【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 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.
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.
ObjectiveTo analyze the clinical characteristics and evaluate the effect and safety of anti-vascular endothelial growth factor (VEGF) therapy in retinopathy of prematurity (ROP) in Sichuan province. MethodsA retrospective study. From January 2013 to January 2022, 156 patients (306 eyes) with ROP who received intravitreal anti-VEGF therapy for the first time in the Department of Ophthalmology, West China Hospital of Sichuan University were selected. According to the type of anti-VEGF drugs, the children were divided into intravitreal injection of ranibizumab (IVR) group and intravitreal injection of conbercept (IVC) group; IVC group was divided into hospital group and referral group according to the different paths of patients. After treatment, the patients were followed up until the disease degenerated (vascular degeneration or complete retinal vascularization) or were hospitalized again for at least 6 months. If the disease recurred or progressed, the patients were re-admitted to the hospital and received anti-VEGF drug treatment, laser treatment or surgical treatment according to the severity of the disease. Clinical data of these children was collected, including general clinical characteristics: gender, gestational age at birth (GA), birth weight (BW), history of oxygen inhalation; pathological condition: ROP stage, zone, whether there were plus lesions; treatment: treatment time, postmenstrual gestational age at the time of the first anti-VEGF drug treatment; prognosis: re-treat or not, time of re-treatment, mode of re-treatment; adverse events: corneal edema, lens opacity, endophthalmitis, retinal injury, and treatment-related systemic adverse reactions. The measurement data between groups were compared by t test, and the count data were compared by χ2 test or rank sum test. ResultsOf the 306 eyes of 156 children with ROP, 74 were male (47.44%, 74/156) and 82 were female (52.56%, 82/156). Each included child had a history of oxygen inhalation at birth. The GA was (28.43±2.19) (23.86-36.57) weeks, BW was (1 129±335) (510-2 600) g, and the postmenstrual gestational age was (39.80±3.04) (31.71-49.71) weeks at the time of the first anti-VEGF drug treatment. All patients were diagnosed as type 1 ROP, including 26 eyes (8.50%, 26/306) of aggressive ROP (A-ROP), 39 eyes (12.74%, 39/306) of zone Ⅰ lesions, and 241 eyes (78.76%, 241/306) of zone Ⅱ lesions. The children were treated with intravitreal injection of anti-VEGF drugs within 72 hours after diagnosis. Among them, 134 eyes (43.79%, 134/306) of 68 patients were treated with IVR, and 172 eyes (56.21%, 172/306) of 88 patients were treated with IVC. In IVC group, 67 eyes of 34 patients (38.95%, 67/172) were in the hospital group and 105 eyes of 54 patients (61.05%, 105/172) were in the referral group. 279 eyes (91.18%, 279/306) were improved after one treatment, 15 eyes (4.90%, 15/306) were improved after two treatments, and 12 eyes (3.92%, 12/306) were improved after three treatments. The one-time cure rate of IVR group was lower than that of IVC group, but the difference was not statistically significant (χ2=1.665, P=0.197). In different ROP categories, IVC showed better therapeutic effect in A-ROP, and its one-time cure rate was higher than that in IVR group, with statistically significant difference (χ2=7.797, P<0.05). In the hospital group of IVC group, the GA, BW and the postmenstrual gestational age at first time of anti-VEGF drug treatment were lower than those in the referral group, and the difference was statistically significant (t=－2.485, －2.940, －3.796; P<0.05). The one-time cure rate of the hospital group and the referral group were 94.94%, 92.38%, respectively. The one-time cure rate of the hospital group was slightly higher than that of the referral group, but the difference was not statistically significant (χ2=0.171, P=0.679). In this study, there were no ocular and systemic adverse reactions related to drug or intravitreal injection in children after treatment. ConclusionsCompared with the characteristics of ROP in developed countries, the GA, BW and postmenstrual gestational age of the children in Sichuan province are higher. Both IVR and IVC can treat ROP safely and effectively. There is no significant difference between the two drugs in the overall one-time cure effect of ROP, but IVC performed better in the treatment of A-ROP in this study.
Objective To observe the incidence of retinopathy of prematurity (ROP) at different altitudes in Yunnan Province. MethodsA retrospective case-control study. From July 1, 2010 to June 30, 2019, 1 352 premature infants (Kunming group) and 579 premature (Dehong group) infants who received ROP screening in the Neonatology Department of Kunming Maternal and Child Health Hospital and the Neonatology Department of Dehong Dai and Jingpo Autonomous Prefecture People's Hospital were included in the study. A wide field digital retinal imaging system combined with binocular indirect ophthalmoscope and scleral oppressor was used for fundus examination. Inspection results were recorded according to the international ROP classification. The incidence of ROP in recent 10 years was retrospectively analyzed. Independent sample t test was used for comparison between groups. ResultsAmong the 1 352 preterm infants in Kunming group, 716 were males and 636 were females. The birth weight was (1 765.75±357.64) g; gestational age of birth were (32.51±2.07) weeks. The altitude of the residence was (1 920±30) m. Among 579 premature infants in Dehong group, 302 were males and 277 were females. The birth weight was (1 762.54±401.73) g; gestational age of birth were (32.10±2.36) weeks. The altitude of the residence was (920±80) m. There was no significant difference in sex composition ratio (χ2=0.10, P=0.75) and birth weight (t=0.17, P=0.87) between the two groups (P≥0.05). Gestational age and elevation of residence were compared, and the difference was statistically significant (t=3.82, 35.15; P＜0.01). ROP was detected in 72 cases 144 eyes (5.32%, 72/1 352) in Kunming group and 55 cases 110 eyes (9.5%, 55/579) in Dehong group. Both cases were binocular. There was significant difference in the detection rate of ROP between the two groups (χ2=11.49, P＜0.01). ROP stages 1 to 3 in Kunming and Dehong groups were 128 (88.89%, 128/144), 6 (4.17%, 6/144), 6 (4.17%, 6/144) eyes and 18 (16.36%, 18/110), 66 (60.00%, 66/110), 22 (20.00%, 22/110) eyes. The acute ROP (A-ROP) was 4 (2.78, 4/144) and 4 (3.63%, 4/110) eyes in Kunming and Dehong groups, respectively. There were significant differences in the detection rates of ROP in stages 1 to 3 between the two groups (χ2=11.26, 66.48, 15.86, 0.76; P＜0.05). There was no significant difference in the detection rate of A-ROP (χ2=0.76, P＞0.05). ConclusionThe detection rate of ROP in high altitude area of Yunnan Province is significantly lower than that in low altitude area.
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.
ObjectiveTo analyze independent factors for treatment-requiring retinopathy of prematurity (TR-ROP) and establish a predictive nomogram model for TR-ROP. MethodA retrospective cohort study. A total of 6 998 preterm infants who were born at Guangdong Women's and Children's Hospital between January 1, 2012 and March 31, 2022 and were screened for retinopathy of prematurity (ROP) were included in the study. TR-ROP was defined as type 1 ROP and aggressive ROP; 22 independent factors including general information, maternal perinatal conditions, interventions and neonatal diseases related to ROP were collected. The infants were divided at the level at an 8:2 ratio according to clinical experience, with 5 598 in the training cohort and 1 400 in the validation cohort. t test was used for comparison of quantitative data and χ2 test was used for comparison of counting data between groups. Multivariate logistic regression analysis was carried out for the indicators with differences in the univariate analysis. The visualized regression analysis results of R software were used to obtain the histogram. The accuracy of the nomogram was verified by C-index and receiver operating characteristic curve (ROC curve). ResultsAmong the 6 998 children tested, 4 069 were males and 2 920 were females. Gestational age was (33.69±3.19) weeks; birth weight was (2 090±660) g. There were 376 cases of TR-ROP (5.4%, 376/6 998). The results of multivariate logistic regression analysis showed that gestational age [odds ratio (OR) =0.63, 95% confidence interval (CI) 0.47-0.85, P=0.002], intrauterine distress (OR=0.30, 95%CI 0.10-0.99, P=0.048), bronchopulmonary dysplasia (OR=0.23, 95%CI 0.09-0.60, P=0.003), hypoxic-ischemic encephalopathy (OR=5.40, 95%CI 1.45-20.10, P=0.012), blood transfusion history (OR=4.05, 95%CI 1.50-10.95, P=0.006) were the independent influencing factors of TR-ROP. Based on this and combined with birth weight, a nomogram prediction model was established. The C-index of the training set and validation set were 0.940 and 0.885, respectively, and the area under ROC curve were 0.945 (95%CI 0.930-0.961) and 0.931 (95%CI 0.876-0.986), respectively. The sensitivity and specificity were 86.2%, 94.0% and 83.2%, 93.3%, respectively. ConclusionsGestational age, intrauterine distress, bronchopulmonary dysplasia, hypoxic-ischemic encephalopathy and blood transfusion history are the independent factors influencing the occurrence of TR-ROP. The TR-ROP nomogram prediction model based on independent influencing factors has high sensitivity and specificity.
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.