Risk Of Retinopathy Of Prematurity Research Articles

The association of cytokine levels and postnatal factors with retinopathy of prematurity.

Prematurity has been known to trigger several cellular pathways, leading to the clinical occurrence of retinopathy of prematurity (ROP). This study compared the levels of a panel of serum cytokines in premature infants with and without ROP. This is a prospective observational study. Premature infants at 36-38 weeks' gestational age were recruited, their clinical data recorded, and serum samples collected and assayed for 18 cytokines. Based on follow-up examinations, patients were divided into two groups: No ROP and ROP. The ROP group was further divided into two subgroups: non-vision-threatening ROP (non-VTROP), and vision-threatening ROP (VTROP). On univariate analysis, among the clinical parameters, gestation age, birth weight, duration of invasive ventilation, and duration of stay in neonatal intensive care unit (NICU) were found to be significant. The univariate analysis also showed an association between raised levels of VEGF-D and IL-8 in the VTROP group. Multiple logistic regression indicated that gestation age was a significant risk factor across all subgroups. Additionally, VEGF-D levels were found to be significantly associated with VTROP. Higher VEGF-D levels are associated with an increased risk of severe ROP that requires treatment and could potentially be used as a biomarker.

Eyedealistic Vision: Optimizing Oxygenation to Reduce Severe Retinopathy of Prematurity in the Neonatal Intensive Care Unit.

Rates of severe retinopathy of prematurity (ROP) continue to rise globally despite advances in healthcare. Differences in practices related to optimizing oxygenation is among key factors that increase the risk of severe ROP. A recent increase in severe ROP rates at 2 local neonatal intensive care units (NICUs) prompted further investigation into potential preventative practices. The project team's goal was to reduce rates of severe ROP by 20% in the 2 participating units. A level IV and level III NICU were targeted, including 255 infants at risk for ROP. Interventions included staff education, implementation of new established oxygen guidelines, as well as use of order sets, and alarm limits. Compliance rates and severe ROP rates before and after new guideline implementation were assessed. After implementing the new guidelines, average alarm limit compliance met project goals of 90% at both sites. Severe ROP rates declined from 10% to 7% in the level IV NICU site and from 6% to 0% in the level III NICU site during the 24-month study period from 2022 to 2023. Education and increased understanding regarding risk factors for ROP patients are crucial to successfully implementing and sustaining standardized oxygenation guidelines. Including the entire healthcare team and patient families is key to successful QI initiatives and improving patient outcomes. Further research is needed for optimal standardized oxygen alarm limits for this patient population. One of the leading causes of childhood blindness is retinopathy of prematurity (ROP).1 ROP is a disease of the retina that affects premature infants, with the highest risk to very low birthweight (VLBW) infants born with a gestational age of less than 30 to 32weeks or infants weighing less than 1500 grams.2 There are 5 stages of ROP. Stages 1 and 2 are considered mild and resolve on their own. Stage 3 is considered moderate-severe and sometimes resolves independently, with many cases requiring treatment. Stages 4 and 5 ROP are deemed severe and require treatment.

Trends in Retinopathy of Prematurity Among Preterm Infants in California, 2012 to 2021

The incidence of retinopathy of prematurity (ROP) has been increasing in the US since 2003. Understanding the progression of and racial disparities in ROP incidence in California can provide a contrasting perspective that may guide future research and practice in the management and prevention of ROP. To describe how the screening and incidence of ROP among very preterm infants in California changed from January 1, 2012, to December 31, 2021. This study used a cohort of very preterm infants (defined as infants born prior to 32 weeks' gestational age or weighing less than 1500 g) admitted to 60 neonatal intensive care units across California from January 1, 2012, to December 31, 2021. Among this cohort, several factors were examined, including (1) the clinical and sociodemographic covariates of the population with and without ROP, (2) trends in screening for ROP, and (3) the incidence of ROP in total and by race and ethnicity. Data analysis was performed in April 2024. Race and ethnicity and other birthing parental and infant descriptive characteristics. Incidence rates of ROP and severe ROP. The primary measures were rates of ROP screening and incidence rates of ROP and severe ROP. Time trends in the risk of ROP and severe ROP were estimated using robust Poisson regression models. In this cohort of 39 269 very preterm infants (<32 weeks' gestational age) eligible for ROP screening, the mean (SD) infant gestational age was 28.6 (2.6) weeks. The mean (SD) birth weight was 1075 (274) g, and 48.6% of infants were female. The birthing parents of the population were 12.6% Asian, 13.3% Black, 44.9% Hispanic White or Hispanic other race, 0.7% Native American/Alaskan, 24.7% non-Hispanic White, and 1.0% Pacific Islander. From January 1, 2012, to December 31, 2021, in California, ROP screening rates remained steady at 95% or greater for eligible infants less than 30 weeks of gestational age for all race and ethnic subgroups. In this study cohort among all very preterm infants (<32 weeks' gestational age), the incidence of ROP decreased from 31% in 2012 to 29% in 2021. Incidence rates of ROP among Asian and Hispanic individuals decreased the most quickly compared to other racial and ethnic groups, narrowing disparities. In this cohort study, in contrast to increasing national trends, the total incidence of and racial and ethnic disparities in ROP incidence remained steady or decreased from 2012 to 2021 in California.

Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study.

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. We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. 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. 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.

Red Blood Cell Transfusion for Incidence of Retinopathy of Prematurity: Prospective Multicenter Cohort Study.

Retinopathy of prematurity (ROP) is a leading cause of visual impairment and blindness in preterm infants. This study sought to investigate the association between red blood cell (RBC) transfusion and ROP in very preterm infants (VPIs) to inform clinical strategies for ROP prevention and treatment. We designed a prospective multicenter cohort study that included VPIs and follow-up data from January 2017 to December 2022 at 3 neonatal clinical medicine centers. They were categorized into a transfusion group (infants who received an RBC transfusion within 4 wk) and a nontransfusion group. The relationship between RBC transfusion and ROP incidence was assessed using binary logistic regression, with subgroup analyses based on gestational age, birth weight, sex, and sepsis status. Inverse probability of treatment weighting and propensity score matching were applied to account for all potential confounding factors that could affect ROP development, followed by sensitivity analysis. The study included 832 VPIs, including 327 in the nontransfusion group and 505 in the transfusion group. The transfusion group had a lower average birth weight and gestational age and a greater incidence of ROP, ≥stage 2 ROP, and severe ROP. Logistic regression analysis revealed that the transfusion group had a significantly greater risk of ROP (adjusted odds ratio [aOR] 1.70, 95% CI 1.14-2.53, P=.009) and ≥stage 2 ROP (aOR 1.68, 95% CI 1.02-2.78, P=.04) but not severe ROP (aOR 1.75, 95% CI 0.61-5.02, P=.30). The trend analysis also revealed an increased risk of ROP with an increasing number of transfusions and a larger volume of blood transfused (P for trend<.001). Subgroup analyses confirmed a consistent trend, with the transfusion group at a higher risk for ROP across all subgroups. Inverse probability of treatment weighting and propensity score matching analyses supported the initial findings. For VPIs, RBC transfusion significantly increases the risk of ROP, and the risk increases with an increasing number of transfusions and volume of blood transfused.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

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.

Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.

The Third Epidemic of Blindness: Early ROP Screening vs. KIDROP Conventional Screening of Retinopathy of Prematurity in Neonates- A Prospective Cohort Study

Aim: To assess the benefits of initiating early Retinopathy of Prematurity (ROP) screening compared to conventional KIDROP screening and study the incidence, severity, and risk factors of ROP. Methods: Preterm neonates born with weight &lt; 2000 g and/or &lt; 36 weeks of gestation admitted to the Level III-A neonatal intensive care unit (NICU), BLDE (Deemed to be University), Shri B. M. Patil Medical College, Hospital and Research Centre, were enrolled in the study. The in-house retina specialist performed Early ROP screening at 10-14 days of life, depending on the gestational age at birth. Subsequently, KIDROP conventional screening was done at 3 to 6 weeks of life by the Karnataka Internet Assisted Diagnosis for Retinopathy of Prematurity (KIDROP) team once weekly. ROP findings were recorded as per the standard ICROP norms. The data was analyzed for gestational age, birth weight, and systemic factors predisposing to ROP. Results: The incidence of Early ROP was 14% (7/50). Of the neonates diagnosed with ROP, 43% had a gestational age of &lt; 30 weeks, and 86% had birth weight in the group 1000- 1500 g. The incidence of type 1 ROP is 28.5% (2/7). The significant predictors of the increased risk of ROP were birth weight, gestational age, prolonged oxygen therapy, synchronized intermittent mandatory ventilation (SIMV), sepsis, patent ductus arteriosus (PDA), and nutrition, including MOM &amp; Parenteral Nutrition. Conclusion: Early enrolment of neonates for ROP screening in the NICU itself ensures early diagnosis and timely intervention and also ensures compliance and routine follow-up of these neonates. 14% had early ROP, which suggests the need to redefine the ROP screening criteria.

Early-Onset Sepsis as an Early Predictor for Retinopathy of Prematurity: A Meta-analysis.

Neonatal sepsis has been established as a risk factor for retinopathy of prematurity (ROP) but previous meta-analyses have predominately focused on late-onset sepsis (LOS). This meta-analysis aims to explore the association between early-onset sepsis (EOS) and the risk of ROP. Observational studies reporting (unadjusted) data on proven EOS in neonates with ROP were included. PubMed, Embase, and Cochrane Library were searched. Proven EOS was defined as a positive blood or cerebrospinal fluid culture. Effect sizes were calculated by using logistic random-effects models and meta-regression analyses. Primary outcomes were any stage ROP and severe ROP (≥stage 3, type I, aggressive [posterior] ROP, plus disease or requiring treatment). Potential confounders explored were gestational age at birth, birth weight, small for gestational age, maternal steroid use, necrotizing enterocolitis, LOS, and mechanical ventilation duration. Seventeen studies reporting the incidence of proven EOS in neonates with ROP were included. Proven EOS showed no significant association with any stage ROP (odds ratio [OR] = 1.90; 95% confidence interval [CI]: 0.96-3.79, p = 0.067) but heterogeneity between studies was significantly high. Neonates with proven EOS had an increased risk for severe ROP (OR = 2.21; 95% CI: 1.68-2.90), and no significant confounders influencing this effect size were found in the meta-regression analysis. Neonates with proven EOS are at increased risk of severe ROP. Neonatologists need to be aware that EOS is an early predictor of ROP and should adapt their policy and treatment decisions where possible to reduce ROP. · This meta-analysis reveals a 2.2-fold increased risk of severe ROP in neonates with proven EOS.. · Future studies should distinguish between EOS and LOS when investigating risk factors of ROP.. · Treatment decisions should be adapted where possible in neonates with EOS before ROP screening begins..

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial

BackgroundPreterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP.MethodsBORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions.ResultsResults in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk.ConclusionsThe interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.Trial registrationProspectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Predicting Retinopathy of Prematurity Risk Using Plasma Levels of Insulin-like Growth Factor 1 (IGF1), Tumor Necrosis Factor-Alpha (TNF-Alpha), and Neonatal Parameters.

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. 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. 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). 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.

The impact of a multidisciplinary intervention to reduce severe retinopathy of prematurity in Kampala, Uganda.

To address the threat of retinopathy of prematurity (ROP) in Sub-Saharan Africa (SSA), the Stop Infant Blindness in Africa (SIBA) project introduced a comprehensive program, including subspecialty training and oxygen management equipment. A before-and-after retrospective cohort study compared preterm infants < 1750 g or < 34 weeks' gestation before (2022) and after (2023) program implementation. Outcomes included: the proportion with severe ROP, the proportion with Zone III vascularization on first examination, and factors associated with severe ROP. Overall, 140 infants were screened before and 122 after program implementation. The proportion with Zone III vascularization increased from 16.1% (N = 11) pre-intervention to 44.9% (N = 32) post-intervention (p = 0.001). The proportion with severe ROP decreased from 27.8% (N = 19) to 12.8% (N = 9, p = 0.03). Factors predicting severe ROP on adjusted analyses were gestational age and blood transfusion. In SSA, introduction of a comprehensive program to prevent and treat ROP can decrease the risk of severe ROP.

Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non-consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA-metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC-MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti-inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm-born infants.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

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.

Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/− 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = − 0.2 and r = − 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

Effect of Kangaroo Mother Care on Retinopathy of Prematurity in Neonates Less Than 1,800 g or Below 34 Weeks of Gestation

Introduction KMC (Kangaroo Mother Care) is an established intervention to reduce mortality and morbidity in low birth weight (LBW) neonates. A multitude of risk factors and preventive strategies for ROP (retinopathy of prematurity) have been studied, however, the effect of KMC on ROP has not been reported. This study aims to study the effect of KMC on ROP in neonates with birth weights between 1,000 and 1,800 g. Methods The babies who received effective KMC (&gt;6 hours per 24 hours for three consecutive days) were analysed in the intervention group and those with ineffective KMC were analysed in the control group. Variables significant in univariate analysis were entered into backward regression models in multivariate analysis. Odds ratios and 95% confidence intervals were calculated. P values &lt; .05 are taken as significant. Results Of 783 neonates enrolled, 66 (8.4%) developed ROP (any stage). The incidence of ROP requiring intervention was 1.02%. Effective KMC reduced the risk of ROP by 95%, RR 0.05 (0.02–0.12) and number needed to treat = 5. The proportion of neonates with ROP in zone 1 and stage 3 was more in the ineffective KMC (42.4% vs. 1.5%) group than in the effective KMC group (51.5% vs. 0%) ( P &lt; .001). Ineffective KMC, gestation &lt;30 weeks, small for gestation, obstetric complications, asphyxia, sepsis, higher initial PEEP and lack of breastfeeding were significant risk factors for developing ROP. Conclusion KMC, an effective intervention to improve the mortality and morbidity in LBW neonates, was significantly associated with the reduction of any stage ROP and ROP needing intervention, potentially preventing a significant cause of childhood blindness.

Occult retinal neovascularization following intravitreal bevacizumab and laser treatment for retinopathy of prematurity

BackgroundWe present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression.Case presentationThe patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted.ConclusionsWorsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.

Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity

ObjectiveTo identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). Study designWe retrospectively analyzed two different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks’ gestation (January 2003 through April 2021, n=38,013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n=118). ResultsFor Cohort1, after adjusting for potential confounders, stage III CAM (n=5,554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.78–0.94]. CAM of stage I (n=3,277) and II (N=4,319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05–0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01–0.93). ConclusionsAfter adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Tear Proteomics in Infants at Risk of Retinopathy of Prematurity: A Feasibility Study.

This feasibility study investigated the practicability of collecting and analyzing tear proteins from preterm infants at risk of retinopathy of prematurity (ROP). We sought to identify any tear proteins which might be implicated in the pathophysiology of ROP as well as prognostic markers. Schirmer's test was used to obtain tear samples from premature babies, scheduled for ROP screening, after parental informed consent. Mass spectrometry was used for proteomic analysis. Samples were collected from 12 infants, which were all adequate for protein analysis. Gestational age ranged from 25 + 6 to 31 + 1 weeks. Postnatal age at sampling ranged from 19 to 66 days. One infant developed self-limiting ROP. Seven hundred one proteins were identified; 261 proteins identified in the majority of tear samples, including several common tear proteins, were used for analyses. Increased risk of ROP as determined by the postnatal growth ROP (G-ROP) criteria was associated with an increase in lactate dehydrogenase B chain in tears. Older infants demonstrated increased concentration of immunoglobulin complexes within their tear samples and two sets of twins in the cohort showed exceptionally similar proteomes, supporting validity of the analysis. Tear sampling by Schirmer test strips and subsequent proteomic analysis by mass spectrometry in preterm infants is feasible. A larger study is required to investigate the potential use of tear proteomics in identification of ROP. Tear sampling and subsequent mass spectrometry in preterm infants is feasible. Investigation of the premature tear proteome may increase our understanding of retinal development and provide noninvasive biomarkers for identification of treatment-warranted ROP.

Identifying associations of human surfactant protein A SNPs and allelic variants with retinopathy of prematurity

Retinopathy of prematurity (ROP) is the primary cause of childhood blindness worldwide. Previous studies showed that allelic single nucleotide polymorphic (SNP) variants of the human surfactant protein A genes (SP-A1, SP-A2) are associated with the development of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). In this work, we hypothesized that SP-A SNPs and allelic variants are associated with altered risk of ROP in prematurely born infants. To test this hypothesis, we used a modified PCR-based method to detect variants of the SP-A1 and SP-A2 genes in a cohort of preterm infants. Infants born at &lt;32 weeks’ gestation and/or&lt;1500 grams were enrolled. Scavenged blood samples or cheek swabs were collected and DNA was extracted using the QIAamp DNA Mini Kit. We measured SNPs in SP-A1 and SP-A2 using Taqman probes for allelic discrimination by PCR or PCR/RFLP/sequencing method. Associations of SP-A1 and SP-A2 SNP allele frequencies with ROP and BPD were determined using chi-square and logistic regression analyses. Our results show that, of the total patient cohort (n=59), 42 patients had a BPD diagnosis (23 with ROP and 36 without ROP). DNA analysis of these samples identified associations of SP-A1 and SP-A2 SNPs and variants with ROP. For SP-A1, the following SNP associations were found for ROP using chi-square: rs1059047 (p=0.44), rs1136450 (p=0.63), rs1136451 (p=0.21), rs1059057 (p=0.52). For SP-A2, the following SNPs associations were identified with ROP: rs1059046 (p=0.51), rs17886395 (p=0.050), rs1965707 (p=0.031), rs1965708 (p=0.46). Logistic regression analysis indicated an association of ROP with the SP-A1 6A2 variant (p-value = 0.47, OR (6A2/*)=0.8036, 95%CI [0.2299 - 2.8082], OR (6A2/6A2) = 0.4327, 95%CI [0.1063 - 1.7615]), which conferred protection, as well as an association of ROP with SP-A2 6A2 (p-value = 0.0055) with decreased risk when 1A2 variant is present. We conclude that SP-A1/SP-A2 polymorphisms are associated with the presence of ROP in infants with BPD. The 6A4 SP-A1 and SP-A2 1A2 appear to confer protection in babies against ROP. Further studies will determine the mechanisms of this protective effect. Indiana University, University of Chicago Metcalf Internship Program Grant, The University of Oklahoma Health Sciences Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.