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At least 19 recordsLinked to original sources
PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (&#x2264;30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗
PubMed2026

Assessment of Methodological Bias in Studies Reporting Racial Differences in Retinopathy of Prematurity in the United States.

PURPOSE: To assess methodological biases in studies reporting racial and ethnic differences in retinopathy of prematurity (ROP). METHODS: Systematic review of peer-reviewed studies published between 2014 and 2024 that reported on ROP outcome measures by race, ethnicity, or social determinants of health (SDOH). Three reviewers independently assessed each observation for selection and collider bias using definitions derived from perinatal epidemiology literature. Findings were also compared using a structured comparative synthesis between studies with and without identified methodological bias. RESULTS: A structured PubMed search identified 78 articles; 13&#x2009;met inclusion criteria, with one study contributing two distinct analytical approaches, yielding 14 total observations. Survivorship bias was identified in 6 of 14 observations (42.9%), primarily due to the exclusion of infants who died prior to ROP screening. Potential collider bias was most common, found in 9 of 14 observations (64.3%), and was introduced through adjustment or stratification by gestational age and/or birthweight. Three studies did not exhibit either assessed biases. Among studies with identified bias, 8 of 10 observations reported lower ROP risk among Black versus White infants, whereas 3 of 4 observations without identified bias reported higher ROP risk or incidence among Black infants. CONCLUSION: Methodological biases in ROP studies investigating race or ethnicity are prevalent. Adjustment for gestational age or birthweight may introduce spurious race-ROP associations and contribute to paradoxical findings. Further exploration of the impact of SDOH on disease outcomes may reduce the misattribution of race as a biological risk factor and improve the interpretation of ROP disparities.

Collider bias↗
PubMed2026

Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.

IMPORTANCE: Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. OBJECTIVE: To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. DESIGN, SETTING, AND PARTICIPANTS: This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. EXPOSURES: All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. MAIN OUTCOMES AND MEASURES: Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage &#x2265;3 and/or treated) and postnatal age. RESULTS: A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; &#x3b2;&#x2009;=&#x2009;0.68; 95% CI,&#x2009;0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; &#x3b2;&#x2009;=&#x2009;0.21; 95% CI,&#x2009;0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. CONCLUSIONS AND RELEVANCE: In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03201588.

Humans↗
PubMed2025

Retinal hypoxia reversal with PLGA-oxygen nanobubbles.

Pathologies associated with retinal hypoxia, including diabetic retinopathy, central/branch retinal artery occlusion (CRAO/BRAO), central/branch retinal vein occlusion (CRVO/BRVO), retinopathy of prematurity, sickle cell retinopathy, etc., have limited effective therapeutic intervention strategies. To address this shortcoming, herein we propose a biocompatible and biodegradable poly (lactic-co-glycolic acid) shell-based oxygen nanobubbles (PLGA-ONBs) platform, formulated with PLGA, polyvinyl alcohol (PVA), and NaHCO3. The formulation of a novel PLGA-ONBs was proposed, and the synthesis process was optimized with respect to dependent (sonication power, PVA, and NaHCO3 concentrations) and response (hydrodynamic diameter and oxygen capacity) variables. The optimized formulation has a concentration of (13.8 &#xb1; 0.01) &#xd7; 1010 particles per ml with a hydrodynamic diameter of 142.83 &#xb1; 11.46 nm, and oxygen loading capacity of 47.2 &#xb1; 2.4 mg L-1. After 4 weeks of storage, the ONBs were found to have an oxygen concentration of 38.9 &#xb1; 2.9 mg L-1, indicating excellent oxygen retention capability. The PLGA-ONBs tested in vitro in Muller and R28 retinal cell lines demonstrated excellent biocompatibility and potential to mitigate hypoxia. In addition, the PLGA-ONBs treatment on hypoxic cells demonstrated restoration of mRNA expression of three key hypoxic genes (HIF-1&#x3b1;, PAI-1, and VEGF-A) to normoxic states, indicating hypoxia reversal potential. Biosafety of the PLGA-ONBs was demonstrated in a rabbit model, demonstrating promise in clinical translation. The PLGA-ONBs developed exhibited excellent oxygen loading and retention, potential in hypoxia mitigation, and a safety profile that could be a promising route to treating ischemic diseases of the eye.

Polylactic Acid-Polyglycolic Acid Copolymer↗
PubMed1979

Retrolental fibroplasia.

Retrolental fibroplasia is more accurately referred to as retinopathy of prematurity. Host factors most clearly incriminated are the maturity of the infant and the time in oxygen therapy. A continuum of retinopathy ranges from abnormal arborization of terminal retinal vessels to a detached retina incorporated in a cicatrix behind the lens. Every high-risk infant should be examined by indirect ophthalmoscopy prior to discharge from the nursery. A thorough knowledge of the natural course of the disease is essential because many cases will resolve spontaneously.

Humans↗
PubMed2026

Umbilical Cord-Derived Cell-Based Interventions for Bronchopulmonary Dysplasia and Related Complications in Preterm Infants: A Bayesian Sparse-Data Meta-Analysis.

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with limited disease-modifying therapies. We evaluated umbilical cord-derived cell-based interventions for BPD and related complications in preterm infants. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-based systematic review and meta-analysis were registered in PROSPERO. PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to June 14, 2026. Comparative clinical studies of umbilical cord-derived cell-based interventions in preterm infants at risk of or diagnosed with BPD were included. Outcomes included BPD, BPD severity, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs). Bayesian random-effects meta-analysis used a binomial-normal hierarchical model to estimate pooled odds ratios (ORs), 95% credible intervals (CrIs), prediction intervals, and heterogeneity. Twelve studies were included. Umbilical cord-derived cell-based interventions showed a possible protective effect on overall BPD (OR, 0.48; 95% CrI, 0.14-1.20). Stronger associations were observed for severe BPD (OR, 0.17; 95% CrI, 0.01-0.85), moderate or severe BPD (OR, 0.28; 95% CrI, 0.09-0.70), and ROP stage &#x2265;3 (OR, 0.17; 95% CrI, 0.02-0.65). No conclusive benefit or harm was observed for death, PPHN, PDA, IVH, NEC, or LOS. No treatment-related serious AEs were identified. However, prediction intervals were generally wide, and the certainty of evidence was low to very low for most outcomes. Umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage &#x2265;3. Current evidence remains limited, and larger randomized trials with standardized outcomes and long-term follow-up are needed.

Humans↗
PubMed1977

Lipoperoxide level of the retina of chick embryo exposed to high concentration of oxygen.

To approach the mechanism of degeneration of the retina in retinopathy of prematurity, a model experiment using chick embryo was carried out. Upon exposing chick embryo at various stages to a high concentration of oxygen at 2 atm pressure, lipoperoxide levels of both the blood and the retina were elevated. The change in lipoperoxide level of the liver was not significant, except for a slight increase at the 9th day of incubation. Upon exposing chick embryo of the 14th day to high concentration of oxygen at ambient pressure, lipoperoxide levels of both the blood and the retina were elevated at 6 h and 12 h of exposure, but significant change was not observed in the lipoperoxide level of the liver.

Animals↗
PubMed1979

Observations of vitamin E in experimental oxygen-induced retinopathy.

Retrolental fibroplasia (RLF) is a proliferative retinopathy observed in premature infants. Its relationship to oxygen has led to both clinical and laboratory research into the potential benefits of the antioxidant tocopherol in this disorder. Although the clinical trials to date have only suggested a beneficial result, studies in the kitten model demonstrate two significant actions of tocopherol in protecting against this retinopathy, only one of which is predicted by theory. These data support the need for prospective controlled trials in human premature infants.

Animals↗
PubMed1979

Sequelae of caffeine treatment in preterm infants with apnea.

Growth, neurologic, and ophthalmologic assessments were done in 21 low-birth-weight infants given caffeine for neonatal apnea and in 21 matched control infants. Caffeine significantly decreased the need for and the duration of mechanical ventilation. No difference in growth and development was noted between the control and caffeine-treated infants. A high incidence of cicatricial retrolental fibroplasia was observed in both control (10/21) and caffeine-treated infants (7/18).

Apnea↗
PubMed1979

Current advances in perinatal medicine.

The enhancement of pulmonary maturation with the resultant ability to prevent hyaline membrane disease has given rise to the use of a number of drugs experimentally including corticosteroids, thyroxine, aminophylline, heroin, and several suggested others for this purpose. In clinical use to date only the corticosteroids have been widely utilized in man but it is clear that these agents are capable of effecting an advancement in the maturation of the surfactant system of the lung and a subsequent reduction in the incidence of severity of hyaline membrane disease. However, all agents which act by the enhancement of maturation also carry with them a resultant arrest to replication of tissues and there have been demonstrable effects on both the lung and possibly the brain of the organisms to whom these agents have been administreted. In this connection it is, therefore, important to realize that the advantages gained from these agents may be counterbalanced by disadvantages from their usage and that a reasoned and careful approach in each individual case is mandatory when use of such agents is considered. Experimental and clinical studies suggest the possibility that Vitamin E acting as a free radical scavenger may be important in the prevention of oxygen toxicity both to the eye (retrolental fibroplasia) as well as ameliorating the oxygen component of the destructive effects of respirator lung disease (bronchopulmonary dysplasia). The action of Vitamin E under these circumstances is not dependent upon its actual quantitative level in the plasma of premature infants but in utilization to its excess. Although phototherapy has been universally and widely used since 1958, precise studies of its mechanism of action have not been revealing. Recent work has suggested that following exposure to photoirradiation, bilirubin in its unconjugated form can be seen to appear in the excretory bile ducts suggesting the transport of unconjugated bilirubin through the liver. More recent evidence has also suggested that this occurrence is the result of internal rotation following light exposure of one of the double bonded rings which effectively converts the molecule from a lipid soluble to a water soluble and thereby excretable form. These studies would not only account for an appropriate explanation of the quantitative reduction in bilirubin observed but carry with them the other important consideration that the amount of light exposure necessary to accomplish this is strikingly less than the previously considered photooxidation reaction. The clinical implications of these findings may suggest a reevaluation of the quanta of light which has been used for purposes of phototherapy to date.

Adrenal Cortex Hormones↗
PubMed1979

[Risk of damage to the organ of vision in low birth weight infants].

The authors presented their own material of years 1974-1977. During this period 8788 children were born, in it 737 (8,3%) with low birth weight (below 2500 g). Retrolental fibroplasia was diagnosed in 4 children, it was 0,5% of newborns with low birth weight, and 0,04% of the all live-borns. The retrolental fibroplasia was diagnosed in: 1) the child born in 27 week of pregnancy with 1000 g of body weight, 2) in two children born in 32-33 week of pregnancy with 1450 g and 1350 g of body weight, 3) in a child born in 31 week of pregnancy with 1600 g of body weight. The infants were nursed in incubators with about 30% of oxygen during 36 to 46 days. Contemporary hypoglycemia, hypoproteinemia, atelectasia of lungs with respiratory insufficiency were diagnosed. In the discussion the authors underlined the role of immaturity and hypoxia of the premature baby, which play the role in the secondary injury of vessel's walls of retina. The disturbancy of carbohydrate and protein metabolism were certainly secondary pathogenic agent sin retrolental fibroplasia. There exists the necessity of oxygen therapy of premature baby, but to take cre of the infant in the incubator does not mean the necessity of oxygen therapy . Even with controlled oxygen dosage in incubator the retrolental fibroplasia may occur as a result of relative hyperoxydation induced by the constriction of retina vessels. The authors underlined the necessity of repeated ophthalmologic examination of premature babies in about every 2 weeks, what makes very early diagnosis possible.

Child, Preschool↗
PubMed1977

Retinal enzyme activities under hypoxic conditions prior to neovascularization.

In an effort to demonstrate biochemical changes occuring in malperfused retinas, oxygen-induced retrolental fibroplasia was produced in kittens. Immediately before the onset of vasoproliferations, that is in the stage of maximal hypoxia, the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were determined. The activity of MDH was found to be significantly decreased, whereas the activities of the other enzymes showed no major changes.

Animals↗
PubMed1978

The status at two years of low-birth-weight infants born in 1974 with birth weights of less than 1,001 gm.

A two-year follow-up study of 43 infants of birth weight less than or equal to 1,000 gm born during 1974 revealed the following: average height at two years was between the tenth and twenty-fifth percentiles; average weight between the third and tenth percentiles. Fifteen (35%) developed lower respiratory tract infections during the first two years. Seven (16%) had retrolental fibroplasia. Major neurologic defects occurred in four (9%); severe developmental delay (mean developmental quotient less than 80) was found in nine others (21%). Defects of the central nervous system were closely associated with a neonatal history of intracranial hemorrhage or seizures or both.

Body Height↗
PubMed1978

Monitoring critically ill newborn infants with digital capillary blood samples: an alternative.

Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely.

Arteries↗