Progression Of Retinopathy Of Prematurity Research Articles

Isolated Retinal Neovascularization in Retinopathy of Prematurity: Clinical Associations and Prognostic Implications

Isolated retinal neovascularization (IRNV) is a common finding in patients with stage 2 and 3 retinopathy of prematurity (ROP). This study aims to further classify the clinical course and significance of these lesions (previously described as "popcorn" based on clinical appearance) in patients with ROP as visualized with ultra-widefield optical coherence tomography (UWF-OCT). Single center, retrospective case series. Images were collected from 136 babies in the Oregon Health and Science University neonatal intensive care unit. A prototype UWF-OCT device captured en face scans (>140°), which were reviewed for the presence of IRNV along with standard zone, stage, and plus classification. In a cross-sectional analysis we compared demographics and the clinical course of eyes with and without IRNV. Longitudinally, we compared ROP severity using a clinician-assigned vascular severity score (VSS) and compared the risk of progression among eyes with and without IRNV using multivariable logistic regression (MLR). Differences in clinical demographics and disease progression between patients with and without IRNV. Of the 136 patients, 60 developed stage 2 or worse ROP during their disease course, 22 of whom had IRNV visualized on UWF-OCT (37%). On average, patients with IRNV had lower birth weights (BW) (660.1g vs 916.8g, p = 0.001), gestational age (GA) (24.9 vs 26.1 weeks, p = 0.01), and were more likely to present with ROP in zone I (63.4% vs 15.8%, p < 0.001). They were also more likely to progress to stage 3 (68.2% vs 13.2%, p < 0.001) and receive treatment (54.5% vs 15.8%, p = 0.002). Eyes with IRNV had a higher peak VSS (5.61 vs 3.73, p < 0.001) and averaged a higher VSS throughout their disease course. On MLR, IRNV was independently associated with progression to stage 3 (p = 0.02) and requiring treatment (p = 0.03), controlling for GA, BW, and initial zone 1 disease. In this single center study, we found that IRNV occurs in higher risk babies and was an independent risk factor for ROP progression and treatment. These findings may have implications for OCT-based ROP classifications in the future.

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression.

Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of β1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.

IL1R2 promotes retinal angiogenesis to participate in retinopathy of prematurity by activating the HIF1α/PFKFB3 pathway

Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.

Thrombocytopenia as a Clinical Biomarker of Retinopathy of Prematurity: A Systematic Review

Highlights: This is the first systematic review investigating thrombocytopenia and its association with retinopathy of prematurity The findings suggest that thrombocytopenia could serve as a potential clinical biomarker for screening ROP, considering its quick, affordable, and widespread availability for examination purposes. Abstract Retinopathy of prematurity (ROP) is the leading cause of childhood blindness and occurs due to the underdevelopment of retinal blood vessels in premature infants. Platelets are essential in the regulation of angiogenesis. Hence, thrombocytopenia might aid in the progression of ROP. This systematic review aims to look into the relationship between thrombocytopenia and retinopathy of prematurity. The PubMed and Cochrane Library databases were accessed to include retrospective case-control and cross-sectional studies, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In our review, 9 records were analyzed. All research was done in the period between 2017 and 2022 . Seven studies have reported the prevalence of thrombocytopenia in infants with retinopathy of prematurity (ROP), ranging from 18.37% to 71%. In preterm children without ROP, the occurrence of thrombocytopenia is between 5.71% and 21%. Seven studies have significantly identified thrombocytopenia as a risk factor for ROP, with the Odd Ratio (OR) for thrombocytopenia ranging from 2.8 to 6.69 . Therefore, thrombocytopenia in premature infants could be thought of as a potential clinical biomarker for Type-1 ROP screening. Additionally, this discovery implied that thrombocytopenia can contribute to the pathophysiology of ROP. The crucial platelet count threshold in ROP requires additional investigations.

The Effects of Early Enteral and Parental Nutrition on Retinopathy of Prematurity: A Systematic Review.

The management of preterm newborns must consider the severe problem of retinopathy of prematurity (ROP). A systematic review has been conducted to effectively acknowledge how enteral and parenteral early nutrition affect the growth and progression of ROP. The study summarizes recent findings from various sources to give insight into the relationship between dietary practices and ROP risks. When untreated, retinopathy of prematurity (ROP) may cause severe vision loss or blindness in premature newborns. The latter two phases of ROP progression are the most serious. A child's early nutrition, both orally and intravenously, significantly impacts the severity and progression of ROP. This systematic review aims to examine the evidence linking early nutrition to ROP in premature infants. The study used Embase, Scopus, and PubMed to conduct our search. ROP, premature newborns, and nutrition were keywords used to find relevant papers. Nine research studies made it through the screening process and offered important information on the impact of diet on ROP. These studies support the idea that poor nutrition is a driving force behind the onset of ROP. The risk of ROP has been associated with postnatal development, hyperglycemia, polyunsaturated fatty acid levels, and the presence of breast milk. The outlook for ROP has also been discovered to be affected by the length of time the patient has received parenteral feeding. The incidence and severity of ROP may be mitigated by providing better nutrition to premature newborns. This comprehensive study concludes that early nutrition, both enteral and parenteral, substantially influences the development and progression of ROP in premature newborns. The significance of nutrition in newborn care is highlighted by the possibility that improved dietary methods might aid in preventing and treating this vision-threatening illness.

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

Effect of blood sampling management on reducing blood transfusions in very preterm infants.

Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re-evaluation of transfusion practices in preterm infants.

Potential Role of Bilirubin in Preventing Retinopathy of Prematurity.

One of the most common problems in preterm neonates is retinopathy of prematurity (ROP). It has been shown antioxidants may be effective in preventing the development and progression of ROP. Considering the antioxidant properties of bilirubin, we decided to investigate the bilirubin level in neonates with ROP and compare it with healthy neonates. This case-control study was performed on VLBW neonates admitted to the NICU of Ghaem Hospital in Mashhad between 2014 and 2020 for a Jaundice evaluation. Complete neonate's characteristics, maternal history and laboratory results were collected in a questionnaire. Then the neonates were examined for ROP by a fellowship of the retina of an ophthalmologist at 32 weeks or four weeks after birth. The highest bilirubin levels during their hospitalization were also recorded. Of 427 neonates examined, 121 (37.7%) had a normal eye examination, and 266 (62.3%) had ROP. The mean weight, gestational age and bilirubin were 1455.8 ± 431.4 grams, 31.6 ± 2.3 weeks and 8.8 ± 2.4 mg/dl, respectively. There was a significant difference between controls and neonates with ROP with regard to birth weight, duration of intermittent positive pressure ventilation (IPPV), duration of oxygen therapy, first and fifth minute Apgar scores, the maximum level of bilirubin and gestational age (P < 0.05). It was observed that the maximum level of bilirubin was lower in neonates with higher stages of ROP. According to the results of this study, higher levels of bilirubin in neonates may be a protective factor against ROP. Moreover, increased levels of bilirubin are associated with reduced severity of ROP. Therefore, prophylaxis phototherapy in premature infants may need to be reconsidered.

SELENOP rs3877899 Variant Affects the Risk of Developing Advanced Stages of Retinopathy of Prematurity (ROP).

The significance of selenoproteins for the incidence of prematurity and oxidative-damage-related diseases in premature newborns is poorly understood. The latter are at risk for ROP as well as BPD, IVH, PDA, RDS, and NEC, which is particularly high for newborns with extremely low gestational age (ELGA) and extremely low birth weight (ELBW). This study evaluates the hypothesis that variation in the selenoprotein-encoding genes SELENOP, SELENOS, and GPX4 affects the risk of ROP and other comorbidities. The study included infants born ≤ 32 GA, matched for onset and progression of ROP into three groups: no ROP, spontaneously remitting ROP, and ROP requiring treatment. SNPs were determined with predesigned TaqMan SNP genotyping assays. We found the association of the SELENOP rs3877899A allele with ELGA (defined as <28 GA), ROP requiring treatment, and ROP not responsive to treatment. The number of RBC transfusions, ELGA, surfactant treatment, and coexistence of the rs3877899A allele with ELGA were independent predictors of ROP onset and progression, accounting for 43.1% of the risk variation. In conclusion, the SELENOP rs3877899A allele associated with reduced selenium bioavailability may contribute to the risk of ROP and visual impairment in extremely preterm infants.

Cord blood transforming growth factor-β-induced as predictive biomarker of retinopathy of prematurity in preterm infants.

To determine whether 14 inflammation-, angiogenesis-, and adhesion-related proteins in cord blood (CB), alone or in combination with conventional perinatal factors, could predict retinopathy of prematurity (ROP) in preterm infants. Data from 111 preterm infants (born at ≤ 32.0weeks) were retrospectively reviewed. The levels of endoglin, E-selectin, HSP70, IGFBP-3/4, LBP, lipocaline-2, M-CSFR, MIP-1α, pentraxin 3, P-selectin, TGFBI, TGF-β1, and TNFR2 were assessed in stored CB samples collected at birth using ELISA kits. The primary endpoints included severe ROP (≥ stage 3) and type 1 ROP requiring treatment. ROP was diagnosed in 29 infants (26.1%), among whom 14 (12.6%) had severe ROP and seven (6.3%) had type 1 ROP. Multivariate logistic regression showed that decreased CB TGFBI levels were significantly associated with severe ROP and type 1 ROP after adjusting for gestational age at birth. Stepwise regression analysis allowed to design prediction models with good accuracy, which comprised low CB TGFBI levels and low birth weight (BW) as predictors for severe ROP (area under the curve [AUC] = 0.888), and low CB endoglin levels and low BW as predictors for type 1 ROP (AUC = 0.950). None of the other CB proteins evaluated were found to be associated with severe ROP or type 1 ROP. Low CB TGFBI levels are associated with severe ROP and type 1 ROP, independently of gestational age. Moreover, combined predictive models based on CB TGFBI and endoglin levels, along with BW data, may act as good indicators at birth for the neonatal risk of ROP progression.

Опыт использования моно и комбинированного лечения ретинопатии недоношенных с применением лазерной коагуляции сетчатки и введения ингибиторов сосудистого эндотелиального фактора роста

Retinopathy of prematurity (ROP) is one of the main causes of blindness and visual impairment in young children. Laser coagulation of the avascular retina is a generally recognized method of treating active progressive ROP. The efficiency of laser coagulation depends on the type of ROP. Combined treatment is used when one of the types of monotherapy is ineffective. Purpose. To evaluate the effectiveness of mono and combined treatment of ROP using laser coagulation and introduction of vascular endothelial growth factor inhibitors. Material and methods. In the period 2020–2022, 403 babies born prematurely were under observation. The diagnosis of ROP was made to 170 (42 %) children. 47 (27 %) patients needed treatment. Mono laser coagulation was performed in 32 (68 %) patients, and 9 (19.1 %) were administered introduction of vascular endothelial growth factor inhibitors. Conclusions. Combined treatment was carried out on 6 (12.7 %). In all cases of PH treatment, a positive result was achieved with the preservation of vision. If we consider the PH of the scar phase of the 3rd degree as an unfavorable outcome, then success is achieved only in 95.6 % of cases. Combined treatment proved to be justified and effective – in our observation in 6.4 % of cases. The results of our study confirm the expediency of monitoring children after the introduction of vascular endothelial growth factor inhibitors until they reach the postconceptual age of 70–80 weeks. Keywords: retinopathy of prematurity, laser photocoagulation of the retina, inhibitors of vascular endothelial growth factor, combined treatment, monotherapy

A risk scoring model to predict progression of retinopathy of prematurity for Indonesia.

Retinopathy of prematurity (ROP) is a serious eye disease in preterm infants. Generally, the progression of this disease can be detected by screening infants regularly. In case of progression, treatment can be instituted to stop the progression. In Indonesia, however, not all infants are screened because the number of pediatric ophthalmologists trained to screen for ROP and provide treatment is limited. Therefore, other methods are required to identify infants at risk of developing severe ROP. To assess a scoring model's internal and external validity to predict ROP progression in Indonesia. To develop a scoring model and determine its internal validity, we used data on 98 preterm infants with ROP who had undergone one or more serial eye examinations between 2009 and 2014. For external validation, we analyzed data on 62 infants diagnosed with ROP irrespective of the stage between 2017 and 2020. Patients stemmed from one neonatal unit and three eye clinics in Jakarta, Indonesia. We identified the duration of oxygen supplementation, gestational age, socio-economic status, place of birth, and oxygen saturation monitor setting as risk factors for developing ROP. We developed two models-one based on the duration of supplemental oxygen and one on the setting of the oxygen saturation monitor. The ROP risk and probabilistic models obtained the same sensitivity and specificity for progression to Type 1 ROP. The agreement, determined with the Kappa statistic, between the ROP risk model's suitability and the probabilistic model was excellent. The external validity of the ROP risk model showed 100% sensitivity, 73% specificity, 76% positive predictive value, 100% negative predictive value, positive LR +3.7, negative LR 0, 47% pre-test probability, and 77% post-test probability. The ROP risk scoring model can help to predict which infants with first-stage ROP might show progression to severe ROP and may identify infants who require referral to a pediatric ophthalmologist for treatment.

Incidence, risk factors, progression, and involution in retinopathy of prematurity at a tertiary care center in South India.

Retinopathy of prematurity (ROP) is a vasculoproliferative disorder of immature retina, seen in preterm babies. Multiple risk factors attribute to this condition. Our aim was to correlate the role of any early neonatal surgeries with low gestational age (GA) and birth weight (BW) on preterm babies as a risk factor on the progression of ROP. A prospective, cohort study conducted in a hospital in South India over 3 years, including 600 babies with GA <35 weeks and BW <2500 g. Babies were divided into Group A (ROP) and Group B (no ROP). Group A included A1 (severe ROP) and A2 (nonsevere ROP) based on early treatment of ROP classification. We compared various risk factors of ROP, specifically the association of any early neonatal surgery undergone by these babies, on progression of ROP. The Chi-square test, unpaired t-test, and one-way analysis of variance tests were used for the comparisons and considered statistically significant if P < 0.05. 28.7% babies developed ROP, with 37.6% requiring treatment (Aggressive ROP in 2.1% of babies). Low GA and BW, longer duration on ventilator, respiratory distress syndrome, apnea of prematurity, Patent Ductus Arteriosus, sepsis, anemia, thrombocytopenia, history of blood transfusion, and history of early neonatal surgery under GA were associated with babies with ROP (P < 0.005), strongly with severe ROP. The most common surgeries undergone by the babies developing ROP were inguinal herniotomy under general anesthesia. The study predicts preterm babies undergoing early surgical interventions are at risk of progressing to severe ROP, hence warranting frequent follow-ups.

Role of deferred retinal laser following intravitreal injection of bevacizumab in treatment of severe retinopathy of prematurity.

The purpose is to determine the advantages and role of supplemental deferred retinal laser treatment following intravitreal bevacizumab (IVB) monotherapy in cases of severe retinopathy of prematurity (ROP) requiring treatment. This is a retrospective study involving preterm infants diagnosed with treatment requiring ROP, treated initially with bevacizumab monotherapy who subsequently received deferred laser treatment during the study period from April 2019 to March 2021. Deferred laser treatment was done when recurrence of ROP or plus disease was noted or nonprogression of retinal vasculature was noted on two consecutive examinations over 2 weeks. The main outcomes measured were the ability of the treatment to prevent ROP progression or recurrence and anatomic outcome at the last follow-up visit. Twenty-three eyes of 14 neonates were treated with a deferred laser treatment following the initial intravitreal injection of Bevacizumab. The mean postmenstrual age at which IVB was given was 34+6 ± 1+3 weeks. The mean duration between IVB and retinal laser was 5+3 ± 3+4 weeks. The mean weight at the time of injection was 1317.8 ± 231.8 g. The mean weight of the infants at the time of the laser was 2050 ± 813.9 g. None of the eyes developed recurrence or adverse anatomical outcomes following laser till the last available follow-up. In our small number of subjects, blinding complications of ROP were prevented by using a deferred laser treatment protocol following initial bevacizumab therapy in treatment requiring ROP. It is better suited in cases where compliance for long-term follow-up after bevacizumab therapy cannot be ensured.

Antenatal risk factors for retinopathy of premature

This literature review presents the antenatal risk factors for the development of retinopathy of prematurity (ROP). Despite advances in antenatal and neonatal therapeutic interventions, screening, and follow-up, ROP remains a potentially vision-threatening retinopathy that requires careful monitoring and timely intervention to prevent the progression of adverse visual impairment or blindness. ROP is a multifactorial disease. The main risk factors are low gestational age and low birth weight. Recent experimental and clinical data support the hypothesis that multiple antenatal factors are involved in the etiology and progression of ROP. These factors include the age of the mother, maternal diseases, pregnancy-associated maternal pathologies, use of drugs to correct these conditions, and inflammatory process. Their roles are ambiguous and often contradictory. The physiology of the mother and placenta can significantly influence the risk of ROP development in preterm infants. The placenta connects the mothers body and the fetus, and it functions in the exchange of nutrients and oxygen between the mother and the fetus. Therefore, any pathological changes in the mothers body entail changes in the placenta, which this directly affects the fetus. A sudden loss of placental support is detrimental to the development of infants in the immediate postnatal period. Thus, these factors should be taken into account when assessing the risk of ROP development to predict and prevent poor vision in children.

Risk factors associated with Retinopathy of Prematurity development and progression

Several studies propose that Retinopathy of Prematurity (ROP) is a multifactorial disorder implicating many prenatal and postnatal factors. The objective of our study was to determine the incidence and the risk factors that influenced ROP development and progression. We retrospectively compiled data of preterms with birth weight (BW) ≤ 1.500 g and/or gestational age (GA) < 32 weeks, or BW between 1.501 and 2.000 g and/or GA ≥ 32 weeks with oxygen supply > 72 h or unstable clinical course screened for ROP in Regional University Hospital of Málaga from 2015 to 2018. 202 infants (44.7%) developed ROP and 66 exhibited progression (32.7% of ROP infants). In the univariate analysis, many risk factors were associated with ROP. In the subsequent multivariate analysis, GA, oxygen therapy and weight at 28 days of life, mechanical ventilation duration, non-invasive ventilation, surfactant administration and late-onset sepsis were independently associated with the development. However, oxygen therapy duration, late-onset sepsis and weight at 28 days were associated with the progression. The ROP development and progression risk factors were different. Our results are important to facilitate screening, early diagnosis and ROP treatment while reducing unneeded examinations.

Impact of Birth and Hospitalization Factors in Retinopathy of Prematurity

Background: Retinopathy of Prematurity (ROP) is a pathologic condition in the retina characterized by abnormal vasoproliferation. We aim to investigate the correlation of different birth- and hospitalization-related factors in the progression of ROP.&#x0D; Methods: This historical cohort study performed in the ophthalmology center of Ayatollah Rouhani Hospital in Babol (Babol University of Medical Sciences, Babol, Iran), included 828 infants (gestational age &lt;35 weeks and birth weight &lt;2500 g). Also, data were collected from the history of hospitalized premature infants. &#x0D; Results: The lower gestational weight of infants has been observed in ROP infants (1418.05±547.09 g) compared to non-ROP infants (1917.31±486.01 g) (p&lt;0.001). In addition, the average gestational age of ROP infants (30.28±2.34 weeks) was younger than non-ROP infants (33.26±1.00 weeks) (p=0.042). Increase in the duration of hospitalization increased 6% the chance of ROP in infants (OR=1.06; 95%CI: [1.05,1.08]) (p&lt;0.001). Furthermore, increase in the count of blood replacement decreased 29% the chance of complete remission of ROP (OR=0.71; 95%CI: [0.51,0.95]) (p=0.029). The blood group does not have an impact on ROP development or remission. &#x0D; Conclusion: More birth weight of premature infants is associated with less chance of ROP incidence. Moreover, the lower gestational age is related to more chances of ROP.

Association of inflammatory and angiogenic biomarkers in maternal plasma with retinopathy of prematurity in preterm infants.

To investigate whether various novel inflammatory and angiogenic biomarkers in maternal plasma, alone or in combination with baseline antenatal factors, could predict retinopathy of prematurity (ROP) in preterm infants. A retrospective cohort study was conducted on 140 premature singleton neonates born to women with preterm birth (≤32 weeks) and screened for ROP. Maternal blood obtained at the time of admission was assayed for CRP, endoglin, endostatin, IGFBP-2, IGFBP-3, IL-6, LBP, MMP-8, PlGF, S100A8/A9, TGFBI, and VEGFR-1. The primary outcome measures included severe ROP (stage 3 or higher) and type 1 ROP requiring treatment. ROP was present in 25.7% (36/140) of the study population, including 20 (14.3%) cases of severe ROP and 14 (10%) with type 1 ROP. Multiple logistic regression analyses revealed significant associations between high concentrations of maternal plasma LBP and severe ROP, and between elevated plasma IL-6 and LBP levels and type 1 ROP (all P < 0.05), while adjusting for confounders (i.e., gestational age [GA] at sampling). Prenatal prediction models for severe ROP and type 1 ROP were developed by combining plasma IL-6 or LBP levels with GA at sampling, which showed good discriminatory power (area under the curve = 0.747 and 0.854, respectively). IL-6 and LBP in maternal plasma were found to be independently associated with severe ROP and type 1 ROP. Prediction models based on these biomarkers along with GA at sampling may serve as good prenatal indicators for the neonatal risk of ROP progression in women at risk of preterm birth.

Influence of Anaemia on Multifactorial Disease Retinopathy of Prematurity: A Prospective Observational Study.

Background: Retinopathy of prematurity (ROP), a preventable cause of childhood blindness, is a severe complication of preterm (PT) birth treatment.Purpose: The purpose of this study is to analyse the risk factors (RF) associated with the development and progression of ROP. Particular focus is on the contribution of anaemia towards the development and progression of ROP.Methods: This study is a prospective observational study done in the Department of Paediatrics at Meenakshi Mission Hospital & Research Centre, Madurai, over 12 months from May 2013 to April 2014. The study included all consecutively admitted neonates born in and out of the hospital with gestational age (GA) less than or equal to 35 weeks or birth weight (BW) less than or equal to 2 kg and assessed for the gestational, perinatal, and postnatal RF. In addition, at the time of ROP screening, haemoglobin (Hb) and haematocrit (Hct) were checked. The statistical analysis was performed by Stata 11.1 (StataCorp LLC, College Station, TX).Result: The incidence of ROP in our study (46.7%) is higher than previously reported in India. In our study, GA and weight of the neonate at birth have a significant association with ROP incidence. Anaemia in our study is significantly associated with ROP incidence but not as an independent RF. The outcome of various stages of ROP is statistically significant, showing early stages 1 and 2 have more chances of spontaneous regression, and stages 3 and 4 are more likely to need treatment. Two cases in our study with stage 4 ROP had no complications, and none had stage 5 disease.Conclusion: Anaemia should be avoided or corrected in PT newborns as it is a potential and avoidable RF for ROP development. The limitation of our study is the small sample size, and probably more extensive randomized trials will help make this association clear. We recommend ROP screening for PT babies with GA less than 35 weeks and BW less than 2 kg who have the RF amounting to screening and done as per protocol.

Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway

ABSTRACT Retinopathy of prematurity (ROP), which is characterized by retinal neovascularization (RNV), is a major cause of neonatal blindness. The primary treatment for ROP is anti-vascular endothelial growth factor (VEGF) therapy, which is costly and can rapidly lead to desensitization. Celastrol, a bioactive compound extracted from Tripterygium wilfordii Hook F. (“Thunder of God Vine”), has been shown to exert anticancer and anti-inflammatory effects. However, whether celastrol has antiangiogenic activity and can suppress inflammation to inhibit ROP progression is unclear. This was investigated in the present study in vitro as well as in vivo using a mouse model of oxygen-induced retinopathy (OIR). Our results showed that celastrol treatment reduced neovascular and avascular areas in the retina and inhibited microglia activation and inflammation in OIR mice. Celastrol also inhibited proliferation, migration, and tube formation in cultured human retinal microvascular endothelial cells, and reversed the activation of the microRNA (miR)-17-5p/hypoxia-inducible factor (HIF)-1α/VEGF pathway in the retina of OIR mice. These results indicate that celastrol alleviates pathologic RNV in the retina by protecting neuroglia and suppressing inflammation via inhibition of miR-17-5p/HIF-1α/VEGF signaling, and thus has therapeutic potential for the prevention and treatment of ROP. Abbreviations: BSA, bovine serum albumin; COX2, cyclooxygenase 2; ECM, endothelial cell medium; FBS, fetal bovine serum; HDAC, histone deacetylase; HIF-1, hypoxia-inducible factor 1; HRMEC, human retinal microvascular endothelial cell; Hsp70, heat shock protein; IB4, isolectin B4; ICAM-1, intercellular adhesion molecule 1; IL-1β/6, interleukin 1 beta/6; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein 1; miRNA, microRNA; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappa B; OIR, oxygen-induced retinopathy; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PI3K, phosphatidylinositol-3-kinase; qRT-PCR, quantitative real-time PCR; RNV, retinal neovascularization; ROP, retinopathy of prematurity; RTCA, real-time cell analyzer; RVO, retinal vaso-obliteration; TNF-α, tumor necrosis factor alpha; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.