Objective To observe the effect of assisted reproductive technology (ART) on retinopathy of prematurity (ROP) in preterm infants. MethodsA retrospective clinical study. From January 2016 to January 2020, 639 preterm infants who were hospitalized at Children's Hospital of Zhengzhou University and underwent fundus screening at a gestational age ≤32 weeks were included in the study. There were 366 males and 273 females. Gestational age at birth were (28.3±1.4) weeks; birth weight were (1 153.8±228.8) g. Severe ROP was detected in 60 cases (9.4%, 60/639); 120 were ART recipients, and 519 were naturally conceived, and were divided into the ART group and the control group accordingly. The incidence of gestational diabetes mellitus (χ2=21.675), pulmonary surfactant application (χ2=13.558), and twin births (yes) (χ2=145.568) in mothers of the children examined in both groups were significantly higher than that of the control group, and the difference were statistically significant in all cases (P＜0.001). Comparison of quantitative data between groups was performed by t-test, and comparison of count data was performed by χ2 test; logistic regression was used to analyze the effect of ART on the incidence of ROP. ResultsOf the 60 cases of severe ROP, 18 (15.0%, 18/120) and 42 (8.1%, 42/519) cases were in the ART group and control group, respectively. The incidence of severe ROP was significantly higher in the ART group than in the control group, and the difference was statistically significant (χ2=4.680, P=0.024). Compared with the control group, the incidence of severe ROP was significantly higher in the ART group for gestational age at birth ＜28 weeks and birth weight ＜1 000 g, and the differences were statistically significant (χ2=10.116, 3.785; P=0.002, 0.037). Logistic regression analysis showed that ART was a non-independent risk factor for the occurrence of ROP (P＞0.05). ConclusionAssisted reproductive technology may have a certain influence on the occurrence of ROP, which is not an independent factor.
【摘要】 目的 探讨早产儿视网膜病变（retinopathy of prematurity，ROP）的发生率及危险因素。 方法 收集2007年12月-2008年12月在四川省人民医院、成都市妇幼保健院、成都市妇产科医院住院的85例体重≤2 000 g或有严重疾病的早产儿,自出生后4~6周或矫正胎龄32周开始筛查，至周边视网膜血管化。 结果 85例早产儿中，有9例发生ROP，发病率10.58%。其中出生体重lt;1 500 g的早产儿ROP发病率为17.07%，孕周lt;30周的早产儿ROP发病率为40%。 结论 低体重、胎龄小、吸氧为早产儿发生ROP的重要危险因素；尽早进行眼底筛查是早期发现、诊断及治疗ROP的关键。【Abstract】 Objective To investigate the occurrence and risk factors of retinopathy of prematurity (ROP). Methods A total of 85 premature infants were enrolled from Sichuan provincial people′s hospital, Chengdu maternal and child health hospital, and Chengdu obstetric and gynecology hospital. The infants were born between December 2007 and December 2008, with a birth weight less than 2 000 g. The ocular funds examination was carried out four to six weeks after the birth or at the 32nd week of the corrected gestational age;the infants were followed up until the retina was entirely vascularized. Results ROP was found in 9 of the 85 premature infants, with a percentage of 10.58%. About 17.07% premature infants with a birth weight less than 1500 g and 40% infants with a gestational age shorter than 30 weeks had ROP. Conclusions A lower birth weight, a shorter gestational age and oxygen usage are the risk factors of ROP. It′s important to examine the ocular fundus in premature infants as early as possible so as to identify, diagnose and treat ROP at an early stage.
ObjectiveTo observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR). MethodsA retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed. ResultsThe time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, pre-threshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes. ConclusionsThe lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.
ObjectiveTo investigate the postnatal changes in urinary metabolic amino acid levels in infants with retinopathy of prematurity (ROP) and their effect on ROP, and to analyze the amino acid metabolic pathways that may be involved in the development of ROP. MethodsA retrospective cohort study. From January 2020 to December 2023, 65 premature infants with severe ROP (ROP group) who were hospitalized, born with gestational age ＜32 weeks in Children's Hospital Affiliated to Zhengzhou University were included in the study. Fifty premature infants with matched sex and gestational age and no ROP were selected as the control group. Urine amino acids and their derivatives were detected by gas chromatography-mass spectrometry. The two groups were compared by independent sample t test. The metabonomics of urinary amino acids was analyzed by orthogonal partial least squares discriminant analysis (OPLS-DA) model. The variable projection importance (VIP) score ＞1 suggested that the substance was two groups of differentially expressed amino acids. The predictive value of urinary amino acids for severe ROP was compared by using the receiver's operating characteristic (ROC) curve and the area under the curve. After t test and metabolomics analysis, the two groups of amino acids with large differences were normalized and compared by Pearson correlation analysis. The Kyoto Encyclopedia of Genes and Genomes database was used to analyze the metabolic pathways of differentially expressed amino acids involved in ROP. ResultsCompared with the control group, the concentrations of oxalic acid -2 and thiodiacetic acid-2 in urine metabolites of children in ROP group were significantly decreased, while the concentrations of 4-hydroxybutyric acid-2, 3-methylpentadienoic acid-2(1), 2-ketoglutarate-ox-2(2) and 3, 6-epoxy-dodecanedioic acid-2 were significantly increased, with statistical differences (t=0.036, 0.005, 0.038, 0.032, 0.022, 0.011; P＜0.05). The results of OPLS-DA analysis showed that amino acids of urinary metabolites in ROP group and control group were distributed in the left and right regions of the scatter plot, and there was a satisfactory separation trend between the two groups (R2Ycum=0.057 4, Q2cum=0.025 7, P＜0.05). As shown in the S-Plot, the amino acids biased towards two stages are glycolic acid-2, phosphoric acid-3, oxalic acid-2, thiodiacetic acid-2, 4-hydroxybutyric acid-2, 3-methylcrotonylglycine-1, 3-methylpentadienoic acid-2(1), 2-ketoglutarate-ox-2(2) and 3, 6-epoxy- dodecanedioic acid-2, respectively. Eleven differentially expressed amino acids with VIP score ＞1 were screened, among which the highest VIP score was oxalate-2, glycerate-3, phosphoric acid-3, 3-methylcrotonylglycine-1, uranoic acid -3 and thiodiacetic acid-2. The difference of amino acid concentration between the two groups was the highest in 4-hydroxybutyric acid-2 and thiodiacetic acid-2. The correlation between oxalic acid-2 and glycerate-3 was the highest (r=0.830, P＜0.001), and most amino acids were positive correlated. ROC curve fitting analysis showed that the combined prediction of 11 differenly-expressed amino groups had the largest area under the curve (0.816), the cutoff value was 0.531, and the sensitivity and specificity were 83.1% and 70.0%, respectively. The enrichment analysis of these 11 amino acids with significant differences suggested that the main pathways involved included butyrate metabolism, glyoxylic acid and dicarboxylic acid metabolism and lipoic acid metabolism. ConclusionAbnormal amino acid metabolism of 4-hydroxybutyrate-2, 3-methylpentadienoic acid-2(1), thiodiacetic acid-2, 2-ketoglutarate-ox-2(2), 3, 6-epoxy-dodecanedioic acid-2 may have a certain effect on the occurrence of ROP.
Retinopathy of Prematurity (ROP) is a blinding eye disease characterized by abnormal retinal vascular proliferation and is a major cause of visual impairment in children. Its pathogenesis is complex, involving multiple factors such as hyperoxia exposure, hypoxic compensation, oxidative stress, inflammatory responses, and abnormal angiogenesis, with oxidative stress playing a central role. It is characterized by excessive production of reactive oxygen species and impaired antioxidant function, leading to retinal vascular endothelial cell damage, formation of avascular areas, and abnormal vascular proliferation. Studies have shown that oxidative stress can promote the development and progression of ROP through vascular damage, nitrooxidative stress synergy, and interference with cellular metabolism. Current treatment strategies mainly include antioxidant agents (such as vitamin C, vitamin E, and lutein), signal pathway regulatory agents (such as nuclear factor erythroid 2-related factor 2 activators, signal transducer and activator of transcription 3 inhibitors), corticosteroids (such as Triamcinolone and Dexamethasone), and adrenergic receptor antagonists (such as Propranolol), but their efficacy and safety still require further validation. In the future, multidisciplinary collaboration should be strengthened to further explore the interactions between oxidative stress and other pathological mechanisms, and long-term follow-up studies should be conducted to develop safer and more effective strategies for the prevention and treatment of ROP, thereby improving the visual outcomes of preterm infants.
ObjectiveTo observe and analyze the correlation between erythrocyte count and hemoglobin level in early life and retinopathy of prematurity (ROP). MethodsA clinical retrospective study. From January 2020 to December 2022, a total of 303 premature infants, who underwent fundus screening in Children's Hospital of Henan Province were included. There were 219 males and 84 females, with the average gestational age of (30.36±1.52) weeks and the average birth weight of (1 368.43±171.37) g. Early life was defined as 14 days after birth. According to the screening results, patients were divided into ROP group and no ROP group (control group). The results of red blood cell count, hematocrit and hemoglobin concentration of the two groups were compared and observed on the 3rd, 7th and 14th day after birth. The measurement data were compared by t-test, and the count data were compared by χ2 test. The risk factors of ROP were analyzed by logistic regression. The correlation between red blood cell count as well as hemoglobin concentration in early life and ROP was analyzed by receiver operating characteristics (ROC) curve. ResultsAmong the 303 premature infants screened, a total of 101 preterm infants were included in the ROP group, with the average gestational age of (30.39±1.48) weeks. And a total of 202 preterm infants were included in the control group, with the average gestational age of (30.35±1.55) weeks. There was no significant difference between the two groups in sex composition ratio (χ2=0.296) and gestational age (t=0.251) (P＞0.05). There were significant differences in birth weight (t=－2.024), blood transfusion times (U=－4.957), invasive mechanical ventilation duration (U=－2.215) and continuous positive airway pressure ventilation time (U=－5.224) between the two groups (P＜0.05). The incidence of periventricular leukomalacia (χ2=5.069), bronchopulmonary dysplasia (χ2=9.794) and sepsis (χ2=8.041) were significantly different (P＜0.05). The average hemoglobin level of patients in the ROP group on the 3rd, 7th and 14th day after birth were lower than those in the control group (t=－3.813, －2.753, －2.847; P＜0.05). Logistic regression analysis showed that low frequency of blood transfusion [odds ratio (OR)=1.241, 95% confidence interval (CI) 1.016-1.517] and short duration of continuous positive airway pressure (OR=1.128, 95%CI 1.031-1.234) were protective factors for ROP. The ROC curve analysis indicated that the abnormal threshold values of hematocrit and hemoglobin were the highest on the 14th day after birth, which were 115.5 g/L and 36.25% respectively. The sensitivities were 88.1% and 83.2%, respectively. ConclusionRed blood cell count and hemoglobin level in early life of preterm infants may have a certain correlation with the occurrence and development of ROP.
ObjectiveTo investigate the prognosis and differences of visual function and fundus structure in retinopathy of prematurity (ROP) undergoing anti-vascular endothelial growth factor agents (VEGF) or laser photocoagulation treatment with long-term follow-up. MethodsRetrospective case control series. From January 2010 to December 2021, A total of 35 children (63 eyes) with ROP who were first diagnosed in Department of Ophthalmology, Peking University People's Hospital and followed up for as long as 5 years were included. Among them, 21 males (36 eyes) and 15 females (27 eyes) were enrolled. The average gestational age (GA) of the children at birth was 29.30±1.77 weeks. Among the included 12 aggressive ROP (A-ROP) eyes and 51 pre-threshold type 1 ROP eyes, no retinal detachment occurred. Each eye received only intravitreal injection of anti-VEGF agents or laser monotherapy after diagnosis, and divided into anti-VEGF group or laser group according to the treatment. Thirty-five eyes of 20 infants were included in the anti-VEGF group and 28 eyes of 15 infants were included in the laser group. GA, birth weight (BW) and postmenstrual age receiving first treatment were compared and no significant difference between the two groups was defined (P=0.844, 0.859, 0.694). The number of A-ROP, pre-threshold type 1 ROP eyes were also compared, and statistically significance can be defined (P=0.005). During the follow-up period, best corrected visual acuity (BCVA), refractive status, visual field, optical coherence tomography (OCT) and fluorescein fundus angiography (FFA) were performed. The BCVA examination was carried out using the international standard decimal visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. Refractive status was calculated as spherical equivalent (SE). Comparative observation of 5-year outcomes including BW, GA, fundus examination at the initial diagnosis, and BCVA, refractive status, visual field defect, central foveal thickness (CFT), subfoveal choroidal thickness (SFCT) and abnormality of peripheral retina in FFA were performed between the two groups. Differences between groups were compared using t test or nonparametric test for measurement data, and χ2 test was used for comparison between groups in enumeration data. ResultsFive years after treatment, retinal avascular areas were seen around the eyes in the anti-VEGF treatment group, with a size of 2.32±1.84 optic disc diameters, and 1 eye had fluorescein leakage at the junction of the peripheral avascular areas; eyes in the laser treatment group old photocoagulation spots were seen in the peripheral retina, and no fluorescein leakage was seen. The logMAR BCVA of the eyes in the anti-VEGF treatment group and laser treatment group were 0.15 (0.00, 0.20), 0.10 (0.00, 0.16), respectively; SE were 0.50 (－1.25, 1.31), 0.38 (－4.25, 1.75) D, respectively; mean defect (MD) values of visual field were 2.70 (1.20, 4.80), 4.25 (2.83, 6.98) dB; CFT, SFCT were 225.00±29.31, 287.18±68.56 μm and 237.17±32.81, 279.79±43.61 μm. There was no significant difference in logMAR BCVA, CFT and SFCT between the two groups (P=0.363, 0.147, 0.622); the lower quartile of SE and visual field MD value in the laser treatment group were significantly higher than those in the laser treatment group, but there was no significant difference in the median SE (P=0.109), and there was a statistically significant difference in the median MD value of the visual field (P=0.037). ConclusionsAnti-VEGF agents and laser therapy can achieve similar good visual prognosis for early ROP, and the peripheral visual field can be preserved to a greater extent, however, the peripheral visual field defect in the laser group is more significant than that in the anti-VEGF group. For ROP without retinal detachment, the thickness of the retina and choroid in the fovea is generally normal.
Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.
Retinopathy of prematurity (ROP) is a blinding eye disease of neonates. Early screening and regular follow-up can prevent the disease from leading to serious functional impairment. Rop is classified by the World Health Organization as the prevention target of avoidable blindness in neonates. Since the National Health Commission of the People's Republic of China issued "Guidelines for the treatment of oxygen and the prevention and treatment of retinopathy in prematurity" in 2004, the Ophthalmology Group of the Chinese Academy of Ophthalmology has actively promoted the screening and treatment of ROP, and updated "Guidelines for screening retinopathy of prematurity" in China in 2014. After nearly 20 years of hard work, the disease of stage 5 ROP in China has basically disappeared. In order to reasonably grasp the classification criteria of ROP and the indications of drug treatment, Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association organize experts in related fields to reach consensus opinions through serious, comprehensive and full discussion, and update the classification of ROP in China and the Chinese translation of new terms with reference to international standard terms. The standard of anti-vascular endothelial growth factor drug treatment indication is also added to provide reference for clinicians in clinical practice.