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We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p

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]

Objective: Our study aims to evaluate and compare the macular microvascular condition of the intravitreal Bevacizumab (IVB)-treated retinopathy of prematurity (ROP) cases to the preterm cases without ROP and spontaneously regressed ROPs. Methods: It is a retrospective cohort of 50 premature neonates visited from 2016 to 2017 for ROP screening in Nikookari Eye Hospital and recalled for re-evaluation in 2022. These patients were classified into three groups based on their medical documents: 1. Preterm cases without ROP (PT), 2. Spontaneously regressed ROPs (SR), and 3. IVB-treated ROPs (IVB). All the included cases underwent a thorough ophthalmic exam, cyclo-refraction, Best-corrected visual acuity (BCVA) assessment, and macular optical coherence tomography angiography (OCTA). The foveal thickness, foveal avascular zone (FAZ) area, foveal, parafoveal, and perifoveal vascular density (VD) were evaluated as the quantitative variables. Results: Twenty-five male and 25 female cases with a median age of 5.0 entered the study. Twenty-six eyes were evaluated in the PT group, 50 in the SR group, and 24 in the IVB group. The SR group consisted of 25 zone-2 and 25 zone-3 ROPs. In comparison, the IVB group consisted of 9 zone-1 and 15 zone-2 ROPs (p: < 001). Also, zone-2 cases were more advanced in the IVB group. The IVB-treated eyes demonstrated a significantly higher foveal superficial capillary plexus (SCP) VD than the others (28.5% vs. 23.1 and 22.9, respectively, in PT and SR, p:0.008). However, the parafoveal deep capillary plexus (DCP) VD was lower than the PT cases (48.5% vs. 53.4, p:0.034). The FAZ area was also smaller than the PT cases (0.113 vs.0.219 mm2, p:0.032). The FAZ area was significantly positively correlated with the foveal SCP and DCP VD and negatively correlated with parafoveal DCP VD (CC: -0.770, -0.719, 0.377, respectively, p: < 0.001). Conclusion: In the long term, although the IVB-treated ROP cases experience an excellent visual outcome comparable to those without ROP, they may show some macular microvascular changes. These changes might be related to the effect of IVB or the nature of more advanced stages of ROP. [ABSTRACT FROM AUTHOR]

Background: To investigate the quantitative vascular and structural differences in the foveal region of the eyes in retinopathy of prematurity children with or without anti-vascular endothelial growth factor (VEGF) therapy and healthy children using optical coherence tomography angiography (OCTA). Methods: This cross-sectional study analyzed 75 eyes from 44 subjects, categorized into four groups: ROP children treated with Conbercept or Ranibizumab, spontaneously regressed ROP, and healthy age-matched children. Using spectral-domain OCT and OCTA, we assessed parameters like central foveal thickness (CFT), foveal avascular zone (FAZ), superficial/deep capillary plexus (SCP/DCP), and choroidal vessel density (VD) at the fovea. Correlations between foveal microvasculature, preterm status and visual acuity were evaluated. Results: Significant differences were found in FAZ area, CFT, and VD-SCP (parafoveal) among the groups. The FAZ area was smaller in ROP children (with/without treatment) than in healthy counterparts(p = 0.009). CFT was higher in the Ranibizumab and spontaneously regressed groups compared to healthy ones (p = 0.043, p = 0.037), while Conbercept-treated children showed no significant difference (p = 0.886). Foveal VD trends were higher in groups A, B, and C compared to group D. FAZ area correlated negatively with CFT, VD-SCP (foveal), and VD-DCP (foveal) (p < 0.001, p < 0.001, p = 0.001), and positively with choroidal VD (p = 0.012). CFT showed positive correlations with VD-SCP (foveal) and VD-DCP (foveal) (p = 0.003, p = 0.001). Conclusion: ROP children exhibit a smaller FAZ area compared to healthy group, with no significant difference noted when comparing the use of different anti-VEGF agents. ROP children have a thicker CFT than healthy children, except for those treated with Conbercept. Furthermore, microvascular irregularities were correlated with central foveal thickness. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) remains a major cause of childhood blindness. Its pooled prevalence worldwide is 31.9%, and that of severe ROP is 7.5% among prematurely born babies. Investigating risk factors is essential for improving early detection and treatment outcomes. Purpose: To determine the frequency and stages of ROP cases and evaluate the treatment methods for premature infants at the Medical University of Vienna. Methods: In this retrospective study, 352 children who underwent ROP screening between 2018 and 2021 with a gestational age (GA) ≤ 32 weeks and/or a birth weight (BW) ≤ 1500 g were included. Results: ROP was found in 144 (40.9%) of the 352 screened premature infants, with 17 (4.8%) requiring treatment. Significant risk factors included GA and BW, while sex and pregnancy type were not significant. The mean GA was 27.7 ± 2.5 weeks, and the mean BW was 989.1 ± 359.7 g. Infants with ROP had a lower GA (25.9 ± 1.7 weeks) and BW (778.6 ± 262.4 g) than those without ROP (28.9 ± 2.2 weeks; 1134.9 ± 345.9 g). GA and BW were significantly lower in infants developing ROP (p < 0.001). Stage 2 ROP was the most common severity in 74 children (51.4%). Laser therapy was the most common first-line treatment, used in 11 infants (64.7%), followed by anti-VEGF therapy, used in 6 infants (35.3%). Children were treated within 1.0 ± 0.6 days on average. Of the 17 infants treated, 14 (82.4%) showed initial regression. Three infants (17.6%) required re-treatment: two with initial anti-VEGF therapy and one after laser therapy. Conclusions: The findings provide insights into ROP's prevalence and treatment preferences at a university tertiary care center. GA and BW were confirmed to be significant predictors, aiding in early detection and informing treatment decisions. These insights will enable comparisons with similar studies and contribute to improved patient care. [ABSTRACT FROM AUTHOR]

Background: Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods: Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman's correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results: Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions: Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases. [ABSTRACT FROM AUTHOR]

Background Aim Study Design Results Conclusions Relevance to Clinical Practice Retinopathy is frequently seen in the neonatal intensive care unit (NICU), and its examination is a painful procedure for infants.This randomized active‐controlled trial aimed to investigate the impact of multisensory stimulation (MSS) on neonatal pain during retinopathy of prematurity (ROP) examinations, in comparison with a white noise (WN) and control group receiving standard care.Conducted as a three‐arm, randomized controlled trial, the study was implemented in the NICU of a local university hospital. Recruitment spanned from July 2023 to November 2023, with preterm infants (gestational age < 37 weeks) randomly assigned to either a MSS, WN or a control group. MSS components included visual, auditory, tactile, olfactory and gustatory stimuli, all designed to create a synergistic, comforting environment for the infant during the procedure. Procedural pain, heart rate and oxygen saturation were assessed at various stages before and after ROP examinations.Analysis of 90 participants revealed that the MSS group exhibited lower Premature Infant Pain Profile (PIPP) scores than the WN and control groups (mean difference: −2.12, 95% confidence interval [CI]: −2.62 to −1.62; odds ratio [OR]: 0.004, 95% CI [0.001, 0.012], p < 0.001). Additionally, heart rates were significantly lower in the MSS group (mean difference: −15.3 beats/min, 95% CI: −20.5 to −10.1; OR: 0.025, 95% CI [0.008, 0.073], p < .001) and oxygen saturation levels were higher (mean difference: 3.2%, 95% CI: 1.8% to 4.6%; OR: 1.12, 95% CI [1.05, 1.20], p < .001) than in the other groups.MSS emerges as a favourable, safe and non‐pharmacological intervention for pain management in ROP and similar procedures.Multisensory stimulation can be effectively integrated into the routine care provided by critical care nurses during retinopathy of prematurity examinations in preterm infants. This non‐pharmacological intervention offers a practical approach for critical care nurses to reduce procedural pain and improve physiological stability in this vulnerable population. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To assess the predictive performance of DIGIROP‐v1.0 models in identifying treatment‐requiring ROP among infants undergoing ROP screening at a tertiary neonatal intensive care unit in Greece.Retrospective cohort analysis of 640 consecutive screened preterm infants with gestational age (GA) 240/7 to 306/7 weeks and known ROP outcome in the 2nd Neonatology Department of Aristotle University of Thessaloniki (2009–2021). The primary outcome was the development of type 1 ROP according to the Early Treatment of ROP criteria or treatment based on the ophthalmologist's judgement. Sensitivity, specificity, area under the curve (AUC) with corresponding 95% confidence intervals (CI) and calibration plots for the DIGIROP‐v1.0 models were displayed.The DIGIROP‐Birth‐v1.0 model correctly identified 35/43 treated infants (sensitivity 81.4% [95% CI, 66.6%–91.6%], specificity 61.5% [95% CI, 57.4%–65.4%], AUC 0.82 [95% CI, 0.75–0.90]). During the postnatal weeks 6–14 the sensitivity of the DIGIROP‐Screen‐v1.0 model ranged from 82.6% to 100%. Eleven infants, all with severe comorbidities, that is, congenital malformation(s), syndrome(s), hydrocephalus or history of intestinal surgery, that were treated, were missed by the model, but met criteria for screening according to DIGIROP‐v1.0 models' recommendations, and to our unit's routine standards.The DIGIROP‐v1.0 models resulted in lower sensitivity and higher specificity in this Greek cohort compared with the Swedish development group. Despite higher GA and BW, infants in our cohort had higher incidence of treated ROP than in Sweden, resulting in an under‐estimation of their risk for treatment‐requiring ROP. Further validation of the DIGIROP‐v2.0 models and potential adjusting are recommended to maximize generalizability in populations with different characteristics. [ABSTRACT FROM AUTHOR]

Objective: The objective is to study to what extent the development of retinopathy of prematurity (ROP) is associated with assisted conception (AC) and in vitro fertilization (IVF) in a tertiary referral hospital. Materials and Methods: This study is a retrospective observational cohort study. Very-low-birth weight (VLBW) infants with gestational age (GA) <32 weeks or birth weight <1500 g were admitted to the neonatal unit of a tertiary care hospital between January 1, 2011, and December 31, 2021. The study determined the degree of ROP developed according to the type of fertilization used for conception. Main outcome measures were ROP prevalence in pregnancies obtained after IVF/intracytoplasmic sperm injection (ICSI) in the period from January 1, 2011, to December 31, 2021, in a tertiary hospital. Results: Of the 408 infants included in the study sample, 105 (25.7%) were born following AC and 12.4% of these developed ROP. In our sample, the practice of IVF was not associated with an increase in the incidence of VLBW infants (R² = 0.12; P = .29). Conclusion: Conception achieved via AC or IVF is not significantly associated with ROP in any degree of severity. [ABSTRACT FROM AUTHOR]

To evaluate whether providing clinicians with an artificial intelligence (AI)-based vascular severity score (VSS) improves consistency in the diagnosis of plus disease in retinopathy of prematurity (ROP). Multireader diagnostic accuracy imaging study. Eleven ROP experts, 9 of whom had been in practice for 10 years or more. RetCam (Natus Medical Incorporated) fundus images were obtained from premature infants during routine ROP screening as part of the Imaging and Informatics in ROP study between January 2012 and July 2020. From all available examinations, a subset of 150 eye examinations from 110 infants were selected for grading. An AI-based VSS was assigned to each set of images using the i-ROP DL system (Siloam Vision). The clinicians were asked to diagnose plus disease for each examination and to assign an estimated VSS (range, 1–9) at baseline, and then again 1 month later with AI-based VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye examination from the Imaging and Informatics in ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis. Mean linearly weighted κ value for plus disease diagnosis compared with RSD. Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPR) for labels 1 through 9 compared with RSD for plus disease. Expert agreement improved significantly, from substantial (κ value, 0.69 [0.59, 0.75]) to near perfect (κ value, 0.81 [0.71, 0.86]), when AI-based VSS was integrated. Additionally, a significant improvement in plus disease discrimination was achieved as measured by mean AUC (from 0.94 [95% confidence interval (CI), 0.92–0.96] to 0.98 [95% CI, 0.96–0.99]; difference, 0.04 [95% CI, 0.01–0.06]) and AUPR (from 0.86 [95% CI, 0.81–0.90] to 0.95 [95% CI, 0.91–0.97]; difference, 0.09 [95% CI, 0.03–0.14]). Providing ROP clinicians with an AI-based measurement of vascular severity in ROP was associated with both improved plus disease diagnosis and improved continuous severity labeling as compared with an RSD for plus disease. If implemented in practice, AI-based VSS could reduce interobserver variability and could standardize treatment for infants with ROP. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

The International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), acknowledged that plus-like retinopathy of prematurity (ROP) vascular changes occurs along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photograph reference image set for grading plus-like changes and compared intergrader agreement of the set with standard grading with no plus, preplus, and plus disease. Retinal photographic grading and expert consensus opinion. The development set included 34 international ICROP3 committee members. The validation set included 30 ophthalmologists with ROP expertise (15 ICROP3 committee members and 15 non-ICROP3 members) Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on the 34 ICROP3 committee members' gradings and consensus image reviews, were used to establish standard photographs for the plus (P) score. Study participants graded 150 fundus photographs 2 ways, separated by a 1-week washout period: (1) no plus, preplus, or plus disease and (2) choosing the closest P score image. Intergrader agreement measured by intraclass correlation coefficient. Intergrader agreement was higher using the P score (intraclass correlation coefficient, 0.75; 95% confidence interval, 0.71–0.79) than no plus, preplus, or plus disease (intraclass correlation coefficient, 0.67; 95% confidence interval, 0.62–0.72). Mean ± standard deviation P scores for images with mode gradings of no plus, preplus, and plus disease were 2.5 ± 0.7, 4.8 ± 0.8, and 7.4 ± 0.8, respectively. Intergrader agreement of plus-like vascular change in ROP using the P score is high. We now incorporate this 9-image reference set into ICROP3 for use in clinician daily practice alongside zone, stage, and plus assessment. P score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of the International Classification of Retinopathy of Prematurity. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Apnea of prematurity (AOP) occurs in 85% of neonates ≤34 weeks of gestational age. AOP is frequently associated with intermittent hypoxia (IH). This narrative review reports on the putative relationship of AOP with IH and the resulting oxidative stress (OS). Preterm infants are susceptible to OS due to an imbalance between oxidant and antioxidant systems with the excessive free radical load leading to serious morbidities that may include retinopathy of prematurity, bronchopulmonary dysplasia, and neurodevelopmental delay. Current therapeutic approaches to minimize the adverse effects of AOP and optimize oxygen delivery include noninvasive ventilation and xanthine inhibitor therapy, but these approaches have only been partially successful in decreasing the incidence of AOP and associated morbidities. [ABSTRACT FROM AUTHOR]

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP. [ABSTRACT FROM AUTHOR]

Objective: Pathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization. Methods: OIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation. Results: In OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV. Conclusions: Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases. [ABSTRACT FROM AUTHOR]

Background: Bovine colostrum (BC) with liposomal delivery system (LDS) is a promising supplement to premature infant formula in absence of mother own milk. We propose that BC with LDS can target multiple etiological factors that threaten the developing retina, making premature infant less liable for retinopathy of prematurity (ROP). The aim of this study was to evaluate the effect of BC with LDS in the prevention of ROP. Methods: This was a single center, randomized, controlled trial. Two hundred and eleven preterm infants of gestational age ≤ 32weeks were admitted to the NICU of Alexandria University Children Hospital, Egypt, and randomly allocated into either non-BC group (n = 105) or BC group (n = 106). Patients in BC group received 3.5 ml /kg/day of BC for 14 days. All patients were monitored for development of ROP, anemia, late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC), in addition to growth assessment. Multivariate binary logistic regression analysis was performed to determine factors predicting ROP development. Results: Compared with the non-BC group, BC group was associated with a significantly lower incidence of ROP (5/100 vs. 16/100, respectively) with a p-value of 0.033. The administration of BC significantly decreased serum C- reactive protein (CRP) level and increased weight on day-14 of the study in comparison with the CRP level and birthweight at the beginning of study, with Cohen's D= -0.184, D = -2.246, respectively. Patients with suspected sepsis were significantly less in BC than non-BC group, p = 0.004. Patients with BC had significantly higher hemoglobin level on day-14 than non-BC-group, with median (IQR) 12.2 (11.0–13.9) and 11.7 (10.5–12.9), respectively. BC intake is one of factors that decreased development of ROP in univariate analysis. Nevertheless, weight gain and birth weight were the most significant factors affecting ROP development in multivariate-regression model. Conclusion: BC may reduce the incidence of ROP in preterm neonates aged ≤ 32 weeks. This might be due to keeping better Hb level and growth rate, as well as anti-inflammatory properties through its ability to decrease CRP level. Trial registration: This work was registered on 06/13/2022 in clinicaltrial.gov with ID no.: NCT05438680 and URL:https://classic.clinicaltrials.gov/ct2/show/NCT05438680?term=NCT05438680&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To investigate the validity of WINROP use in multi‐ethnic population in a tertiary centre in Singapore.Birth weight, gestational age, and weekly weight measurements of four hundred two preterm infants (<32 weeks gestation) born between year 2011 and 2019 were entered into WINROP algorithm. Based on their weekly weight gain, WINROP algorithm would signal an alarm if the infant is at risk for type 1 ROP requiring treatment. The WINROP result is then compared with the ophthalmological findings. All the infants were screened based on the hospital ROP screening protocol. The negative predictive value, positive predictive value, sensitivity and specificity were calculated.Among all the infants enrolled, 31 infants developed type 1 ROP. WINROP successfully signalled 23 out of 31 correctly. The calculated sensitivity was 74.2 % and specificity was 48.0 %. The positive predictive value was 10.6% and negative predictive value was 95.7%.Our study showed that when WINROP is applied to our multi‐ethnic population, it has a moderate sensitivity of 74.2% and a high predictive negative value of 95.7%. We would not recommend it to be used a solitary screening method but it can be used to better risk stratify preterm infants at risk of type 1 ROP, particularly in resource limited settings. [ABSTRACT FROM AUTHOR]

Purpose: To assess retinopathy of prematurity (ROP) practice patterns during the coronavirus (COVID-19) pandemic. Methods: A survey on ROP practice patterns during the COVID-19 pandemic was sent to the American Academy of Ophthalmic Executives, the International Pediatric Ophthalmology and Strabismus Council members, and to various national societies on May 19, 2020. The survey closed on the 31st of June 2020. Results: Two hundred ninety-two ophthalmologists from 41 countries responded to the survey. Most replies originated in Asia (48%) and North America (38%). During the COVID-19 pandemic compared to the pre-COVID-19 period, respondents reported a reduction of 15% in the number of NICU inpatients and 19.8% of the ROP outpatients' follow-up visits. The number of ROP outpatients' follow-up visits and inpatients' exams was significantly greater in North America than in Asia (72.0% versus 37.2% and 87.8% versus 49.6%, respectively, P < 0.001). Only 14% of the ophthalmologists adopted new screening guidelines, and 7.2% reported changing their preferred treatment. In 50% of responders, laser photocoagulation was the preferred treatment. A significantly higher percentage of ophthalmologists reported using telemedicine during the pandemic, 29.8% (n = 85/285), and 15.6% (44/282) prior to the pandemic (χ2 = 15.51, p < 0.001). Conclusions: During the COVID-19 pandemic, fewer ROP screening and follow-up visits were conducted on premature infants; these findings were especially prominent among physicians in Asia. Telemedicine usage increased during the pandemic. This study highlights the need to maintain screening protocols for ROP during pandemics. The utility of technological measures could enable this, along with adequate prevention of physical contact. [ABSTRACT FROM AUTHOR]

The diagnosis of retinopathy of prematurity (ROP) is primarily image-based and suitable for implementation of artificial intelligence (AI) systems. Increasing incidence of ROP, especially in low and middle-income countries, has also put tremendous stress on health care systems. Barriers to the implementation of AI include infrastructure, regulatory, legal, cost, sustainability, and scalability. This review describes currently available AI and imaging systems, how a stable telemedicine infrastructure is crucial to AI implementation, and how successful ROP programs have been run in both low and middle-income countries and high-income countries. More work is needed in terms of validating AI systems with different populations with various low-cost imaging devices that have recently been developed. A sustainable and cost-effective ROP screening program is crucial in the prevention of childhood blindness. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine the frequency of ROP development in premature infants hospitalized in the neonatal intensive care unit and/or referred to the ROP Diagnostic Unit of our hospital and to emphasize the importance of cooperation between ophthalmologists and neonatologists in the treatment and follow-up of infants with ROP. Materials and Methods: The findings of 287 premature infants who were followed and treated in the neonatal intensive care unit between January 2017 and November 2022 and then referred to the ROP Diagnostic Unit were retrospectively analyzed. They were classified according to birth weight and gestational age. They were divided into 4 groups according to birth weight (under 1000 g, between 1000-1250 g, between 1250-1500 g and over 1500 g) and 3 groups according to gestational age (under 28 weeks, between 29-32 weeks and over 33 weeks). ROP development rates were determined in these groups. Those who developed retinopathy of prematurity were classified according to their stages. Results: A total of 287 premature infants (141 boys and 146 girls) were included in the study. Twenty-eight of the premature babies were Syrian (9.8%). Mean gestational age at birth was 32.34 weeks (min. 24, max. 37) and mean birth weight was 1830.12 g (min. 750 g, max. 4000 g). 34 babies (11.8%) had stage 1 ROP and 12 babies (4.1%) had stage 2 ROP. 14 babies (4.9%) had plus. Due to the rapid progression of the clinic, 20 patients (7%) with stage 2 or higher ROP and plus were referred to an advanced center with ROP treatment center certification. Conclusion: Premature babies born under 34 weeks of gestation should be examined for retinopathy of prematurity. Early diagnosis of retinopathy of prematurity is very important to prevent blindness due to ROP, even if treatment is not possible according to local conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the feasibility of implementing telescreening for retinopathy of prematurity (ROP) using the ICON GO® widefield camera operated by a non-physician healthcare professional (NPHP). We hypothesized that images captured by an NPHP are adequate to evaluate ROP changes without further examinations. Secondly, the level of agreement between independent ROP graders were evaluated based on the fundus photographs. Methods: National ROP screening criteria were gestational age (GA) < 32 weeks or birthweight (BW) < 1500 g. Exclusion criteria were children hospitalized and born outside the Capital Region and examinations not performed by an NPHP. The screenings were performed using the ICON GO®. The NPHP selected the best images for evaluation by an on-site ophthalmologist, regarding whether re-examination was necessary and if so, whether the re-examination was beneficial. Lastly, the images were re-evaluated by an independent off-site ophthalmologist. Results: A total of 415 screening sessions on 165 patients performed by an NPHP were included. Re-examination was necessary in three screening sessions and beneficial in two. The level of agreement between the on-site and off-site ophthalmologists regarding ROP screening outcome was k = 0.82, ROP stage k = 0.69, plus disease k = 0.69, and lastly ROP zone k = 0.37. Of the screened children, ninety-seven (58.8%) had no ROP at any time points, sixty-two (37.6%) had some stage of ROP not requiring treatment, and six (3.6%) received ROP treatment. Conclusions: Telemedicine screening for ROP with the ICON GO® camera performed by an NPHP was feasible with an almost-perfect agreement and negligible need for re-examinations. The approach effectively identified children needing treatment, supporting the use of telescreening in ROP management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of prematurity (ROP) is a severe condition primarily affecting premature infants with a gestational age (GA) of 30 weeks or less and a birth weight (BW) of 1500 g or less. The objective of this review is to examine the risk factors, pathogenesis, and current treatments for ROP, such as cryotherapy, laser photocoagulation, and anti-VEGF therapy, while exploring the limitations of these approaches. Additionally, this review evaluates emerging nanotherapeutic strategies to address these challenges, aiming to improve ROP management. Methods: A comprehensive literature review was conducted to gather data on the pathogenesis, traditional treatment methods, and novel nanotherapeutic approaches for ROP. This included assessing the efficacy and safety profiles of cryotherapy, laser treatment, anti-VEGF therapy, and nanotherapies currently under investigation. Results: Traditional treatments, while effective in reducing disease progression, exhibit limitations, including long-term complications, tissue damage, and systemic side effects. Nanotherapeutic approaches, on the other hand, have shown potential in offering targeted drug delivery with reduced systemic toxicity, improved ocular drug penetration, and sustained release, which could decrease the frequency of treatments and enhance therapeutic outcomes. Conclusions: Nanotherapies represent a promising advancement in ROP treatment, offering safer and more effective management strategies. These innovations could address the limitations of traditional therapies, reducing complications and improving outcomes for premature infants affected by ROP. Further research is needed to confirm their efficacy and safety in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. Methods: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). Results: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). Conclusions: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP. [ABSTRACT FROM AUTHOR]

The p21‐activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. Purpose: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. Methods: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. Results: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05). Implications for Practice and Research: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. Methods: We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. Results: ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. Conclusions: These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the quantitative vascular and structural differences in the foveal region of the eyes in retinopathy of prematurity children with or without anti-vascular endothelial growth factor (VEGF) therapy and healthy children using optical coherence tomography angiography (OCTA). Methods This cross-sectional study analyzed 75 eyes from 44 subjects, categorized into four groups: ROP children treated with Conbercept or Ranibizumab, spontaneously regressed ROP, and healthy age-matched children. Using spectral-domain OCT and OCTA, we assessed parameters like central foveal thickness (CFT), foveal avascular zone (FAZ), superficial/deep capillary plexus (SCP/DCP), and choroidal vessel density (VD) at the fovea. Correlations between foveal microvasculature, preterm status and visual acuity were evaluated. Results Significant differences were found in FAZ area, CFT, and VD-SCP (parafoveal) among the groups. The FAZ area was smaller in ROP children (with/without treatment) than in healthy counterparts(p = 0.009). CFT was higher in the Ranibizumab and spontaneously regressed groups compared to healthy ones (p = 0.043, p = 0.037), while Conbercept-treated children showed no significant difference (p = 0.886). Foveal VD trends were higher in groups A, B, and C compared to group D. FAZ area correlated negatively with CFT, VD-SCP (foveal), and VD-DCP (foveal) (p

Abstract Objective Our study aims to evaluate and compare the macular microvascular condition of the intravitreal Bevacizumab (IVB)-treated retinopathy of prematurity (ROP) cases to the preterm cases without ROP and spontaneously regressed ROPs. Methods It is a retrospective cohort of 50 premature neonates visited from 2016 to 2017 for ROP screening in Nikookari Eye Hospital and recalled for re-evaluation in 2022. These patients were classified into three groups based on their medical documents: 1. Preterm cases without ROP (PT), 2. Spontaneously regressed ROPs (SR), and 3. IVB-treated ROPs (IVB). All the included cases underwent a thorough ophthalmic exam, cyclo-refraction, Best-corrected visual acuity (BCVA) assessment, and macular optical coherence tomography angiography (OCTA). The foveal thickness, foveal avascular zone (FAZ) area, foveal, parafoveal, and perifoveal vascular density (VD) were evaluated as the quantitative variables. Results Twenty-five male and 25 female cases with a median age of 5.0 entered the study. Twenty-six eyes were evaluated in the PT group, 50 in the SR group, and 24 in the IVB group. The SR group consisted of 25 zone-2 and 25 zone-3 ROPs. In comparison, the IVB group consisted of 9 zone-1 and 15 zone-2 ROPs (p:

Retinopathy of prematurity (ROP) is a complex and unresolved problem in pediatric ophthalmology, leading to visual disability. Low birth weight and prematurity are the main risk factors, and they form the basis of clinical recommendations for screening for ROP in all children under 35 weeks of gestational age and weighing less than 2000 g. However, many researchers point to other risk factors that can be divided into maternal, prenatal and perinatal. In this review, we consider maternal diabetes mellitus as a risk factor for ROP. Changes in the retina in premature infants and mothers with diabetes mellitus have some common features, since pathological angiogenesis occurs at the basis of these diseases. In addition, diabetes is a risk factor for preterm birth, and prematurity is a leading cause of neonatal morbidity, including the development of ROP. This suggests that maternal diabetes mellitus may have both direct and indirect effects on the development of ROP. To develop predictive models, an understanding of risk factors for ROP, the pathophysiology of retinal vascular diseases, and diseases of prematurity is necessary.

Abstract Background Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman’s correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.

The purpose was to establish reference values for macular thickness, binocular vision, and stereopsis in premature infants aged 5-9 years and 10-13 years who underwent laser photocoagulation of avascular retinal zones due to retinopathy of prematurity (ROP); to assess and compare the data in an age-related perspective. Methods. Data from 24 premature infants who underwent ophthalmological examination, including optical coherence tomography, Titmus Stereo Fly Test, and the Worth 4 Dot Test, at ages 5-9 years and again at ages 10-13 years were analyzed. All children had undergone laser photocoagulation of avascular retinal zones due to ROP in infancy. Results. At ages 5-9 years, the mean central macular volume was 9.2 mm3, and the retinal thickness in the central fovea was 313.7 μm. At ages 10-13 years, the mean central macular volume was 9.1 mm3, and the retinal thickness in fovea was 320.8 μm. Normal binocular vision and stereopsis were observed in 79.2% and 33.3% of the children at the first time point, and in 87.5% and 45.8% at the second time point. Conclusions. No statistically significant difference in the central macular volume and macular thickness was detected between the two time points, (p>0.05). The thickest part of the macula was identified in the inner macula, followed by the outer macula, with the nasal quadrant being the thickest. Despite the anatomical peculiarities, high rates of binocular vision were observed at both time points, along with stereopsis at the second examination.

OBJECTIVE The objective of the study was to determine the incidence, patterns, and risk factors for the development of retinopathy of prematurity (ROP) in infants weighing >1500 g at birth. MATERIALS AND METHODS A retrospective analysis was done of the ROP screening records between April 2019 and March 2022. All the infants with birth weight >1500 g who underwent ROP screening were included. Data collected included demographic details, details of the risk factors (respiratory distress syndrome [RDS], hypoxia, anemia, septicemia, patent ductus arteriosus, congenital heart disease [CHD], i.e., atrial septal defects or ventricular septal defects, and multiple gestations), and ocular examination findings. Statistical analyses included calculation of mean, range, Chi-square test, and bivariate logistic regression for associations of risk factors with ROP. RESULTS ROP was noted in 16.6% of the 336 eyes of 168 infants. The mean birth weight and mean gestational age (GA) of the infants were 1850 ± 33 g and 33.33 weeks ± 1.71 weeks, respectively. Eighteen eyes (32.1%) had Stage I, 17 eyes (30.35%) had Stage II, and 11 eyes (19.64%) had Stage III ROP in Zone II. Aggressive ROP was seen in 8 eyes (14.28%) and stage 5 ROP in two eyes (0.59%). Male gender, GA, CHD, and RDS showed a statistically significant association with the development of ROP in these infants. CONCLUSION ROP was seen in 16.66% of our subjects. Treatment was required in 6.25% of infants. Risk factors for the development of ROP were low gestational age, male gender, the presence of RDS, and congenital heart disease.

Background: Retinopathy of prematurity (ROP) is a vaso-proliferative retinal disease which can cause blindness if not diagnosed early. The various risk factors associated with ROP other than pre mature birth and low birth weight are high flow oxygen, sepsis , multiple transfusions, multiple births, respiratory distress syndrome, apnoeic episodes, intraventricular haemorrhage. Poor antenatal care, unavailability, poor access and poorly monitored neonatal care are some of the factors contributing to increase in the number of ROP cases in developing countries. Objective: To study ROP in preterm and high risk neonates in a tertiary care hospital. To assess and record changes of ROP and the associated risk factors in the study population.. To document the staging of ROP. To determine the outcome of Retinopathy of Prematurity and the different modalities of treatment used. Material & Method: This study was conducted on 262 eyes of 131 neonates over a period of 18 months. All Pre term neonates having gestational age of less than or equal to 32 weeks and birth weight less than or equal to 1500gms and other older neonates more than 32 weeks of gestation and more than 1500gms of birth weight with risk factors for developing Retinopathy of prematurity (i.e on oxygen supplementation, Respiratory distress syndrome, Sepsis, Multiple blood transfusions, Apnoeic episodes, Intraventricular haemorrhage) , admitted and referred to our institute within the study period were screened for Retinopathy of Prematurity. Neonates observed having ROP were followed up till complete regression of ROP. Results: In our study ROP was observed in 18.32 % of neonates. There was significant relation of birth weight and gestational age with retinopathy of prematurity. Also risk factors like Respiratory distress syndrome and mechanical ventilation were significantly associated with retinopathy of prematurity. The treatment requiring cases of Retinopathy of Prematurity were 6.11% i.e 8 neonates. All the treatable cases were given ROP Laser therapy while 6 neonates were also given intra- vitreal injections of bevacizumab. Conclusion: Low birth weight, Prematurity, Respiratory distress syndrome, Mechanical ventilation were the risk factors significantly associated with ROP. Prompt screening and early diagnosis of ROP can help in reducing devastating complications and thus prevent blindness.

Abstract Background Bovine colostrum (BC) with liposomal delivery system (LDS) is a promising supplement to premature infant formula in absence of mother own milk. We propose that BC with LDS can target multiple etiological factors that threaten the developing retina, making premature infant less liable for retinopathy of prematurity (ROP). The aim of this study was to evaluate the effect of BC with LDS in the prevention of ROP. Methods This was a single center, randomized, controlled trial. Two hundred and eleven preterm infants of gestational age ≤ 32weeks were admitted to the NICU of Alexandria University Children Hospital, Egypt, and randomly allocated into either non-BC group (n = 105) or BC group (n = 106). Patients in BC group received 3.5 ml /kg/day of BC for 14 days. All patients were monitored for development of ROP, anemia, late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC), in addition to growth assessment. Multivariate binary logistic regression analysis was performed to determine factors predicting ROP development. Results Compared with the non-BC group, BC group was associated with a significantly lower incidence of ROP (5/100 vs. 16/100, respectively) with a p-value of 0.033. The administration of BC significantly decreased serum C- reactive protein (CRP) level and increased weight on day-14 of the study in comparison with the CRP level and birthweight at the beginning of study, with Cohen’s D= -0.184, D = -2.246, respectively. Patients with suspected sepsis were significantly less in BC than non-BC group, p = 0.004. Patients with BC had significantly higher hemoglobin level on day-14 than non-BC-group, with median (IQR) 12.2 (11.0–13.9) and 11.7 (10.5–12.9), respectively. BC intake is one of factors that decreased development of ROP in univariate analysis. Nevertheless, weight gain and birth weight were the most significant factors affecting ROP development in multivariate-regression model. Conclusion BC may reduce the incidence of ROP in preterm neonates aged ≤ 32 weeks. This might be due to keeping better Hb level and growth rate, as well as anti-inflammatory properties through its ability to decrease CRP level. Trial registration This work was registered on 06/13/2022 in clinicaltrial.gov with ID no.: NCT05438680 and URL: https://classic.clinicaltrials.gov/ct2/show/NCT05438680?term=NCT05438680&draw=2&rank=1 .

BACKGROUND/AIMS: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants. METHODS: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA. RESULTS: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 μm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 μm/week (95% CI: -0.9 to -0.6). CONCLUSION: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

This paper assesses the preferred treatment patterns for retinopathy of prematurity (ROP) and examine trends in anti-vascular endothelial growth factor (VEGF) use for ROP. Methods: A retrospective survey consisting of 14 questions was distributed to paediatric ophthalmology interest groups internationally. Main outcome measures included treatment patterns, proportion of anti-VEGF use in different stages of ROP; and comparison of first-line treatments as well as repeat anti-VEGF treatments. Results: Fifty-four ophthalmologists from 11 different countries responded to the survey. The number of respondents per question, except one, ranged between 50–54. Per annum, there was an average number of 394 infants screened by each respondent. Anti-VEGF was the preferred treatment method for aggressive (A)-ROP (64.1%), Type 1 ROP in zone 1 (71.7%), and Type 1 ROP in posterior zone 2 (56.6%). The majority used laser as the first-line treatment of Type 1 ROP in anterior zone 2 (73.6%) and Type 1 ROP in zone 3 (79.2%). Laser was the preferred treatment modality utilised in infants requiring repeat treatment following anti-VEGF injection. The preferred anti-VEGF agent was bevacizumab administered at a dose of 0.625 mg. Conclusions: Anti-VEGF as first-line therapy has been increasing. Anti-VEGF appears to be the first-line treatment of choice for A-ROP, Type 1 ROP in zone 1 and posterior zone 2 and laser for Type 1 ROP in anterior zone 2 and zone 3.

Purpose: To investigate peripapillary retinal nerve fiber layer (pRNFL) thickness changes in preterm children with or without retinopathy of prematurity (ROP) history compared to full-term children. Methods: A retrospective comparative cohort study assessing pRNFL thickness was completed in children aged 4–8 years. Four groups of children were included (n = 30 each group): children with a history of ROP who were treated with intravitreal bevacizumab, children with ROP who received no treatment, and preterm children without ROP compared to age- and gender-matched full-term children. Results: A total of 120 eyes from 120 children were enrolled in this study. Both treated and regressed ROP children showed a significantly thinner pRNFL in the nasal quadrant compared to full-term children (P = 0.017 and P = 0.008, respectively). The pRNFL in the superior quadrant of treated ROP children was thinner than the preterm and control groups (P = 0.015 and P = 0.023, respectively), whereas the inferior quadrant of treated ROP children was thinner than the preterm group alone (P = 0.008). The pRNFL thickness in the temporal quadrant was comparable between groups (P = 0.129). The average spatial distribution profile of pRNFL thickness in treated ROP children was significantly thinner than in the preterm group (P = 0.041). Conclusion: pRNFL thickness is significantly altered in children with a prior history of treated ROP with thinning of the nasal and superior quadrants compared to full-term children.

Objectives: To evaluate the characteristics and surgical outcomes of late-onset rhegmatogenous retinal detachment (RRD) associated with regressed retinopathy of prematurity (ROP) and the status of fellow eyes. Materials and Methods: Retrospective review of consecutive cases undergoing surgery for regressed ROP-related RRD and the fellow eyes between 2012-2022. Demographic data, fundus findings, retinal detachment characteristics, surgical procedures, and anatomic and functional outcomes were analyzed. Anatomic success was defined as retinal attachment after silicone oil removal at final follow-up. Results: Fifteen eyes of 14 patients with a history of regressed ROP underwent surgical repair for RRD at a mean age of 12 (range, 3-26) years. Primary surgical intervention yielded a 53% failure rate overall. This rate was 33% for scleral buckling (SB), 100% for pars plana vitrectomy (PPV), and 40% for combined SB-PPV surgery. Eyes with posterior cicatricial changes and/or proliferative vitreoretinopathy (PVR) demonstrated a higher tendency for recurrence. The final anatomic success rate was 73% after a mean number of 2.3 (range, 1-5) surgeries. The chances of restoring useful vision diminished with repeated surgery despite the improvement in anatomic success. In the fellow eyes, peripheral retinal pathologies were universally observed, with posterior cicatricial changes noted in 33%. Conclusion: The study reveals a significant initial failure rate in surgical treatment of cases with late-onset RRD associated with regressed ROP, particularly in eyes with posterior cicatricial changes or PVR, suggesting the need for a combined surgical approach as an initial strategy in such high-risk cases. The consistent presence of retinal abnormalities in fellow eyes calls for proactive monitoring and potential prophylactic intervention.

Abstract Background Retinopathy of prematurity (ROP) is a leading cause of avoidable blindness in children, particularly in Latin America, where hyperoxia is a significant risk factor. This study evaluated resource availability and use for administering and monitoring supplemental oxygen in Mexico. Methods In 2011, an observational study in which 32 government neonatal intensive care units (NICUs) across Mexico were visited. Data collected included occupancy, staffing levels, and equipment to deliver and monitor supplemental oxygen. Preterm infants receiving oxygen were observed. In 2023, 13 NICUs were revisited, and similar data collected. Staffing levels were benchmarked against Argentinian and US recommendations. Results In 2011, only 38% of NICUs had adequate medical and staffing levels to meet recommended cot-to-staff ratios for all shifts. Staffing ratios were worse during weekends and at night than during weekdays. Only 25.5% of cots had blenders, and 80.1% had saturation monitors. 153 infants were observed 87% of whom were being monitored. Upper and lower oxygen saturations were ≥ 96% in 53%, and ≤ 89% in 8%, respectively. Alarm settings were inadequate, as 38% and 32% of upper and lower alarms were switched off and 16% and 53% were incorrectly set, respectively. In the 13 NICUs with data from 2011 and 2023, cot-to-staff ratios deteriorated over time, and in 2023 no unit had recommended ratios for all shifts. Equipment provision did not change, with similar proportions of babies in oxygen being monitored (79% 2011; 75% 2023). Rates of hyperoxia decreased slightly from 54% in 2011 to 49% in 2023. More upper alarms were set (46% 2011; 75% 2023), but a higher proportion were incorrectly set (52% 2011; 68% 2023). Conclusions Between 2011 and 2023, cot-to-staff ratios worsened, and equipment for safe oxygen delivery and monitoring remained insufficient. Despite available monitoring equipment, oxygen saturations often exceeded recommended levels, and alarms were frequently not set or incorrectly configured. Urgent improvements are needed in healthcare workforce numbers and practices, along with ensuring adequate equipment for safe oxygen delivery.

Abstract Purpose The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II. Methods The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated. Results One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p 0.05). Conclusions Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group.

Abstract Introduction Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. Objective To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. Methods A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. Results ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. Conclusions We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.

AIM: To quantitatively assess the changes in mean vascular tortuosity (mVT) and mean vascular width (mVW) around the optic disc and their correlation with gestational age (GA) and birth weight (BW) in premature infants without retinopathy of prematurity (ROP). METHODS: A single-center retrospective study included a total of 133 (133 eyes) premature infants [mean corrected gestational age (CGA) 43.6wk] without ROP as the premature group and 130 (130 eyes) CGA-matched full-term infants as the control group. The peripapillary mVT and mVW were quantitatively measured using computer-assisted techniques. RESULTS: Premature infants had significantly higher mVT (P=0.0032) and lower mVW (P=0.0086) by 2.68 (104 cm-3) and 1.85 μm, respectively. Subgroup analysis with GA showed significant differences (P=0.0244) in mVT between the early preterm and middle to late preterm groups, but the differences between mVW were not significant (P=0.6652). The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA (P=0.0211 and P=0.0006, respectively). For each day increase in GA at birth, mVT decreased by 0.1281 (104 cm-3) and for each 1 g increase in BW, mVT decreased by 0.006 (104 cm-3). However, GA (P=0.9402) and BW (P=0.7275) were not significantly correlated with mVW. CONCLUSION: Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP. Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.

The medical industry is undergoing an active digital transformation, including the creation of electronic databases, cloud security systems, mobile health monitoring devices, and telemedicine tools. Artificial intelligence (AI), one of the most important technological achievements of the last decade, is gradually gaining momentum in various areas of practical medicine. The cutting edge of AI, neural networks, offers promising approaches to the improvement of clinical examination quality. The review presents data of studies focusing on the use of AI tools in the diagnosis of the most common ophthalmic diseases: diabetic retinopathy, macular degeneration, retinopathy of prematurity, glaucoma, cataracts, and ophthalmic oncology. We discuss both the advantages of neural networks in the diagnosis and monitoring of eye diseases, and outline the difficulties of their implementation, including ethical and legal conflicts.

Nigeria has the third largest incidence of premature birth, after India and China. Most babies that will require treatment for retinopathy of prematurity (ROP) have birth weight (BW) less than 1500g and gestational age (GA) less than 32 weeks, with initial eye examination within the first 30 days of life. This report aims to present the findings in three babies with vision threatening ROP that developed at less than 30 days of life. Routine screening for ROP was conducted for three babies. One was born GA 33 weeks, BW 1.6kg, screened for ROP on the 13th day of life, while the other two were a set of twins born at GA of 33 weeks, both BW 1.3kg, screened for ROP first on the 16th day of life. The twins were found CC –BY 4.0 to have arborizing vessels at the initial exam, which progressed to stage 3 pre-plus ROP by the 23rd day of life. The 3rd child had stage -3 plus disease at the first screening, warranting immediate LASER therapy. The screening criteria of Nigeria ROP group is BW ≤ 1500g or GA of ≤ 34 weeks, with the first eye examination within the first 30 days of life. These case reports show that larger babies can also develop sight threatening ROP within the first two weeks of life. There is a need for constant review of ROP screening criteria and timing based on locally available data

Abstract This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4–16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization

AIM: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP). METHODS: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information. RESULTS: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion. CONCLUSION: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

Background Methods Results Conclusions To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP).Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups.A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair.Reduced gut microbial diversity may be associated with ROP development in high‐risk preterm infants. Further research is needed to comprehend how early‐life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of retinal vascularization plays pathogenic roles in retinopathy of prematurity (ROP). Hypoxia-inducible factor 1 alpha (HIF1A) is activated by hypoxia and contributes to ROP progression. Herein, we clarified the mechanism underlying HIF1A activation in human retinal vascular endothelial cells (HRECs) under hypoxia. Methods: Protein expression was assayed by immunoblot analysis. Cell migration, microtubule formation, invasion, proliferation, and viability were detected by wound-healing, tube formation, transwell, EdU, and CCK-8 assays, respectively. Bioinformatics was used to predict the deubiquitinase-HIF1A interactions and RNA binding proteins (RBPs) bound to USP33. The impact of USP33 on HIF1A deubiquitination was validated by immunoprecipitation (IP) assay. RNA stability analysis was performed with actinomycin D (Act D) treatment. The ELAVL1/USP33 interaction was assessed by RNA immunoprecipitation experiment. Results: In hypoxia-exposed HRECs, HIF1A and USP33 protein levels were upregulated. Deficiency of HIF1A or USP33 suppressed cell migration, proliferation and microtubule formation of hypoxia-exposed HRECs. Mechanistically, USP33 deficiency led to an elevation in HIF1A ubiquitination and degradation. USP33 deficiency reduced HIF1A protein levels to suppress the proliferation and microtubule formation of hypoxia-induced HRECs. Moreover, the RBP ELAVL1 stabilized USP33 mRNA to increase USP33 protein levels. ELAVL1 decrease repressed the proliferation and microtubule formation of hypoxia-induced HRECs by reducing USP33. Conclusion: Our study identifies a novel ELAVL1/USP33/HIF1A regulatory cascade with the ability to affect hypoxia-induced pathological proliferation, angiogenesis, and migration in HRECs. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. Methods: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1–7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. Results: The ACS 1–7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1–7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. Conclusions: An ACS-to-delivery interval of 1–7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further. [ABSTRACT FROM AUTHOR]