【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.
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 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.
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.
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 major cause of vision loss and blindness among premature infants. Timely screening, diagnosis, and intervention can effectively prevent the deterioration of ROP. However, there are several challenges in ROP diagnosis globally, including high subjectivity, low screening efficiency, regional disparities in screening coverage, and severe shortage of pediatric ophthalmologists. The application of artificial intelligence (AI) as an assistive tool for diagnosis or an automated method for ROP diagnosis can improve the efficiency and objectivity of ROP diagnosis, expand screening coverage, and enable automated screening and quantified diagnostic results. In the global environment that emphasizes the development and application of medical imaging AI, developing more accurate diagnostic networks, exploring more effective AI-assisted diagnosis methods, and enhancing the interpretability of AI-assisted diagnosis, can accelerate the improvement of AI policies of ROP and the implementation of AI products, promoting the development of ROP diagnosis and treatment.
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 observe and analyze thyroxine levels in children with retinopathy of prematurity (ROP) and its effect on severe ROP. MethodsA retrospective clinical study. From January 2022 to December 2023, a total of 64 premature infants with severe ROP (ROP group), hospitalized in the Children's Hospital Affiliated to Zhengzhou University and with a gestational age ≤32 weeks, were included. According to a 1:2 ratio, 128 premature infants without ROP, matched for sex and gestational age, were selected as the control group. Thyroid function tests were performed 7 to 14 d after birth. The levels of thyroid-stimulating hormone, triiodothyronine, free triiodothyronine, thyroxine (T4), and free T4 (FT4) were compared and observed between the two groups. The quantitative data between groups were compared by independent samples t-test or Mann-Whitney U test; the count data were compared by χ2 test. Logistic regression was used to analyze the correlation between various variables and the occurrence of severe ROP. The predictive efficacy of the differential indicators was assessed by receiver operating characteristic (ROC) curve. ResultsCompared with the control group, T4 and FT4 levels were significantly lower in children in the ROP group, and the difference was statistically significant (t=2.572, 2.704; P=0.011, 0.008). The results of univariate logistic regression analysis showed that the Apgar scores at 1 and 5 minutes, as well as sepsis, T4, FT4, and bronchopulmonary dysplasia (BPD), were significantly associated with the occurrence of severe ROP (P＜0.05). The results of multivariate logistic regression analysis indicated that FT4 and BPD are independent risk factors for the occurrence of severe ROP (P＜0.05). The ROC curve analysis revealed that T4 had a sensitivity of 80.9% and specificity of 43.3%, while FT4 showed a sensitivity of 46.8% and specificity of 75.0%, with abnormal cutoff values set at 98.4 nmol/L for T4 and 15.65 pmol/L for FT4. ConclusionsThe T4 and FT4 level of children with severe ROP are lower than that of children without ROP in the early postnatal period. The T4 and FT4 level in the early postnatal period may have a certain correlation with the occurrence of severe ROP.