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A systematic study on the prevention and treatment of retinopathy of prematurity in China.

ABSTRACT: To identify the prevention situation, the main factors influencing prevention effects and to develop control measures over retinopathy of prematurity in China.Using stratified random sampling method, we randomly selected 23 provincial and ministerial hospitals (8 in Guangdong province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180 district and county hospitals (76 in Guangdong province, 57 in Hunan province and 47 in Shaanxi province) in China. A total of 284 hospitals were enrolled in the study, with questionnaires distributed investigating the status and constrain factors of ROP presentation. Significant outcomes were analyzed thereafter by SPSS 19.0.The screening rate of ROP in medical institutions from eastern, central and western China were 84.6%, 35.0% and 56.7%, respectively. The screening rate of tertiary and secondary medical institutions were 84.6% and 25.7% in the eastern, 35.0% and 4.9% in the central, 56.7% and 5.9% in the western region. Screening was carried out better in the tertiary than that in the secondary and primary institutions. Treatment for ROP was available in 15.7% of all the tertiary hospitals surveyed. Lack of professionals, equipments and technologies were considered to be major restrain factors for screening.The ROP screening and treatment status have demonstrated significant regional diversity due to uneven distribution of medical resources in China. Developed areas had established intraregional cooperation models, whereas less-developed areas should consider set up a large-scale, three-level ROP prevention network. It is of paramount importance that education and training towards ophthalmologists should be vigorously strengthened. It is strongly recommended that implement ROP telemedicine and integrated ROP prevention and management platforms through the Internet should be established.

SUBMITTER: Xu S

PROVIDER: S-EPMC5813392 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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A systematic study on the prevention and treatment of retinopathy of prematurity in China.

Xu Shuman S Liang Zhijiang Z Du Qiyun Q Li Zhankui Z Tan Guangming G Nie Chuan C Yang Yang Y Lv Xuzai X Zhang Chunyi C Luo Xianqiong X

BMC ophthalmology 20180214 1

<h4>Background</h4>To identify the prevention situation, the main factors influencing prevention effects and to develop control measures over retinopathy of prematurity in China.<h4>Methods</h4>Using stratified random sampling method, we randomly selected 23 provincial and ministerial hospitals (8 in Guangdong province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180 district and county hospi ...[more]

PMID: 29444655

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Project description:Retinopathy of prematurity (ROP) is the most common cause of childhood blindness worldwide and is caused by oxygen therapy necessary to prevent mortality after premature birth. We have previously demonstrated the efficacy of systemic hypoxia inducible factor (HIF) stabilization through HIF prolyl hydroxylase inhibition (HIF PHi) in protecting retinal vasculature from oxygen toxicity in a mouse model of ROP or oxygen induced retinopathy (OIR). We definitively demonstrated that hepatic HIF-1 can be activated to confer this protection using systemic dimethyloxalylglycine (DMOG) to prevent HIF-1α degradation. In this study we compare Roxadustat, a small molecule stabilizer of HIF-1 currently in phase 3 clinical trials for increasing erythropoiesis in adult patients with chronic kidney disease, to DMOG. We demonstrate that Roxadustat induces vascular protection during hyperoxia to induce the coordinated sequential growth of retinal vasculature with a 3-fold reduction in oxygen induced capillary loss (p-=0.001). In order to define the molecular mechanism of protection, we further compared the transcriptome of both liver and retina after systemic treatment with Roxadustat or DMOG. Similar gene expression profiles were identified in liver but very different effects on transcription were found in retinal tissues because Roxadustat, in contrast to DMOG, directly targets retina, confirmed by western blot and by rescue of the hepatic HIF-1 KO, two criteria that DMOG treatment is unable to fulfill. Systems pharmacologic analysis demonstrates that Roxadustat induces typical HIF regulated genes critical to aerobic glycolysis in liver and retinal tissues whereas DMOG, acting through either secreted hepatokines or by influence of systemic DMOG, downregulates cell adhesion/extracellular matrix interaction pathways while increasing expression of histone cluster genes. Stratification of liver transcriptomes to secreted gene products again shows close consensus of hepatic genes induced by both small molecules, and includes upregulation of a plethora of angiogenic proteins such as plasminogen activator inhibitor (PAI-1), erythropoietin (EPO), and orosomucosoid 2 (ORM2). Secondary validation of these transcripts by serum ELISA confirms secretion of EPO and PAI-1 into blood from liver. These findings definitively demonstrate that HIF stabilization can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect, hepatic HIF-1 stabilization and increased serum angiokines. Systems pharmacology analysis therefore explains why intermittent, low dosage of small molecule HIF stabilizers creates a profound protective phenotype, because both pathways can take advantage of cytoprotection induced by the liver and by retina synergistically. These data provide a rationale for considering low dose, intermittent systemic administration of Roxadustat, currently in phase 3 trials in adults with chronic kidney disease, to eradicate ROP in children.

Dataset Information

A systematic study on the prevention and treatment of retinopathy of prematurity in China.

Publications

A systematic study on the prevention and treatment of retinopathy of prematurity in China.

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