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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

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]

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]

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]