BACKGROUND: Chronic placental inflammation (CPI) has been implicated in the pathogenesis of diseases in premature infants, whereas retinopathy of prematurity (ROP) is a major complication primarily affecting preterm and very low-birth-weight (VLBW) infants. This study aims to investigate the association between CPI and ROP in VLBW infants. METHODS: We performed a retrospective review of clinical records of VLBW infants born between 2013 and 2016. Placental pathology findings including CPI cases were analyzed using logistic regression to study infants’ morbidities and other clinical characteristics. RESULTS: A total of 402 infants with a mean (standard deviation) gestational age of 28.5 (2.8) weeks and birth weight of 1,027.2 (304.4) g were included. The incidence of ROP was 24.1%. CPI was found in 90 infants (22.4%), among which 28.9% (26 of 90) developed ROP, and 21.1% (19 of 90) underwent laser photocoagulation. Lower gestational age, lower birth weight, longer duration of oxygen supply, and presence of CPI were associated with the development of ROP. After adjustment for gestational age, birth weight, sex, duration of oxygen supply, and other overlapping placental pathology, CPI was associated with the odds for type 1 ROP that required laser photocoagulation (adjusted odds ratio, 2.739; 95% confidence interval, 1.112 to 6.749; p = .029). CONCLUSIONS: CPI was associated with severe ROP requiring treatment with laser photocoagulation in VLBW infants.
Birth Weight ; Gestational Age ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Inflammation ; Light Coagulation ; Logistic Models ; Odds Ratio ; Oxygen ; Pathology ; Retinopathy of Prematurity ; Retrospective Studies ; Risk Factors

Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.
Adult ; Birth Weight ; Bronchopulmonary Dysplasia/complications/*epidemiology ; Chorioamnionitis/classification/*epidemiology/pathology ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Neutrophil Infiltration/immunology ; Placenta/pathology ; Pre-Eclampsia/*epidemiology/pathology ; Pregnancy ; Respiratory Distress Syndrome, Newborn/complications/*epidemiology ; Retinopathy of Prematurity/complications/*epidemiology ; Retrospective Studies ; Tertiary Care Centers

A 6-year-old boy was referred to our hospital with symblepharon and lateral canthal deformity in both eyes, which developed 6 years ago. The patient was born at 27 weeks gestation. He had received cryotherapy for retinopathy of prematurity. One month after cryotherapy, he developed a conjunctival scar with symblepharon in both eyes and underwent symblepharon lysis at another hospital 5 years prior. Ocular examination revealed an extensive conjunctival hypertrophic scar with symblepharon and limitation of extraocular movements. An excisional biopsy, lateral canthoplasty, and symblepharon lysis with conjunctival autograft from the contralateral eye were performed in the left eye. Histopathologic examination revealed diffuse proliferation and infiltration of collagenous tissue.
Biopsy ; Child ; Cicatrix, Hypertrophic/diagnosis/*etiology ; Conjunctiva/pathology ; Conjunctival Diseases/diagnosis/*etiology ; Cryotherapy/*adverse effects ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Male ; Retinopathy of Prematurity/*therapy

OBJECTIVETo evaluate the efficacy and safety of the bedside diode laser photocoagulation for severe retinopathy of prematurity in neonatal intensive care unit (NICU).

METHODData of 103 patients with prethreshold or threshold retinopathy of prematurity (ROP), treated with diode laser photoablation after vecuronium-induced anesthesia and mechanical ventilation from March 2009 to July 2011 in NICU of Bayi Children's Hospital.

RESULTTotally 199 eyes in 103 patients received laser therapy with at least 5 months follow up. Among these eyes, zone I disease was found in 76 eyes (38.2%) of 39 infants, zone II disease was found in 123 eyes (61.8%)of 64 infants and additional disease was found in 180 eyes of 91 infants. After treatment 191 (96.0%) of 199 eyes had favorable outcomes and 8 developed to partial retinal detachment. The rate of favorable outcomes in zone I diseases and zone 2 diseases were 89.5% and 100% respectively. The laser therapy was undertaken in all patients safely and the use of ventilator was stopped quickly [after a mean of (6.7 ± 1.3) h].

CONCLUSIONBedside laser photocoagulation in NICU is a safe and effective treatment mode for severe ROP and should be used widely.

Anesthesia ; methods ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Lasers, Semiconductor ; Light Coagulation ; methods ; Male ; Perioperative Nursing ; Retina ; pathology ; surgery ; Retinopathy of Prematurity ; pathology ; surgery ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the effects of marrow mesenchymal stem cell (BMSC) transplantation on retinal cells apoptosis and changes to neurotrophin-3 (NT-3 and ciliary neurotrophic factor (CNTF) in rats with retinopathy of prematurity (ROP).

METHODSSeven-day-old Sprague-Dawley rats were randomly divided into normal control (CON), ROP, BMSC transplantation (BMSCs were transplanted 5 days after oxygen conditioning) and phosphate buffered saline (PBS) groups. The ROP model was prepared according to the classic hyperoxygen method. Seven days after transplantation, TUNEL/DAPI, NT-3/API and CNTF/DAPI double-labeled immunofluorescence were used to examine the effects of BMSC transplantation on both the apoptosis of retinal cells and the expression of NT-3 and CNTF protein in the retinal cells of the ROP rats.

RESULTSSeven days after BMSC transplantation, there were few TUNEL+ DAPI+ cells observed in the CON group. There were fewer TUNEL+DAPI+ cells observed in the BMSC group than in the ROP group (P<0.01), but there was no significant difference between the ROP and PBS groups (P>0.05). There were few NT-3+DAPI+ cells and CNTF+DAPI+ cells in the CON group. There were more NT-3+DAPI+ and CNTF+DAPI+ cells in the ROP group than in the CON group, but there was no significant difference between the ROP and CON groups (P>0.05). More NT-3+DAPI+ and CNTF+DAPI+ cells were observed in the BMSC group compared with the ROP group (P<0.01), and there was no significant difference in either NT-3+DAPI+ or CNTF+DAPI+ cells between the ROP and PBS groups (P>0.05).

CONCLUSIONSBMSC transplantation therapy could alleviate the apoptosis of retinal cells in ROP rats, and its mechanisms might be associated with promoting the expression of NT-3 and CNTF protein in retinal cells.

Animals ; Apoptosis ; Bone Marrow Cells ; physiology ; Cell Proliferation ; Ciliary Neurotrophic Factor ; analysis ; Female ; Humans ; In Situ Nick-End Labeling ; Infant, Newborn ; Male ; Mesenchymal Stem Cell Transplantation ; Neurotrophin 3 ; analysis ; Rats ; Rats, Sprague-Dawley ; Retina ; pathology ; Retinopathy of Prematurity ; metabolism ; therapy

PURPOSE: Retinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. Recently, advances in neonatal care have led to improved survival rates for preterm infants, and ROP has increased in incidence. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects in an animal model of ROP and in primary retinal cell cultures of neonatal rat via nitric oxide (NO)-modulating actions using western blotting and real-time PCR with inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) antibodies and mRNAs. METHODS: In an in vivo oxygen-induced retinopathy (OIR) model, cyclic hyperoxia was induced with 80% O2 for one day and 21% O2 for one day from P1 to P14 in newborn Sprague-Dawley (SD) rats. Resveratrol was injected intravitreally for seven days and rats were sacrificed at P21. In vitro OIR primary retinal cell culture was performed using P0-2 SD rats. Hyperoxia injuries were induced through 100% O2 exposure for six hours. Western blotting and real-time PCR using iNOS, eNOS, nNOS antibodies and primers were performed in the rat model of ROP and the dispersed retinal cell culture. RESULTS: In both in vivo and in vitro OIR, the expression of iNOS antibody and mRNA was increased and of eNOS and nNOS were reduced in the resveratrol-treated group. CONCLUSIONS: In conclusion, resveratrol appeared to exert retinal protective effects via modulation of NO-mediated mechanism in in vivo and in vitro OIR models.
Analysis of Variance ; Animals ; Animals, Newborn ; Blotting, Western ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Humans ; Infant, Newborn ; Nitric Oxide Synthase/*metabolism ; Oxygen/toxicity ; RNA/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Retina/drug effects/pathology ; Retinopathy of Prematurity/*metabolism/pathology/*prevention & control ; Reverse Transcriptase Polymerase Chain Reaction ; Stilbenes/*pharmacology

OBJECTIVETo explore VEGF siRNA's effect on the immature fetal retinal microvascular endothelial cells in vitro.

METHODThe fresh retinal micrangium was primarily cultured to obtain microvascular endothelial cells. CoCl2 was used to simulate oxygen-deficient conditions. siRNA directed against human VEGF was designed and chemically synthesized. There were 3 groups in our experiment: VEGF siRNA group, hypoxia control group, and negative siRNA control group. The fetal retinal micrangium vascular endothelial cells were transfected by using liposome. The expression levels of VEGF mRNA and protein were evaluated by RT-PCR and Western blotting 24, 48, 72 h after transfection, cell proliferation was evaluated by MTT method.

RESULTThe expression levels of VEGF mRNA decreased by 21.05%, 79.67%, and 90.48% 24 h, 48 h, and 72 h after transfection as compared to those in hypoxia control group, the expression level of VEGF protein had decreased by 14.58%, 66.97%, and 81.61% as compared to those in hypoxia control group. The siRNA could decrease cell proliferation under hypoxia too, the multiplication rate after 12, 24, 48, and 72 h decreased by 15.0%, 42.9%, 78.3% and 65.9%.

CONCLUSIONVEGF siRNA could down-regulate the expression of VEGF in immature fetal retinal microvascular endothelial cells and suppressed cell proliferation. Application of siRNA to inhibit expression of VEGF may be a hopeful way to prevent and cure ROP.

Cell Hypoxia ; Cell Line ; Endothelial Cells ; metabolism ; Humans ; Infant, Newborn ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Retina ; metabolism ; pathology ; Retinal Vessels ; cytology ; metabolism ; Retinopathy of Prematurity ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo evaluate the role of different oxygen concentration (FiO2) and different period of oxygen exposure on oxygen-induced retinopathy (OIR) in neonatal mice and to provide evidences for proper clinical oxygen therapy.

METHODSTwo hundred and four 7-day-old (P7) C57BL/6J mice were exposed to different FiO2 30%, 50% and 75% for 5, 7 and 9 days. The mice were divided into eight groups: groups 1 - 3 (n = 24 in each) were exposed to 30% oxygen for 5, 7 and 9 days, respectively; groups 4 - 6 (n = 24 in each) were exposed to 50% oxygen for 5, 7 and 9 days, respectively; group 7 (n = 30) was exposed to 75% hyperoxia for 5 days; group 8 (n = 30) was exposed to room air. Proliferative neovascular responses were estimated by observing vascular patterns in adenosine diphosphate-ase (ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections.

RESULTS(1) Vascular patterns in retina flat-mounts: a) When FiO2 was 30%, the entire vascular pattern was completely normal after 5 and 7 days exposure; although the deep vascular system seemed slightly constricted after 9 days exposure, it recovered 2 days later and matured at P21. b) When FiO2 was 50%, after 5 days exposure (group 4), the larger vessels constricted and central perfusion decreased moderately; after exposing to room air for 2 days, neovascularization was seen; however, the entire vascular pattern was almost normal at P17. After 7 days of exposure to 50% O2 (group 5), the vascular pattern recovered a bit, seemed to be better than that of group 4; after 9 days of exposure to 50% O2 (group 6), only slight constriction could be seen and it disappeared 2 days later and all vessels matured later. c) When FiO2 was 75%, after 5 days exposure to hyperoxia, the larger vessels became tortuous and constricted, central perfusion became decreased obviously; after exposing to room air for 2 days, neovascularization was seen; and this response was maximal at P17 - P21. However, the mortality of nurser mice and pups increased dramatically when the duration of hyperoxia was prolonged. (2) Quantitative results in cross-sections: neovascular nuclei extending into the vitreous reached (41.9 +/- 2.8) per section in 75% oxygen group, while less than 1 in every other groups, which was statistically different (P < 0.0001).

CONCLUSIONSFiO2 and the duration of hyperoxia could affect retinal vascular development. Low and moderate FiO2 could induce reversible vessel changes, while high FiO2 induced irreversible changes which should be avoided in clinic.

Animals ; Disease Models, Animal ; Humans ; Hyperoxia ; pathology ; Infant, Newborn ; Mice ; Mice, Inbred C57BL ; Oxygen ; adverse effects ; Oxygen Inhalation Therapy ; adverse effects ; Retinal Neovascularization ; pathology ; Retinal Vessels ; pathology ; Retinopathy of Prematurity ; pathology