Changes of the peripapillary vascular parameters inpremature infants without retinopathy of prematurityusing U-net segmentation

AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the optic disc and their correlation with gestational age(GA)and birth weight(BW)in premature infants without retinopathy of prematurity(ROP).METHODS:A single-center retrospective study included a total of 133(133 eyes)premature infants[mean corrected gestational age(CGA)43.6wk]without ROP as the premature group and 130(130 eyes)CGA-matched fullterm infants as the control group.The peripapillary mVT and mVW were quantitatively measured using computerassisted techniques.RESULTS:Premature infants had significantly higher mVT(P=0.0032)and lower mVW(P=0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,respectively.Subgroup analysis with GA showed significant differences(P=0.0244)in mVT between the early preterm and middle to late preterm groups,but the differences between mVW were not significant(P=0.6652).The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(P=0.0211 and P=0.0006,respectively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(P=0.9402)and BW(P=0.7275)were not significantly correlated with mVW.CONCLUSION:Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP.Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.

Nomogram to predict severe retinopathy of prematurity in Southeast China

AIM:To define the predictive factors of severe retinopathy of prematurity(ROP)and develop a nomogram for predicting severe ROP in southeast China.METHODS:Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children’s Hospital were included.Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively.Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction,which was compared with WINROP model and Digirop-Birth model.RESULTS:Infants from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University(n=478)were randomly allocated into training(n=402)and internal validation group(n=76).Infants from Taizhou Women and Children’s Hospital were set as external validation group(n=76).Severe ROP were found in 52 of 402 infants,12 of 76 infants,and 7 of 76 infants in training group,internal validation group,and external validation group,respectively.Birth weight[odds ratio(OR),0.997;95%confidence interval(CI),0.996-0.999;P<0.001],multiple births(OR,1.885;95%CI,1.013-3.506;P=0.045),and non-invasive ventilation(OR,0.288;95%CI,0.146-0.570;P<0.001)were identified as predictive factors for the prediction of severe ROP,by univariate analysis and multivariate analysis.For predicting severe ROP based on the internal validation group,the areas under receiver operating characteristic curve(AUC)was 78.1(95%CI,64.2-92.0)for the nomogram,32.9(95%CI,15.3-50.5)for WINROP model,70.2(95%CI,55.8-84.6)for Digirop-Birth model.In external validation group,AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model(80.2 versus 51.1 and 63.4).The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model.The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability.CONCLUSION:Birth weight,multiple births,and noninvasive ventilation are independent predictors of severe ROP.The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China.

Human umbilical cord mesenchymal stem cells derivedexosomes on VEGF-A in hypoxic-induced mice retinal astrocytes and mice model of retinopathy of prematurity

AIM:To observe the effect of human umbilical cord mesenchymal stem cells(hUCMSCs)secretions on the relevant factors in mouse retinal astrocytes,and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A(VEGF-A)and to observe the therapeutic effect on the mouse model of retinopathy of prematurity(ROP).METHODS:Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group.MTT assay,flow cytometry,reverse transcription-polymerase chain reaction(RT-PCR)and Western blot were used to detect related indicators.Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored.At last,the efficacy of exosomes of UCMSCs in a mouse ROP model was explored.Graphpad6 was used to comprehensively process data information.RESULTS:The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation.Reactive oxygen species(ROS)and hypoxia inducible factor-1α(HIF-1α)of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased,and the ROP cell model was established after 6h of hypoxia.The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α,the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent.Compared with the ROP cell model group,the expression of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signal pathway related factors in the hUCMSCs exocrine group is significantly decreased.The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1αin ROP model tissues.HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion.CONCLUSION:In a hypoxia induced mouse retinal astrocyte model,hUCMSCs exosomes are found to effectively reduce the expression of HIF-1αand VEGF-A,which are positively correlated with the concentration of hUCMSCs exosomes.HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1αand VEGF-A proteins in ROP mice,and are positively correlated with drug dosage.Besides,they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

Recurrence risk factors of intravitreal ranibizumab monotherapy in retinopathy of prematurity:a retrospective study at one center

AIM:To identify risk factors of recurrence of this disorder after intravitreal ranibizumab(IVR)monotherapy.METHODS:Totally 33 eyes of 19 patients who underwent initial IVR treatments for type 1 retinopathy of prematurity(ROP)at our center were retrospectively reviewed between April 1,2016 and December 31,2017.Patient demographics,the side of ROP,multiple gestations,Apgar scores,zone,stage,plus disease,postmenstrual age at injection,surfactant therapy,blood transfusion therapy,hemorrhage before IVR,hemorrhage after IVR,gestational diabetes mellitus,pregnancy-induced hypertension,anemia,intraventricular hemorrhage,sepsis,respiratory distress syndrome,carbohemia,and congenital heart defects were recorded.Adjusted hazard ratios(HRs)and 95%confidence intervals were determined after adjusting for potential confounders using multivariate proportional Cox regression.RESULTS:Of the 33 eyes,12(36.4%)had ROP recurrences 45.3(5.1,50.9)mo after initial IVR treatments.The independent risk factors for ROP recurrences were zone(ⅡvsⅠ,HR:0.056,P=0.003)and gestational diabetes mellitus(no vs yes,HR:0.095,P<0.001).The mean uncorrected visual acuity for four recurrence eyes was 0.46 logMAR(0.13,0.70)at 55.0(51.0,58.9)mo after the initial IVR treatment.The mean uncorrected visual acuity for 10 eyes without recurrence was 0.46 logMAR(0.19,0.63)at 48.0(43.8,58.4)mo after the initial IVR treatment.CONCLUSION:Two independent risk factors for type 1 ROP recurrence after IVR treatment involving zoneⅠand gestational diabetes mellitus are identified,and the mean uncorrected visual acuity is 0.46 logMAR at 51.0(44.0,58.9)mo.The findings of this study are important for followup management and for improving the visual function of ROP patients.

Comprehensive prevention strategies for retinopathy of prematurity:a literature review

Retinopathy of prematurity(ROP)is a kind of disease that can be seen in premature infants.It may cause a series of short-and longterm complications such as poor vision in premature infants,causing irreversible damage to them.Therefore,if we can prevent this disease,we can solve the above problems.This study summarized some factors that influence ROP,such as low gestational age,low birth weight,irrational oxygen use,anemia,blood transfusion,and thrombocytopenia;and also summarized a series of interventions that can prevent or delay the progression of ROP,such as reducing blood transfusion,the application of antenatal corticosteroids,and delaying clip umbilical cord,which can provide some reference for better clinical practice of preventing ROP.

Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP.METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab.Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment.Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment.Adverse outcomes included progression to retinal detachment.RESULTS The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 years.CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

Treatment of retinopathy of prematurity: a review of conventional and promising new therapeutic options

Retinopathy of prematurity (ROP), a retinal vascular disease of premature infants, continues to be a major cause of preventable childhood blindness all over the world. The incidence of ROP varies among countries, being influenced by the quality of the level of neonatal intensive care. Here, we discuss the potential treatments that are now available or will soon or probably be available for ROP. Although ablation of the avascular retina with laser photocoagulation remains the current gold standard and well established therapy for ROP, some new therapeutic options including angiostatic therapies are being explored based on our knowledge of the pathophysiology of the ROP and complications and efficacy of laser treatment. However, prevention of the development of severe ROP and screening for ROP seem to be the best strategy in avoiding visual impairment caused by ROP in premature infants. New therapeutic interventions including vascular endothelial growth factor antibody administration, gene therapy and supplemental therapies should be supported with evidence-based data for the treatment of ROP.

Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran

AIM: To determine the incidence and risk factors of retinopathy of prematurity(ROP) and the sensitivity of current screening criteria in a tertiary eye center in Tehran, Iran. METHODS: In a cross-sectional observational study, neonates weighing ≤2000 grams at birth or born <34 wk gestational age(GA) and all other infants at risk of ROP admitted to the neonatal intensive care unit(NICU) or referred to our ROP clinic were investigated. The incidence of ROP and severe ROP(i.e. patients needing treatment) were determined. The associations between risk factors and the development and severity of ROP were assessed. We also examined the sensitivity of the current national screening guideline in Iran. RESULTS: Among 207 infants, the incidence of ROP and severe ROP was 33.3% and 11.1%, respectively. Mean GA and birth weight(BW) were significantly lower in ROP vs non-ROP infants(29±2 wk vs 33±3 wk, P<0.001;1274±489 g vs 1916±550 g, P<0.001, respectively). Univariate analysis displayed significant association between ROP incidence and GA, BW, NICU admission period, blood transfusion, surfactant usage, sepsis, intraventricular hemorrhage and patent ductus arteriosus(P<0.05 for all). BW [relative risk(RR): 0.857(0.711-0.873), P<0.001], GA [RR: 0.788(0.711-0.873), P<0.001] and blood transfusion [RR: 1.888(0.995-3.583), P=0.052] were independent ROP risk factors. The sensitivity of country-specific screening guidelines was 95.7% and 100% for overall and severe ROP detection, respectively. CONCLUSION: ROP incidence is relatively high in Iran. Identifying ROP risk factors results in more accurate screening and reduces the risk of irreversible vision loss. The ROP screening criteria utilized in Iran are efficient at the present time.

The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity（ROP） is a retinal vascular disorder frequently found in premature infants.Different therapeutic strategies have been developed to treat ROP.However,there are still many children with ROP suffering by severe limitations in vision or even blindness.Recently,ROP has been suggested to be caused by abnormal development of the retinal vasculature,but not simply resulted by retinal neovascularization which takes about 4 to 6 wk after birth in premature infants.Thus,instead of focusing on how to reduce retinal neovascularization,understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful,which may lead to identify novel target（s） for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force.In this review,we discussed recent studies about,1） the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy（OIR;a ROP in animal model） and in premature infants with ROP;2） the preclinical and clinical research on preventive treatment of early OIR and ROP.We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.

Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization （clock hours） in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

Fluorescein angiography of retinal vascular involution after intravitreal injection of ranibizumab for retinopathy of prematurity

AIM: To describe the involution patterns of vessel growth of retina through fluorescein angiography(FA) of children, who had been under treatment up to 1 y previously intravitreal ranibizumab(IVR) as monotherapy for retinopathy of prematurity(ROP). METHODS: This is a retrospective study. The medical information and FA of 17 children(34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters(DD) were analyzed. RESULTS: Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts(100%,34/34 eyes). Popcorn abnormalities were found in most of the eyes(94.1%, 32/34 eyes). Furthermore, in many cases(23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes(5.9%) showed damage of retinal capillary bed and 3 eyes(8.8%) showed large area of retinal pigment epithelium(RPE) atrophy. CONCLUSION: Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.

Spontaneous regression of retinopathy of prematurity:incidence and predictive factors

AIMTo evaluate the incidence of spontaneous regression of changes in the retina and vitreous in active stage of retinopathy of prematurity(ROP) and identify the possible relative factors during the regression.

Retinopathy of prematurity: Past, present and future

Retinopathy of prematurity(ROP) is a vasoproliferative disorder of the retina occurring principally in new born preterm infants. It is an avoidable cause of childhood blindness. With the increase in the survival of preterm babies, ROP has become the leading cause of preventable childhood blindness throughout the world. A simple screening test done within a few weeks after birth by an ophthalmologist can avoid this preventable blindness. Although screening guidelines and protocols are strictly followed in the developed nations, it lacks in developing economies like India and China, which have the highest number of preterm deliveries in the world. The burden of this blindness in these countries is set to increase tremendously in the future, if corrective steps are not taken immediately. ROP first emerged in 1940 s and 1950 s, when it was called retrolental fibroplasia. Several epidemics of this disease were and are still occurring in different regions of the world and since then a lot of research has been done on this disease. However, till date very few comprehensive review articles covering all the aspects of ROP are published. This review highlights the past, present and future strategies in managing this disease. It would help the pediatricians to update their current knowledge on ROP.

Analysis of risk factors for retinopathy of prematurity

AIM: To analyze the incidence and risk factors for retinopathy of prematurity (ROP). METHODS: A retrospective analysis was conducted on 568 premature infants from September 2005 to December 2010 with birth weight (BW) equal to or less than 2 500g or a gestational age (GA) at birth of 34 weeks or less. All of the members were examined by indirect binocular ophthalmoscopy. RESULTS: ROP occurred with an incidence rate of 10.7% among 568 premature infants, and stages 3 and above ROP occurred with an incidence rate of 2.5%. This study showed the infants were more prone to develop ROP with short geststional age, low BW, long time of oxygen inhalation, and severe infants diseases. Twins had a significantly higher rate of ROP (18.3%) than singleton babies (9.8%), ROP were severer in twins than singleton babies. CONCLUSION: Short GA, low BW, long time of oxygen inhalation, severe infants diseases, and non-singleton babies were the most significant risk factors associated with ROP.

Systemic changes and adverse effects induced by retinopathy of prematurity screening

AIM: To estimate the potential systemic events during and after retinopathy of prematurity (ROP) screening. ' METHODS: A prospective and descriptive designed study was conducted to detect the physiologic and pathological changes 24h before, during, and 72h after ROP screening. Control blood pressure (BP), saturation, pulse rate, and body temperature were routinely taken at various time internals before and after screening. Adverse effects pertain to cardiovascular system, respiratory system, gastric system, urinary system and nervous system were retrospect 0-72h after ROP screening at a 24-hour interval. RESULTS: Totally 1254 prematurity babies receiving ROP screening during Jan. 1st 2013 to Dec. 31th 2013 were enrolled in our survey. Compared to control vital sign data taken before the examination, there was a fluctuation in the diastolic BP with the increased 3.03 mm Hg (P=0.04) after 3 doses of mydriatic drops. Immediately after the examination, there was a further 12.64 mm Hg (P<0.01) increase in systolic BP and a 7.24 mm Hg (P<0.01) in diastolic BP. The mean pulse rate during examination was 22.4 bpm (P<0.01) higher than the 133.3 +/- 9.0 bpm control level. The oxygen saturation shared an average drop of 5% (P<0.01) during screening. In prematurity with postconceptional age less than 31wk, the incidence of apnea (23.5%), necrotizing enterocolitis (NEC) (8.7%), gastric residual (25.4%) and upper digestive tract hemorrhage (6.4%) also demonstrated a significant rise (P<0.01). CONCLUSION: In our study sample, ROP screening was associated with NEC, gastric residual and upper digestive tract hemorrhage. These gastrointestinal side effects, along with breath activity pattern change and vital signs indicators fluctuation, may be results of additional stress responses.

Screening for retinopathy of prematurity:a report from upper Egypt

AIM： To detect the incidence of retinopathy of prematurity （ROP） in a tertiary referral neonatal intensive care unit in upper Egypt and to describe the obstacles faced during implementing the screening protocol for the first time. METHODS： Consecutive infants were enrolled at birth and screened for ROP. We used the UK ROP guideline （May 2008） for infant selection, follow up and treatment. Repeat examinations were performed until retinal vascularisation was complete. RESULTS： Fifty-two infants were enrolled： 24 males and 28 females. Mean gestational age was 31.3wk （±2.8 SD） and mean birth weight was 1234,6 g （±221.1 SD）. Incidence of ROP was 36.5% （stages 1, 2, 3 and 4a were 9.6%, 9.6%, 15.4% and 1.9% respectively）, no stages 4b or 5 were found in this series. Six infants （11.5%） died during screening without ROP, 25 infants （48.1%） were discharged from screening with retinal vascularisation reaching zone III, 5 infants （9.6%） were treated with indirect diode with or without additional cryotherapy and 16 infants （30.8%） were lost to follow up. In this series gestational age rather than birth weight was found significantly correlated and predictive （P〈0.05） with ROP stages. CONCLUSION： ROP in a single site in upper Egypt appears to have comparable incidence to other areas worldwide. The main screening obstacle was missing cases due to the absence of a national ROP screening protocol.

The process of retinal vascularization in retinopathy of prematurity after ranibizumab treatment in China

AIM: To explore the process of retinal vascularization and risk factors for retinopathy of prematurity(ROP) treated with intravitreal ranibizumab(IVR) as monotherapy.METHODS: Infants with type 1 ROP who received IVR as primary treatment from August 2014 to October 2016 at Peking University People’s Hospital’s Ophthalmology Department were included in the study. All eyes received 0.25 mg ranibizumab at initial treatment. Retinal vascularization was evaluated clinically. Potential risk factors were also recorded and examined.RESULTS: Retinal vascularization was completed in 126 eyes(62.7%), and retinal vascularization terminated in zone II and zone III with 16 eyes(7.9%) and 44 eyes(21.9%), respectively, after more than 1-year follow-up. In multivariate regression analysis, lower birth weight(BW), severity of ROP and repeated injections were found to be risk factors for peripheral avascular area(P<0.05). CONCLUSION: In our retrospective study, 29.8% of the ROP eyes treated with ranibizumab have peripheral avascular area at the last follow-up. Lighter BW and the severity of ROP are risk factors. Furthermore, repeated injections also increase the risk of retinal peripheral avascular area remaining in ROP patients.

One-year experience in the retinopathy of prematurity: frequency and risk factors, short-term results and follow-up

· AIM: As a result of the increase in premature births and the advances in neonatal intensive care, retinopathy of prematurity (ROP) remains one of the most important causes of childhood blindness worldwide. The main factors in the development of ROP are gestational age, birth weight and oxygen therapy. ROP continues to gain importance due to the increasing survival rates of more immature babies. · METHODS: Between January 2007 and October 2008, 203 premature infants treated at the Neonatal Intensive Care Unit (NNICU) were prospectively enrolled and the relationship between known risk factors and the occurance of ROP was studied. · RESULTS: ROP in various stages developed in 86 cases (42.4%). Statistically significant correlations were found between the development of ROP and birth weight (P < 0.0001) gestational age (P <0.0001), oxygen treatment and its duration (P <0.0001 and P =0.002), mechanical ventilation (MV) and its duration (P =0,0001 and P =0.0001), apnea(P = 0.001), intraventricular hemorrhage (IVH) (P =0.046), sepsis (P =0.0001), use of erythropoietin (EPO) (P =0.003), the number of blood transfusions and frequency (P =0.0001 and P =0.0001), surfactant application (P =0.0001), the presence of patent ductus arteriosus (PDA) (P =0.001) or bronchopu- lmonary dysplasia (BPD) (P =0.0001). No significant correlations were found between the occurance of ROP and maternal pre-eclampsia (P =0.293), multiple pregnancy (P = 0.218), or hyperbilirubinemia (P =0.494). Severity of ROP was related significantly with birth weight (P =0.0001), but no significant correlation between severity of ROP and gestational age was present. · CONCLUSION: Early description and reduction of the risk factors related with the occurance of ROP with the help of routine screening programs may warrant the prevention of visual loss, however early ophthalmic diagnosis and treatment are still mandatory to provide better visual rehabilitation. ·

Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants

AIM： To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity（ROP） risk among Chinese infants. METHODS： Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS： Of the nine polymorphisms, only two showed significant associations： ACE insertion deletion（ID） polymorphism（P=0.031） and TNF-308 G/A polymorphism（P〈0.001）. The former was associated with a reduced ROP risk [ID genotype, adjusted OR（aOR）： 0.603, 95%CI： 0.427-0.893, P=0.034; DD genotype, aOR： 0.468, 95%CI： 0.229-0.626, P=0.002], while the latter showed an increased risk（GA genotype, aOR： 1.956, 95%CI： 1.396-2.465, P〈0.001; AA genotype, aOR： 2.809, 95%CI： 1.802-4.484, P〈0.001）. The association was also noted at the allele level（ACE D allele a OR： 0.698, 95%CI： 0.294-0.883, P〈0.001; TNF-308A allele a OR： 1.776, 95%CI： 1.446-2.561, P〈0.001）. CONCLUSION： The ACE ID polymorphism can protect against ROP development while the TNF-308G/A can increase the risk of the disease among Chinese infants.

Expression profiles of long noncoding RNAs in retinopathy of prematurity

Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ROP.Seven-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model.Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP mice.Compared with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated mRNAs.Differentially expressed genes were involved in ocular development and related metabolic pathways.The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways.Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment.This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).