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PURPOSE Adams-Oliver syndrome is a rare, inherited disorder of embryologic development that affects multiple systems. Ocular manifestations have been poorly characterized due to the low prevalence and high mortality of the disease when it is associated with internal organ and/or ophthalmic manifestations. We present a case of Adams-Oliver syndrome in a 13-year-old patient whose multimodal retinal imaging findings helped direct management. METHODS Case report reviewing medical records and imaging. PATIENTS Single patient. RESULTS Visual acuity upon presentation was 20/40 in each eye. Ultra-widefield fluorescein angiography revealed peripheral non-perfusion with terminal vascular bulbs, as well as leakage from a temporal fibrovascular complex in the left eye. Fundus autofluorescence imaging showed hyperautofluorescence associated with optic disc drusen and the fibrovascular complex. Treatment with targeted laser photocoagulation was associated with regression of the neovascularization. CONCLUSIONS Retinal manifestations of Adams-Oliver syndrome as observed with ultra-widefield fundus imaging may resemble those of familial exudative vitreoretinopathy and retinopathy of prematurity. Treatment of avascular retina with panretinal photocoagulation can be considered.

Background Breastfeeding has several benefits for both the infants and mothers. This study assessed breastfeeding knowledge, attitudes, and practices (KAP) among mothers of infants with Retinopathy of Prematurity (ROP). Methods A cross-sectional study was conducted among mothers of infants with ROP visiting the ROP clinic in a selected tertiary care centre. A total of 100 mothers were selected through the convenience sampling method and interviewed using a structured questionnaire. Result A significant number of mothers had average to poor knowledge (81%) with a mean score of 8.32 ± 2.7. More than half of the mothers had poor practices related to breastfeeding with a mean score of 7.6 ± 2.4. The attitudes of the mothers towards breastfeeding was either neutral or positive towards formula feeding. Conclusion The KAPs of mothers regarding breastfeeding were inadequate. Intervention measures are recommended for promoting breastfeeding practices among the mothers of infants with ROP.

The aim of this study was to evaluate the incidence, severity, and treatment modalities of retinopathy of prematurity (ROP) in moderate and late preterm infants with a gestational age (GA)31 + 6 weeks.ROP screening results of preterm infants with GA31 + 6 weeks to 36 + 6 weeks between March 2013 and January 2019 were evaluated retrospectively. Infants were divided into 2 groups according to GA as 32-33 + 6 weeks (moderate preterm) and 34-36 + 6 weeks (late preterm). In these groups, any ROP and severe ROP (requiring treatment) development rates and ROP types and treatment modalities were evaluated.A total of 4156 preterm infants, 1875 (45.1%) female and 2281 (54.9%) male, were included. Overall, 1466 (35.2%) of the infants were moderate preterm and 2690 (64.8%) were late preterm. The incidences of any ROP and severe ROP were 22% and 2.5%, respectively. The rate of severe ROP was 5.3% in moderate preterm infants and 0.9% in late preterm infants. Significant correlations were determined between duration of hospital stay, birth weight (BW), and GA with ROP development (r = +0.415, r = -0.258, r = -0.199, respectively; p0.001 for all). Of 102 patients (2.5%) requiring treatment, 64 (62.7%) had laser, 34 (33.3%) had intravitreal bevacizumab (IVB), 2 (1.9%) had sequential IVB and laser, and 2 (1.9%) had vitreoretinal surgery.ROP seems to still be an important health problem in moderate and late preterm infants in our country according to data from screening high-risk preterm infants with a GA31 + 6 weeks. In this cohort, ROP development correlates with GA, BW, and duration of hospitalization significantly.

Background We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. Methods A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. Results Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p Conclusions In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

Purpose To validate the performance of postnatal growth and retinopathy of prematurity (G-ROP) screening criteria in a Taiwanese cohort. Design Screening evaluation with retrospective data Method Premature infants who underwent retinopathy of prematurity (ROP) screening between January 2015 and April 2019 at a tertiary hospital were examined. Infants with known final ROP results and complete longitudinal weight records were included. G-ROP screening criteria, both original and simplified (G-ROP 180 g), were applied as the prediction model for type 1 ROP; sensitivity and specificity were analyzed. The reduction in the number of infants requiring ROP screening and the number of funduscopic examinations were calculated. Result A total of 303 infants with documented ROP outcomes and complete weight gain records were examined; 103 infants developed ROP, of whom 29 developed type 1 ROP, while the other 200 did not develop ROP. For the detection of type 1 ROP, the sensitivity and specificity of the original G-ROP screening criteria were 96.6% and 42.3%, and 100% and 31% for the simplified G-ROP 180 g model, respectively. The reduction in the number of infants requiring screening and funduscopic examinations was 32.6% and 33.5% for the original G-ROP criteria, and 28.1% and 23.2% for the G-ROP 180 g model, respectively. Conclusion Both the original G-ROP and G-ROP 180 g criteria attained high sensitivities in detecting type 1 ROP in the current Taiwanese cohort, with the G-ROP 180 g model outperforming the original one. Validation and modification may be required before applying G-ROP screening criteria to different populations.

BACKGROUND: Increased cardiorespiratory events with bradycardia and oxygen desaturation have been reported in very low birthweight (VLBW) infants following stressors such as immunizations. These events are difficult to quantify and may be mild. Our group developed an automated algorithm to analyze bedside monitor data from NICU patients for events with bradycardia and prolonged oxygen desaturation (BDs) and used this to compare BDs 24 hours before and after potentially stressful interventions. METHODS: We included VLBW infants from 2012–2017 with data available around at least one of four interventions: two-month immunizations, retinopathy of prematurity (ROP) examinations, ROP therapy, and inguinal hernia surgery. We used a validated algorithm to analyze electrocardiogram heart rate and pulse oximeter saturation data (HR, SpO2) to quantify BD events of HR

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined. STUDY DESIGN: This retrospective case-control study including infants

Erythropoietin (EPO) is a glycoprotein hormone that regulates hematopoiesis in the human body. The presence of EPO and its receptors in different tissues indicates that this hormone has extramedullary effects in other tissues, including the eye. We focus on the biological roles of this hormone in the development and normal physiologic functions of the eye. Furthermore, we explore the role of EPO in the management of different ocular diseases – including diabetic retinopathy, retinopathy of prematurity, inherited retinal degeneration, branch and central retinal vein occlusion, retinal detachment, traumatic optic neuropathy, optic neuritis, methanol optic neuropathy, nonarteritic anterior ischemic optic neuropathy, glaucoma, and scleral necrosis.

To determine the long-term cognitive outcomes in children who underwent intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP).Prospective cohort study.This single-center study enrolled 186 children between 3 and 6 years of age and included 101 children in the final analysis: premature without ROP (group 1), ROP not needing treatment (group 2), IVB monotherapy (group 3), IVB plus laser therapy (group 4), and laser monotherapy (group 5). The Full-Scale Intelligence Quotient (FSIQ) was evaluated by the Wechsler Preschool and Primary Scale of Intelligence Test at baseline and then annually for 1-2 years and compared among groups.The age at cognitive evaluation was 4.5-4.9 years at baseline and 6.1-7.0 years at the last follow-up. The FSIQ was comparable among the groups at both time points (P = .08 and .50, respectively). Severe cognitive impairment (FSIQ70) was more common in group 4 at baseline (4%, 22%, 13%, 33%, and 0% in groups 1-5, respectively; P = .03) but did not differ among the groups at the last follow-up (6%, 0%, 4%, 22%, and 0%; P = .22). After adjusting for sex, Apgar score, neonatal adverse events, and days on mechanical ventilation, IVB was not associated with FSIQ either at baseline or at the last follow-up.At 4.5 to beyond 6 years of age, children who underwent IVB monotherapy had comparable cognitive outcomes compared to the other premature children without prior IVB. Children who underwent IVB plus laser showed higher severe cognitive impairment at 4.5 years of age.

The uncontrolled growth of blood vessels is a major pathological factor in human eye diseases that can result in blindness. This effect is termed ocular neovascularization and is seen in diabetic retinopathy, age-related macular degeneration, glaucoma and retinopathy of prematurity. Current treatments for these diseases include laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents and vitreoretinal surgery. Although strategies to inhibit VEGF have proved to be dramatically successful in some clinical studies, there remains the possibility of significant adverse effects regarding the blockade of crucial physiological roles of VEGF and the invasive nature of the treatments. Moreover, it is evident that other pro-angiogenic factors also play important roles in the development of these diseases, as seen in cases in which anti-VEGF therapies have failed. Therefore, new types of effective treatments are required. In this review, we discuss a promising strategy for the treatment of ocular neovascular diseases, i.e., the inhibition of hypoxia-inducible factor (HIF), a master regulator of angiogenesis. We also summarize promising recently investigated HIF inhibitors as treatments for ocular diseases. This review will facilitate more comprehensive approaches to understanding the protective aspects of HIF inhibition in the prevention of ocular diseases.

To focus on the longitudinal evaluation of high-risk infants for the development of retinopathy of prematurity (ROP) at a single tertiary neonatal intensive care unit (NICU), and to evaluate evolving demographics of ROP and the transition of treatment-warranted disease.Retrospective cohort study.A consecutive retrospective review was performed of all infants screened for ROP between 1990 and 2019 at the Jackson Memorial Hospital neonatal intensive care unit. All inborn infants meeting a birth criteria of32 weeks' gestational age (GA) or a birthweight (BW) of 1500 g were included. Longitudinal demographic, diagnostic, and treatment data were reported.Between January 1, 1990, and June 20, 2019, a total of 25,567 examinations were performed and 7436 patients were included. Longitudinal trends over 3 decades demonstrated a decreasing incidence of ROP (P.05). Although the mean BW and GA increased over 3 decades, patients with ROP demonstrated lower BW and GA over time (P.05). The prevalence of micro-premature infants (as defined by BW750 g) continues to rise over time. Micro-preemies demonstrated increasing severity of zone and stage grading, plus disease, and propensity to require treatment (P.05). The rate of progression of ROP to stage 4 and 5 disease has decreased over time, and there has been an associated increased adoption of intravitreal bevacizumab as primary and salvage therapy.Understanding the evolution of ROP infants and treatment over time is critical in identifying high-risk infants and in reducing the incidence of severe-stage ROP. Micro-prematurity is one of the significant risk factors for treatment-warranted ROP that continues to increase as neonatal care improves. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Automatic blood vessel segmentation from retinal images plays an important role in the diagnosis of many systemic and eye diseases, including retinopathy of prematurity. Current state-of-the-art research in blood vessel segmentation from retinal images is based on convolutional neural networks. The solutions proposed so far are trained and tested on images from few available retinal blood vessel segmentation datasets, which might limit their performance when given an image with retinopathy of prematurity signs. In this paper, the performance of three high-performing convolutional neural networks for retinal blood vessel segmentation is evaluated in the context of blood vessel segmentation on retinal images exhibiting retinopathy of prematurity. The main motive behind the study is to test if existing public datasets suffice to develop a high performing predictor that could assist an ophthalmologist in retinopathy of prematurity diagnosis. To do so, the authors created a dataset consisting solely of retinopathy of prematurity images. Retinal blood vessels are manually labeled in the images by two observers, including an ophthalmologist experienced in retinopathy of prematurity treatment. Experimental results show that all three solutions have difficulties in detecting the retinal blood vessels of infants due to a lower contrast compared to images from public datasets as demonstrated by significant drop in classification sensitivity. All three solutions segment alongside retinal also choroidal blood vessels which are not used to diagnose retinopathy of prematurity, but instead represent noise and are confused with retinal blood vessels. Through observations and numerical analysis of experimental data, it is concluded that existing solutions for retinal blood vessel segmentation need improvement oriented toward using more detailed datasets or deeper models in order to assist the ophthalmologist in retinopathy of prematurity diagnosis.

PURPOSE: To describe a case of monocular retinopathy of prematurity (ROP)-like vasculopathy without oxygen supplementation in the dog. METHODS: Fundus photographs (RetCam), spectral-domain optical coherence tomography (sdOCT), confocal scanning laser ophthalmoscopy (cSLO), and fluorescein angiography (FA), as well as postmortem histology and immunohistochemistry (Collagen IV and anti-vWF antibodies), were carried out to characterize the vascular abnormalities. RESULTS: Ophthalmic examination showed peripheral and mid-temporal avascular areas in the tapetal region, neovascularization and abnormally dilated and tortuous retinal vessels in the left eye. sdOCT demonstrated not only cross-sectional views of preretinal fibrovascular proliferation but also extensive proliferation extraretinally into the vitreous. FA emphasized demarcation of vascular and avascular zones with neovascular tufts “popcorns.” Histology and immunohistochemistry confirmed presence of abnormally dilated vessels and the intravitreal blood vessels. CONCLUSIONS: ROP is a disease of abnormally developed retinal vascularization associated with oxygen supplementation therapy, potentially causing blindness in premature infants. Although the mechanism of ROP-like vasculopathy in our case is unclear, it is important to appreciate that the abnormal vascular pattern seen in ROP in premature infants can occur in canines without oxygen administration.

Background The third epidemic of retinopathy of prematurity (ROP) has majorly involved middle income countries in which tailored screening and local guidelines require development. The data regarding ROP prevalence and cutoff numbers for screening in Egypt are lacking. Methods Retrospective analysis of an independent screening effort spanning 2 years (February 2019 to February 2021) and involving 32 neonatal care units within Sharkia governorate, Egypt. Infants of gestational age (GA) ≤ 34 weeks and/or birth weight (BW) ≤ 2000 g were included, as well as those with unstable clinical course. Two eyecare centers located in Sharkia and Cairo governorates served as referral centers for any required interventions. Results Of the 276 screened infants, 133 (48.2%) had some form of ROP that was bilateral in 127 (95.5%) of them. Aggressive posterior ROP (AP-ROP) was detected in both eyes of 24 infants (8.7%). The median (IQR) GA of infants with ROP was 32 (30–34) weeks, and the median (IQR) BW was 1600 (1350–2000) g. Sixty-three infants (47.4%) required treatment. Of the total 84 eyes that primarily were treated, 73 (86.9%) received intravitreal ranibizumab, 8 (9.5%) underwent laser ablation therapy, and 3 eyes (3.6%) underwent surgery. Recurrence rate was 16.7% (14 eyes). Final outcome was favorable in 83 eyes (98.8%). Applying the American Academy criteria would have led to the missing of 36.8% of infants with ROP and 28.6% of those requiring treatment in our sample. Conclusion The incidence of both ROP and AP-ROP in the Egyptian rural setting appears to be in the high end of global reported rates. Prevention measures should urgently be planned and implemented.

Objective: To explore the incidence and trend of ROP over the past 10 years. The secondary objective was to identifyany association between clinical variables and threshold ROP.Materials and Methods: A cross-sectional, retrospective study of infants with

Introduction: In this study, we investigated the effect of drug dose on the progression of retinal vascularization in eyes treated with different doses of intravitreal bevacizumab (IVB). Methods: The patient charts of 259 eyes of 142 patients who were administered 0.3125 mg or 0.625 mg IVB as primary therapy for type 1 retinopathy of prematurity (ROP) or aggressive ROP (A-ROP) were retrospectively evaluated. Eighty-four eyes of 42 infants met all study inclusion criteria and underwent further morphological evaluation. Eyes treated with 0.3125 mg and 0.625 mg bevacizumab were grouped as the low dose and standard dose groups, respectively. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) were measured on pretreatment photographs (PPs) and final fluorescein angiography (FA) images. LTRV, measured in pixels, was converted to DD and FD units and analyzed. All PPs and FA images were captured with 130° PanoCam Pro camera. The difference between final LTRV and pretreatment LTRV was defined as the difference of LTRV. The ratio of difference of LTRV to pretreatment LTRV was defined as the rate of increase of LTRV. Results: Of the 255 eyes, re-treatment rate before 55 weeks postmenstrual age (PMA) was 23% in the eyes treated with 0.3125 mg IVB and 19% in the eyes treated with 0.625 mg IVB (p = 0.362). Of the 42 infants included for further morphological evaluation, the median age at the time of treatment was 36 (35–38) weeks PMA, and the median age at the time of FA imaging was 66 (62–75) weeks PMA. While the difference of LTRV by unit of DD was higher in the low dose group (p = 0.017), this difference was similar between groups by unit of FD (p = 0.412). The ratio of the increase of the LTRV was similar between groups by units of DD and FD (p = 0.081, p = 0.390; respectively). The FD/DD ratio was 4.13 ± 0.49 and 3.26 ± 0.33 at the pretreatment and final sessions, respectively (p = 0.000). Conclusion: The ratio of FD to DD decreased significantly with increasing age. The additional treatment rate and progression of retinal vascularization by unit of FD were similar between the groups. The difference of LTRV by unit of DD was higher in the low dose group. The usage of dif­ferent formulas and methods may affect the evaluation of the progression of retinal vascularization.

Zusammenfassung Hintergrund Das Retina.net ROP-Register erhebt Daten von Kindern, die eine seltene behandlungsbedürftige Frühgeborenenretinopathie (Retinopathy of Prematurity, ROP) entwickeln. Ziel dieser Auswertung ist die Untersuchung der Daten zur behandlungsbedürftigen ROP, Epidemiologie, Therapie und deren Änderungen über einen Zeitraum von 15 Jahren an der Medizinischen Hochschule Hannover. Methoden Analyse der Daten der therapiebedürftigen Fälle der ROP eines Zentrums für die Geburtsjahre 2001 bis 2016 (Therapie in 2002 bis 2017) als Gesamtzeitraum und in 5 Abschnitten. Ergebnisse Es wurden 65 Kinder behandelt (23 weiblich), davon wurden 11 (16,9 %) extern auf ROP gescreent und zur ROP-Behandlung zugewiesen. Für den Zeitraum 2006 bis 2016 lag die Inzidenz der behandlungsbedürftigen ROP unter den gescreenten Kindern bei 4,1 %. Das mittlere Gestationsalter betrug 25,7 Schwangerschaftswochen (SSW) (Standardabweichung [SA] = 1,8), das Geburtsgewicht 763 g (SA = 235), das postmenstruelle Alter bei Behandlung 38,2 Wochen (SA = 3,2), das postnatale Alter 12,4 Wochen (SA = 3,2). Über die Zeit zeigte sich kein signifikanter Unterschied der demografischen Parameter. Am häufigsten (57 Augen bei 31 Kindern) wurde eine Zone II, 3+-Erkrankung behandelt; 58 Kinder erhielten eine Laserkoagulation (N = 114 Augen), 7 Kinder bilateral eine Anti-VEGF-Therapie (Bevacizumab) (N = 14 Augen), welche ab 2014 eingesetzt wurde. Eine Wiederbehandlung bei Wiederaufflammen der behandlungsbedürftigen ROP war in einem Fall nach initialer Laserbehandlung notwendig. Kinder mit behandlungsbedürftiger ROP zeigten häufig neonatologische Komorbiditäten, in mehr als 90 % Beatmung, bronchopulmonale Dysplasie und erhielten Transfusionen. Schlussfolgerung Dies ist die erste monozentrische Auswertung über 15 Jahre im Rahmen des Retina.net ROP-Registers. Ab 2014 sehen wir einen Wechsel von der Laserkoagulation zur Anti-VEGF-Therapie (Bevacizumab), während im betrachteten Kollektiv die demografischen Daten und Behandlungsparameter weitgehend konstant waren.

Background: The efficiency of treatment and prevention of retinopathy of prematurity (ROP) has improved. In addition, the development of a disease screening system to reduce the incidence of disability resulting from this pathology is important. Aim: This study aimed to determine new laboratory criteria for screening and predicting the ROP course through in-depth investigation of the molecules participating in the pathogenesis of ROP. Material and methods: A comprehensive clinical and experimental study was performed to assess the local and systemic levels of 49 cytokines with various biological effects, four monoamines, and angiotensin-II (AT-II) at different stages of the pathological process. In the clinical analysis, 165 preterm infants at risk of ROP development were examined. For the experimental part, the disease course of 145 Wistar infant rats in the developed model of experimental ROP was analyzed. Results: Among cytokines, the seven most promising potential laboratory markers of ROP development and adverse course were as follows: MCP1 95 pg/mL, IGF-II 140 pg/mL, TGFbeta1 18000 pg/mL, and IGF-I 24 pg/mL in the blood serum of preterm infants before the first signs of ROP and VEGF-A 108 pg/mL, TGF-beta2 100 pg/mL, and PDGF-BB 1800 pg/mL at ROP manifestation. Among monoamines, serotonin (17.0 pg/mL) and L-DOPA indicated their prognostic value in the clinical and experimental settings. Moreover, a possible prognostic role of AT-II was found. Conclusion: In this study, methods to improve the ROP screening system are outlined, but further work is necessary to assess the possibility of implementing the results in clinical practice

BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94–98% (n = 126); cohort 2, 92–97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44). CONCLUSION: An oxygen saturation target of 92–97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94–98%.

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

BACKGROUND: Postnatal exposure to red blood cell transfusion (RBCT) in premature infants is an important risk factor for Retinopathy of Prematurity (ROP) progression. We hypothesized that higher number and earlier timing of RBCT are associated with worse ROP severity and result in laser treatment at an earlier postmenstrual age (PMA) in very low birth weight (≤1500 g, VLBW) infants. METHODS: A retrospective medical record review of 631 VLBW infants over a 5-year period was performed. Demographic features and potential clinical risk factors including number of RBCT, ROP severity, and progression to laser treatment were collected to evaluate predictors of severe ROP. ANCOVA, pairwise post-hoc analyses, and multivariate regression were used to determine associations between frequency and timing of RBCT and ROP severity. RESULTS: Of the 456 eligible infants, 61 developed severe ROP (13%). There was significant correlation between number of RBCTs and ROP severity, adjusted for gestational age and birthweight (Adjusted R2 = 0.53; p

Background: Respiratory distress syndrome (RDS) is a common problem in preterm babies due to surfactant deficiency. Initially, babies were given surfactant therapy by intubation, surfactant administration, and extubation (INSURE) method. Minimally invasive surfactant therapy (MIST) is a novel method of surfactant administration without intubation to spontaneously breathing preterm babies with RDS without the removal of continuous positive airway pressure (CPAP). Aim: This study aims to compare the surfactant therapy in preterm babies with RDS through MIST and INSURE technique. Methods: This prospective, observational cohort study was conducted in the neonatology unit of Calcutta National Medical College and Hospital. A total of 212 preterm babies of

BACKGROUND/PURPOSE To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations. METHODS This cross-sectional epidemiological study used census tract-level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site. RESULTS Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P 60 minutes. Similar variables predicted travel distance. CONCLUSION Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.

Background The benefits of mother’s own milk (MOM) for preterm infants have been widely recognized. Many studies have shown that the rate of breastfeeding of premature infants remains very low. Although many studies use measures to promote breastfeeding, few high-quality cluster randomized controlled studies have evaluated the effectiveness of these measures. WeChat is an instant messaging software for smart terminals, and WeChat mini-programs have been widely used to promote health and self-management in China. Based on this background, we designed a randomized controlled study based on WeChat mini-programs to promote MOM feeding of premature infants in the neonatal intensive care unit (NICU). Methods/design This study will evaluate the effectiveness of WeChat mini-programs to increase the consumption of MOM feeding in twelve NICUs in Jiangsu Province, namely, six “intervention” NICUs and six “control” NICUs. The study process is as follows: (1) design and preparation, (2) NICU recruitment and training, (3) interpretation and analysis of baseline data, (4) quality control implementation process, and (5) data analysis feedback and publication of study reports. The primary outcome is the proportion of MOM feeding of premature infants during NICU hospitalization. The secondary outcomes are as follows: (1) time to initiation of MOM feeding (hours) and proportion of first-time MOM feeding (%), (2) duration of parenteral nutrition (days), (3) time to total gastrointestinal feeding (days), (4) hospitalization time and hospitalization cost, and (5) incidence of complications (necrotizing enterocolitis, bronchopulmonary dysplasia, feeding intolerance, late-onset sepsis, retinopathy of prematurity). Discussion This study is the first cluster randomized controlled trial on the intervention of using a WeChat mini-program-based lactation consultant for premature infants in the NICU in China. We hope this study can improve the consumption of MOM by NICU premature infants during hospitalization through the intervention of WeChat mini-programs. Trial registration ClinicalTrials.gov NCT04383379. Registered on May 5, 2020.

PURPOSE To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor. METHODS A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor. RESULTS Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes. CONCLUSION The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.

Purpose To describe the clinical features of severe recurrent fibrovascular proliferation after intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity. Methods This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital. Patients Four patients (seven eyes) with aggressive posterior retinopathy of prematurity. Results The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks' gestational age and one patient at 29 weeks' gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course. Conclusion Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti-vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.

Purpose To determine the incidence and factors associated with lens opacity after lens-sparing vitrectomy (LSV) for retinopathy of prematurity (ROP). Design Retrospective, comparative case series. Participants Among the 141 eyes of 94 patients who underwent LSV for ROP between 2006 and 2019, 108 eyes of 71 patients with a minimum follow-up of 12 months after LSV were investigated. Methods Data were collected from patients’ charts, including gender, gestational age at birth, birth weight, stage of ROP, postmenstrual age (PMA) at LSV, surgical procedure, preoperative injection of anti–vascular endothelial growth factor (VEGF) agents, subsequent retinal surgeries, and lensectomy during follow-up. Main Outcome Measures Lens status at last visit, incidence and timing of lensectomy, and risk factors for lens opacity requiring lensectomy. Results Stages of ROP at LSV were 4A, 4B, and 5 in 92 eyes, 13 eyes, and 3 eyes, respectively. The median PMA at LSV was 40.6 weeks. Thirty-two eyes received anti-VEGF therapy before LSV. Lens opacity was found in 17 eyes (15.7%), of which 10 eyes (9.3%) underwent lensectomy. The period between LSV and lensectomy ranged from 21 days to 131.9 months (median, 21.1 months). Eleven other eyes (10.2%) underwent lensectomy as part of a reoperation for worsening of ROP. A total of 80 eyes (74.1%) preserved clear lenses at the latest follow-up examination after surgery (median, 6.8 years; range, 1–14 years). The Kaplan–Meier estimate showed that the proportion of patients with phakia at 5 and 10 years was 92.4% and 89.0%, respectively. Multivariate Cox regression analysis revealed that eyes with the use of tamponade at LSV (P = 0.005; odds ratio [OR], 25.68; 95% confidence interval [CI], 4.187–157.5) and young PMA at LSV (P = 0.033; OR, 1.047; 95% CI, 1.012–1.099) were associated significantly with lens opacity requiring lensectomy. However, anti-VEGF therapy was not associated with lens opacity requiring lensectomy. Conclusions Nearly 10% of eyes required lensectomy because of lens opacity after LSV for ROP. The development of lens opacity requiring lensectomy seems to be associated with the use of tamponade and young PMA at LSV.

Background The current study aimed to evaluate growth and neurodevelopmental status in patients with retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB). Methods This historical cohort study was conducted on neonates with ROP who were treated with IVB and age and birth weight-matched controls who did not need IVB. Apgar score less than five, history of blood transfusion and history of infectious diseases were among exclusion criteria. Indirect ophthalmoscopic examinations were performed till complete retinal vascularization. Growth and neurodevelopmental status were evaluated by Age and Stages Questionnaire (ASQ) at the ages of 6, 12, and 18 months. Developmental milestones were assessed in five areas (gross motor, fine motor, personal-social status, problem-solving, and relationship) and overall issues. Results A total of 34 cases and 36 controls were included in the present study. Birth weight and corrected gestational age were not statistically different between the groups. In a follow-up period of 18 months, bevacizumab was effective as a primary treatment in the treatment of severe cases of ROP. There was no significant difference between the two groups regarding the five areas and overall issues in follow-up intervals (P > 0.05). Conclusions The obtained results did not show any growth and neurodevelopmental differences between treatment-naïve infants and those receiving IVB for the treatment of ROP.

Purpose: To evaluate risk factors and outcomes of preferred practice for infants with aggressive posterior retinopathy of prematurity (APROP) at a tertiary eye center in India. Methods: This was an observational study of infants with APROP where patients were divided into three groups after 2 weeks of initial treatment depending on the treatment received: anti-VEGF only, laser only, and combination of anti-VEGF injection followed by laser within 2 weeks of anti-VEGF injection (combined group). All infants were evaluated for risk factors and followed up at 1, 2, 4, 8, and 12 weeks to determine treatment outcomes in terms of regression, vascular re-growth, progression, and recurrence of the disease. Results: Sixty eyes of 31 infants were included in the study, with 26 eyes in the anti-VEGF only group, 19 eyes in the laser-only group, and 15 eyes in the combined group. Infants in the combined group presented late with lower birth weight (BW), smaller gestational age (GA), and a history of longer duration of ventilatory support. After 3 months of follow-up, regression occurred in 73.08% in the anti-VEGF only group, 89.5% in the laser-only group, and 86.66% in the combined group ( P = .07). Zone of vascularization was greater in the anti-VEGF only group and the combined group compared to the laser-only group. Disease recurrence was seen in 27% in the anti-VEGF group, none in the laser-only group, and 13.33% in the combined group ( P < .001). However, progression to stage 4 ROP requiring surgery was noted in 2 eyes in the laser-only group. Conclusions: Infants with APROP who have a lower GA or BW or require longer ventilatory support are possibly a subset best suited for planned combination therapy. A combination of anti-VEGF therapy followed by laser treatment within 2 weeks allows for early regression, a stable course, lower recurrence, and a larger area of retinal vascularization. [ J Pediatr Ophthalmol Strabismus . 2021;58(6):370–376.]

Background: Premature infants often develop blindness in one or both eyes due to disparity in retinal growth. This condition is termed as retinopathy of prematurity (ROP). Aim: The aim of the study is to study the postnatal weight gain pattern of preterm infants (Age < 32 weeks) and risk factors of ROP in a tertiary care center and to validate the lower birth weight and gestational age (GA) for ROP. Methods: Hospital-based study on 110 preterm neonates admitted in the neonatal intensive care unit (NICU) who fulfilled the criteria for ROP screening. On screening, 55 neonates were identified to have ROP and 55 neonates identified to have no ROP. The profiles of ROP and risk factors were documented according to the International Classification for ROP recommendations. The data were analyzed for GA, birth weight, and risk factors predisposing to ROP. Results: A total of 110 preterm neonates were screened, out of which, 55 had ROP. The mean GA (P = 0.002), Apnea (P = 0.001), ventilation (P = 0.001), and surfactant (P = 0.001) were observed a significant difference. Further, a significant difference in weight gain pattern in the two groups (P < 0.05) was also observed. The group without ROP had a better weight gain pattern than the group with ROP. Conclusion: Our study revealed prematurity, low birth weight, and birth weight increasing patterns were found to be strong predictors of ROP. GA, apnea, ventilation, and surfactant were found to be statistically significant factors associated with ROP.

Pathological angiogenesis (PA) contributes to various ocular diseases, including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, which are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) can suppress vascular inflammation. However, the function of rTMD1 in VEGF-induced PA remains unknown. In this study, we found that rTMD1 inhibited VEGF-induced angiogenesis in vitro. In an oxygen induced retinopathy (OIR) animal model, rTMD1 treatment significantly decreased retinal neovascularization but spared normal physiological vessel growth. Furthermore, loss of TMD1 significantly promoted PA in OIR. Meanwhile, hypoxia-inducible factor-1α, the transcription factor that upregulates VEGF, was suppressed after rTMD1 treatment. The levels of interleukin-6, and intercellular adhesion molecule-1 were also significantly suppressed. In conclusion, our results indicate that rTMD1 not only has dual effects to suppress PA and inflammation in OIR, but also can be a potential HIF-1α inhibitor for clinical use. These data bring forth the possibility of rTMD1 as a novel therapeutic agent for PA.

Introduction: Preterm babies often suffer from various systemic illnesses and struggle for survival in the neonatal intensive care unit (NICU). These preterm babies are at risk of developing ROP which is a potentially blinding condition. The presence of predisposing maternal and neonatal factors contributes for the development of ROP. Determining the association of risk factors with the development of ROP is essential in improving the screening and management of ROP. Aim: To determine maternal, neonatal risk factors and influence of retinal immaturity at first screening for development of ROP. Settings and design: Prospective, observational study conducted at a level of 3 PICU & department of ophthalmology. Methods and Materials: All the preterm infants with gestational age ? 37 weeks admitted in NICU were first screened by 2 to 3 weeks of chronological age and followed up till the completion of retinal vascularization and regression of ROP following treatment. The zone of retinal vascularization at first screening and various maternal and neonatal risk factors were noted. Results: Out of 166 babies screened, 18.67% progressed to ROP. Of the 36 babies with immature retina 58% developed ROP, while 7.7% neonates with mature retina developed ROP. Gestational age, birth weight, retina immaturity, respiratory distress syndrome and anaemia of prematurity were statistically significant for ROP. Statistical analysis: Descriptive statistics was used to identify the association of risk factors with the development of ROP. Each risk factor was analyzed by univariate & multivariate logistic regression. Conclusions: Low birth weight, low gestational age, immature retina and neonatal risk factors have a significant influence on the development of ROP. Key Messages: Low birth weight, low gestational age and retinal immaturity are important risk factors for Retinopathy of prematurity. Keywords: Immature retina, Gestational age, Birth weight, Neonatal/maternal risk factors

Premature birth is an important cause of neonatal mortality and neonatal morbidity. Most premature births are known to be induced by cytokines released for different reasons. Inadequate congenital immune response in premature infants may contribute to increased susceptibility to infection. The aim of the study is to determine the IL-1β, TLR4, PGE2, and TAC profiles in cord blood with characteristics specific to pregnancy and the correlation with neonatal complications caused by premature birth. The study included 26 neonates, 11 girls and 15 boys, born from 24-42 weeks of gestation. Of these, 13 were term and 13 were preterm . For IL-β, PG-E2, TLR4 and TAC levels, 1 mL of cord blood sample was taken from preterm and term neonates. Data related to demographic data, clinical status of patients and outcomes were obtained from electronic medical records and files. Cytokine values obtained from premature neonates were statistically high in terms of TLR4, IL1 and PGE2 compared to term infants. The TRL4 and IL1 values for premature infants with necrotizing enterocolitis and retinopathy of prematurity were lower compared to those without NEC and ROP. In spite of negative correlations between TAC and the other three cytokines, a statistically significant correlation was not identified. TLR4, IL1 and PGE2 were negatively correlated with weight and gestational week, contrarily TAC measurements were positively correlated with weight and gestational week. Measurements of cytokine concentrations in cord blood are among important biomarkers showing degree of inflammation and may assist in predicting neonatal complications and play an effective role in development of specific treatments.

Background. Retinopathy of prematurity (RP) is the main reason for visual disability in premature survivors. RP increases chances for re-hospitalization and re-admission for special help by 1.5–4 times. It can lead to blindness in childhood. Risk factors for RP are mechanical ventilation and oxygen as well as weight gain problems in the postnatal period. The purpose was to assess the influence of different elements of intensive care on the development of severe RP, particularly, respiratory support strategies. Materials and methods. Simple retro-prospective blind non-randomized trial in two separate medical centers of Dnipro enrolled 122 premature neonates with the gestational age of 28–32 weeks from 2016 till 2020. The endpoint for assessment was the development of moderate and severe RP. We performed a univariate logistic regression analysis to analyze the odds ratio and 95% confidence interval (95% CI) for main risk factors. The confidence p level was 0.05. Results. Eighteen percent of premature neonates presented with moderate or severe RP on the 14th day of intensive care according to routine ophthalmologic examination. The moderate and severe RP was associated with an increase in length of noninvasive respiratory care by 4 times (p = 0.01), prolonged conventional ventilation by two-fold (p = 0.33), CPAP length by 4.5 times (p = 0.05), longer usage of additional oxygen (FiO2 > 30 %) by 4 times (p = 0.01). AUC for all these predictors ranged from 0.63 to 0.68. We found the following main predictors of retinopathy. According to statistics, every single day of respiratory support increases the chance of moderate or severe RP by 7–9 % depending on ventilation method, and caffeine citrate usage increases this chance by 6 times. Every 100 g of weight decrease is associated with a 16% increase in RP development risk (p = 0.03). Conclusions. Any respiratory support increases the risk of moderate and severe RP. Thus, the usage of these intensive care modalities can’t be preventive. Attentive modes of weight control should help in the prophylaxis of RP development as well as usual ophthalmologic examinations., Актуальність. Ретинопатія посідає одне з головних місць у структурі дитячої інвалідності із зору та виявляється серед всіх недоношених дітей, які вижили. Ретинопатія недоношених збільшує частоту повторних госпіталізацій та звернень до стаціонару в 1,5–4 рази, а також інвалідизує пацієнтів. Вважається, що основними факторами ризику ретинопатії є оксигенотерапія та штучна вентиляція легень. Мета дослідження: проаналізувати вплив різних елементів інтенсивної терапії та особливостей респіраторної підтримки на розвиток середньотяжких та тяжких форм ретинопатії недоношених. Матеріали та методи. Були досліджені 122 недоношені новонароджені дитини строком гестації 28–32 тижні з дихальними розладами, які перебували на лікуванні в стаціонарі з першої доби життя на базі двох клінічних установ — КП «Дніпропетровська обласна дитяча клінічна лікарня» ДОР» та КП «Дніпропетровський обласний перинатальний центр зі стаціонаром» ДОР» у період із 2016 по 2020 р. Як кінцевий результат дослідження обраний розвиток середньотяжкої та тяжкої ретинопатії недоношених. Для прогнозування середньотяжкої та тяжкої ретинопатії недоношених проводили уніваріантний логістичний регресійний аналіз з обчисленням відношення шансів та 95% довірчого інтервалу (95% ДІ). Критичний рівень р при перевірці статистичних гіпотез був прийнятий < 0,05. Результати. При проведенні аналізу визначено, що розвиток ретинопатії середньої тяжкості та тяжкої ретинопатії реєструвався у 18 % новонароджених груп спостереження з 14-ї доби проведення інтенсивної терапії. Визначено, що розвиток середньотяжкої та тяжкої ретинопатії асоційований зі збільшенням тривалості неінвазивної штучної вентиляції легень (ШВЛ) у 4 рази (р = 0,01), ШВЛ — у 2,3 рази (р = 0,33), проведення СРАР — у 4,5 рази (р = 0,05), тривалості кисневої терапії з FiO2 > 30 % — у 4 рази (р = 0,01). Площа під ROC-кривою для усіх предикторів була приблизно однаковою та коливалась у межах 0,63–0,68. Висновки. Будь-яка респіраторна підтримка є вагомим фактором ризику розвитку ретинопатії недоношених, тобто будь-яка вентиляція не може бути превентивною при лікуванні недоношеного новонародженого. Пріоритетом залишаються адекватний набір ваги в постнатальному періоді та часті офтальмологічні огляди.

Retinopathy of prematurity (RP) is a complex pathology among prematurely born children, which requires a comprehensive approach, including both prevention of the development of more severe stages of the disease, leading to poor vision and irreversible loss of visual functions, and the organization of dispensary observation and rehabilitation. Modern organization of dispensary observation, which is based on a detailed study of the etiology, pathogenesis, as well as the interaction of local and systemic factors on visual functions, can significantly reduce the visual disability of children as a result of this disease.

A preterm infant who underwent bilateral laser photocoagulation for the treatment of stage 3 retinopathy of prematurity (ROP) is presented because she was incidentally diagnosed with grade 3 lipemia retinalis by dilated fundoscopy at post-laser 2 weeks. Meticulous ophthalmologic examination is imperative in premature newborns for not only ROP screening but also detecting any concomitant ocular abnormalities, which can be sight-threatening or even life-threatening. © 2021 by Turkish Ophthalmological Association.

Background: Retinopathy of prematurity (ROP) is the leading cause of blindness among prematurely born children. The incidence of any stage of ROP in children born before the 31st gestational week in Europe and the USA is between 10-45%. The purpose of this study was to show characteristics of ROP between 2015 and 2019 at the Neonatal Intensive Care Unit of the University Medical Centre Ljubljana (NICU-Lj), which is the larger of the two tertiary referral centres in Slovenia and in which more than two thirds of Slovenian very low birth weight children are treated. Methods: All prematurely born children screened for ROP at NICU-Lj between 2015 and 2019 were included in the study. The following parameters were recorded: number of children screened, total number of exams, number of exams per child, number of children with ROP, ROP stages, number of children who needed ROP treatment and number of treatments per child treated. Results: Between 2015 and 2019, 82-130 prematurely born children fulfilled ROP screening criteria each year. A total of 1,412 exams were performed over the period of five years (range: 239-386 per year). Every child had one or more ROP screening exams (range: 1-10). Extremely preterm children born before the 27th week of gestation had more exams (average: 5 exams/child) compared to other prematurely born children (average: 1.5 exams/child). The number of prematurely born children with any stage of ROP ranged from 17 to 30 per year. ROP of any stage was present in 18.75% (2015), in 17.7% (2016), in 23% (2017), in 29.3% (2018), and in 24.1% (2019). More than 70% of all babies with ROP were born before the 27th gestational week. The most mature baby with ROP was born with 29 6/7 weeks of gestational age. Every year, 15-35% of babies with ROP received laser treatment. Conclusions: ROP is an important disease in prematurely born children. During the period 2015-2019, the incidence of any stage of ROP and of serious ROP requiring treatment was comparable. The screening and treatment of ROP requires intense cooperation between paediatric ophthalmologists and neonatologists in order to prevent blindness in prematurely born children.

Purpose Stage is an important feature to identify in retinal images of infants at risk of retinopathy of prematurity (ROP). The purpose of this study was to implement a convolutional neural network (CNN) for binary detection of stages 1, 2, and 3 in ROP and to evaluate its generalizability across different populations and camera systems. Design Diagnostic validation study of CNN for stage detection. Participants Retinal fundus images obtained from preterm infants during routine ROP screenings. Methods Two datasets were used: 5943 fundus images obtained by RetCam camera (Natus Medical, Pleasanton, CA) from 9 North American institutions and 5049 images obtained by 3nethra camera (Forus Health Incorporated, Bengaluru, India) from 4 hospitals in Nepal. Images were labeled based on the presence of stage by 1 to 3 expert graders. Three CNN models were trained using 5-fold cross-validation on datasets from North America alone, Nepal alone, and a combined dataset and were evaluated on 2 held-out test sets consisting of 708 and 247 images from the Nepali and North American datasets, respectively. Main Outcome Measures Convolutional neural network performance was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), sensitivity, and specificity. Results Both the North American– and Nepali-trained models demonstrated high performance on a test set from the same population: AUROC, 0.99; AUPRC, 0.98; sensitivity, 94%; and AUROC, 0.97; AUPRC, 0.91; and sensitivity, 73%; respectively. However, the performance of each model decreased to AUROC of 0.96 and AUPRC of 0.88 (sensitivity, 52%) and AUROC of 0.62 and AUPRC of 0.36 (sensitivity, 44%) when evaluated on a test set from the other population. Compared with the models trained on individual datasets, the model trained on a combined dataset achieved improved performance on each respective test set: sensitivity improved from 94% to 98% on the North American test set and from 73% to 82% on the Nepali test set. Conclusions A CNN can identify accurately the presence of ROP stage in retinal images, but performance depends on the similarity between training and testing populations. We demonstrated that internal and external performance can be improved by increasing the heterogeneity of the training dataset features of the training dataset, in this case by combining images from different populations and cameras.

Aim. To identify risk factors for the development of retinopathy of prematurity and features of the ophthalmological status in dynamics, after two years. Materials and methods. The analysis of outpatient records of 638 premature babies for three years was carried out, of which 309 girls (48.44%) and 329 boys (51.56%) were observed in the consulting and diagnostic office for the identification and monitoring of children with retinopathy of prematurity in Tyumen. Results. The study showed that boys developed more severe stages of PH. The analysis of gestation periods in the groups revealed its significant effect on the development of PH (p < 0.05). Patients with a gestation period from 24 weeks to 27.5 weeks are 1.7 times more common in patients of groups 2 and 3 compared to group 1. There was a significant (p ≤ 0.03) increase in the proportion of patients with extremely low body weight (from 500 to 1000 grams) in groups 2 and 3 compared to group 1. In all groups, the majority of patients have anemia, a syndrome of respiratory disorders. Bronchopulmonary dysplasia and intra-ventricular hemorrhages of 3-4 degrees are more common in patients in groups 2 and 3 with a significance level of p = 0.003 and p = 0.001, respectively. The analysis of the clinical course of PH showed the dependence of spontaneous regression of the disease on the stage: it occurred only in patients of groups 1 and 2. Laser retinal coagulation was required in 82.6% of cases in patients of group 3, after which induced self-regression occurred. The inability to perform laser retinal coagulation was noted in 4.3% of cases due to the severity of the somatic status. Dynamic observation of the ophthalmological status for two years showed the absence of pathology in patients of group 1 and its increase depending on the severity of PH: in patients of group 2 in 15% of cases, in patients of group 3 in 65.22%. The revealed ophthalmological pathology includes accelerated refractogenesis, refractive errors, pathology of binocular vision, atrophy of the optic nerve, congenital glaucoma. Conclusion. Further study of risk factors for retinopathy of prematurity, methods of its treatment and their influence on the state of ophthalmological status in dynamics is required. Children who have undergone retinopathy need careful observation by an ophthalmologist throughout the entire period of growth and formation of visual functions.

Актуальність. Ретинопатія недоношених (РН) є специфічною хворобою саме глибоко недоношених дітей і посідає одне з головних місць у структурі дитячої інвалідності по зору, однак цьому стану можна запобігти завдяки своєчасному хірургічному втручанню. Для запобігання тяжким ускладненням у всьому світі застосовують планові профілактичні огляди очного дна в дітей із групи ризику розвитку РН кожні 2 тижні. Це надійна та перевірена роками методика, недоліками якої можна вважати завдання дитині додаткового медичного навантаження та потреба в досить дорогому офтальмологічному обладнанні, наявності в медперсоналу специфічних навичок для проведення огляду очей недоношеної новонародженої дитини. Через це вважаємо актуальним пошук додаткових засобів прогнозування розвитку цієї хвороби. Зважаючи на наявність доказаного зв’язку рівня фактора росту ендотелію судин (ФРЕС) в середовищах організму з розвитком РН, ми зацікавились можливістю побудувати методику прогнозування розвитку РН на основі цього зв’язку. Мета: встановити зв’язок між змінами рівня ФРЕС у сльозовій рідині дітей із групи ризику розвитку РН із появою та/або прогресуванням цієї хвороби. Матеріали та методи. До дослідження увійшли 23 дитини з групи ризику розвитку РН (вага при народженні ≤ 1500 г та термін гестації ≤ 32 тижнів). Одночасно зі скринінговим оглядом очного дна проводився відбір сльозової рідини. Для цього використовували стерильний клаптик фільтровального паперу з подальшою заморозкою (патент України на корисну модель № 121473, МПК А61В 3/00 від 11.12.2017. Бюл. № 23). Рівень ФРЕС визначали методом імуноферментного твердофазного аналізу. Отримані дані підлягали статистичній обробці з використанням критерію Стьюдента та W-критерію Вілкоксона. Результати. Виявлено, що рівень ФРЕС у сльозі недоношених дітей із групи ризику розвитку РН підвищується при появі або прогресуванні цієї хвороби. В той же час ми бачимо відсутність змін рівня ФРЕС у сльозі новонароджених, які мали нормальний розвиток сітківки без проявів хвороби в динаміці. Висновки. Виявлено статистично значуще підвищення рівня ФРЕС у сльозі недоношених дітей у динаміці при прогресуванні ретинопатії або при відсутності позитивної динаміки., Актуальность. Ретинопатия недоношенных (РН) является специфическим заболеванием, связанным с недоношенностью. Она занимает одно из главных мест в инвалидизации по зрению в детском возрасте. Однако развитие серьезных осложнений при РН можно предотвратить своевременным вмешательством. Для этого во всем мире принята система скрининговых осмотров детей из группы риска развития РН каждые 2 недели. Это надежная и проверенная методика, которая, однако, имеет свои особенности: дополнительная нагрузка недоношенного ребенка медицинскими процедурами, необходимость наличия дорогостоящего специфического оборудования, специальных навыков у медперсонала для проведения осмотра глазного дна этой группы пациентов. Поэтому считаем актуальным поиск дополнительных возможностей прогнозирования развития РН. Связь уровня фактора роста эндотелия сосудов (ФРЭС) с развитием РН на сегодня доказана, и нам представляется интересной возможность разработки методики прогнозирования РН на основе этой связи. Цель: показать связь уровня ФРЭС в слезной жидкости детей из группы риска развития РН с появлением и/или прогрессированием этого заболевания. Материалы и методы. В исследование вошли 32 ребенка из группы риска развития РН (вес при рождении ≤ 1500 г и срок гестации ≤ 32 недель). Вместе со скрининговым осмотром проводили отбор слезной жидкости. Для этого использовали стерильную фильтровальную бумагу с последующей заморозкой (патент Украины на полезную модель № 121473, МПК А61В 3/00 от 11.12.2017. Бюл. № 23). Уровеь ФРЭС определяли методом иммуноферментного твердофазного анализа. Полученные данные были статистически обработаны с использованием критерия Стьюдента и W-критерия Вилкоксона. Результаты. Выявлено, что уровень ФРЭС в слезе недоношенных детей из группы риска развития РН повышается при появлении или прогрессировании этого заболевания. В то же время изменения отсутствовали у детей без проявлений РН в динамике. Выводы. Выявлено статистически значимое повышение уровня ФРЭС в слезе недоношенных детей в динамике при прогрессировании болезни или при отсутствии положительной динамики., Background. The retinopathy of prematurity (ROP) is a specific pathology of premature newborns. ROP can lead to blindness, but it is predictable with early treatment. To prevent severe complications, all pediatric ophthalmologists use screening for premature newborns every 2 weeks before the retina becomes to normal condition, or the ROP appears. But every-two-week screening disturbs such babies, needs the special equipment and high skills of ophthalmologists and nurses to provide this procedure. Such features make us to look for additional ways to diagnose the ROP. Today we know the relation between the vascular-endothelial growth factor (VEGF) levels and the ROP onset. In this study, we searched the method of the ROP prediction based on changing of VEGF levels. The purpose was to find the relation between the changes of VEGF level in the tears in premature newborns of the risk group and the state of ROP. Materials and methods. The study involved 32 newborns of the risk group for the ROP (weight of birth was less than 1500 g, gestation age was under 32 weeks). At the moment of screening, we took the tears from babies. To collect the tears, we used the sterile sheet of filter paper with further freezing. The VEGF level was determined by the solid immunoassay analysis. The data obtained were statistically processed with Student’s and Wilcoxon criterions. Results. VEGF level in tears in premature newborns of the risk group for ROP was found to be higher if associated with onset or the progression of this disease. Also no changes were determined in babies with normal retina growth without ROP. Conclusions. Statistically significant increase in VEGF level in tears was found in premature babies with ROP onset or its progression.

Background Red reflex test (RRT) is a simple, non-invasive method that can be performed easily by pediatricians during the clinical examination in neonatal period, infancy and childhood. Abnormal reflexes can lead to prompt diagnosis of several ocular disorders, with potentially severe consequences on patient's vision, cognitive function and even life. Aim To underline the contribution of pediatricians to early detection of vision and life threatening diseases by using RRT effectively. Methods For the present systematic review, PubMed searches were performed using the key words "red reflex and newborn"; "red reflex and neonate"; "red reflex and complications"; "red reflex and necessity"; "red reflex and retinoblastoma"; "red reflex and congenital cataract"; "red reflex and glaucoma"; "red reflex and prematurity"; "red reflex and leukocoria"; "red reflex and blindness"; "red reflex sensitivity and specificity"; "red reflex and differential diagnosis"; "red reflex and guidelines". The relevant articles were selected without language restrictions. When a full-text publication was not available, their English abstracts were used. In some cases, studies from the reference lists of the selected articles provided useful information. The research took place in September 2020, in the Ophthalmology Department of University Hospital of Alexandroupolis. Results A total of 45 articles were selected according to the used key words. After reviewing data from these articles, it is supported that red reflex remains an effective tool of undeniable importance for early detection of severe eye conditions, such as cataract, retinoblastoma, retinopathy of prematurity and glaucoma. Although literature reports some limitations of RRT, including a notable percentage of false positive tests, the inability to detect small, peripheral retinoblastomas and the lower sensitivity for posterior segment pathology, it is widely accepted that the benefits from the regular evaluation of the test on public health are significant. Therefore, RRT has been established by international guidelines and should be an essential component of pediatricians clinical practice. Red reflex implementation should be incorporated in pediatricians educational programs, so that they would be able to provide quality services and safe diagnoses. Conclusion The implementation of RRT should be encouraged in all neonatal/pediatric departments. Prompt education of pediatricians should be empowered in order to achieve careful vision screening, according to current guidelines.

Background and aim Retinopathy of prematurity (ROP) is the major ocular problem of preterm infants that occurs with abnormal proliferation of immature retinal vessels. Although pentoxifylline (PTX) was reported to inhibit vasculogenesis and neovascularization in experimental studies, there is no clinical data about the effects of PTX treatment on the development and severity of ROP. This clinical study aimed to investigate the possible effects of PTX on the development of ROP. Materials and methods A single-centre retrospective study was conducted including preterm infants who were hospitalised in the neonatal intensive care unit between 2015-2017 years. Infants were divided into two groups in terms of PTX administration for adjuvant therapy, as PTX and non-PTX groups. Results A total of 211 infants were included in the study [gestational age 29 (27-31) weeks, birth weight 1140 (960-1340) g]. From these, 97 infants (46%) were given PTX treatment. The two groups were similar in terms of demographic data and baseline clinical characteristics. Any stage of ROP was detected in 47.4% of infants in the PTX group, which was significantly higher than those in the non-PTX group (27.2%) (p = 0.002). The incidence of advanced-stage ROP in the PTX group (10.3%) was also higher than in the non-PTX group (2.6%) (p = 0.021). Repeated usage of PTX was not found to be related to the development of ROP (p = 0.059). The time of PTX administration was similar between the ROP and no-ROP groups (median; one vs one week, p = 0.825). Surfactant therapy, duration of hospital stay, and PTX treatment were found as significant risk factors for ROP in the logistic regression analysis. Conclusions In contrast to the experimental studies and also promising results of PTX treatment in some neonatal morbidities, it may be associated with increased incidence and stage of ROP.

Optical coherence tomography (OCT) is widely applied in diagnosis and management of retina diseases particularly macular diseases in adult retina practices. However, it has been under-utilized in pediatric retinal diseases especially in neonates and infants. Utilization of OCT in primary macular diseases in this age group is also uncommon and is less reported. Challenges involved in image acquisition and limitations with available devices technique can explain the limited research and accurate data availability in the literature in this field. Purpose of this review article is to summarize the use of OCT and its importance in various infantile retinal pathologies such as vascular diseases, tumors, retinal dystrophies, and optic nerve pathologies with primary focus on neonates and infants, along with infant choroid. In addition, we also discuss about future directions including OCT angiography for infants.

Introduction: Acute angle-closure glaucoma (AACG) is typically considered a disease of adulthood. However, AACG may occasionally be seen in children. The clinical presentation is similar to adults, including headache, vomiting, and eye pain. However, the etiology of angle closure in children is different and most often associated with congenital anterior segment abnormalities. A precipitating factor of AACG in children with previous established, anterior segment abnormalities is eye dilation, which may occur during routine ophthalmological examination with topical mydriasis, or physiologic mydriasis upon entering a dark room. Case Report: We describe a 5-year-old child with a history of severe prematurity and retinopathy of prematurity (ROP) presenting with bilateral AACG following a routine outpatient, dilated ophthalmological examination. While angle-closure glaucoma has previously been reported in cases of ROP, a bilateral acute attack of AACG following pupil dilation in regressed ROP has hitherto been unreported. Conclusion: Given the association of ROP and AACG, it can be expected that as the survival rate of premature infants improves, the incidence of ROP and AACG may also increase. It is therefore prudent for the emergency physician to have AACG on the differential for pediatric patients with headache and eye pain.

To compare the effectiveness of cycled lighting (CL) or continuous near darkness (CND) on weight in preterm infants.Total 147 infants with a gestational age 25-32 weeks and/or a birth weight 750-1500 g were included in the study. The infants were classified into two groups: CL and CND. Weight on postnatal day 14, weight at corrected 35 weeks, mean rectal temperature and serum growth hormone, cortisol, melatonin levels at 35 weeks' post menstrual age (PMA), weekly weight gain, full enteral feeding time, duration of mechanical ventilation, retinopathy of prematurity (ROP), length of stay in the hospital, weight and length at three and six months corrected age were compared between the groups.There were no differences between weights on postnatal day 14. Anthropometric parameters and mean rectal temperatures of groups also were not different at 35 weeks' PMA. There were no differences among the groups in duration of full enteral feeding time, length of stay in hospitalization, duration of mechanical ventilation, ROP and anthropometric parameters. Further, serum growth hormone, cortisol, and melatonin levels were similar between the groups at 35 weeks' PMA.CL and CND did not have any advantages over each other.ZIEL: Vergleich der Wirksamkeit von zyklischer Beleuchtung (CL) oder kontinuierlicher Dunkelheit (CND) auf das Gewicht bei Frühgeborenen.Insgesamt 147 Säuglinge mit einem Gestationsalter von 25 bis 32 Wochen und / oder einem Geburtsgewicht von 750 bis 1500 g wurden in die Studie eingeschlossen. Die Säuglinge wurden in zwei Gruppen eingeteilt: CL und CND. Gewicht am 14. postnatalen Tag, Gewicht nach korrigierten 35 Wochen, mittlere Rektaltemperatur und Serumwachstumshormon, Cortisol, Melatoninspiegel 35 Wochen nach der Menstruation (PMA), wöchentliche Gewichtszunahme, volle enterale Fütterungszeit, Dauer der mechanischen Beatmung, Retinopathie Frühgeborenen (ROP), Verweildauer im Krankenhaus, Gewicht und Dauer im korrigierten Alter von drei und sechs Monaten wurden zwischen den Gruppen verglichen.Am postnatalen Tag 14 gab es keine Unterschiede zwischen den Gewichten. Die anthropometrischen Parameter und die mittleren Rektaltemperaturen der Gruppen unterschieden sich auch nach 35 Wochen PMA nicht. Es gab keine Unterschiede zwischen den Gruppen hinsichtlich der Dauer der vollständigen enteralen Fütterungszeit, der Dauer des Krankenhausaufenthalts, der Dauer der mechanischen Beatmung, der ROP und der anthropometrischen Parameter. Darüber hinaus waren die Serumwachstumshormon-, Cortisol- und Melatoninspiegel zwischen den Gruppen nach 35 Wochen PMA ähnlich.CL und CND hatten keine Vorteile gegenüber einander.

Purpose: To report the clinical outcomes of combined sparing laser photocoagulation and intravitreal bevacizumab treatment compared to conventional laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity (APROP). Methods: A medical chart review was performed on all consecutive eyes with APROP that were treated with conventional laser photocoagulation or laser photocoagulation and intravitreal bevacizumab (IVB) injection between July 2019 and August 2020. The data were recorded for time to reversal of plus disease, time to total regression of retinopathy of prematurity (ROP) after intervention, total laser spots and area, proportion of eyes with satisfactory anatomical outcomes, and adverse events. Outcomes of the two groups were compared. Results: Sixteen eyes of 8 infants with APROP were included in the analysis. Eight eyes of 4 infants received combined sparing laser photocoagulation and IVB treatment, and 8 eyes of 4 infants received conventional laser photocoagulation. All 8 eyes in the combined treatment group and 6 of 8 eyes in the conventional treatment group showed regression of ROP with a satisfactory anatomical outcome. The average time to total regression of ROP was 34 days in the combined treatment group and 56 days in the conventional treatment group ( P = .005). The number of laser spots was significantly lower in the combined treatment group ( P = .03). Conclusions: Combined sparing laser photocoagulation and IVB treatment for eyes with APROP achieved ROP regression twice as fast, had fewer laser spots, and had a satisfactory anatomical outcome in comparison to conventional laser photocoagulation. [ J Pediatr Ophthalmol Strabismus . 2021;58(5):292–297.]