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Khoshtinat N, Moayeri M, Fakhredin H, Farahani AD, Ghassemi F, Mahmoudi A, Bazvand F, Nabavi A. Association of hypertensive disorders of pregnancy and gestational diabetes mellitus with developing severe retinopathy of prematurity. Int J Retina Vitreous 2025; 11:52. [PMID: 40296179 PMCID: PMC12036211 DOI: 10.1186/s40942-025-00635-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/24/2025] [Indexed: 04/30/2025] Open
Abstract
PURPOSE To evaluate the impact of hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and their combined presence (GDM-HDP) as perinatal risk factors for severe retinopathy of prematurity (ROP). METHODS The hospital records of all premature infants referred to a tertiary center between 2020 and 2022 were retrospectively reviewed. Infants born to mothers with GDM, HDP, or both were selected for analysis. Demographic variables, perinatal risk factors, as well as clinical and treatment characteristics of the infants were collected and analyzed. RESULTS A total of 1161 infants and 2322 eyes, including HDP group (1110 eyes from 555 infants), GDM group (944 eyes from 472 infants), and GDM-HDP group (268 eyes from 134 infants), were enrolled. The mean gestational age (GA) and birth weight (BW) for all infants were 31.6 ± 2.5 weeks and 1572 ± 427 g, respectively. A higher percentage of eyes (76.5%) in the GDM group were classified as ROP or incomplete vascularization compared to the HDP group (71.6%), with the prevalence of severe ROP also higher in the GDM group (13.5%) than in the HDP group (9.9%; P < 0.05 for both comparisons). The rates of ROP and severe ROP were similar between the GDM and GDM-HDP groups. When considering only infants with BW < 1500, the GDM group still exhibited a higher rate of ROP and severe ROP compared to the HDP group. Treatment was required in 17.5% of eyes in the GDM group, 16.8% in the GDM-HDP group, and 13.9% in the HDP group (P = 0.071). CONCLUSION GDM is a higher risk factor for ROP and developing severe ROP than HDP. However, the data indicate that careful monitoring and management of both GDM and HDP during pregnancy may be crucial in mitigating the risk of severe ROP.
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Affiliation(s)
- Narges Khoshtinat
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Maryam Moayeri
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Hanieh Fakhredin
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Afsar Dastjani Farahani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Fariba Ghassemi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Alireza Mahmoudi
- Department of Ophthalmology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA
| | - Fatemeh Bazvand
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Farabi Hospital, Tehran, Iran
| | - Amin Nabavi
- Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA.
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Olsen DA, Nielsen AA, Sørensen F, Forman JL, Brandslund I, Greisen G, Slidsborg C. Postnatal growth and metabolic blood biomarkers in preterm infants developing reversible retinopathy of prematurity. BMJ Open Ophthalmol 2025; 10:e001975. [PMID: 40086803 PMCID: PMC11907033 DOI: 10.1136/bmjophth-2024-001975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 02/14/2025] [Indexed: 03/16/2025] Open
Abstract
PURPOSE To investigate predictive potential of growth and metabolic blood biomarkers in the development of milder, reversible retinopathy of prematurity (ROP) stages. METHODS Biomarkers were obtained from blood samples collected every second postnatal week in a prospective, longitudinal cohort study including 108 infants born with a gestational age (GA) <32 weeks in four hospitals in the Capital Region of Denmark, 2018-2019. ROP diagnoses were obtained from the electronic medical record system together with demographic, clinical and laboratory data. Measurement of glucose was summarised as mean and SD for every postnatal week and growth was summarised as increment in weight, head circumference (biparietal diameter) and length every postnatal week. The predictive potential of each biomarker and each marker of growth in turn were evaluated in univariate receiver operating characteristics curve analyses and in multivariate analyses including GA and small for gestational age (SGA) as known predictors. RESULTS The strongest isolated postnatal predictor of ROP was weight gain at the second postnatal week with an area under the curve (AUC) of 0.80 (95% CI: 0.70 to 0.89). However, it only added insignificantly to the AUC (0.85; 95% CI: 0.76 to 0.93, adj. p=0.89) compared with GA and SGA alone (AUC=0.80, 95% CI: 0.70 to 0.90). Mean glucose in PNA weeks 1-4, glycaemic variability as measured by glucose SD weeks 1-3 PNA, and concentrations of adiponectin/glucose (mean) ratio were also associated with ROP diagnosis (AUCs ranging from 0.679 to 0.77) but did also not contribute significantly to the AUC compared with GA and SGA alone. CONCLUSIONS Postnatal growth and metabolic blood biomarkers were significantly associated with milder, reversible ROP, but none of these gave prediction over and above GA and SGA. Due to the small sample sizes, potential predictors could only be investigated in univariate analyses. Larger studies are needed to fully explore the predictive potential of all the biomarkers.
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Affiliation(s)
- Dorte Aalund Olsen
- Department of Biochemistry and Immunology, University of Southern Denmark, Vejle County, Vejle, Denmark
| | - Aneta Aleksandra Nielsen
- Department of Biochemistry and Immunology, University of Southern Denmark, Vejle County, Vejle, Denmark
| | - Frederik Sørensen
- University of Copenhagen Section of Biostatistics, Kobenhavn, Denmark
| | - Julie Lyng Forman
- University of Copenhagen Section of Biostatistics, Kobenhavn, Denmark
| | - Ivan Brandslund
- Department of Biochemistry and Immunology, University of Southern Denmark, Vejle County, Vejle, Denmark
| | - Gorm Greisen
- Department of Neonatology, Rigshospitalet, Copenhagen, Denmark
| | - Carina Slidsborg
- Ophthalmology, Copenhagen University Hospital, Copenhagen, Denmark
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Fevereiro-Martins M, Santos AC, Marques-Neves C, Guimarães H, Bicho M, on behalf of the GenE-ROP Study Group. Influence of Functional Variations in Genes of Neurotrophins and Neurotransmitter Systems on the Development of Retinopathy of Prematurity. Int J Mol Sci 2025; 26:898. [PMID: 39940677 PMCID: PMC11816744 DOI: 10.3390/ijms26030898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 01/20/2025] [Accepted: 01/20/2025] [Indexed: 02/16/2025] Open
Abstract
Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; (A.C.S.); (C.M.-N.); (M.B.)
- Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental-ISAMB, Laboratório Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
- Departamento de Oftalmologia, Hospital Cuf Descobertas, Rua Mário Botas, 1998-018 Lisboa, Portugal
| | - Ana Carolina Santos
- Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; (A.C.S.); (C.M.-N.); (M.B.)
- Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental-ISAMB, Laboratório Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
| | - Carlos Marques-Neves
- Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; (A.C.S.); (C.M.-N.); (M.B.)
- Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental-ISAMB, Laboratório Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Centro de Estudos das Ciências da Visão, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal
| | - Hercília Guimarães
- Departamento de Ginecologia-Obstetrícia e Pediatria, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Manuel Bicho
- Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; (A.C.S.); (C.M.-N.); (M.B.)
- Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental-ISAMB, Laboratório Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
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Xu WY, Dai YY, Yang SX, Chen H, Huang YQ, Luo PP, Wei ZH. Betaine combined with traditional Chinese medicine ointment to treat skin wounds in microbially infected diabetic mice. World J Diabetes 2025; 16:99745. [PMID: 39817220 PMCID: PMC11718449 DOI: 10.4239/wjd.v16.i1.99745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/21/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Skin wounds are highly common in diabetic patients, and with increasing types of pathogenic bacteria and antibiotic resistance, wounds and infections in diabetic patients are difficult to treat and heal. AIM To explore the effects of betaine ointment (BO) in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice. METHODS By detecting the minimum inhibitory concentrations (MICs) of betaine and plant monomer components such as psoralen, we prepared BO with betaine as the main ingredient, blended it with traditional Chinese medicines such as gromwell root and psoralen, and evaluated its antibacterial effects and safety in vitro and in vivo. The skin infection wound models of ordinary mice and diabetic mice were constructed, and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO. RESULTS The MICs of betaine against microorganisms such as Staphylococcus aureus (S. aureus), Candida albicans and Cryptococcus neoformans ranged from 4 to 32 μg/mL. Gromwell root and psoralea, both of which contain antimicrobial components, mixed to prepare BO with MICs ranging from 16 to 64 μg/mL, which is 32-256 times lower than those of Zicao ointment, although the MIC is greater than that of betaine. After 15 days of treatment with BO for USA300-infected ordinary mice, the wound scab removal rates were 83.3%, while those of mupirocin ointment and Zicao ointment were 66.7% and 0%, respectively, and the differences were statistically significant. In diabetic mice, the wound scab removal rate of BO and mupirolacin ointment was 80.0%, but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing. CONCLUSION The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S. aureus-infected ordinary mice and diabetic mice.
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Affiliation(s)
- Wen-Yan Xu
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yuan-Yuan Dai
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Shi-Xian Yang
- Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Hao Chen
- Department of Pathology, Wannan Medical College, Wuhu 241002, Anhui Province, China
| | - Yan-Qiang Huang
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Guangxi Zhuang Autonomous Region Engineering Research Center of Clinical Prevention and Control Technology and Leading Drug for Microorganisms with Drug Resistance in Border Ethnic Areas, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Pei-Pei Luo
- Department of Gastroenterology, Wujin People’s Hospital Affiliated to Jiangsu University, Changzhou 213004, Jiangsu Province, China
| | - Zhong-Heng Wei
- Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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Lagacé M, Tam EWY. Neonatal dysglycemia: a review of dysglycemia in relation to brain health and neurodevelopmental outcomes. Pediatr Res 2024; 96:1429-1437. [PMID: 38972961 DOI: 10.1038/s41390-024-03411-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/27/2024] [Accepted: 06/29/2024] [Indexed: 07/09/2024]
Abstract
Neonatal dysglycemia has been a longstanding interest of research in neonatology. Adverse outcomes from hypoglycemia were recognized early but are still being characterized. Premature infants additionally introduced and led the reflection on the importance of neonatal hyperglycemia. Cohorts of infants following neonatal encephalopathy provided further information about the impacts of hypoglycemia and, more recently, highlighted hyperglycemia as a central concern for this population. Innovative studies exposed the challenges of management of neonatal glycemic levels with a "u-shape" relationship between dysglycemia and adverse neurological outcomes. Lately, glycemic lability has been recognized as a key factor in adverse neurodevelopmental outcomes. Research and new technologies, such as MRI and continuous glucose monitoring, offered novel insight into neonatal dysglycemia. Combining clinical, physiological, and epidemiological data allowed the foundation of safe operational definitions, including initiation of treatment, to delineate neonatal hypoglycemia as ≤47 mg/dL, and >150-180 mg/dL for neonatal hyperglycemia. However, questions remain about the appropriate management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to continue to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes. IMPACT STATEMENT: Safe operational definitions guide the initiation of treatment of neonatal hypoglycemia and hyperglycemia. Innovative studies exposed the challenges of neonatal glycemia management with a "u-shaped" relationship between dysglycemia and adverse neurological outcomes. The importance of glycemic lability is also being recognized. However, questions remain about the optimal management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes.
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Affiliation(s)
- Micheline Lagacé
- Faculty of Medicine, Clinician Investigator Program, University of British Columbia, Vancouver, BC, Canada
- Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Emily W Y Tam
- Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
- Neurosciences and Mental Health, SickKids Research Institute, Toronto, ON, Canada.
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Fevereiro-Martins M, Santos AC, Marques-Neves C, Bicho M, Guimarães H, on behalf of the GenE-ROP Study Group. Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1154. [PMID: 39457121 PMCID: PMC11505647 DOI: 10.3390/children11101154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND/OBJECTIVES Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. METHODS We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. RESULTS ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. CONCLUSIONS These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
- Department of Ophthalmology, Cuf Descobertas Hospital, Rua Mário Botas, 1998-018 Lisboa, Portugal
| | - Ana Carolina Santos
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
| | - Carlos Marques-Neves
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Center for the Study of Vision Sciences, University Ophthalmology Clinic, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal
| | - Manuel Bicho
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
| | - Hercília Guimarães
- Department of Gynecology—Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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Maurya M, Liu CH, Bora K, Kushwah N, Pavlovich MC, Wang Z, Chen J. Animal Models of Retinopathy of Prematurity: Advances and Metabolic Regulators. Biomedicines 2024; 12:1937. [PMID: 39335451 PMCID: PMC11428941 DOI: 10.3390/biomedicines12091937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/08/2024] [Accepted: 08/15/2024] [Indexed: 09/30/2024] Open
Abstract
Retinopathy of prematurity (ROP) is a primary cause of visual impairment and blindness in premature newborns, characterized by vascular abnormalities in the developing retina, with microvascular alteration, neovascularization, and in the most severe cases retinal detachment. To elucidate the pathophysiology and develop therapeutics for ROP, several pre-clinical experimental models of ROP were developed in different species. Among them, the oxygen-induced retinopathy (OIR) mouse model has gained the most popularity and critically contributed to our current understanding of pathological retinal angiogenesis and the discovery of potential anti-angiogenic therapies. A deeper comprehension of molecular regulators of OIR such as hypoxia-inducible growth factors including vascular endothelial growth factors as primary perpetrators and other new metabolic modulators such as lipids and amino acids influencing pathological retinal angiogenesis is also emerging, indicating possible targets for treatment strategies. This review delves into the historical progressions that gave rise to the modern OIR models with a focus on the mouse model. It also reviews the fundamental principles of OIR, recent advances in its automated assessment, and a selected summary of metabolic investigation enabled by OIR models including amino acid transport and metabolism.
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Affiliation(s)
| | | | | | | | | | | | - Jing Chen
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
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Esmail J, Sakaria RP, Dhanireddy R. Early Hyperglycemia Is Associated with Increased Incidence of Severe Retinopathy of Prematurity in Extremely Low Birth Weight Infants. Am J Perinatol 2024; 41:e2842-e2849. [PMID: 37699520 DOI: 10.1055/a-2173-8360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/14/2023]
Abstract
OBJECTIVE Preterm infants have a higher rate of hypoglycemia and hyperglycemia, both of which have been associated with increased neonatal morbidities. The aim of this study was to evaluate the incidence of abnormal glucose homeostasis during the first 72 hours of life and study its association with major morbidities in infants admitted to our neonatal intensive care unit (NICU). STUDY DESIGN This was a retrospective single-center study. We extracted demographic, maternal, and patient information and blood glucose levels for the first 72 hours of life for all infants with birth weight ≤1,000 g admitted to the NICU from January 2017 to December 2019. Continuous data were presented as mean ± standard deviation or as median with interquartile range. Categorical data were presented as frequency and percentage. Student's t-tests and Mann-Whitney U test were used to analyze continuous data and chi-squared test or Fisher's exact test were used to analyze categorical data. Logistic regression analysis was performed to study the relation between hyperglycemia and various morbidities after controlling for gestational age (GA). Statistical significance was set at p < 0.05. RESULTS Of the 235 infants included in the study, 49% were hypoglycemic at admission to the NICU. Infants that were small for GA and those with history of maternal β-blocker use had a higher incidence of hypoglycemia. Hypoglycemia at admission was not associated with increased mortality or any major morbidities. Seventy-three percent infants who were hypoglycemic or euglycemic at birth developed iatrogenic hyperglycemia during the first 72 hours of life. The incidence of retinopathy of prematurity (ROP) and severe ROP was higher in infants with hyperglycemia on univariate analysis. However, on multivariate analysis, after adjusting for GA, no difference was noted in the incidence of ROP between the two groups. Multivariate analysis could not be performed for severe ROP due to inadequate sample size. CONCLUSION Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants. Neonatologists should aim to maintain euglycemia in these infants to decrease the risk of adverse outcomes. KEY POINTS · Preterm infants have a high rate of both hypoglycemia and hyperglycemia.. · Majority of infants who were euglycemic or hypoglycemic at birth develop iatrogenic hyperglycemia.. · Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants..
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Affiliation(s)
- Jihan Esmail
- College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Rishika P Sakaria
- Division of Neonatology, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
- Department of Neonatology, Sheldon B. Korones Newborn Center, Regional One Health, Memphis, Tennessee
| | - Ramasubbareddy Dhanireddy
- Division of Neonatology, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
- Department of Neonatology, Sheldon B. Korones Newborn Center, Regional One Health, Memphis, Tennessee
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Au SCL. Importance of well-designed meta-analyses in assessing medical and surgical treatments. World J Meta-Anal 2023; 11:313-316. [DOI: 10.13105/wjma.v11.i7.313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/10/2023] [Accepted: 11/29/2023] [Indexed: 12/14/2023] Open
Abstract
When evaluating the efficacy of medical or surgical treatments, the most robust study design is often considered to be the high-quality randomized clinical trial (RCT). However, the true answer lies in the meta-analysis of high-quality RCTs. While RCTs have their merits, meta-analyses possess two crucial qualities that make them superior: Generalizability and the ability to verify replicability across different trials. A well-designed meta-analysis, defined here as a systematic review that pools data, holds significant advantages over individual RCTs. Retrospective and observational surgical research is prone to biases that are not mutually offsetting; instead, they accumulate. Selection bias, transfer bias, and assessment bias all taint retrospective studies more than randomized trials, making the novel treatment appear more effective than it truly is. Pooling studies suffering from these limitations in a meta-analysis amplifies these biases, causing an overestimation of treatment benefits. This becomes particularly concerning when the treatment itself carries substantial risks, as is often the case in surgical journals. The consequences can result in harm or even death for patients. While a well-designed meta-analysis is the best tool for assessing medical and surgical treatments, a weak meta-analysis amplifies biases and promotes flawed data. Thoughtful readers must become proficient in honing their methodological toolkits, delving deeper into topics like heterogeneity and publication bias. It is essential to avoid wasting time on meta-analyses drawing data from retrospective or observational research regarding surgical treatments.
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Affiliation(s)
- Sunny Chi Lik Au
- Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, China
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Harman JC, Pivodic A, Nilsson AK, Boeck M, Yagi H, Neilsen K, Ko M, Yang J, Kinter M, Hellström A, Fu Z. Postnatal hyperglycemia alters amino acid profile in retinas (model of Phase I ROP). iScience 2023; 26:108021. [PMID: 37841591 PMCID: PMC10568433 DOI: 10.1016/j.isci.2023.108021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/03/2023] [Accepted: 09/19/2023] [Indexed: 10/17/2023] Open
Abstract
Nutritional deprivation occurring in most preterm infants postnatally can induce hyperglycemia, a significant and independent risk factor for suppressing physiological retinal vascularization (Phase I retinopathy of prematurity (ROP)), leading to compensatory but pathological neovascularization. Amino acid supplementation reduces retinal neovascularization in mice. Little is known about amino acid contribution to Phase I ROP. In mice modeling hyperglycemia-associated Phase I ROP, we found significant changes in retinal amino acids (including most decreased L-leucine, L-isoleucine, and L-valine). Parenteral L-isoleucine suppressed physiological retinal vascularization. In premature infants, severe ROP was associated with a higher mean intake of parenteral versus enteral amino acids in the first two weeks of life after adjustment for treatment group, gestational age at birth, birth weight, and sex. The number of days with parenteral amino acids support independently predicted severe ROP. Further understanding and modulating amino acids may help improve nutritional intervention and prevent Phase I ROP.
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Affiliation(s)
- Jarrod C. Harman
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Aldina Pivodic
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Anders K. Nilsson
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Myriam Boeck
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Hitomi Yagi
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Katherine Neilsen
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Minji Ko
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Jay Yang
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Michael Kinter
- Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
| | - Ann Hellström
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Zhongjie Fu
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
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11
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Angelis D, Jaleel MA, Brion LP. Hyperglycemia and prematurity: a narrative review. Pediatr Res 2023; 94:892-903. [PMID: 37120652 DOI: 10.1038/s41390-023-02628-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 04/15/2023] [Indexed: 05/01/2023]
Abstract
Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research.
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Affiliation(s)
- Dimitrios Angelis
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Mambarambath A Jaleel
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Luc P Brion
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
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12
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Fu Z, Lundgren P, Pivodic A, Yagi H, Harman JC, Yang J, Ko M, Neilsen K, Talukdar S, Hellström A, Smith LEH. FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP. Angiogenesis 2023; 26:409-421. [PMID: 36943533 PMCID: PMC10328855 DOI: 10.1007/s10456-023-09872-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 03/04/2023] [Indexed: 03/23/2023]
Abstract
Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).
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Affiliation(s)
- Zhongjie Fu
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Pia Lundgren
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Aldina Pivodic
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hitomi Yagi
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
| | - Jarrod C Harman
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Jay Yang
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Minji Ko
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Katherine Neilsen
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | | | - Ann Hellström
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lois E H Smith
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
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13
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Eroglu SA, Unsal AIA, Abdullayev OK, Guler D, Turkmen MK, Özkan SB, Demirci B, Omurlu IK. The role of hepatic and renal functions in the development of retinopathy of prematurity: Is proteinuria a new risk factor? Int Ophthalmol 2023; 43:483-490. [PMID: 35930082 DOI: 10.1007/s10792-022-02445-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/17/2022] [Indexed: 10/16/2022]
Abstract
PURPOSE To investigate the association of hepatic and renal parameters with the development of retinopathy of prematurity (ROP) in premature infants with a gestational age ≤ 32 weeks. METHODS Medical records of 240 preterm infants were reviewed retrospectively, 85 of them were grouped as type 1, type 2 ROP, and control group. The 4th week hepatic and renal function test results of the groups, on the day of their first ROP examinations, were compared for the risk of development of ROP and the development of type 1 ROP. RESULTS In this study, 12, 35, and 38 infants were enrolled in the type 1, type 2 ROP, and control group, respectively. The average gestational age and birth weight were higher; however, the duration of oxygen treatment was lower in the control group (p < 0.001). The blood glucose level was significantly higher in the type 1 ROP group than in the other groups (p = 0.023). The mean of total serum bilirubin of the type 1 ROP group was significantly lower than those of the type 2 ROP and control group (p = 0.032). Proteinuria was present in 85.7% of preterms with treatment-requiring ROP and proteinuria increased the risk of ROP by 3.9 times (OR with 95% CI 3.9 (1.19-12.75), p = 0.042). CONCLUSION We found significantly higher blood glucose and lower total bilirubin level in the type 1 ROP group. Moreover, our findings suggest that proteinuria may not be only a comorbidity factor but also related to a higher frequency of ROP and type 1 ROP in preterm infants.
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Affiliation(s)
- Sayime Aydin Eroglu
- Department of Ophthalmology, Bakircay University Cigli Training and Research Hospital, Izmir, Turkey.
| | - Ayse Ipek Akyuz Unsal
- Department of Ophthalmology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | | | - Duygu Guler
- Department of Ophthalmology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | - Munevver Kaynak Turkmen
- Department of Neonatology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | | | - Buket Demirci
- Department of Medical Pharmacology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | - Imran Kurt Omurlu
- Department of Biostatistics, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
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14
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Rath CP, Shivamallappa M, Muthusamy S, Rao SC, Patole S. Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2022; 107:269-280. [PMID: 34330757 DOI: 10.1136/archdischild-2020-321449] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 07/15/2021] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To explore the association between hyperglycaemia and adverse outcomes in very preterm infants. DESIGN Systematic review and meta-analysis. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. Subgroup analysis was conducted based on study design (cohort and case control). MAIN OUTCOME MEASURES Association between hyperglycaemia in preterm neonates (<32 weeks or <1500 g) and mortality and morbidities. FINDINGS Forty-six studies (30 cohort and 16 case control) with data from 34 527 infants were included. Meta-analysis of unadjusted ORs from cohort studies found hyperglycaemia to be significantly associated with mortality, any-grade intraventricular haemorrhage (IVH), severe IVH, any-stage retinopathy of prematurity (ROP), severe ROP, sepsis, chronic lung disease and disability. However, pooling of adjusted ORs found significant associations only for mortality (adjusted OR (CI): 2.37 (1.40 to 4.01); I2: 36%; 6 studies), 'Any grade IVH' (adjusted OR (CI): 2.60 (1.09 to 6.20); I2: 0%; 2 studies) and 'Any stage ROP' (adjusted OR (CI): 3.70 (1.55 to 8.84); I2: 0%; 2 studies). Meta-regression analysis found glucose levels >10 mmol/L to be associated with increased odds of mortality compared with <10 mmol/L. Pooled analysis from case-control studies were similar to cohort studies for most outcomes but limited by small sample size. Longer duration of hyperglycaemia was associated with adverse outcomes. GRADE of evidence was 'Low' or 'Very low'. CONCLUSION Hyperglycaemia in very preterm infants is associated with higher odds of mortality, any-grade IVH and any-stage ROP. A limitation was lack of availability of adjusted ORs from many of the included studies. PROSPERO REGISTRATION NUMBER CRD42020193016.
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Affiliation(s)
- Chandra Prakash Rath
- Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.,Neonatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Madhusudhan Shivamallappa
- Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.,Neonatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Saravanan Muthusamy
- Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.,Neonatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Shripada C Rao
- Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia .,Neonatology, Perth Children's Hospital, Nedlands, Western Australia, Australia.,School of Medicine, University of Western Australia, Crawley, Western Australia
| | - Sanjay Patole
- Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.,School of Medicine, University of Western Australia, Crawley, Western Australia
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15
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Ozgur Gursoy O, Gurer HG, Yildiz Eren C, Erdogan Ozgur P, Gursoy H. The association of various obstetric and perinatal factors with retinopathy of prematurity. Int Ophthalmol 2022; 42:2719-2728. [DOI: 10.1007/s10792-022-02260-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 03/12/2022] [Indexed: 10/18/2022]
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16
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Fu Z, Yan W, Chen CT, Nilsson AK, Bull E, Allen W, Yang J, Ko M, SanGiovanni JP, Akula JD, Talukdar S, Hellström A, Smith LEH. Omega-3/Omega-6 Long-Chain Fatty Acid Imbalance in Phase I Retinopathy of Prematurity. Nutrients 2022; 14:1333. [PMID: 35405946 PMCID: PMC9002570 DOI: 10.3390/nu14071333] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/17/2022] [Accepted: 03/21/2022] [Indexed: 11/17/2022] Open
Abstract
There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA's protection against ROP.
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Affiliation(s)
- Zhongjie Fu
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - Wenjun Yan
- Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA;
| | - Chuck T. Chen
- Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20814, USA;
| | - Anders K. Nilsson
- Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden; (A.K.N.); (A.H.)
| | - Edward Bull
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - William Allen
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - Jay Yang
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - Minji Ko
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - John Paul SanGiovanni
- BIO5 Institute, Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA;
| | - James D. Akula
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
| | - Saswata Talukdar
- Cardiometabolic Diseases, Merck Research Laboratories, Boston, MA 02115, USA;
| | - Ann Hellström
- Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden; (A.K.N.); (A.H.)
| | - Lois E. H. Smith
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Z.F.); (E.B.); (W.A.); (J.Y.); (M.K.); (J.D.A.)
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17
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Trott M, Smith L, Veronese N, Pizzol D, Barnett Y, Gorely T, Pardhan S. Eye disease and mortality, cognition, disease, and modifiable risk factors: an umbrella review of meta-analyses of observational studies. Eye (Lond) 2022; 36:369-378. [PMID: 34272511 PMCID: PMC8807837 DOI: 10.1038/s41433-021-01684-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 06/22/2021] [Accepted: 07/01/2021] [Indexed: 02/06/2023] Open
Abstract
Globally, 2.2 billion people live with some form of vision impairment and/or eye disease. To date, most systematic reviews examining associations have focused on a single eye disease and there is no systematic evaluation of the relationships between eye diseases and diverse physical and mental health outcomes. Moreover, the strength and reliability of the literature is unclear. We performed an umbrella review of observational studies with meta analyses for any physical and/or mental comorbidities associated with eye disease. For each association, random-effects summary effect size, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence from convincing to weak. 34 studies were included covering 58 outcomes. No outcomes yielded convincing evidence, six outcomes yielded highly suggestive results (cataract positively associated with type 2 diabetes, open-angled glaucoma positively associated with myopia and diabetes, diabetic retinopathy positively associated with cardiovascular disease and cardiovascular mortality, and retinopathy of prematurity positively associated with chorioamnionitis), eight outcomes yielded suggestive results (diabetic retinopathy positively associated with all-cause mortality and depression, diabetic macular oedema positively associated with dyslipidaemia, cataract positively associated with gout, nuclear sclerosis positively associated with all-cause mortality, open angled glaucoma positively associated with migraine and hypertension, and age-related macular degeneration positively associated with diabetes), and 18 outcomes yielded weak evidence. Results show highly suggestive or suggestive evidence for associations between several types of eye diseases with several comorbid outcomes. Practitioners and public health policies should note these findings when developing healthcare policies.
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Affiliation(s)
- Mike Trott
- Vision and Eye Research Institute (VERI), School of Medicine, Anglia Ruskin University, Cambridge, UK.
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK
| | - Nicola Veronese
- National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy
- University of Palermo, Department of Geriatrics, Palermo, Italy
| | - Damiano Pizzol
- Italian Agency for Development Cooperation (Khartoum), Khartoum, Sudan
| | - Yvonne Barnett
- School of Life Sciences, Anglia Ruskin University, Cambridge, UK
| | - Trish Gorely
- Department of Nursing and Midwifery, University of the Highlands and Islands, Centre for Health Sciences, Inverness, UK
| | - Shahina Pardhan
- Vision and Eye Research Institute (VERI), School of Medicine, Anglia Ruskin University, Cambridge, UK
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18
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Association between neonatal hyperglycemia and retinopathy of prematurity: a meta-analysis. Eur J Pediatr 2021; 180:3433-3442. [PMID: 34114080 DOI: 10.1007/s00431-021-04140-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/27/2021] [Accepted: 05/31/2021] [Indexed: 02/05/2023]
Abstract
Through a meta-analysis, we aimed to investigate whether neonatal hyperglycemia was associated with an increased risk of retinopathy of prematurity (ROP) by summarizing all available observational evidence. We searched online databases for studies published prior to December 2020; 26745 neonates with 3227 cases of ROP in 11 case-control studies and 997 neonates with 496 cases of hyperglycemia in 5 cohort studies were included. The results showed that the association between hyperglycemia and the occurrence of ROP was statistically significant in case-control studies (OR 3.93, 95% CI 2.36-6.53) and cohort studies (OR 1.70, 95% CI 1.11-2.60). Besides, the borderline significant association between the duration of hyperglycemia and ROP was observed in case-control studies (MD = 1.96, 95% CI 0.90-3.03; adjusted OR = 1.08, 95% CI 1.01-1.15). Furthermore, we found that the mean blood glucose level is higher in the ROP group than the non-ROP group in case-control studies (MD = 14.86, 95% CI 5.06-24.66) and the mean blood glucose level is higher in the hyperglycemia group than in the non-hyperglycemia group (MD = 86.54, 95% CI 11.03-162.05). However, after adjusting other confounders, the association between the mean blood glucose level and ROP varied in cohort studies (OR 1.96, 95% CI 1.23-3.13) and case-control studies (OR 1.02, 95% CI 1.00-1.05).Conclusion: This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. Further studies will be required to achieve a firm conclusion for hyperglycemia and ROP and promote a better understanding of the prevention of ROP.Trial registration: CRD42021228733 What is Known: • Hyperglycemia including the duration and daily mean blood glucose concentration has been associated with the risk of developing ROP in some clinical studies. Current evidence cannot reach a consensus on whether neonatal hyperglycemia is a risk factor for ROP. What is New: • This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. • While the association between the mean blood glucose level and ROP remains inconclusive.
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19
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Tomita Y, Usui-Ouchi A, Nilsson AK, Yang J, Ko M, Hellström A, Fu Z. Metabolism in Retinopathy of Prematurity. Life (Basel) 2021; 11:1119. [PMID: 34832995 PMCID: PMC8620873 DOI: 10.3390/life11111119] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/11/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
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Affiliation(s)
- Yohei Tomita
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Y.T.); (J.Y.); (M.K.)
| | - Ayumi Usui-Ouchi
- Department of Ophthalmology, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan;
| | - Anders K. Nilsson
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 413 19 Gothenburg, Sweden; (A.K.N.); (A.H.)
| | - Jay Yang
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Y.T.); (J.Y.); (M.K.)
| | - Minji Ko
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Y.T.); (J.Y.); (M.K.)
| | - Ann Hellström
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 413 19 Gothenburg, Sweden; (A.K.N.); (A.H.)
| | - Zhongjie Fu
- Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (Y.T.); (J.Y.); (M.K.)
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20
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Bahmani T, Karimi A, Rezaei N, Daliri S. Retinopathy prematurity: a systematic review and meta-analysis study based on neonatal and maternal risk factors. J Matern Fetal Neonatal Med 2021; 35:8032-8050. [PMID: 34256661 DOI: 10.1080/14767058.2021.1940938] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Retinopathy of prematurity is the abnormal development of retinal arteries in preterm neonates less than 32 weeks and weighing 1500 g, and less, which can lead to visual impairment during life and blindness. This study aims to investigate the relationship between some clinical characteristics of neonates and mothers with Retinopathy of prematurity in the world via a systematic review and meta-analysis. MATERIALS AND METHODS The present study is a systematic review and meta-analysis on the relationship between maternal and neonatal clinical variables with Retinopathy of prematurity in the world from the beginning of 2000 to the end of 2020. Accordingly, all English articles published on the topic were searched in scientific databases of Web of Science, PubMed, Google Scholar, Science Direct, and Scopus. The articles were searched independently by two researchers. Statistical analysis of data was performed using fixed and random effects model statistical tests in the meta-analysis, Cochran, meta-regression, I2 index, Funnel plot, and Begg's by STATA software program, version 14. RESULT A total of 191 studies with a sample size of 140,921 persons were including in the meta-analysis. Accordingly, Preterm delivery ≤28 weeks (OR:6.3, 95% CI:4.9-8.1), Birth Weight ≤1000 g (OR:5.8, 95% CI:4.8-6.8), Birth Weight ≤1500 g (OR:4.8, 95% CI:3.8-6.1), PROM (OR:1.2, 95% CI:1.0-1.4), induced fertility (OR:1.9, 95% CI:1.1-3.0) and Chorioamnionitis (OR:1.5, 95% CI:1.0-2.2) There was a statistically significant association with retinopathy. CONCLUSION Based on the results of the present meta-analysis, the risk of retinopathy of prematurity in neonates born at 28 weeks and less, LBW (weight 1500 g and less), neonatal hypotension, chorioamnionitis, and induced fertility increases.
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Affiliation(s)
- Tahereh Bahmani
- School Medicine, Ilam University of Medical Science, Ilam, Iran
| | - Arezoo Karimi
- Department of Epidemiology, School of Public Health, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Nazanin Rezaei
- Department of Midwifery, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran
| | - Salman Daliri
- Clinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Shahroud, Iran
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Wang J, Wu K, Wang D. A novel regulatory network of linc00174/miR-150-5p/VEGFA modulates pathological angiogenesis in diabetic retinopathy. Can J Physiol Pharmacol 2021; 99:1175-1183. [PMID: 34081870 DOI: 10.1139/cjpp-2021-0036] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Diabetic retinopathy (DR) has been regarded as a sight-threatening vascular complication of diabetes mellitus (DM). Accumulating evidence has identified the involvement of long non-coding RNAs (lncRNAs) in DR pathogenesis. We aim to investigate the role and underlying mechanism of linc00174 in DR process. METHODS Samples of human vitreous humour from proliferative DR and non-diabetic individuals were collected to examine the levels of linc00174. Human retinal microvascular endothelial cells (HRMECs) exposed with high glucose were employed to simulate the pathological statues of DR. shRNA specifically targeting linc00174 was applied. CCK-8, transwell, and matrigel tube formation were performed to evaluate cell proliferation, migration and angiogenesis. Bioinformatics analysis and luciferase reporter assay were conducted to verify the linc00174/miR-150-5p/VEGFA regulatory network. Western blotting was employed to determine the expression of VEGFA. RESULTS Linc00174 was significantly elevated in patients with DR, as well as HG-stimulated HRMECs, of which knockdown repressed HG-induced proliferation, migration and angiogenesis. miR-150-5p was identified as a downstream effector to be involved in linc00174-mediated protective effects. miR-150-5p directly bound to the 3'-UTR of VEGFA. The linc00174/miR-150-5p/VEGFA axis was confirmed in retinal vascular dysfunction. CONCLUSION Linc00174 deteriorates diabetic retinal microangiopathy via regulating miR-150-5p/VEGFA pathway, indicating a novel therapeutic target for DR treatment.
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Affiliation(s)
| | - Kunfang Wu
- Huizhou Municipal Central Hospital, Huizhou, China;
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GLYCEMIC VARIABILITY IS ASSOCIATED WITH TREATMENT REQUIRING RETINOPATHY OF PREMATURITY: A Case-Control Study. Retina 2021; 41:711-717. [PMID: 32804832 DOI: 10.1097/iae.0000000000002949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To assess the association between glycemic variability (GV) and Type 1 retinopathy of prematurity (ROP) in infants with birth weights of less than 1,251 g. METHODS A case-control study of infants with birth weights of less than 1,251 g who developed Type 1 ROP (n = 20) was conducted. Controls had a less severe ROP or no eye disease and were individually matched for gestational age and birth weight (n = 40). Odds ratios of ROP were calculated based on multiple factors including oxygen exposure, respiratory support, incidence of hyperglycemia, and GV. For glucose measurements, a continuous glucose monitoring system was used. RESULTS There were no significant differences in gender, antenatal steroid administration, severity of illness, and Apgar score. Univariate analyses suggest increased risk for the development of Type 1 ROP based on incidence of intraventricular hemorrhage Grade 3 or 4 (P = 0.048), duration of oxygen exposure (P = 0.003), incidence of hyperglycemia over 150 mg/dL (P = 0.01), and GV according to significantly higher SD (P = 0.002), coefficient of variation (P = 0.001), and mean amplitude of glucose excursion (P = 0.008). Using a multiple regression model, increased risk of Type 1 ROP was only found to be associated with duration of oxygen exposure and higher GV. CONCLUSION Our study demonstrates a relationship between GV and the development of severe ROP.
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Abstract
Hyperglycemia after birth is common in extremely preterm infants (<28 weeks of gestation). Lower gestational age, lower birthweight, presence of severe illness, and higher parenteral glucose intake increase the risk for hyperglycemia, while provision of higher amounts of amino acids and lipids in parenteral nutrition and early initiation and faster achievement of full enteral feeding decrease the risk. Hyperglycemia is associated with increased mortality and morbidity in the neonatal period. Limited data show an association with long-term adverse effects on growth, neurodevelopment, and cardiovascular and metabolic health. Lowering the glucose infusion rate and administration of insulin are the 2 treatment options. Lowering the glucose infusion could lead to calorie deficits and long-term adverse effects on growth and neurodevelopment. Conversely, insulin use increases the risk for hypoglycemia and requires close blood glucose monitoring and frequent adjustments to glucose infusion and insulin dosage. Randomized trials of varying strategies of nutrient provision and/or insulin therapy and long-term follow-up are needed to improve clinical care and overall health of extremely preterm infants with hyperglycemia.
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Affiliation(s)
- Sara Ramel
- Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, MN
| | - Raghavendra Rao
- Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, MN.,Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN
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Ashina M, Fujioka K, Ueda K, Miki A, Iijima K. Aggressive posterior retinopathy of prematurity in a preterm infant with congenital hyperinsulinemia without persistent hyperglycemia. Pediatr Neonatol 2020; 61:665-666. [PMID: 32741723 DOI: 10.1016/j.pedneo.2020.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 06/09/2020] [Accepted: 07/01/2020] [Indexed: 11/29/2022] Open
Affiliation(s)
- Mariko Ashina
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazumichi Fujioka
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Kaori Ueda
- Department of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Akiko Miki
- Department of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazumoto Iijima
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
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Kermorvant-Duchemin E, Le Meur G, Plaisant F, Marchand-Martin L, Flamant C, Porcher R, Lapillonne A, Chemtob S, Claris O, Ancel PY, Rozé JC. Thresholds of glycemia, insulin therapy, and risk for severe retinopathy in premature infants: A cohort study. PLoS Med 2020; 17:e1003477. [PMID: 33306685 PMCID: PMC7732100 DOI: 10.1371/journal.pmed.1003477] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/19/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Hyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants. METHODS AND FINDINGS In 2 independent, monocentric cohorts of preterm infants born at <30 weeks' gestation (Nantes University Hospital, 2006-2016, primary, and Lyon-HFME University Hospital, 2009-2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21-maximum value of glycemia (MaxGly1-21) and mean of daily maximum values of glycemia (MeanMaxGly1-21)-using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly1-21 and MeanMaxGly1-21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14-1.27, p < 0.001) and OR 1.70 (95% CI 1.48-1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05-1.32, p = 0.008) and OR 1.53 (95% CI 1.20-1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13-5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13-1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy. CONCLUSIONS In this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation.
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Affiliation(s)
- Elsa Kermorvant-Duchemin
- AP-HP, Necker-Enfants Malades University Hospital, Department of Neonatal Medicine, Paris, France
- INSERM (UMRS1138), Cordeliers Research Center, Paris, France
- Université de Paris, Paris, France
- * E-mail:
| | - Guylène Le Meur
- Department of Ophthalmology, Nantes University Hospital, Nantes, France
| | - Frank Plaisant
- Department of Neonatal Medicine, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
| | - Laetitia Marchand-Martin
- Obstetrical, Perinatal, and Pediatric Epidemiology Team, Centre of Research in Epidemiology and Statistics, INSERM (UMR1153), Paris, France
| | - Cyril Flamant
- Department of Neonatal Medicine, Nantes University Hospital, Nantes, France
- INRA (UMR1280), Physiologie des Adaptations Nutritionnelles, IMAD, Centre de Recherche en Nutrition Humaine Ouest, Nantes, France
| | - Raphaël Porcher
- Université de Paris, Paris, France
- Obstetrical, Perinatal, and Pediatric Epidemiology Team, Centre of Research in Epidemiology and Statistics, INSERM (UMR1153), Paris, France
| | - Alexandre Lapillonne
- AP-HP, Necker-Enfants Malades University Hospital, Department of Neonatal Medicine, Paris, France
- Université de Paris, Paris, France
| | - Sylvain Chemtob
- Department of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, Québec, Canada
| | - Olivier Claris
- Department of Neonatal Medicine, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
- Lyon University, EA, Lyon, France
| | - Pierre-Yves Ancel
- Université de Paris, Paris, France
- Obstetrical, Perinatal, and Pediatric Epidemiology Team, Centre of Research in Epidemiology and Statistics, INSERM (UMR1153), Paris, France
| | - Jean-Christophe Rozé
- Department of Neonatal Medicine, Nantes University Hospital, Nantes, France
- INRA (UMR1280), Physiologie des Adaptations Nutritionnelles, IMAD, Centre de Recherche en Nutrition Humaine Ouest, Nantes, France
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Cakir B, Hellström W, Tomita Y, Fu Z, Liegl R, Winberg A, Hansen-Pupp I, Ley D, Hellström A, Löfqvist C, Smith LE. IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants. JCI Insight 2020; 5:140363. [PMID: 33004691 PMCID: PMC7566718 DOI: 10.1172/jci.insight.140363] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 08/31/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Hyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood. METHODS In 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy. RESULTS The highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001). CONCLUSION In extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP. TRIAL REGISTRATION ClinicalTrials.gov NCT02760472 (Donna Mega). FUNDING This study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Skåne Council Foundation for Research and Development, the Linnéa and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas Vänner. In extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased retinopathy of prematurity severity.
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Affiliation(s)
- Bertan Cakir
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Yohei Tomita
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Zhongjie Fu
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raffael Liegl
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Winberg
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Örebro University Hospital, Örebro, Sweden
| | - Ingrid Hansen-Pupp
- Department of Pediatrics, Institute of Clinical Sciences Lund, Lund University, Lund, Sweden.,Skane University Hospital, Lund, Sweden
| | - David Ley
- Department of Pediatrics, Institute of Clinical Sciences Lund, Lund University, Lund, Sweden.,Skane University Hospital, Lund, Sweden
| | - Ann Hellström
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Chatarina Löfqvist
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lois Eh Smith
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Vishnu Tewari V, Chandra Shaw S, Shridhar G. Neonatal hyperglycemia and retinopathy of prematurity. Med J Armed Forces India 2020; 76:480-481. [DOI: 10.1016/j.mjafi.2020.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/18/2020] [Indexed: 11/30/2022] Open
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Movsas TZ, Muthusamy A. Feasibility of neonatal haemoglobin A1C as a biomarker for retinopathy of prematurity. Biomarkers 2020; 25:468-473. [PMID: 32552079 DOI: 10.1080/1354750x.2020.1783573] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Retinopathy of prematurity (ROP) is a potentially serious eye disorder affecting very preterm infants. Non-proliferative ROP (NP-ROP), also known as Early Stage ROP, is characterized by deficient retinal angiogenesis. Proliferative ROP (P-ROP), also known as Late Stage ROP, is characterized by pathologic angiogenesis. The use of neonatal haemoglobin A1C as a biomarker for ROP has not yet been evaluated. MATERIALS AND METHODS We modified the Haemoglobin A1C assay for use with neonatal dried blood spots (DBS) and then assessed A1C levels via Elisa immunoassay on DBS from 43 preterm infants (with gestational ages 26-28 weeks). We measured A1C on DBS collected at <1 week and 4 weeks of chronological age. RESULTS Compared to matched counterparts without ROP, there is significantly lower HbA1c in infants who develop NP-ROP, this occurs at Week 4 (p=0.004), but is not seen at Week 1; there is significantly higher HbA1c in infants with P-ROP, this occurs both at Week 1 (p<0.05) and Week 4 (p=0.005). CONCLUSIONS The A1C test, modified for use with DBS, is a feasible biomarker for ROP; low A1C is a potential biomarker for non-proliferative ROP and high A1C is for proliferative ROP.
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Affiliation(s)
- Tammy Z Movsas
- Zietchick Research Institute (ZRI), Plymouth, MI, USA.,Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA
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Vannadil H, Moulick P, Khan M, Shankar S, Kaushik J, Sati A. Hyperglycaemia as a risk factor for the development of retinopathy of prematurity: A cohort study. Med J Armed Forces India 2020; 76:95-102. [PMID: 32020976 PMCID: PMC6994749 DOI: 10.1016/j.mjafi.2019.04.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 04/28/2019] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Retinopathy of prematurity (ROP) is a preventable cause of childhood blindness. Without treatment, over 45% of eyes can develop permanent visual loss. Hyperglycaemia has recently been described as a risk factor for the development of retinopathy of prematurity (ROP), a proliferative vascular disease of the retina that primarily affects premature infants. The characteristic neoproliferative growth of blood vessels in the retina is very well under stood with the clinical and experimental experiences with Diabetic retinopathy. The purpose of this study was to evaluate a possible relation between glucose levels in VLBW (Very Low Birth Weight) infants and development of ROP. METHOD All at risk infants of a Neonatal Intensive Care Unit (NICU) of a tertiary care centre in western India were included in the study. The blood sugar values of the neonates were recorded at multiple times during their first week of life. On completion of 31 weeks of gestational age or 04 weeks of birth age, the neonates were subjected to ROP screening as per standard protocols. RESULT A total of 103 neonates were included in the study and were subjected to ROP screening. A total of 32 neonates developed ROP at the end of the study. It was found with statistical significance that the neonates with higher average blood glucose values in the initial period of life had higher incidence of ROP at the time of screening with a Relative Risk of 2.506 (CI = 1.287, 4.882). CONCLUSION A high average blood glucose level in neonates during the first week of life is an indicator for developing ROP at a later date. These neonates should be kept under close follow up in order to facilitate timely detection and prompt intervention.
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Affiliation(s)
- Harikrishnan Vannadil
- Resident, Department of Ophthalmology, Armed Forces Medical College, Pune 411040, India
| | - P.S. Moulick
- Consultant (Ophthalmology), Command Hospital (Eastern Command), Kolkata, India
| | - M.A. Khan
- Professor (Ophthalmology), Command Hospital (Air Force), Bengaluru 07, India
| | - Sandeep Shankar
- Associate Professor, Department of Ophthalmology, Armed Forces Medical College, Pune 411040, India
| | - Jaya Kaushik
- Associate Professor, Department of Ophthalmology, Armed Forces Medical College, Pune 411040, India
| | - Alok Sati
- Associate Professor, Department of Ophthalmology, Armed Forces Medical College, Pune 411040, India
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Han X, Kong J, Hartnett ME, Wang H. Enhancing Retinal Endothelial Glycolysis by Inhibiting UCP2 Promotes Physiologic Retinal Vascular Development in a Model of Retinopathy of Prematurity. Invest Ophthalmol Vis Sci 2019; 60:1604-1613. [PMID: 30995317 PMCID: PMC6892377 DOI: 10.1167/iovs.19-26553] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Purpose We address the hypothesis that uncoupling protein 2 (UCP2), a cellular glucose regulator, delays physiologic retinal vascular development (PRVD) by interfering with glucose uptake through glucose transporter 1 (Glut1). Methods In the rat 50/10 oxygen-induced retinopathy (OIR) model, retinal Glut1 and UCP2 were measured and compared to room air (RA)-raised pups at postnatal day 14 (p14). Pups in OIR and RA received intraperitoneal genipin, an UCP2 inhibitor, or control every other day from p3 until p13. Analyses at p14 included avascular/total retinal area (AVA), Western blots of retinal UCP2 and Glut1, and immunostaining of Glut1 in retinal cryosections. Intravitreal neovascular/total retinal area (IVNV) was analyzed at p18, and electroretinograms were performed at p26. Glut1 and phosphorylated VEGFR2 (p-VEGFR2), glucose uptake, adenosine triphosphate (ATP) production, and cell proliferation were measured in human retinal microvascular endothelial cells (hRMVECs) pretreated with genipin or transfected with UCP2siRNA, Glut1siRNA, or control siRNA when incubated with VEGF or PBS. Results At p14, OIR pups had increased AVA with decreased Glut1 and increased UCP2 in the retina compared to RA retinas. Intraperitoneal genipin increased retinal Glut1 and reduced AVA. Compared to control, treatment with genipin or knockdown of UCP2 significantly increased Glut1, glucose uptake, ATP production, VEGF-induced p-VEGFR2 and cell proliferation in hRMVECs. Knockdown of Glut1 inhibited VEGF-induced p-VEGFR2. Genipin-treated OIR pups with decreased AVA at p14 had reduced IVNV at p18 and increased amplitudes in a- and b-waves at p26. Conclusions Extending PRVD by increasing retinal endothelial glucose uptake may represent a strategy to prevent severe retinopathy of prematurity and vision loss.
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Affiliation(s)
- Xiaokun Han
- The John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States.,Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.,State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Jun Kong
- Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - M Elizabeth Hartnett
- The John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
| | - Haibo Wang
- The John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
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Fu Z, Löfqvist CA, Liegl R, Wang Z, Sun Y, Gong Y, Liu CH, Meng SS, Burnim SB, Arellano I, Chouinard MT, Duran R, Poblete A, Cho SS, Akula JD, Kinter M, Ley D, Pupp IH, Talukdar S, Hellström A, Smith LE. Photoreceptor glucose metabolism determines normal retinal vascular growth. EMBO Mol Med 2019; 10:76-90. [PMID: 29180355 PMCID: PMC5760850 DOI: 10.15252/emmm.201707966] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The neural cells and factors determining normal vascular growth are not well defined even though vision‐threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation. Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling early ROP, hyperglycemia caused photoreceptor dysfunction and delayed neurovascular maturation associated with changes in the APN pathway; recombinant mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth. APN deficiency decreased retinal mitochondrial metabolic enzyme levels particularly in photoreceptors, suppressed retinal vascular development, and decreased photoreceptor platelet‐derived growth factor (Pdgfb). APN pathway activation reversed these effects. Blockade of mitochondrial respiration abolished AdipoRon‐induced Pdgfb increase in photoreceptors. Photoreceptor knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN pathway might prevent hyperglycemia‐associated retinal abnormalities and suppress phase I ROP in premature infants.
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Affiliation(s)
- Zhongjie Fu
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Chatarina A Löfqvist
- Section for Ophthalmology, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Raffael Liegl
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Zhongxiao Wang
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ye Sun
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Yan Gong
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Chi-Hsiu Liu
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Steven S Meng
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Samuel B Burnim
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ivana Arellano
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Rubi Duran
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Alexander Poblete
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Steve S Cho
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - James D Akula
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Michael Kinter
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - David Ley
- Pediatrics, Department of Clinical Sciences, Skåne University Hospital and University of Lund, Lund, Sweden
| | - Ingrid Hansen Pupp
- Pediatrics, Department of Clinical Sciences, Skåne University Hospital and University of Lund, Lund, Sweden
| | | | - Ann Hellström
- Section for Ophthalmology, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Lois Eh Smith
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
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Villamor-Martinez E, Cavallaro G, Raffaeli G, Mohammed Rahim OMM, Gulden S, Ghazi AMT, Mosca F, Degraeuwe P, Villamor E. Chorioamnionitis as a risk factor for retinopathy of prematurity: An updated systematic review and meta-analysis. PLoS One 2018; 13:e0205838. [PMID: 30332485 PMCID: PMC6192636 DOI: 10.1371/journal.pone.0205838] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 10/02/2018] [Indexed: 12/23/2022] Open
Abstract
The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) is difficult to establish, because CA-exposed and CA-unexposed infants frequently present different baseline characteristics. We performed an updated systematic review and meta-analysis of studies reporting on the association between CA and ROP. We searched PubMed and EMBASE for relevant articles. Studies were included if they examined preterm or very low birth weight (VLBW, <1500g) infants and reported primary data that could be used to measure the association between exposure to CA and the presence of ROP. Of 748 potentially relevant studies, 50 studies met the inclusion criteria (38,986 infants, 9,258 CA cases). Meta-analysis showed a significant positive association between CA and any stage ROP (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.74). CA was also associated with severe (stage ≥3) ROP (OR 1.63, 95% CI 1.41 to 1.89). Exposure to funisitis was associated with a higher risk of ROP than exposure to CA in the absence of funisitis. Additional meta-analyses showed that infants exposed to CA had lower gestational age (GA) and lower birth weight (BW). Meta-regression showed that lower GA and BW in the CA-exposed group was significantly associated with a higher risk of ROP. Meta-analyses of studies with data adjusted for confounders could not find a significant association between CA and ROP. In conclusion, our study confirms that CA is a risk factor for developing ROP. However, part of the effects of CA on the pathogenesis of ROP may be mediated by the role of CA as an etiological factor for very preterm birth.
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Affiliation(s)
- Eduardo Villamor-Martinez
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands
| | - Giacomo Cavallaro
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Genny Raffaeli
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Owais M. M. Mohammed Rahim
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands
| | - Silvia Gulden
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Amro M. T. Ghazi
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands
| | - Fabio Mosca
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Pieter Degraeuwe
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands
| | - Eduardo Villamor
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands
- * E-mail:
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Lenhartova N, Matasova K, Lasabova Z, Javorka K, Calkovska A. Impact of early aggressive nutrition on retinal development in premature infants. Physiol Res 2018; 66:S215-S226. [PMID: 28937236 DOI: 10.33549/physiolres.933677] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The normal retinal development is interrupted by preterm birth and a retinopathy of prematurity (ROP) may develop as its consequence. ROP is characterized by aberrant vessel formation in the retina as a response to multiple risk factors influencing the process of retinal angiogenesis. Insulin-like growth factor I (IGF-1) and vascular endothelial growth factor (VEGF) play an important role in the process of normal retinal vascularization. Insufficient nutrition during the first 4 postnatal weeks results in low serum levels of IGF-1, which is essential for correct retinal vessels formation, ensuring survival of the newly formed endothelial cells. Low IGF-1 level results in stop of angiogenesis in the retina, leaving it avascular and prompting the onset of ROP. Keeping the newborns in a positive energetic balance by providing enough nutrients and energy has a beneficial impact on their growth, neurodevelopment and decreased incidence of ROP. The best way to achieve this is the early parenteral nutrition with the high content of nutrients combined with early enteral feeding by the own mother´s breast milk. Multiple studies confirmed the safety and efficacy of early aggressive nutrition but information about its long-term effects on the metabolism, growth and development is still needed.
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Affiliation(s)
- N Lenhartova
- Clinic of Neonatology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital, Martin, Slovakia.
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Kim SJ, Port AD, Swan R, Campbell JP, Chan RVP, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol 2018; 63:618-637. [PMID: 29679617 DOI: 10.1016/j.survophthal.2018.04.002] [Citation(s) in RCA: 330] [Impact Index Per Article: 47.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 04/05/2018] [Accepted: 04/09/2018] [Indexed: 01/09/2023]
Abstract
Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP.
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Affiliation(s)
- Sang Jin Kim
- Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA; Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Alexander D Port
- Department of Ophthalmology, Weill Cornell Medical College, New York, New York, USA
| | - Ryan Swan
- Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, USA
| | - J Peter Campbell
- Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - R V Paul Chan
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA; Center for Global Health, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Michael F Chiang
- Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, USA.
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Yim CL, Tam M, Chan HL, Tang SM, Au SCL, Yip WWK, Ko STC, Rong SS, Chen LJ, Ng DSC, Yam JCS. Association of antenatal steroid and risk of retinopathy of prematurity: a systematic review and meta-analysis. Br J Ophthalmol 2018; 102:1336-1341. [DOI: 10.1136/bjophthalmol-2017-311576] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 03/12/2018] [Accepted: 03/18/2018] [Indexed: 02/05/2023]
Abstract
BackgroundRetinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. Use of antenatal steroid can reduce neonatal morbidity and mortality in preterm births, but its effect on ROP remained controversial. We aim to determine the association between antenatal steroid and risk of ROP by a systematic review and meta-analysis.MethodsReported studies on the association between antenatal steroid and risk of ROP or severe ROP were identified from MEDLINE and Embase databases from their inception to November 2016. Outcome measures were ORs with 95% CIs. Extracted data were pooled using a random-effect model or fixed-effect model where appropriate. Heterogeneity was assessed, and sensitivity analysis was performed.ResultsA total of 434 relevant studies were identified, and 28 studies were eligible for the meta-analysis, involving 20 731 neonates with 4202 cases of ROP. Among the 28 studies included, 13 studies provided data evaluating the association between antenatal steroid use and severe ROP, involving 4999 neonates with 792 cases of severe ROP. Antenatal steroid administration was associated with a reduced risk of ROP development (ORunadjusted=0.82, 95% CI 0.68 to 0.98; ORadjusted=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (ORunadjusted=0.58, 95% CI 0.40 to 0.86).ConclusionAntenatal steroid administration is associated with a reduced risk of ROP development and progression to severe ROP. Our results strengthened the indications of antenatal steroid therapy to high-risk mothers giving preterm births, especially in low-income and middle-income countries where antenatal steroid are not yet widely used.
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Cavallaro G, Villamor-Martínez E, Filippi L, Mosca F, Villamor E. Probiotic supplementation in preterm infants does not affect the risk of retinopathy of prematurity: a meta-analysis of randomized controlled trials. Sci Rep 2017; 7:13014. [PMID: 29026199 PMCID: PMC5638943 DOI: 10.1038/s41598-017-13465-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 09/26/2017] [Indexed: 12/13/2022] Open
Abstract
Retinopathy of prematurity (ROP) is a vascular disorder of the developing retina in preterm infants and is a leading cause of childhood blindness. Perinatal infection plays a pathogenic role in ROP. Probiotic supplementation reduces the risk of late onset sepsis (LOS) in preterm infants but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of ROP. Eleven randomized controlled trials (4250 infants; probiotics: 2121) were included in the meta-analysis that showed a significantly decreased rate of LOS with a risk ratio (RR) of 0.807 and a 95% confidence interval (CI) of 0.705 to 0.924 (P = 0.010; fixed effects model) but could not demonstrate a significant effect of probiotics on any stage ROP (RR 1.053, 95% CI 0.903 to 1.228, P = 0.508, 4 studies), or severe ROP (RR 0.841, 95% CI 0.666 to 1.063, P = 0.148, 9 studies). Meta-regression did not show any significant association between the RR for LOS and the RR for severe ROP. In conclusion, our results suggest that infection prevention by probiotics does not affect the risk of developing ROP in preterm infants.
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Affiliation(s)
- Giacomo Cavallaro
- Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy
| | - Eduardo Villamor-Martínez
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, 6202 AZ, Netherlands.
| | - Luca Filippi
- Neonatal Intensive Care Unit, Medical and Surgical Feto-Neonatal Department, "A. Meyer" University Children's Hospital, 50139, Florence, Italy
| | - Fabio Mosca
- Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy
| | - Eduardo Villamor
- Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, 6202 AZ, Netherlands
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37
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Slidsborg C, Jensen LB, Rasmussen SC, Fledelius HC, Greisen G, Cour MDL. Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity. Br J Ophthalmol 2017; 102:14-18. [PMID: 28576764 DOI: 10.1136/bjophthalmol-2016-309187] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 04/15/2017] [Accepted: 04/23/2017] [Indexed: 01/30/2023]
Abstract
BACKGROUND To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). METHODS This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). RESULTS Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). CONCLUSION An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors.
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Affiliation(s)
- Carina Slidsborg
- Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Louise Bering Jensen
- Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Steen Christian Rasmussen
- Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark
| | - Hans Callø Fledelius
- Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Gorm Greisen
- Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Morten de la Cour
- Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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38
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Fu Z, Meng SS, Burnim SB, Smith LE, Lo AC. Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity. Clin Exp Ophthalmol 2017; 45:529-538. [PMID: 28002872 DOI: 10.1111/ceo.12908] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 12/02/2016] [Accepted: 12/16/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. METHODS Mouse pups were exposed to 75% oxygen for 5 days and returned to room air for another 5 days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. RESULTS Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. CONCLUSIONS Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature.
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Affiliation(s)
- Zhongjie Fu
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.,Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Steven S Meng
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Samuel B Burnim
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Lois Eh Smith
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Amy Cy Lo
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.,Research Center of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
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Wang JH, Ling D, Tu L, van Wijngaarden P, Dusting GJ, Liu GS. Gene therapy for diabetic retinopathy: Are we ready to make the leap from bench to bedside? Pharmacol Ther 2017; 173:1-18. [PMID: 28132907 DOI: 10.1016/j.pharmthera.2017.01.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Diabetic retinopathy (DR), a chronic and progressive complication of diabetes mellitus, is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that further damages vision. A major contributor to the pathology is excess production of vascular endothelial growth factor (VEGF), a growth factor that induces formation of new blood vessels and increases permeability of existing vessels. Despite the recent availability of effective treatments for the disease, including laser photocoagulation and therapeutic VEGF antibodies, DR remains a significant cause of vision loss worldwide. Existing anti-VEGF agents, though generally effective, are limited by their short therapeutic half-lives, necessitating frequent intravitreal injections and the risk of attendant adverse events. Management of DR with gene therapies has been proposed for several years, and pre-clinical studies have yielded enticing findings. Gene therapy holds several advantages over conventional treatments for DR, such as a longer duration of therapeutic effect, simpler administration, the ability to intervene at an earlier stage of the disease, and potentially fewer side-effects. In this review, we summarize the current understanding of the pathophysiology of DR and provide an overview of research into DR gene therapies. We also examine current barriers to the clinical application of gene therapy for DR and evaluate future prospects for this approach.
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Affiliation(s)
- Jiang-Hui Wang
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Damien Ling
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Discipline of Ophthalmology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Leilei Tu
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Peter van Wijngaarden
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Gregory J Dusting
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Guei-Sheung Liu
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia.
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40
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Chan PYL, Tang SM, Au SCL, Rong SS, Lau HHW, Ko STC, Ng DSC, Chen LJ, Yam JCS. Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis. Sci Rep 2016; 6:30732. [PMID: 27491726 PMCID: PMC4974497 DOI: 10.1038/srep30732] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 07/06/2016] [Indexed: 11/18/2022] Open
Abstract
The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.
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Affiliation(s)
- Priscilla Y L Chan
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Shu-Min Tang
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Sunny C L Au
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.,Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong
| | - Shi-Song Rong
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Henry H W Lau
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Simon T C Ko
- Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong
| | - Danny S C Ng
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Li Jia Chen
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Jason C S Yam
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
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Tunay ZÖ, Özdemir Ö, Acar DE, Öztuna D, Uraş N. Maternal Diabetes as an Independent Risk Factor for Retinopathy of Prematurity in Infants With Birth Weight of 1500 g or More. Am J Ophthalmol 2016; 168:201-206. [PMID: 27287819 DOI: 10.1016/j.ajo.2016.05.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 05/19/2016] [Accepted: 05/31/2016] [Indexed: 02/05/2023]
Abstract
PURPOSE To evaluate the relationship between maternal diabetes and the development of retinopathy of prematurity (ROP) in infants with a birth weight of 1500 g or more. DESIGN Retrospective case-control study. METHODS Data of 78 premature infants from diabetic mothers were compared with data of 258 controls. We examined the relationship between maternal diabetes and the development of ROP and type 1 ROP, adjusting for multiple risk factors. Multivariable logistic regression analysis was used to identify the risk factors of outcome variables. Prior to multivariable logistic regression analysis, the association of each independent variable with the outcome variables, a univariate estimate was performed. The crude and adjusted odds ratio (OR) values and their 95% confidence intervals (CI) were given. Main outcome measures were the development of ROP and the development of type 1 ROP. RESULTS The study was conducted on 336 preterm infants; 78 were from diabetic mothers and 258 were from nondiabetic mothers. The rate of ROP (78.2% in case group and 14.7% in control group) and the rate of type 1 ROP (20.5% in case group and 4.7% for controls) were found significantly higher in the case group (P = .001 for both). Maternal diabetes was shown to be an independent risk factor for both ROP and type 1 ROP (OR with 95% CI: 25.040 [12.728-49.264]; 6.311 [2.647-15.048], respectively, and P < .001 for both). CONCLUSION Our data suggest that the presence of maternal diabetes is significantly associated with the development of ROP and type 1 ROP in premature infants with a birth weight of 1500 g or more.
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Affiliation(s)
- Zuhal Özen Tunay
- Eye Clinic, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey.
| | - Özdemir Özdemir
- Eye Clinic, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey
| | - Damla Ergintürk Acar
- Eye Clinic, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey
| | - Derya Öztuna
- Biostatistics Department, Ankara University, Ankara, Turkey
| | - Nurdan Uraş
- Neonatology Clinic, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey
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Fu Z, Gong Y, Löfqvist C, Hellström A, Smith LEH. Review: adiponectin in retinopathy. BIOCHIMICA ET BIOPHYSICA ACTA 2016; 1862:1392-400. [PMID: 27155572 PMCID: PMC4885769 DOI: 10.1016/j.bbadis.2016.05.002] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 03/23/2016] [Accepted: 05/03/2016] [Indexed: 02/06/2023]
Abstract
Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases.
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Affiliation(s)
- Zhongjie Fu
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Yan Gong
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Chatarina Löfqvist
- Department of Ophthalmology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ann Hellström
- Department of Ophthalmology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lois E H Smith
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
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Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy. Sci Rep 2016; 6:27082. [PMID: 27256987 PMCID: PMC4891718 DOI: 10.1038/srep27082] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 05/09/2016] [Indexed: 11/08/2022] Open
Abstract
We report our experience with the use of intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). A retrospective review was performed on 138 consecutive infants screened at a single centre over 18 months. Intravitreal ranibizumab was offered in selected cases requiring treatment, such as aggressive posterior ROP or poor mydriasis. 2 eyes of 1 infant received intravitreal ranibizumab alone and 8 eyes of 5 infants received combined intravitreal ranibizumab and laser therapy. 3 out of 8 eyes treated initially with intravitreal ranibizumab monotherapy had persistent disease requiring laser therapy, and 3 out of 5 eyes with initial regression suffered disease recurrence at a mean of 7.6 weeks post-injection. 2 eyes treated first with laser followed by intravitreal ranibizumab had disease regression without recurrence. Our cohort demonstrate a significant rate of persistent disease and recurrence in ROP eyes treated initially with intravitreal ranibizumab monotherapy, which is greater and earlier than that reported for intravitreal bevacizumab in the BEAT-ROP study. Intravitreal ranibizumab may be useful as an initial treatment in selected cases of ROP when laser therapy as first line is suboptimal. However, close monitoring is important and adjunctive laser therapy may subsequently be needed in a majority of cases.
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Lee BS. Glucose Homeostasis Disorders in Premature Infants. NEONATAL MEDICINE 2015. [DOI: 10.5385/nm.2015.22.3.133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Byong Sop Lee
- Division of Neonatology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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