BACKGROUND: This research aimed to identify the clinical profile and risk factors of retinopathy of prematurity (ROP) among \"at-risk\" newborns treated at a sick newborn care unit (SNCU) located at high altitude in North India, with the intention of contributing to formulate regional and national ROP screening guidelines.
METHODS: In a prospective observational study from 2021 to 2022, outborn and inborn babies eligible for ROP screening were screened.
RESULTS: Total 39/122 screened neonates had laser for Type 1 ROP, and 22/39 (56.4%) had aggressive ROP (AROP). The average birth weight (BW) was 1803.87 g, and the average gestational age was 34 weeks. Respiratory distress, bronchopulmonary dysplasia, sepsis, and apnea were present in 57.3%, 13%, 52.5%, and 25.4%, respectively. Sight-threatening ROP was present in 50% below 28+6 weeks, 27% between 29 and 30+6 weeks, 52% between 31 and 33+6 weeks, and 15% with gestation >34 weeks. Two babies with Type 1 ROP weighed >2 kg and one had AROP. Upon regression analysis, BW <1500 g, gestation <32 weeks, oxygen >48 h, clinical sepsis, total SNCU stay >14 days, continuous positive airway pressure support with oxygen >50%, and >10 days to achieve full feeds were associated with severe ROP. Caffeine to treat apnea and kangaroo mother care reduced ROP. None had short-term unfavorable outcome.
CONCLUSIONS: With similar infrastructure and work force shortage in most SNCUs, these findings can be generalized. The burden of Type 1 and AROP is increasing, as seen in higher gestation and BWs. This needs revision of ROP screening criteria at local and national level. It is crucial to emphasize on the importance of pediatrician and ophthalmologist collaboration, early ROP screening, diagnosis, and treatment to stop disease progression to severe ROP.

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UNASSIGNED: To describe fluorescein angiography (FA) parameters observed in premature neonates with retinopathy of prematurity (ROP).
UNASSIGNED: Retrospective case series.
UNASSIGNED: Patients with ROP who underwent FA imaging using Retcam at Holtz Children\'s Hospital from November 2014 to October 2022.
UNASSIGNED: Fluorescein angiography images of the included patients were analyzed with a focus on the timing of angiography phases, including choroidal flush, retinal, and recirculation phases. Gestational age, birth weight (BW), age at imaging, treatment choice, and any FA complications were documented.
UNASSIGNED: Dose of fluorescein administered, onset and duration of each angiography phase, and FA findings in ROP-treated patients.
UNASSIGNED: A total of 72 images of 72 eyes were reviewed. Image quality was deemed suitable for inclusion in 64 eyes (88.9%) of 43 patients. The mean gestational age and BW at birth were 24.4 ± 1.9 weeks and 607.8 ± 141.3 g, respectively. The mean postmenstrual age at FA imaging was 50.5 ± 40.8 weeks. All eyes (100%) received treatment with intravitreal injection of anti-VEGF at a mean age of 35.5 ± 2.4 weeks. The onset and duration of angiography phases were relatively variable within the cohort. Choroidal flush occurred at a mean time of 12.2 seconds (range: 6-22 seconds). A subsequent retinal phase was documented at a mean time of 11.96 seconds (range: 3-22 seconds). Recirculation phase was complete at an average time of 2.15 minutes (range: 1-5.45 minutes) postfluorescein injection. None of patients developed allergic reactions to fluorescein injection, such as rash, respiratory distress, tachycardia, fever, or local injection site reactions.
UNASSIGNED: Angiographic phases on FA in preterm infants with ROP are variable and may occur earlier than the established references for adults.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND: Retinopathy of prematurity (ROP) is an important cause of visual morbidity among preterm infants. The objective of the study was to assess the relationship between the initial hematological parameters of the complete blood count (CBC) and ROP development in preterm neonates.
METHODS: This retrospective cohort study was conducted in a neonatal intensive care unit in Odisha. The hematological parameters of the CBC conducted within the first 48 hours of age, demographic characteristics, neonatal morbidities, and ROP screening findings of preterm neonates (gestational age <34 weeks) were analyzed. Independent risk factors associated with ROP development were identified in a multivariate logistic regression model.
RESULTS: A total of 43 (29.1%) out of 148 neonates had any of the ROP stages (stage 1-26, 2-08, and 3-09). Birth weight (aOR 0.003; 95% CI 0.00, 0.11);hemoglobin (Hb) level (aOR 0.70; 95% CI 0.54, 0.90); presence of respiratory distress syndrome (RDS) (aOR 7.61; 95% CI 1.5, 36.39); and need for packed red blood cell (PRBC) transfusion (aOR 4.26; 95% CI 1.1, 16.44) were independently associated with ROP development. The odds of ROP were higher among the neonates with initial Hb 10.5-15.4 g/dL (OR (95% CI) 3.7(1.5, 8.9), p=0.003) and for neonates with Hb 15.4-17.3 g/dL (OR (95% CI) 2.5(1.01, 6.16), p=0.047) in comparison to neonates with initial Hb >17.3 g/dL.
CONCLUSIONS: Preterm neonates with a lower level of Hb during the early postnatal days are at higher risk for ROP development and need to be prioritized for screening.

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP\'s pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management.

To investigate biometric and refractive results in patients with type 1 retinopathy of prematurity (ROP) treated by intravitreal injection (IVI) of ranibizumab (R) and bevacizumab (B) at the corrected age of 6. This is a single-center retrospective study. Infants diagnosed with type 1 ROP and treated with IVI of either R or B as the primary therapy were included. Data on axial length, anterior chamber depth (ACD), and lens thickness (LT) were obtained using A-scan ultrasound. Cycloplegic refraction, keratometry (K), and best-corrected visual acuity were also documented. Additionally, optical coherence tomography angiography was performed to assess the foveal avascular zone and the density of superficial and deep vessels. We analyzed the structural and functional differences between the 2 groups and compared them with findings from a previous study conducted when these children were between the ages of 1 and 3. The study included 60 eyes from 34 patients, with 34 eyes receiving B and 26 eyes receiving R injections for ROP. In biometric outcomes, there was still a deeper ACD (3.36 ± 0.24 mm in the B group; 3.52 ± 0.21 mm in the R group) and thinner LT (3.63 ± 0.16 mm in the B group; 3.53 ± 0.12 mm in the R group) in the R group, as previously reported at the age of 3. In the refractive aspect, the eyes treated with B had higher myopia at the ages of 1 and 3; however, at the age of 6, refractive errors did not differ significantly between the 2 groups. At the corrected age of 6, the eyes treated with IVI of R were associated with deeper ACD and thinner LT. Interestingly, the emmetropization process resulted in a similar incidence of high myopia at the age of 6, which was different from the outcomes observed at younger ages.

BACKGROUND: Preterm 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.
METHODS: BORN 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.
RESULTS: Results 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.
CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.
BACKGROUND: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

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

BACKGROUND: 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.

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.