OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-β,polyunsaturated fatty acids,and β-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.
Child ; Humans ; Infant, Newborn ; Infant, Premature ; Neovascularization, Pathologic ; therapy ; Retinopathy of Prematurity ; drug therapy ; surgery ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors

PURPOSE: To compare long-term refractive outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) versus laser photocoagulation treatment for retinopathy of prematurity (ROP). METHODS: A total of 52 eyes from 27 ROP patients treated at two tertiary referral-based hospitals from August 2006 to December 2013 were reviewed. The primary outcome was refractive error measured at the age of 4 years, accounting for within-patient inter-eye correlation. Secondary outcomes included the recurrence rate and treatment complications. RESULTS: The mean age at refraction was 4.7 ± 0.3 years in the laser group (n = 30) and 4.4 ± 0.3 years in the anti-VEGF group (n = 22). No significant differences were noted in gestational age, birthweight, post-menstrual age at treatment, or ROP stage/zone distribution between groups. Mean spherical equivalent was also not significantly different (−1.0 diopters in the laser group and −0.3 diopters in the injection group, p = 0.603). Clustered regression analysis revealed that only gestational age was significantly correlated with mean spherical equivalent (p < 0.001; 95% confidence interval, −0.007 to −0.002). Recurrence was noted in four eyes (13.3%) in the laser group, but this difference was not significant (p = 0.128). There were no major systemic complications reported in either group. CONCLUSIONS: Treatment type, whether laser or anti-VEGF injection, does not appear to influence long-term refractive outcomes in ROP. Concern regarding refractive outcomes should not be the most important factor when selecting ROP treatment modality.
Child ; Child, Preschool ; Endothelial Growth Factors ; Gestational Age ; Humans ; Intravitreal Injections ; Laser Therapy ; Light Coagulation ; Recurrence ; Refractive Errors ; Retinopathy of Prematurity ; Vascular Endothelial Growth Factor A

BACKGROUND: Preterm infants have difficulty maintaining body temperature after birth. However, clinical guidelines advocate that neonatal body temperature should be maintained at 36.5°C–37.5°C. PURPOSE: We aimed to investigate the incidence of admission hypothermia in very low birth weight (VLBW) infants and to determine the association of admission temperature with in-hospital mortality and morbidities. METHODS: A cohort study using prospectively collected data involving 70 neonatal intensive care units (NICUs) that participate in the Korean Neonatal Network. From registered infants born between January 2013 and December 2015, 5,343 VLBW infants born at less than 33 weeks of gestation were reviewed. RESULTS: The mean admission temperature was 36.1°C±0.6°C, with a range of 31.9°C to 38.4°C. Approximately 74.1% of infants had an admission hypothermia of <36.5°C. Lower birth weight, intubation in the delivery room and Apgar score <7 at 5 minutes were significantly related to admission hypothermia. The mortality was the lowest at 36.5°C–37.5°C and adjusted odd ratios for all deaths increased to 1.38 (95% confidence interval [CI], 1.04–1.83), 1.44 (95% CI, 1.05–1.97) and 1.86 (95% CI, 1.22–2.82) for infants with admission temperatures of 36.0°C–36.4°C, 35.0°C–35.9°C, and <35.0°C, respectively. Admission hypothermia was also associated with high likelihoods of bronchopulmonary dysplasia, pulmonary hypertension, proven sepsis, pulmonary hemorrhage, air-leak, seizure, grade 3 or higher intraventricular hemorrhage and advanced retinopathy of prematurity requiring laser therapy. CONCLUSION: A large portion of preterm infants in Korea had hypothermia at NICU admission, which was associated with high mortality and several important morbidities. More aggressive interventions aimed at reducing hypothermia are required in this high-risk population.
Apgar Score ; Birth Weight ; Body Temperature ; Bronchopulmonary Dysplasia ; Cohort Studies ; Delivery Rooms ; Hemorrhage ; Hospital Mortality ; Humans ; Hypertension, Pulmonary ; Hypothermia ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Intensive Care Units ; Intensive Care Units, Neonatal ; Intubation ; Korea ; Laser Therapy ; Mortality ; Parturition ; Pregnancy ; Prospective Studies ; Retinopathy of Prematurity ; Seizures ; Sepsis

BACKGROUND: To investigate the incidence of surgical intervention in very low birth weight (VLBW) infants and the impact of surgery on neurodevelopmental outcomes at corrected ages (CAs) of 18–24 months, using data from the Korean Neonatal Network (KNN). METHODS: Data from 7,885 VLBW infants who were born and registered with the KNN between 2013 to 2016 were analyzed in this study. The incidences of various surgical interventions and related morbidities were analyzed. Long-term neurodevelopmental outcomes at CAs of 18–24 months were compared between infants (born during 2013 to 2015, n = 3,777) with and without surgery. RESULTS: A total of 1,509 out of 7,885 (19.1%) infants received surgical interventions during neonatal intensive care unit (NICU) hospitalization. Surgical ligation of patent ductus arteriosus (n = 840) was most frequently performed, followed by laser therapy for retinopathy of prematurity and laparotomy due to intestinal perforation. Infants who underwent surgery had higher mortality rates and greater neurodevelopmental impairment than infants who did not undergo surgery (P value < 0.01, both). On multivariate analysis, single or multiple surgeries increased the risk of neurodevelopmental impairment compared to no surgery with adjusted odds ratios (ORs) of 1.6 with 95% confidence interval (CI) of 1.1–2.6 and 2.3 with 95% CI of 1.1–4.9. CONCLUSION: Approximately one fifth of VLBW infants underwent one or more surgical interventions during NICU hospitalization. The impact of surgical intervention on long-term neurodevelopmental outcomes was sustained over a follow-up of CA 18–24 months. Infants with multiple surgeries had an increased risk of neurodevelopmental impairment compared to infants with single surgeries or no surgeries after adjustment for possible confounders.
Cohort Studies ; Ductus Arteriosus, Patent ; Follow-Up Studies ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Intensive Care, Neonatal ; Intestinal Perforation ; Korea ; Laparotomy ; Laser Therapy ; Ligation ; Mortality ; Multivariate Analysis ; Odds Ratio ; Retinopathy of Prematurity

OBJECTIVETo explore the effects of rat bone mesenchymal stem cell (BMSC) transplantation on retinal neovascularization, and to observe the changes of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factors (VEGF) in rats with oxygen-induced retinopathy (OIR).

METHODSSeventy-two seven-day-old Sprague-Dawley rats were randomly divided into three groups: normal control (CON), model (OIR) and BMSC transplantation. In the BMSC transplantation group, BMSCs were transplanted 5 days after oxygen conditioning. The phosphate buffered saline of the same volume was injected in the CON and OIR groups. The OIR model was prerpared according to the classic hyperoxygen method. At seven days after transplantation, retinal neovascularization was examined by retinal flat-mount staining and hematoxylin eosin (HE) staining. The expression of HIF-1α and VEGF proteins was examined by immunohistochemistry staining and Western blot analysis.

RESULTSThe retinal flat-mount staining results showed that the vessels were well organized in the CON group, but the vessels were irregularly organized, and lots of nonperfusion areas were observed in the OIR group. The large vessels were a bit circuitous, the retinal vessels were relatively organized, and less nonperfusion areas were noted in the BMSC transplantation group. The HE staining results showed that many neovessels and preretinal neovascular (pre-RNC) cells were observed on the internal limiting membrane in the OIR group. There were less pre-RNC cells in the BMSC transplantation group compared with the OIR group (P<0.01). The immunohistochemistry analysis showed that more HIF-1αand VEGFcells were observed in the OIR group compared with the CON group, and less HIF-1αand VEGFcells were observed in the BMSC transplantation group compared with OIR group (P<0.05). The Western blot analysis showed the expression of HIF-1α and VEGF proteins in the OIR group was significantly higher than that in the CON group. The expression of HIF-1α and VEGF proteins in the BMSC transplantation group was lower than that in the OIR group (P<0.01).

CONCLUSIONSBMSC transplantation therapy could alleviate retinal neovascularization in OIR rats, and its mechanisms might be associated with the inhibition of the expression of HIF-1α and VEGF proteins.

Animals ; Animals, Newborn ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit ; analysis ; Male ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley ; Retina ; chemistry ; Retinal Neovascularization ; prevention & control ; Retinopathy of Prematurity ; metabolism ; therapy ; Vascular Endothelial Growth Factor A ; analysis

PURPOSE: Laser therapy for retinopathy of prematurity (ROP) is commonly performed under general anesthesia (GA). However, the use of GA for laser therapy in neonates who have already undergone invasive ventilation may lead to postoperative complications such as severe apnea or the development of ventilator dependency. This study aimed to examine the safety of administering only sedatives instead of GA in extremely low birth weight (ELBW) infants, who are the usual recipients of laser therapy for ROP. METHODS: Among ELBW infants who were admitted to the neonatal intensive care unit (NICU) at Samsung Medical Center between January and December 2012, we studied 30 patients treated with laser therapy for ROP. RESULTS: The mean gestational age of the patients was 24.6±1.9 weeks, with a mean birth weight of 646±140 g. The mean age and weight of patients at the time of laser therapy for ROP was 36.3±2.3 weeks and 1,470±423 g. In terms of sedatives, 14 patients (46.7%) were administered chloral hydrate alone, 14 (46.7%) were administered a combination of chloral hydrate and midazolam, one was administered midazolam alone, and one received fentanyl. Prior to laser therapy, 16 patients (53.5%) had established self-respiration, 13 (43.3%) relied on non-invasive ventilation and one patient relied on invasive mechanical ventilation. Following laser therapy, two patients who initially had exhibited self-respiration required respiratory assistance via non-invasive positive pressure ventilation and no patient required intratracheal intubation. CONCLUSIONS: We conclude that the use of sedatives may be safe for ELBW infants who undergo laser therapy for ROP.
Anesthesia, General* ; Apnea ; Birth Weight ; Chloral Hydrate ; Fentanyl ; Gestational Age ; Humans ; Hypnotics and Sedatives* ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Intensive Care, Neonatal ; Intubation, Intratracheal ; Laser Therapy* ; Midazolam ; Noninvasive Ventilation ; Positive-Pressure Respiration ; Postoperative Complications ; Respiration, Artificial ; Retinopathy of Prematurity* ; Ventilation ; Ventilators, Mechanical

Angiogenesis Inhibitors ; administration & dosage ; therapeutic use ; Female ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Intravitreal Injections ; methods ; Ranibizumab ; administration & dosage ; therapeutic use ; Retinopathy of Prematurity ; drug therapy ; surgery ; Retrospective Studies

Humans ; Infant, Newborn ; Infant, Premature ; Propranolol ; therapeutic use ; Retinopathy of Prematurity ; drug therapy

This study was conducted to describe the incidence, risk factors, and current treatment status of retinopathy of prematurity (ROP) in very-low-birth-weight (VLBW) infants registered in the Korean Neonatal Network database. Medical records of 2,009 VLBW infants born between January 2013 and June 2014 who underwent examination by an ophthalmologist were reviewed. The total incidence of ROP was 34.1%. Of the patients, 11.6% showed ROP stage > or = 3 and 11.5% received treatment of VLBW. Among all infants who received treatment of ROP, 63.6% underwent operation only; 16.9%, anti-vascular endothelial growth factor (anti-VEGF) treatment only; and 19.5%, both operation and anti-VEGF treatment. The mean gestational age (GA) and birth weight (BW) were significantly lower and the prevalence rates of respiratory distress syndrome, patent ductus arteriosus (PDA), invasive ventilator duration, and sepsis were significantly higher in the VLBW infants with ROP than in those without ROP. In the multivariable logistic regression analysis, PDA (odd ratio [OR], 2.1; 95% confidence interval [CI], 1.11-3.79) and invasive ventilator duration (OR, 1.0; 95% CI, 1.00-1.02) were significant risk factors of ROP and ROP stage > or = 3. In conclusion, the high incidence of ROP is associated with low GA and BW, and attempt to reduce the aforementioned risk factors could reduce the incidence of ROP stage > or = 3 in VLBW infants.
Antibodies/therapeutic use ; Birth Weight ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Premature ; *Infant, Very Low Birth Weight ; Logistic Models ; Male ; Odds Ratio ; Prevalence ; Republic of Korea/epidemiology ; Retinopathy of Prematurity/drug therapy/*epidemiology/mortality ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A/immunology