (1) from the UK; two (2) from Canada and six (6) from the US. Cost-effectiveness analysis was the main form of EE conducted (n = 5) and telemedicine screening (n = 3) was found to be highly cost-effective for ROP with the ICER values ranging from £446 to £4,240 per Quality Adjusted Life Year (QALY) in 2021 figures. 73% of included studies complied with the CHEERS checklist for EE. ROP screening and treatment strategies reviewed were highly cost-effective. This review may assist eye health policymakers in planning nationwide screening and treatment programs to combat vision loss and blindness due to ROP. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features. Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment. We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye. In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes. [ABSTRACT FROM AUTHOR]

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. 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. 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). CVD with increased PBF likely increases the risk of ROP. PPHN likely increases the risk of severe ROP. [ABSTRACT FROM AUTHOR]

This study was designed as a prospective, randomized controlled trial. A total of 90 preterm infants who underwent retinopathy of prematurity (ROP) examinations were categorized into three groups, a control group, a white noise group (WN), and a classical music group (CM), each comprising 30 preterm infants. The study data were obtained using an information form and the Premature Infant Pain Profile. During (WN: 9.70±3.02; CM: 11.2±2.28) and after the examination (WN: 3.60±2.11; CM: 3.77±1.83), the preterm infants in the WN and CM groups had lower mean pain scores and heart rates (181.17±15.76 and 3150.10±17.03 vs. 173.30±20.66 and 146.67±18.17, respectively; p<0.001) and higher mean oxygen saturation values (93.60±3.87 and 97.83±1.93 vs. 95.73±2.52 and 98.27±1.82, respectively; p<0.05) than those in the control group; the differences were statistically significant. The WN and CM listened to by the preterm infants during ROP examinations had positive effects on pain and heart rate and oxygen saturation values. [ABSTRACT FROM AUTHOR]

Inter-clinician variation could cause uncertainty in disease management. This is reported to be high in Retinopathy of Prematurity (ROP), a potentially blinding retinal disease affecting premature infants. Machine learning has the potential to quantify the differences in decision-making between ROP specialists and trainees and may improve the accuracy of diagnosis. An anonymized survey of ROP images was administered to the expert(s) and the trainee(s) using a study-designed user interface. The results were analyzed for repeatability as well as to identify the level of agreement in the classification. "Ground truth" was prepared for each individual and a unique classifier was built for each individual using the same. The classifier allowed the identification of the most important features used by each individual. Correlation and disagreement between the expert and the trainees were visualized using the Dipstick™ diagram. Intra-clinician repeatability and reclassification statistics were assessed for all. The repeatability was 88.4% and 86.2% for two trainees and 92.1% for the expert, respectively. Commonly used features differed for the expert and the trainees and accounted for the variability. This novel, automated algorithm quantifies the differences using machine learning techniques. This will help audit the training process by objectively measuring differences between experts and trainees. Training for image-based ROP diagnosis can be more objectively performed using this novel, machine learning-based automated image analyzer and classifier. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a leading cause of blindness in infants thus it is important to raise awareness about this disease. As online platforms are a popular source of medical information; the purpose of this study is to evaluate the credibility of the content of YouTube videos on ROP in the Arabic language. The first 40 relevant videos were included and were independently reviewed by two ophthalmologists employing six assessment tools: reliability, accuracy, quality, comprehensiveness, overall viewer experience, and usefulness. Out of the 40 videos that were analysed, only 29 were considered useful. The mean DISCERN score of the videos was 32 indicating poor quality. Furthermore, 70% of the videos were completely accurate, but only 5% were fully comprehensive. Regarding the global quality score, only four videos were of excellent quality/flow (10%), while 15 were generally poor with the poor flow (37.5%). Viewer experience was assessed as fair to very poor in 22 videos (55%). The overall quality of the content in YouTube videos was poor, rendering this platform an unreliable source of information about ROP. However, given its high level of engagement, the medical community could hone its potential for raising awareness about ROP by creating entertaining useful content. [ABSTRACT FROM AUTHOR]

Chorioamnionitis is a risk factor for fetal and neonatal outcomes. Therefore, predicting histological chorioamnionitis (HCA) and neonatal outcomes using clinical parameters could be helpful in management and preventing morbidities. To determine if parameters of clinical chorioamnionitis (CCA) would be associated with HCA and neonatal outcomes. In this cohort study using a retrospective design, we analyzed the performance of signs of CCA in predicting HCA, and neonatal outcomes. Data were extracted from the electronic health record for all neonates with documented CCA delivered at our institution from 2011 to 2016. We compared our findings based on the old ACOG definition of CCA and the new definition released in 2017 – maternal fever plus any of fetal tachycardia, maternal leukocytosis, and purulent vaginal discharge. Maternal tachycardia and uterine tenderness were removed from the new criteria. Neonatal laboratory samples on admission, 12 h and 24 h were used to define the three time points of neonatal suspected sepsis. There were 530 mothers-infant dyads with chorioamnionitis. Seventy-three were preterm, and 457 were term. Eighty-eight percent of the preterm mothers had CCA, and HCA was present in 62.5% of 72 preterm placentas. Preterm infants with placental HCA significantly had lower birth weight, gestational age, placental weight, and more infants with lower 5-minute Apgar scores, compared to those with no HCA. In preterm infants, maternal urinary tract infection was significantly associated with decreased odds for HCA (OR 0.22, CI 0.10 − 0.71). More preterm babies with suspected sepsis criteria at the 3 time points had HCA (all p ≤.01). In the term cohort, 95.4% and 65.6% had CCA and HCA, respectively. In term infants (n = 457), maternal leukocytosis (p =.002) and prolonged rupture of membranes (PROM; p = 002) were associated with HCA. Suspected sepsis was associated with PROM (p =.04), HCA (p =.0001), and maternal leukocytosis (p ≤.05) in at least 1 of the 3 time points. Though maternal leukocytosis was significantly associated with the presence of HCA in the term cohort, there were no CCA criteria that accurately predicted presence of HCA in either the preterm or the term infants. [ABSTRACT FROM AUTHOR]

Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28 weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system. The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3 years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22 weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (≤1 year, >1 year and ≤2 years, and >2 years and ≤3 years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits. A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3 years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3 years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition. The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3 years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term. [ABSTRACT FROM AUTHOR]

Objective To study the association between gestational age (GA) and weight at birth and the development of retinopathy of prematurity (ROP), and in particular the link between postnatal weight gain during the first 6 weeks and need for ROP treatment. Material and methods Retrospective observational study of premature infants who underwent ophthalmoscopy at Hospital Universitari Vall d’Hebron in Barcelona, Spain, between June 2017 and December 2018. We collected data on obstetric and birth characteristics, comorbidities, GA and weight at birth, and weekly weight for the first 6 weeks. Results Ninety patients with a mean ± SD GA of 26.87 ± 1.90 weeks and a mean birth weight of 884.29 ± 227.40 g were studied. The mean weight at 6 weeks was 1656.89 ± 478.51 g, which corresponds to a gain of 776.17 ± 298.12 g. Thirty-seven patients (41.1%) were diagnosed with ROP and nine (10%) needed treatment. Significant predictors of the need for treatment in patients with ROP were GA (p = .018) and weight at 6 weeks (p = .021). Birth weight was not significant (p = .361). Conclusions GA and weight gain during the first 6 weeks of life are significantly associated with the need for treatment in infants with ROP. Sex and birth weight were not significant predictors. Postnatal weight gain at 6 weeks is predictive of the need for ROP treatment. [ABSTRACT FROM AUTHOR]

Background: Extremely low birth weight (ELBW) infants have significant morbidities and higher mortality. The major morbidities are bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP). Release of proinflammatory cytokines has been implicated in the development of systemic inflammation that contributes to BPD aND ROP. Also, cumulative oxygen exposure in the first 3 days of life and use of mechanical ventilation was associated with 3-fold increase in severe IVH. Therefore, early ventilation and oxygenation may contribute significantly to morbidities in ELBW infants. Respiratory severity score (RSS), a product of Mean airway pressure (MAP) and FiO2, is a steady-state noninvasive assessment tool useful in infants to monitor the severity of respiratory failure. We used RSS, in the first 3 days of life of ELBW infants, to predict neonatal morbidities and mortality. Study design: In a single-center retrospective cohort study in an urban setting, convenience sampling of ELBW infants meeting the study criteria who were mechanically ventilated at birth for the first 3 days of life were included. Time-weighted average RSS was plotted on receiveroperating characteristic (ROC) curve in the first 3 days of life to predict outcomes. Sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios were calculated. Results: A total of 69 infants qualified for the study. RSS in the first 3 days significantly predicted the composite outcome of death, ROP, IVH or BPD with an area under the curve (AUC) of 0.82 (p<0.001). Individually, RSS predicted death, severe ROP and IVH with an AUC of 0.86, 0.77 and 0.71 respectively; but did not predict severe BPD (AUC 0.61). RSS was more sensitive and specific than each of its component; FiO2 and MAP. Weighted RSS in the first 3 days had highnegative predictive value of 98.1% for death between 7 days and 36 weeks, 94.6% for ROP and 91.7% for IVH. Conclusions: This study is the first to show that RSS in the first 3 days of life is a good predictor of composite neonatal outcomes: severe IVH, BPD, ROP, or mortality. Early RSS had a high positive predictive value for the composite outcome of morbidities/mortality and a high specificity for mortality, ROP, and IVH individually. [ABSTRACT FROM AUTHOR]

This article, titled "Racial Differences in Retinopathy of Prematurity–Reply to Letter to the Editor," discusses the findings of a study on racial differences in retinopathy of prematurity (ROP) among premature infants. The authors acknowledge the concerns raised by another researcher regarding the potential for unsubstantiated causal pathways of inherent racial difference. They clarify that their study did not make any inferences about causal relationships between race and ROP, and they agree that socioeconomic factors may mediate the association. The authors also note that they did not attribute the observed racial differences in ROP risk to genetic or physiological differences. They emphasize the need for further investigation into the mechanisms behind these racial differences. The article concludes by addressing a retrospective study that failed to find an association between race and ROP, highlighting the differences in study design and population between the two studies. Overall, the study found racial differences in ROP incidence, with a lower incidence among Black preterm infants compared to White preterm infants, but the reasons for these differences remain unknown. [Extracted from the article]

Coats plus syndrome or cerebroretinal microangiopathy with calcifications and cysts (CMCC) is an exceedingly rare autosomal recessive disorder that predominantly affects the microvasculature in the retina, brain, bones, and gastrointestinal system. Unlike Coats disease, CMCC is bilateral and affects multiple organ systems. Case report We report the case of two brothers with Coats Plus syndrome who presented with variable phenotypic expression. One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients. Aggressive treatment with laser photocoagulation and intravitreal bevacizumab dramatically improved the retinal vascular and exudative changes. Coats Plus syndrome can have a variable phenotypic presentation, including retinal vascular findings. This rare genetic disease should be in the differential diagnosis in patients who present with atypical retinal pathology, including Retinopathy of Prematurity, Familial Exudative Vitreoretinopathy, or Coats disease associated with non-specific multiorgan abnormalities. [ABSTRACT FROM AUTHOR]

Objective:To determine the serum levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) in preterms with retinopathy of prematurity (ROP). Materials and Methods: We included 37 preterm infants. The first blood samples were obtained within the first 5 days of life and repeated at the time of the first ophthalmologic examination for ROP. The levels of ADMA, IGF-1, and VEGF were measured in all samples. Results: ROP was detected in 12 of the subjects (32.4%). We categorized the subjects as non-ROP (Group 1; n = 25), untreated ROP (Group 2; n = 7), and treated ROP (Group 3; n = 5) according to the eye findings. There were no significant differences among the groups for serum levels of ADMA, VEGF, and IGF-1 at the first sampling. Conclusion: We did not find any differences in terms of serum ADMA, IGF-1, and VEGF levels in preterm infants with or without ROP. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic accuracy of the wide-field digital retinal imaging (WFDRI) for the detection of Retinopathy of Prematurity (ROP) in premature infants as compared to the binocular indirect ophthalmoscopy (BIO). This systematic review and meta-analysis included the publications searched through PubMed (Medline), EMBASE, Scopus, Web of Science, Cochrane Library databases and Clinical Trials. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2, the hierarchical summary receiver operating characteristic, meta-regression, publication bias analyses, and the GRADE methodology for the certainty of the overall evidence were conducted. The pooled effect sizes of the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated. Total sixteen eligible studies from 10 articles were included with total 2,537 image interpretations from 697 premature infants. Less than 50% risk of bias and low concern were found in each domain across all articles by QUADAS-2. The pooled effect sizes showed the sensitivity of 0.77 (95% confidence interval (C.I.): 0.69–0.84), specificity of 0.96 (95% C.I.: 0.92–0.98), PLR of 20.9 (95% C.I.: 10.2–42.5), NLR of 0.23 (95% C.I.: 0.17–0.33) and DOR of 89 (95% C.I.: 43–185) as compared to BIO. The income level, setting, mean/median birth weight and gestational age contributed to the significant differences in sensitivity (p < 0.001). No publication bias was found among these 16 studies. The GRADE quality of evidence showed moderate for the pooled sensitivity and high for the pooled specificity. The diagnostic accuracy based on WFDRI is substantial and comparable to BIO, supporting its application in the ROP screening programs. [ABSTRACT FROM AUTHOR]

The G-ROP model was proposed to improve the retinopathy of prematurity (ROP) screening efficiency. It is based on gestational age, birth weight and postnatal weight gain. The current study aimed to validate the G-ROP model's ability to predict ROP in cohorts of premature infants from Egypt and the United Kingdom (UK). We retrospectively reviewed the records of preterm infants born between 1st of January and 30th of June 2018 with a known outcome for ROP screening and regular weight measurements until day 39 after birth. We applied the G-ROP model to the study group and calculated the sensitivity of the model for detecting Early Treatment of ROP (ETROP) study type 1 ROP and for any ROP and calculated the reduction of the number of infants requiring ROP screening by the model application. We applied the G-ROP model on 605 infants (504 from Egypt and 101 from the UK). The model successfully predicted all type 1 ROP cases (100% sensitivity) in both cohorts (95% confidence interval [CI], 91.1–100% in the Egyptian cohort and 65.5–100% in the UK cohort). The model reduced the number of infants requiring screening by 14.1% in the Egyptian cohort and 21.8% in the UK cohort. The G-ROP model was successfully validated for detecting type 1 ROP and in both cohorts from Egypt and the UK. [ABSTRACT FROM AUTHOR]

Retinopathy of Prematurity (ROP) has been suggested to be increasing in Africa. However, it was only previously documented as a cause of blindness in 8 of 48 (16.7%) sub-Saharan African countries. The purpose of this study was to better understand the magnitude and breadth of blindness from ROP in sub-Saharan Africa. A questionnaire was sent to 455 ophthalmologists practicing in sub-Saharan Africa; the questionnaire was available in English, French and Portuguese. Responses were received from 132 of 455 (29%) ophthalmologists to whom the survey was sent. Eighty-three respondents were identified as ROP-involved ophthalmologists and were from 26 of 48 (54%) sub-Saharan African countries. Ophthalmologists in 23 countries reported that they examined at least one child who was blind from ROP during the last 5 years. Sixteen of these countries had not previously reported cases of blindness from ROP in the literature. The perceived occurrence of Type 1 or more severe ROP was reported to be increasing by 31 of 77 (40%) ROP-involved ophthalmologists. ROP-involved pediatric ophthalmologists and retinal surgeons reported the number of infants they examined annually with Type 1 or more severe ROP increased from a median of 1 (range: 0–15) to a median of 4 (range: 0–40) from 2015 to 2019. ROP was estimated to be the cause of blindness for 10% of all blind children examined by ROP-involved pediatric ophthalmologists and retinal surgeons during 2019. ROP is becoming a more important and widespread cause of childhood blindness in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis.Methods: An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (-460 T/C, +936 C/T, -634 G/C, and -2578 C/A), TNF-α (-308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS).Results: A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF - 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74-0.94, POR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54-0.91, POR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67-0.95, POR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59-0.94, POR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, -634 G/C, -2578 C/A, TNF-α - 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05).Conclusions: VEGF polymorphism -460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP. [ABSTRACT FROM AUTHOR]

The article discusses a study on the incidence of retinopathy of prematurity (ROP) across racial groups. The authors express concern that the study's framing and discussion may perpetuate the idea that genetic and physiological differences between racial groups drive disparities. They argue that race is a social construct that incorrectly conflates physical traits with genetic variation, and that observed associations between race and outcomes are socially mediated. The authors caution against assuming that genetics or inherent racial differences can explain disparities in complex chronic disease outcomes, and emphasize the importance of considering mediators and confounders when studying racial differences in health outcomes. [Extracted from the article]

To report and evaluate the incidence and risk factors of retinopathy of prematurity (ROP) and to assess the sensitivity and specificity of Turkish national screening guideline (NSG) in heavier infants with a birth weight (BW) of >1500 g. The data of 1784 preterm infants with BW>1500 g, who were screened between 2009 and 2016 in a university hospital in Turkey, were analyzed retrospectively. The rates of any stage and severe (treatment-requiring) ROP incidence were investigated. The possible protective and risk factors were evaluated with univariate analyses and logistic regression analysis. The rate of any stage ROP was 14.1% (n = 251). Severe ROP was observed in 11 infants (0.6%), and 2 of the infants (0.1%) had a gestational age (GA)>32 weeks, which fell outside of the NSG. In logistic regression analysis, BW, GA, O2 therapy duration, and exchange transfusion were determined to be independent risk factors (respectively, p <.001, p <.001, P =.055, and P =.033). Furthermore, antenatal steroid therapy was determined to have a highly significant protective effect on ROP development (p <.001). The sensitivity of Turkish NSG in identifying severe ROP increased from 82% to 100% with the inclusion of risk factors in addition to GA and BW. This study shows the presence of severe ROP in mature and heavy infants in Turkey. The positive effect of antenatal steroid use and the negative impact of exchange transfusion have been demonstrated for ROP development in mature infants. Possible risk factors should be evaluated with GA and BW to avoid missing severe ROP. [ABSTRACT FROM AUTHOR]

Bevacizumab may affect preterm infants' ongoing organogenesis with its antiangiogenic effects. We aimed to compare neurodevelopmental outcomes (NDO) of preterm infants treated for retinopathy of prematurity (ROP) with laser photocoagulation (LP), intravitreal bevacizumab (IVB) or both treatments, and to find out the effects of IVB on NDO. Medical records of preterm infants with ROP treatment and evaluation for NDO were retrospectively collected between 1 January 2017 and 31 June 2019. Primary outcome was Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) scores including cognitive, language, and motor scores. Secondary outcomes were neurodevelopmental impairments (NDIs) classified as the presence of any of cerebral palsy (CP), sensorineural/mixed hearing loss, visual impairment, and developmental delay with any Bayley-III score <85. Severe NDI (sNDI) was defined as presence of any of CP with a Gross Motor Function Classification Scale of 3, 4, or 5, requirement for hearing aids or cochlear implants, bilateral visual impairment or severe developmental delay with any Bayley-III score <70. LP, IVB, and IVB + LP groups included 32, 12, and 10 patients, respectively. Patent ductus arteriosus treatment rates were as 68.7, 75, and 90% in groups, respectively (p<.05 between LP and IVB + LP groups). Grades 3 and 4 intraventricular hemorrhage (IVH) was lower in LP group than IVB group (9.4% vs. 33.4%, p<.05) while IVB + LP group had no grades 3 and 4 IVH. Other neonatal characteristics were similar (p >.05). CP was in 50%, 28%, and 0% of LP, IVB, and IVB + LP groups (p<.05). There was no difference in median Bayley-III cognitive, language, and motor scores between groups (p >.05). Moderate and severe developmental delays were similar between groups (p >.05) whereas IVB group had more moderate cognitive delay; and more severe cognitive, language, and motor delay. NDI rate was not different (59.3%, 50%, and 40% in groups, p >.05). sNDI was highest in IVB group but not statistically significant (31.2, 41.7, and 10% in groups, p >.05). Multiple logistic regression analysis showed that ROP treatment type and grades 3 and 4 IVH did not have any significant effect on NDO (p >.05). Odds of NDI was not effected by ROP treatment type (p >.05). Patients treated with bevacizumab should be carefully monitored for neurodevelopmental problems, although the frequency of grades 3 and 4 IVH in the bevacizumab group is thought to contribute to higher rates of sNDI and Bayley-III score <70. [ABSTRACT FROM AUTHOR]

Large numbers of preterm infants are born in middle-income countries and neonatal care is improving in these countries. Few studies have compared clinical outcome in preterm infants in a tertiary neonatal unit in a middle-income country with one in a high-income country. To compare the short-term outcome in preterm infants of ≤30 weeks gestation admitted to a tertiary neonatal unit in Bengaluru, India and in London, UK. This was a retrospective observational study using anonymised data from electronic patient records. Preterm infants born at ≤30 weeks gestation admitted to neonatal units in Bengaluru (n = 294) and London (n = 740) over a 5-year period (January 2011 to December 2015) were compared. Fewer mothers in the Bengaluru centre received antenatal steroids (37% vs 73%, p < 0.001). The incidence of retinopathy of prematurity requiring treatment (12.9% vs 7.7%, NS), treated patent ductus arteriosus (32.3% vs 10.7%, NS) and blood culture-positive sepsis (32.4% vs 1.7%, p < 0.001) was higher in infants in the Indian centre. Overall survival was 83% vs 87.2% (NS) in the Bengaluru and the London cohorts, respectively. Survival of infants born at ≤28 weeks gestation was lower in Bengaluru than in London [24 weeks: 33.0% vs 79.3% (NS); 25 weeks: 50.0% vs 78.9%, p = 0.02; 26 weeks: 45.2% vs 86.5%, p < 0.01; 27 weeks: 79.3% vs 91.3% (NS); 28 weeks 82.5% vs 94.1%, p = 0.03]. The survival of infants ≤28 weeks gestation was significantly lower in the Bengaluru centre. Increasing the provision of antenatal corticosteroids may improve the outcome in these infants. BPD: bronchopulmonary dysplasia; CPAP: continuous positive airway pressure; EPR: electronic patient records; HIC: high-income countries; HDU: high dependency unit; hsPDA: haemodynamically significant patent ductus arteriosus; IVH: intraventricular haemorrhage; ITU: Intensive Care Unit, IUGR: intrauterine growth restriction; LAMA: leaving against medical advice; LMIC: low- and middle-income countries; NICU: neonatal intensive care unit; NNFI: National Neonatal Forum of India; NS: not significant; NTS: neonatal transfer service; NNAP: National Neonatal Audit Programme; NHM: National Health Mission; NMR: neonatal mortality rate; NEC: necrotising enterocolitis; NS: not significant; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; SCBU: special care baby unit; VLBW: very low birthweight; WHO: World Health Organization [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP.Objective: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates.Study Design: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP.Result: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial. [ABSTRACT FROM AUTHOR]

In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p <.001, p <.001, p =.022, p =.004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p <.001, p =.019, p =.017, p =.017, respectively). Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is the major ocular problem of preterm infants that occurs with abnormal proliferation of immature retinal vessels. Although pentoxifylline (PTX) was reported to inhibit vasculogenesis and neovascularization in experimental studies, there is no clinical data about the effects of PTX treatment on the development and severity of ROP. This clinical study aimed to investigate the possible effects of PTX on the development of ROP. A single-centre retrospective study was conducted including preterm infants who were hospitalised in the neonatal intensive care unit between 2015–2017 years. Infants were divided into two groups in terms of PTX administration for adjuvant therapy, as PTX and non-PTX groups. A total of 211 infants were included in the study [gestational age 29 (27–31) weeks, birth weight 1140 (960–1340) g]. From these, 97 infants (46%) were given PTX treatment. The two groups were similar in terms of demographic data and baseline clinical characteristics. Any stage of ROP was detected in 47.4% of infants in the PTX group, which was significantly higher than those in the non-PTX group (27.2%) (p = 0.002). The incidence of advanced-stage ROP in the PTX group (10.3%) was also higher than in the non-PTX group (2.6%) (p = 0.021). Repeated usage of PTX was not found to be related to the development of ROP (p = 0.059). The time of PTX administration was similar between the ROP and no-ROP groups (median; one vs one week, p = 0.825). Surfactant therapy, duration of hospital stay, and PTX treatment were found as significant risk factors for ROP in the logistic regression analysis. In contrast to the experimental studies and also promising results of PTX treatment in some neonatal morbidities, it may be associated with increased incidence and stage of ROP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the causes of blindness and visual impairment in children aged 0–7 years attending a Low Vision Centre in Mexico City, Mexico. Methods: Clinical records for patients aged 0–7 years attending the Centre from 2001 to 2015 were retrospectively reviewed. Causes of blindness and visual impairment, affected anatomy, and suspected time period of insult were recorded. Results: 1487 patients were included, 45.9% girls and 54.1% boys. Mean age of presentation was 39 months (SD 27.9 months). 36.0% had associated co-morbidities in addition to their ophthalmic pathology. 39.7% presented with developmental or psychomotor delay. Leading diagnoses were Retinopathy of Prematurity (ROP) (19.6%), optic nerve atrophy (11.5%), and congenital cataract (9.5%). The most affected anatomical regions were retina (33.8%), optic nerve (16.6%), and lens (10.5%). Half of all cases (50.9%) had insults in the prenatal period. Children with developmental delay were more likely to present before the age of one. There is a significant difference in risk of delayed presentation according to diagnosis. Only 13.5% of children with optic nerve atrophy presented to the Centre before the age of one, compared to 28.4% of children with ROP and 23.4% of children with cataract. Conclusion: The most common diagnoses for blindness and visual impairment among children were ROP, optic nerve atrophy, and congenital cataract. Late presentation to the Centre was common. There were significant differences in risk of delayed presentation depending on diagnosis. Co-existing systemic conditions and developmental and psychomotor delay were also common among patients attending the Centre. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) has become the main cause of blindness in children. To study resilience, anxiety and depression, coping style and social support and their correlation in parents of premature infants undergoing outpatient fundus examination for ROP, and thereby provide evidence for clinical intervention. Questionnaire surveys were conducted by using General Information Questionnaire, Connor-Davidson Resilience Scale, Self-rating Anxiety Scale, Self-rating Depression Scale, Social Support Scale, and the Simplified Coping Style Questionnaire. The resilience in the parents scored (63.24 ± 12.97) points, which was lower than that of Chinese norm (t = 2.309, P < 0.05). The scores of anxiety and depression were higher than those of Chinese norm (t = 12.592, t = 2.362, both P < 0.05). The score of social support was lower than that of Chinese norm (t = 3.793, p < 0.01). Resilience was negatively correlated with anxiety and depression (r = -0.287, -0.358, both P < 0.01), and positively correlated with coping tendency and social support (r = 0.299, 0.139, both P < 0.05). These findings suggested that the parents have low resilience, high levels of anxiety and depression, and low level of social support. Medical staff should assess and improve their psychological status. [ABSTRACT FROM AUTHOR]

To investigate VEGF and Ang-2 level changes in the systemic circulation after laser photocoagulation in premature infants with ROP. Methods: Eleven infants (4 girls and 7 boys) had serum levels determined for VEGF and Ang-2, collected 1 day prior to and 7 days after ROP laser therapy. Serum levels of VEGF and Ang-2 were quantified by enzyme-linked immunosorbent assay (ELISA). Results: Serum VEGF levels were significantly lower at 7 days after laser therapy compared to that at 1 day prior to laser therapy (p = 0.045). Serum Ang-2 levels increased significantly at 7 days after laser therapy compared with that at 1 day prior to laser therapy (p = 0.046). Conclusions: Serum VEGF levels in patients with ROP were suppressed and Ang-2 levels elevated significantly after laser therapy. The results suggest that changes in VEGF and Ang-2 serum levels may reflect regression and treatment of ROP. [ABSTRACT FROM AUTHOR]

Purpose: To report the changes in incidence and risk factors of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants over a 15-year period in South China. Methods: The medical records of ELBW infants were retrospectively reviewed through established database of Shenzhen Screening for ROP Cooperative Group. The incidence and severity of ROP were compared among three successive 5-year periods (P1: 2004–2008, P2: 2009–2013, P3: 2014–2018). Gestational age, birth weight, plurality, mode of delivery and gender were analyzed as risk factors for ROP in ELBW infants. Results: Among the 1099 included ELBW infants, 557 (50.7%) had ROP, and 328 (29.9%) had severe ROP. The highest incidence of ROP (87.5%) and severe ROP (82.5%) were seen in P1. From P2 to P3, the incidence of ROP and severe ROP increased from 45.9% to 50.3% for ROP (P <.05) and from 26.4% to 28.3% for severe ROP (P <.05), respectively. Multivariate logistic regression analysis found only gestational age has a significant effect on the incidence of ROP and severe ROP. Conclusions: From 2004 to 2018, the incidence of ROP and severe ROP in ELBW infants in South China was 50.7% and 29.9%, respectively. Controlling for the other risk factors, only gestational age was statistically associated with ROP in ELBW infants. [ABSTRACT FROM AUTHOR]

Clinical relevance: Retinopathy of prematurity is a preventable blinding disorder worldwide. Laser photocoagulation is said to be the gold standard care of treatment. However, various factors are known to affect the outcome.Background: The purpose of this study was to analyse the risk factors in patients with laser treatment requiring retinopathy of prematurity (ROP) and the outcome of 532 nm Nd:YAG laser photocoagulation (LP).Methods: Patients who underwent LP for ROP at a tertiary referral centre between January 2012 and January 2019 were enrolled. Those who were born and followed-up at the institution of the authors were in Group 1 and those who were born and followed-up elsewhere and referred to the authors for treatment were in Group 2. The clinical features, gestational ages, birth weights, and data regarding the treatment were retrospectively reviewed. The need for pars plana vitrectomy was taken as a poor outcome.Results: The mean gestational age and birth rate was 26.7 ± 1.9 weeks and 927.2 ± 263.5 grams, respectively, in Group 1 (57 infants, 111 eyes); and 28.5 ± 2.5 weeks and 1174.8 ± 385 grams, respectively, in Group 2 (66 infants, 131eyes) (p < 0.001 for both). The extent of the disease (p < 0.001), the zone of the disease (p = 0.002), and the timing of LP (p < 0.001) were significantly different between groups. In the whole cohort, the zone (p = 0.006) and stage (p < 0.001) of the disease, aggressive posterior disease (p = 0,009), and tunica vasculosa lentis were found to significantly interfere with the outcome.Conclusion: Eyes with more severe disease undergoing timely treatment and eyes with less severe disease undergoing delayed management had similar prognosis. A favourable outcome was obtained with 532 nm green laser in ROP. [ABSTRACT FROM AUTHOR]

Identifying at-risk infants for retinopathy of prematurity (ROP) is complex in countries with emerging economies as infants that lack conventional risk factors, such as low birth weight (BW) and young gestational age (GA), still go on to develop severe ROP. Potential biomarkers, like serum insulin-like growth factor 1 (IGF-1) and slow postnatal weight gain, have been identified as good predictors for ROP in developed countries. We sought to determine the relationship between IGF-1 levels and ROP in two Latin American countries where the burden of disease is still significant. Prospective cohort study of infants in Guadalajara, Mexico and La Plata, Argentina. Filter-paper bloodspot IGF-1 assays were performed weekly from birth until hospital discharge or 40 weeks' postmenstrual age (PMA). 112 infants were studied with a median BW of 1412 g (range 620 g-2390 g) and a median GA of 33 weeks (range 25–37). There was no significant difference in IGF-1 between infants who developed ROP and those who did not. Low IGF-1 was not associated with ROP in these infants. The lack of an association between ROP and IGF-1 in Latin America supports the observation that growth-based predictive models do not perform as well in this setting where more mature babies still develop severe ROP. [ABSTRACT FROM AUTHOR]

Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA). Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed. Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision. Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to investigate the effect of breast milk and sucrose on pain scores and perfusion index (PI) and to evaluate the alteration in pain and PI during retinopathy of prematurity (ROP) examination.Methods: This prospective randomized controlled study was conducted with preterm infants who were born in our hospital, hospitalized in the neonatal intensive care unit and whose gestational week was <32 weeks and birth weight was <1500 g. The preterm infants who would undergo ROP examination were allocated to three groups according to simple randomization method as follows: group 1: only local anesthetic eye drops, proparacaine HCl ophthalmic solution 0.5%, group 2: proparacaine HCl ophthalmic solution 0.5% plus breast milk, and group 3: proparacaine HCl ophthalmic solution 0.5% plus sucrose 24%. Postductal PI, transcutaneous oxygen saturation and heart rate (HR) values were measured before the eye examination (0), at the 30th, 60th, and 90th seconds (s) of the eye examination and 30 s after lasting of the examination in all infants. Pain was evaluated using Neonatal Infant Pain Scale (NIPS) during the examination.Results: Fifty-one preterm neonates were prospectively enrolled into the study. The HR was higher during and after the examination in all infants according to before the examination (p < .001). Transcutaneous oxygen saturation values significantly decreased during the examination in breast milk and sucrose groups (p = .001 and <.001, respectively). While PI was found to be lower at the 60th s compared to the 30th s of the examination in the proparacaine HCl group, no difference was found between the values before and after the examination. Perfusion index was found to significantly decrease during and after the examination compared to the values before the examination in the breast milk group. Perfusion index values were determined to significantly decrease at the 30th and 60th s of the examination in the sucrose group. The NIPS scores during the examination were determined to be higher compared to the NIPS scores before the examination in all groups (p< .001). In the intergroup comparisons, the NIPS scores were found to be higher in the sucrose group compared to the proparacaine HCl group at the 60th s of the examination and higher than that in the breast milk group at the 90th s of the examination (p = .02 and p = .01, respectively).Conclusions: The present study indicates that alterations may be seen in PI during the ROP examination; in other words, peripheral tissue perfusion could be affected. We consider that eye examination is a very painful procedure, and administering breast milk, sucrose or local anesthetic is not sufficient for reducing pain. [ABSTRACT FROM AUTHOR]

To determine the symmetry of retinopathy of prematurity (ROP) between fellow eyes in a broad-risk cohort. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The objective of this study was to validate the generalizability of the Postnatal Growth and Retinopathy of Prematurity Study screening criteria in a new cohort of infants at risk for retinopathy of prematurity (ROP). This retrospective validation study conducted at a single academic medical center included 484 infants at risk for ROP born between January 14, 2014, and December 21, 2019. The primary outcomes evaluated were sensitivity for both type 1 and type 2 ROP, as defined by the Early Treatment of Retinopathy of Prematurity Study, as well as the reduction in total number of infants requiring ROP examinations. Secondary outcomes included the total number of ROP examinations avoided and the potential cost reduction of eliminating these examinations. In a cohort of 484 infants at risk for ROP, the criteria identified 40 of 40 (100%, 95% confidence interval 91.19%–100%) type 1 ROP cases and 27 of 27 (100%, 95% confidence interval 87.23%–100%) type 2 ROP cases while reducing the total number of infants screened by 35.7%. The Postnatal Growth and Retinopathy of Prematurity Study criteria were found in this study to be generalizable to a cohort of infants at a single teaching institution in central Texas. If applied during the studied interval, these criteria could have significantly reduced the number of infants undergoing ROP examinations and maintained excellent sensitivity for type 1 ROP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between partial pressure of carbon dioxide (PCO2) during the first 3 days of life and retinopathy of prematurity (ROP) in extremely low birthweight (ELBW) infants.Patients and methods: A retrospective evaluation of data on ELBW infants were collected over a period of 4 years. Data during the first 72 hours of life was divided into six, 12-hour epochs. The average highest and overall means of PCO2, PO2, FiO2, and glucose were calculated for each epoch. Logistic regression analysis was used to determine the association between PCO2 and ROP after controlling for covariables.Results: A total of 78 neonates were included: birth weight (BW) (703 ± 157 g) and gestational age (25 ± 1.4 weeks). A total of 45 out of 78 had ROP: stage 1 (N = 8), stage 2 (N = 26), stage 3 (N = 14), and plus (N = 4). The overall mean PCO2 correlated with ROP in the first 72 hours of life (R = 0.31, p = .0069). This correlation was significant in epochs 2 (p = .049), 4 (p = .008) and 6 (p = .038). The average of the highest PCO2 also correlated with ROP in the first 72 hours of life (R = 0.38, p = .0007). This correlation was significant in epochs 2 (p = .0115), 4 (p = .0011), 5 (p = .028) and 6 (p = .037). The correlation between the stage of ROP and PCO2 was significant after controlling for PO2 and glucose concentrations. Other variables that correlated with ROP were the overall means of FiO2 (R = 0.23, p = .04), PO2 (R = 0.39, p = .0005) and glucose (R = 0.39, p = .0004) as well as the average highest concentrations of FiO2 (R = 0.26, p = .025), PO2 (R = 0.38, p = .0008) and glucose (R = 0.34, p = .007).Conclusion: After controlling for confounding variables, ROP correlated with the overall means and average highest PCO2. ROP also correlated with FiO2, PO2 and glucose concentrations. Further studies are needed to define the safe PCO2 range and the effect of PCO2 on the normal development of the retina. [ABSTRACT FROM AUTHOR]