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Aim: The aim of this study was to determine the frequency of ROP development in premature infants hospitalized in the neonatal intensive care unit and/or referred to the ROP Diagnostic Unit of our hospital and to emphasize the importance of cooperation between ophthalmologists and neonatologists in the treatment and follow-up of infants with ROP. Materials and Methods: The findings of 287 premature infants who were followed and treated in the neonatal intensive care unit between January 2017 and November 2022 and then referred to the ROP Diagnostic Unit were retrospectively analyzed. They were classified according to birth weight and gestational age. They were divided into 4 groups according to birth weight (under 1000 g, between 1000-1250 g, between 1250-1500 g and over 1500 g) and 3 groups according to gestational age (under 28 weeks, between 29-32 weeks and over 33 weeks). ROP development rates were determined in these groups. Those who developed retinopathy of prematurity were classified according to their stages. Results: A total of 287 premature infants (141 boys and 146 girls) were included in the study. Twenty-eight of the premature babies were Syrian (9.8%). Mean gestational age at birth was 32.34 weeks (min. 24, max. 37) and mean birth weight was 1830.12 g (min. 750 g, max. 4000 g). 34 babies (11.8%) had stage 1 ROP and 12 babies (4.1%) had stage 2 ROP. 14 babies (4.9%) had plus. Due to the rapid progression of the clinic, 20 patients (7%) with stage 2 or higher ROP and plus were referred to an advanced center with ROP treatment center certification. Conclusion: Premature babies born under 34 weeks of gestation should be examined for retinopathy of prematurity. Early diagnosis of retinopathy of prematurity is very important to prevent blindness due to ROP, even if treatment is not possible according to local conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the feasibility of implementing telescreening for retinopathy of prematurity (ROP) using the ICON GO® widefield camera operated by a non-physician healthcare professional (NPHP). We hypothesized that images captured by an NPHP are adequate to evaluate ROP changes without further examinations. Secondly, the level of agreement between independent ROP graders were evaluated based on the fundus photographs. Methods: National ROP screening criteria were gestational age (GA) < 32 weeks or birthweight (BW) < 1500 g. Exclusion criteria were children hospitalized and born outside the Capital Region and examinations not performed by an NPHP. The screenings were performed using the ICON GO®. The NPHP selected the best images for evaluation by an on-site ophthalmologist, regarding whether re-examination was necessary and if so, whether the re-examination was beneficial. Lastly, the images were re-evaluated by an independent off-site ophthalmologist. Results: A total of 415 screening sessions on 165 patients performed by an NPHP were included. Re-examination was necessary in three screening sessions and beneficial in two. The level of agreement between the on-site and off-site ophthalmologists regarding ROP screening outcome was k = 0.82, ROP stage k = 0.69, plus disease k = 0.69, and lastly ROP zone k = 0.37. Of the screened children, ninety-seven (58.8%) had no ROP at any time points, sixty-two (37.6%) had some stage of ROP not requiring treatment, and six (3.6%) received ROP treatment. Conclusions: Telemedicine screening for ROP with the ICON GO® camera performed by an NPHP was feasible with an almost-perfect agreement and negligible need for re-examinations. The approach effectively identified children needing treatment, supporting the use of telescreening in ROP management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of prematurity (ROP) is a severe condition primarily affecting premature infants with a gestational age (GA) of 30 weeks or less and a birth weight (BW) of 1500 g or less. The objective of this review is to examine the risk factors, pathogenesis, and current treatments for ROP, such as cryotherapy, laser photocoagulation, and anti-VEGF therapy, while exploring the limitations of these approaches. Additionally, this review evaluates emerging nanotherapeutic strategies to address these challenges, aiming to improve ROP management. Methods: A comprehensive literature review was conducted to gather data on the pathogenesis, traditional treatment methods, and novel nanotherapeutic approaches for ROP. This included assessing the efficacy and safety profiles of cryotherapy, laser treatment, anti-VEGF therapy, and nanotherapies currently under investigation. Results: Traditional treatments, while effective in reducing disease progression, exhibit limitations, including long-term complications, tissue damage, and systemic side effects. Nanotherapeutic approaches, on the other hand, have shown potential in offering targeted drug delivery with reduced systemic toxicity, improved ocular drug penetration, and sustained release, which could decrease the frequency of treatments and enhance therapeutic outcomes. Conclusions: Nanotherapies represent a promising advancement in ROP treatment, offering safer and more effective management strategies. These innovations could address the limitations of traditional therapies, reducing complications and improving outcomes for premature infants affected by ROP. Further research is needed to confirm their efficacy and safety in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. Methods: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). Results: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). Conclusions: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP. [ABSTRACT FROM AUTHOR]

The p21‐activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. Purpose: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. Methods: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. Results: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05). Implications for Practice and Research: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. Methods: We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. Results: ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. Conclusions: These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the quantitative vascular and structural differences in the foveal region of the eyes in retinopathy of prematurity children with or without anti-vascular endothelial growth factor (VEGF) therapy and healthy children using optical coherence tomography angiography (OCTA). Methods This cross-sectional study analyzed 75 eyes from 44 subjects, categorized into four groups: ROP children treated with Conbercept or Ranibizumab, spontaneously regressed ROP, and healthy age-matched children. Using spectral-domain OCT and OCTA, we assessed parameters like central foveal thickness (CFT), foveal avascular zone (FAZ), superficial/deep capillary plexus (SCP/DCP), and choroidal vessel density (VD) at the fovea. Correlations between foveal microvasculature, preterm status and visual acuity were evaluated. Results Significant differences were found in FAZ area, CFT, and VD-SCP (parafoveal) among the groups. The FAZ area was smaller in ROP children (with/without treatment) than in healthy counterparts(p = 0.009). CFT was higher in the Ranibizumab and spontaneously regressed groups compared to healthy ones (p = 0.043, p = 0.037), while Conbercept-treated children showed no significant difference (p = 0.886). Foveal VD trends were higher in groups A, B, and C compared to group D. FAZ area correlated negatively with CFT, VD-SCP (foveal), and VD-DCP (foveal) (p

Abstract Objective Our study aims to evaluate and compare the macular microvascular condition of the intravitreal Bevacizumab (IVB)-treated retinopathy of prematurity (ROP) cases to the preterm cases without ROP and spontaneously regressed ROPs. Methods It is a retrospective cohort of 50 premature neonates visited from 2016 to 2017 for ROP screening in Nikookari Eye Hospital and recalled for re-evaluation in 2022. These patients were classified into three groups based on their medical documents: 1. Preterm cases without ROP (PT), 2. Spontaneously regressed ROPs (SR), and 3. IVB-treated ROPs (IVB). All the included cases underwent a thorough ophthalmic exam, cyclo-refraction, Best-corrected visual acuity (BCVA) assessment, and macular optical coherence tomography angiography (OCTA). The foveal thickness, foveal avascular zone (FAZ) area, foveal, parafoveal, and perifoveal vascular density (VD) were evaluated as the quantitative variables. Results Twenty-five male and 25 female cases with a median age of 5.0 entered the study. Twenty-six eyes were evaluated in the PT group, 50 in the SR group, and 24 in the IVB group. The SR group consisted of 25 zone-2 and 25 zone-3 ROPs. In comparison, the IVB group consisted of 9 zone-1 and 15 zone-2 ROPs (p:

Retinopathy of prematurity (ROP) is a complex and unresolved problem in pediatric ophthalmology, leading to visual disability. Low birth weight and prematurity are the main risk factors, and they form the basis of clinical recommendations for screening for ROP in all children under 35 weeks of gestational age and weighing less than 2000 g. However, many researchers point to other risk factors that can be divided into maternal, prenatal and perinatal. In this review, we consider maternal diabetes mellitus as a risk factor for ROP. Changes in the retina in premature infants and mothers with diabetes mellitus have some common features, since pathological angiogenesis occurs at the basis of these diseases. In addition, diabetes is a risk factor for preterm birth, and prematurity is a leading cause of neonatal morbidity, including the development of ROP. This suggests that maternal diabetes mellitus may have both direct and indirect effects on the development of ROP. To develop predictive models, an understanding of risk factors for ROP, the pathophysiology of retinal vascular diseases, and diseases of prematurity is necessary.

Abstract Background Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman’s correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.

The purpose was to establish reference values for macular thickness, binocular vision, and stereopsis in premature infants aged 5-9 years and 10-13 years who underwent laser photocoagulation of avascular retinal zones due to retinopathy of prematurity (ROP); to assess and compare the data in an age-related perspective. Methods. Data from 24 premature infants who underwent ophthalmological examination, including optical coherence tomography, Titmus Stereo Fly Test, and the Worth 4 Dot Test, at ages 5-9 years and again at ages 10-13 years were analyzed. All children had undergone laser photocoagulation of avascular retinal zones due to ROP in infancy. Results. At ages 5-9 years, the mean central macular volume was 9.2 mm3, and the retinal thickness in the central fovea was 313.7 μm. At ages 10-13 years, the mean central macular volume was 9.1 mm3, and the retinal thickness in fovea was 320.8 μm. Normal binocular vision and stereopsis were observed in 79.2% and 33.3% of the children at the first time point, and in 87.5% and 45.8% at the second time point. Conclusions. No statistically significant difference in the central macular volume and macular thickness was detected between the two time points, (p>0.05). The thickest part of the macula was identified in the inner macula, followed by the outer macula, with the nasal quadrant being the thickest. Despite the anatomical peculiarities, high rates of binocular vision were observed at both time points, along with stereopsis at the second examination.

OBJECTIVE The objective of the study was to determine the incidence, patterns, and risk factors for the development of retinopathy of prematurity (ROP) in infants weighing >1500 g at birth. MATERIALS AND METHODS A retrospective analysis was done of the ROP screening records between April 2019 and March 2022. All the infants with birth weight >1500 g who underwent ROP screening were included. Data collected included demographic details, details of the risk factors (respiratory distress syndrome [RDS], hypoxia, anemia, septicemia, patent ductus arteriosus, congenital heart disease [CHD], i.e., atrial septal defects or ventricular septal defects, and multiple gestations), and ocular examination findings. Statistical analyses included calculation of mean, range, Chi-square test, and bivariate logistic regression for associations of risk factors with ROP. RESULTS ROP was noted in 16.6% of the 336 eyes of 168 infants. The mean birth weight and mean gestational age (GA) of the infants were 1850 ± 33 g and 33.33 weeks ± 1.71 weeks, respectively. Eighteen eyes (32.1%) had Stage I, 17 eyes (30.35%) had Stage II, and 11 eyes (19.64%) had Stage III ROP in Zone II. Aggressive ROP was seen in 8 eyes (14.28%) and stage 5 ROP in two eyes (0.59%). Male gender, GA, CHD, and RDS showed a statistically significant association with the development of ROP in these infants. CONCLUSION ROP was seen in 16.66% of our subjects. Treatment was required in 6.25% of infants. Risk factors for the development of ROP were low gestational age, male gender, the presence of RDS, and congenital heart disease.

Background: Retinopathy of prematurity (ROP) is a vaso-proliferative retinal disease which can cause blindness if not diagnosed early. The various risk factors associated with ROP other than pre mature birth and low birth weight are high flow oxygen, sepsis , multiple transfusions, multiple births, respiratory distress syndrome, apnoeic episodes, intraventricular haemorrhage. Poor antenatal care, unavailability, poor access and poorly monitored neonatal care are some of the factors contributing to increase in the number of ROP cases in developing countries. Objective: To study ROP in preterm and high risk neonates in a tertiary care hospital. To assess and record changes of ROP and the associated risk factors in the study population.. To document the staging of ROP. To determine the outcome of Retinopathy of Prematurity and the different modalities of treatment used. Material & Method: This study was conducted on 262 eyes of 131 neonates over a period of 18 months. All Pre term neonates having gestational age of less than or equal to 32 weeks and birth weight less than or equal to 1500gms and other older neonates more than 32 weeks of gestation and more than 1500gms of birth weight with risk factors for developing Retinopathy of prematurity (i.e on oxygen supplementation, Respiratory distress syndrome, Sepsis, Multiple blood transfusions, Apnoeic episodes, Intraventricular haemorrhage) , admitted and referred to our institute within the study period were screened for Retinopathy of Prematurity. Neonates observed having ROP were followed up till complete regression of ROP. Results: In our study ROP was observed in 18.32 % of neonates. There was significant relation of birth weight and gestational age with retinopathy of prematurity. Also risk factors like Respiratory distress syndrome and mechanical ventilation were significantly associated with retinopathy of prematurity. The treatment requiring cases of Retinopathy of Prematurity were 6.11% i.e 8 neonates. All the treatable cases were given ROP Laser therapy while 6 neonates were also given intra- vitreal injections of bevacizumab. Conclusion: Low birth weight, Prematurity, Respiratory distress syndrome, Mechanical ventilation were the risk factors significantly associated with ROP. Prompt screening and early diagnosis of ROP can help in reducing devastating complications and thus prevent blindness.

Abstract Background Bovine colostrum (BC) with liposomal delivery system (LDS) is a promising supplement to premature infant formula in absence of mother own milk. We propose that BC with LDS can target multiple etiological factors that threaten the developing retina, making premature infant less liable for retinopathy of prematurity (ROP). The aim of this study was to evaluate the effect of BC with LDS in the prevention of ROP. Methods This was a single center, randomized, controlled trial. Two hundred and eleven preterm infants of gestational age ≤ 32weeks were admitted to the NICU of Alexandria University Children Hospital, Egypt, and randomly allocated into either non-BC group (n = 105) or BC group (n = 106). Patients in BC group received 3.5 ml /kg/day of BC for 14 days. All patients were monitored for development of ROP, anemia, late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC), in addition to growth assessment. Multivariate binary logistic regression analysis was performed to determine factors predicting ROP development. Results Compared with the non-BC group, BC group was associated with a significantly lower incidence of ROP (5/100 vs. 16/100, respectively) with a p-value of 0.033. The administration of BC significantly decreased serum C- reactive protein (CRP) level and increased weight on day-14 of the study in comparison with the CRP level and birthweight at the beginning of study, with Cohen’s D= -0.184, D = -2.246, respectively. Patients with suspected sepsis were significantly less in BC than non-BC group, p = 0.004. Patients with BC had significantly higher hemoglobin level on day-14 than non-BC-group, with median (IQR) 12.2 (11.0–13.9) and 11.7 (10.5–12.9), respectively. BC intake is one of factors that decreased development of ROP in univariate analysis. Nevertheless, weight gain and birth weight were the most significant factors affecting ROP development in multivariate-regression model. Conclusion BC may reduce the incidence of ROP in preterm neonates aged ≤ 32 weeks. This might be due to keeping better Hb level and growth rate, as well as anti-inflammatory properties through its ability to decrease CRP level. Trial registration This work was registered on 06/13/2022 in clinicaltrial.gov with ID no.: NCT05438680 and URL: https://classic.clinicaltrials.gov/ct2/show/NCT05438680?term=NCT05438680&draw=2&rank=1 .

BACKGROUND/AIMS: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants. METHODS: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA. RESULTS: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 μm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 μm/week (95% CI: -0.9 to -0.6). CONCLUSION: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

This paper assesses the preferred treatment patterns for retinopathy of prematurity (ROP) and examine trends in anti-vascular endothelial growth factor (VEGF) use for ROP. Methods: A retrospective survey consisting of 14 questions was distributed to paediatric ophthalmology interest groups internationally. Main outcome measures included treatment patterns, proportion of anti-VEGF use in different stages of ROP; and comparison of first-line treatments as well as repeat anti-VEGF treatments. Results: Fifty-four ophthalmologists from 11 different countries responded to the survey. The number of respondents per question, except one, ranged between 50–54. Per annum, there was an average number of 394 infants screened by each respondent. Anti-VEGF was the preferred treatment method for aggressive (A)-ROP (64.1%), Type 1 ROP in zone 1 (71.7%), and Type 1 ROP in posterior zone 2 (56.6%). The majority used laser as the first-line treatment of Type 1 ROP in anterior zone 2 (73.6%) and Type 1 ROP in zone 3 (79.2%). Laser was the preferred treatment modality utilised in infants requiring repeat treatment following anti-VEGF injection. The preferred anti-VEGF agent was bevacizumab administered at a dose of 0.625 mg. Conclusions: Anti-VEGF as first-line therapy has been increasing. Anti-VEGF appears to be the first-line treatment of choice for A-ROP, Type 1 ROP in zone 1 and posterior zone 2 and laser for Type 1 ROP in anterior zone 2 and zone 3.

Purpose: To investigate peripapillary retinal nerve fiber layer (pRNFL) thickness changes in preterm children with or without retinopathy of prematurity (ROP) history compared to full-term children. Methods: A retrospective comparative cohort study assessing pRNFL thickness was completed in children aged 4–8 years. Four groups of children were included (n = 30 each group): children with a history of ROP who were treated with intravitreal bevacizumab, children with ROP who received no treatment, and preterm children without ROP compared to age- and gender-matched full-term children. Results: A total of 120 eyes from 120 children were enrolled in this study. Both treated and regressed ROP children showed a significantly thinner pRNFL in the nasal quadrant compared to full-term children (P = 0.017 and P = 0.008, respectively). The pRNFL in the superior quadrant of treated ROP children was thinner than the preterm and control groups (P = 0.015 and P = 0.023, respectively), whereas the inferior quadrant of treated ROP children was thinner than the preterm group alone (P = 0.008). The pRNFL thickness in the temporal quadrant was comparable between groups (P = 0.129). The average spatial distribution profile of pRNFL thickness in treated ROP children was significantly thinner than in the preterm group (P = 0.041). Conclusion: pRNFL thickness is significantly altered in children with a prior history of treated ROP with thinning of the nasal and superior quadrants compared to full-term children.

Objectives: To evaluate the characteristics and surgical outcomes of late-onset rhegmatogenous retinal detachment (RRD) associated with regressed retinopathy of prematurity (ROP) and the status of fellow eyes. Materials and Methods: Retrospective review of consecutive cases undergoing surgery for regressed ROP-related RRD and the fellow eyes between 2012-2022. Demographic data, fundus findings, retinal detachment characteristics, surgical procedures, and anatomic and functional outcomes were analyzed. Anatomic success was defined as retinal attachment after silicone oil removal at final follow-up. Results: Fifteen eyes of 14 patients with a history of regressed ROP underwent surgical repair for RRD at a mean age of 12 (range, 3-26) years. Primary surgical intervention yielded a 53% failure rate overall. This rate was 33% for scleral buckling (SB), 100% for pars plana vitrectomy (PPV), and 40% for combined SB-PPV surgery. Eyes with posterior cicatricial changes and/or proliferative vitreoretinopathy (PVR) demonstrated a higher tendency for recurrence. The final anatomic success rate was 73% after a mean number of 2.3 (range, 1-5) surgeries. The chances of restoring useful vision diminished with repeated surgery despite the improvement in anatomic success. In the fellow eyes, peripheral retinal pathologies were universally observed, with posterior cicatricial changes noted in 33%. Conclusion: The study reveals a significant initial failure rate in surgical treatment of cases with late-onset RRD associated with regressed ROP, particularly in eyes with posterior cicatricial changes or PVR, suggesting the need for a combined surgical approach as an initial strategy in such high-risk cases. The consistent presence of retinal abnormalities in fellow eyes calls for proactive monitoring and potential prophylactic intervention.

Abstract Background Retinopathy of prematurity (ROP) is a leading cause of avoidable blindness in children, particularly in Latin America, where hyperoxia is a significant risk factor. This study evaluated resource availability and use for administering and monitoring supplemental oxygen in Mexico. Methods In 2011, an observational study in which 32 government neonatal intensive care units (NICUs) across Mexico were visited. Data collected included occupancy, staffing levels, and equipment to deliver and monitor supplemental oxygen. Preterm infants receiving oxygen were observed. In 2023, 13 NICUs were revisited, and similar data collected. Staffing levels were benchmarked against Argentinian and US recommendations. Results In 2011, only 38% of NICUs had adequate medical and staffing levels to meet recommended cot-to-staff ratios for all shifts. Staffing ratios were worse during weekends and at night than during weekdays. Only 25.5% of cots had blenders, and 80.1% had saturation monitors. 153 infants were observed 87% of whom were being monitored. Upper and lower oxygen saturations were ≥ 96% in 53%, and ≤ 89% in 8%, respectively. Alarm settings were inadequate, as 38% and 32% of upper and lower alarms were switched off and 16% and 53% were incorrectly set, respectively. In the 13 NICUs with data from 2011 and 2023, cot-to-staff ratios deteriorated over time, and in 2023 no unit had recommended ratios for all shifts. Equipment provision did not change, with similar proportions of babies in oxygen being monitored (79% 2011; 75% 2023). Rates of hyperoxia decreased slightly from 54% in 2011 to 49% in 2023. More upper alarms were set (46% 2011; 75% 2023), but a higher proportion were incorrectly set (52% 2011; 68% 2023). Conclusions Between 2011 and 2023, cot-to-staff ratios worsened, and equipment for safe oxygen delivery and monitoring remained insufficient. Despite available monitoring equipment, oxygen saturations often exceeded recommended levels, and alarms were frequently not set or incorrectly configured. Urgent improvements are needed in healthcare workforce numbers and practices, along with ensuring adequate equipment for safe oxygen delivery.

Abstract Purpose The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II. Methods The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated. Results One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p 0.05). Conclusions Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group.

Abstract Introduction Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. Objective To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. Methods A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. Results ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. Conclusions We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.

AIM: To quantitatively assess the changes in mean vascular tortuosity (mVT) and mean vascular width (mVW) around the optic disc and their correlation with gestational age (GA) and birth weight (BW) in premature infants without retinopathy of prematurity (ROP). METHODS: A single-center retrospective study included a total of 133 (133 eyes) premature infants [mean corrected gestational age (CGA) 43.6wk] without ROP as the premature group and 130 (130 eyes) CGA-matched full-term infants as the control group. The peripapillary mVT and mVW were quantitatively measured using computer-assisted techniques. RESULTS: Premature infants had significantly higher mVT (P=0.0032) and lower mVW (P=0.0086) by 2.68 (104 cm-3) and 1.85 μm, respectively. Subgroup analysis with GA showed significant differences (P=0.0244) in mVT between the early preterm and middle to late preterm groups, but the differences between mVW were not significant (P=0.6652). The results of the multiple linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA (P=0.0211 and P=0.0006, respectively). For each day increase in GA at birth, mVT decreased by 0.1281 (104 cm-3) and for each 1 g increase in BW, mVT decreased by 0.006 (104 cm-3). However, GA (P=0.9402) and BW (P=0.7275) were not significantly correlated with mVW. CONCLUSION: Preterm birth significantly affects the peripapillary vascular parameters that indicate higher mVT and narrower mVW in premature infants without ROP. Alterations in these parameters may provide new insights into the pathogenesis of ocular vascular disease.

The medical industry is undergoing an active digital transformation, including the creation of electronic databases, cloud security systems, mobile health monitoring devices, and telemedicine tools. Artificial intelligence (AI), one of the most important technological achievements of the last decade, is gradually gaining momentum in various areas of practical medicine. The cutting edge of AI, neural networks, offers promising approaches to the improvement of clinical examination quality. The review presents data of studies focusing on the use of AI tools in the diagnosis of the most common ophthalmic diseases: diabetic retinopathy, macular degeneration, retinopathy of prematurity, glaucoma, cataracts, and ophthalmic oncology. We discuss both the advantages of neural networks in the diagnosis and monitoring of eye diseases, and outline the difficulties of their implementation, including ethical and legal conflicts.

Nigeria has the third largest incidence of premature birth, after India and China. Most babies that will require treatment for retinopathy of prematurity (ROP) have birth weight (BW) less than 1500g and gestational age (GA) less than 32 weeks, with initial eye examination within the first 30 days of life. This report aims to present the findings in three babies with vision threatening ROP that developed at less than 30 days of life. Routine screening for ROP was conducted for three babies. One was born GA 33 weeks, BW 1.6kg, screened for ROP on the 13th day of life, while the other two were a set of twins born at GA of 33 weeks, both BW 1.3kg, screened for ROP first on the 16th day of life. The twins were found CC –BY 4.0 to have arborizing vessels at the initial exam, which progressed to stage 3 pre-plus ROP by the 23rd day of life. The 3rd child had stage -3 plus disease at the first screening, warranting immediate LASER therapy. The screening criteria of Nigeria ROP group is BW ≤ 1500g or GA of ≤ 34 weeks, with the first eye examination within the first 30 days of life. These case reports show that larger babies can also develop sight threatening ROP within the first two weeks of life. There is a need for constant review of ROP screening criteria and timing based on locally available data

Abstract This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4–16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization

AIM: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP). METHODS: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information. RESULTS: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion. CONCLUSION: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

Background Methods Results Conclusions To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP).Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups.A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair.Reduced gut microbial diversity may be associated with ROP development in high‐risk preterm infants. Further research is needed to comprehend how early‐life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of retinal vascularization plays pathogenic roles in retinopathy of prematurity (ROP). Hypoxia-inducible factor 1 alpha (HIF1A) is activated by hypoxia and contributes to ROP progression. Herein, we clarified the mechanism underlying HIF1A activation in human retinal vascular endothelial cells (HRECs) under hypoxia. Methods: Protein expression was assayed by immunoblot analysis. Cell migration, microtubule formation, invasion, proliferation, and viability were detected by wound-healing, tube formation, transwell, EdU, and CCK-8 assays, respectively. Bioinformatics was used to predict the deubiquitinase-HIF1A interactions and RNA binding proteins (RBPs) bound to USP33. The impact of USP33 on HIF1A deubiquitination was validated by immunoprecipitation (IP) assay. RNA stability analysis was performed with actinomycin D (Act D) treatment. The ELAVL1/USP33 interaction was assessed by RNA immunoprecipitation experiment. Results: In hypoxia-exposed HRECs, HIF1A and USP33 protein levels were upregulated. Deficiency of HIF1A or USP33 suppressed cell migration, proliferation and microtubule formation of hypoxia-exposed HRECs. Mechanistically, USP33 deficiency led to an elevation in HIF1A ubiquitination and degradation. USP33 deficiency reduced HIF1A protein levels to suppress the proliferation and microtubule formation of hypoxia-induced HRECs. Moreover, the RBP ELAVL1 stabilized USP33 mRNA to increase USP33 protein levels. ELAVL1 decrease repressed the proliferation and microtubule formation of hypoxia-induced HRECs by reducing USP33. Conclusion: Our study identifies a novel ELAVL1/USP33/HIF1A regulatory cascade with the ability to affect hypoxia-induced pathological proliferation, angiogenesis, and migration in HRECs. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. Methods: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1–7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. Results: The ACS 1–7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1–7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. Conclusions: An ACS-to-delivery interval of 1–7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe target oxygen saturation (SpO 2) ranges used for premature infants in United States' neonatal intensive care units (NICUs) and to describe if these target SpO 2 ranges have changed in recent years. Study Design A 29-question survey focused on target SpO 2 practices and policies was distributed via the NICU medical directors listservs for the American Academy of Pediatrics Section of Neonatal-Perinatal Medicine and Pediatrix Medical Group between August and October of 2021. Results were collected via Research Electronic Data Capture (REDCap). Results We received responses representing 170 unique, levels 2, 3, and 4 NICUs from 36 states. Most NICUs (130, 78%) have recently changed their SpO 2 targets in response to target SpO 2 clinical trials. Over time, the most commonly reported target SpO 2 range has shifted from 88–92% to 90–95. Of NICUs that changed limits, the most common lower SpO 2 limits increased from 88 to 90% and the upper SpO 2 limits changed from 92 to 95%. The interquartile range for lower SpO 2 limit shifted from 85–88% to 88–90% and the IQR for upper SpO 2 limit decreased from 92–95 to 94–95%. Most NICUs had designated conditions that would allow for deviations from standard target SpO 2 ranges. These most commonly include pulmonary hypertension (152, 95%), severe bronchopulmonary dysplasia (81, 51%), and retinopathy of prematurity (51, 32%). Conclusion Oxygen saturation limits have changed over time with an overall increase in targeted SpO 2. However, there remains considerable interunit variation in SpO 2 policies. There is a need to achieve consensus to optimize clinical outcomes. Key Points What are the SpO 2 ranges in United States' NICUs? There is a shift in SpO 2 ranges for preterm infants in NICUs across United States. Variability still persists in SpO 2 ranges for preterm infants in United States' NICUs. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Prematurity is a risk factor for strabismus, but the roles of intermediate factors like retinopathy of prematurity (ROP) and neurological lesions are less understood. We aimed to identify neonatal risk factors for strabismus at age 5.5 in preterm children.Data were extracted from the étude épidémiologique sur les petits âges gestationnels 2 cohort, a French prospective population‐based study of preterm children born in 2011 with gestational age of 34 weeks or less. Strabismus was recorded during a medical interview at 5.5 years. Using a directed acyclic graph, intermediate and confounding factors were identified. Total and direct effects of gestational age on strabismus risk were analysed using generalised estimating equation.Among 2419 children assessed, 274 (52.6% male) presented strabismus at 5.5 years. The direct effect of gestational age remained significant after adjustment (p < 0.001). In the complete imputed model: maternal smoking during pregnancy (odds ratio, OR 1.8; 95% confident interval, 95% CI 1.3–2.6), neonatal severe cerebral lesions (OR 2.9, 95% CI 1.8–4.6) and severe ROP (OR 4.2, 95% CI 1.9–9.0) were independent risk factors.Special attention is needed regarding strabismus screening at age 5.5 in preterm children, even without severe cerebral lesions and ROP. Smoking cessation during pregnancy should be encouraged. [ABSTRACT FROM AUTHOR]

\nIntroduction: The aim of the study was to analyse the clinical and demographic features of infants with gestational age (GA) of 32–37 weeks and birth weight (BW) of >1,500 g who developed treatment requiring retinopathy of prematurity (ROP). Methods: Data on the infants with a GA of 32–37 weeks and BW >1,500 g who developed treatment requiring ROP (TR-ROP) were collected retrospectively from the 33 ROP centres in Turkiye. GA, BW, type of hospital, neonatal intensive care units (NICUs) level, presence of an ophthalmologist and neonatologist in the same hospital, length of stay in NICU, duration of oxygen therapy, comorbidities, type of ROP, and timing for TR-ROP development were analysed. Results: A total of366 infants were included in the study. Mean GA and BW were 33 ± 1 weeks and 1,896 ± 316 g, respectively. Duration of hospitalization was 3–4 weeks in 46.8% of them. The first ROP examination was performed at postnatal 4–5 weeks in 80.3% of infants, which was significantly later in level 2 and lower NICUs and non-university clinics. At the first ROP examination, any stage of ROP was detected in 90.9% and TR-ROP was detected in 15.3% of the infants. The mean postnatal week of TR-ROP development was 6.16 ± 2.04. Conclusion: Routine ROP screening thresholds need to be expanded in hospitals with suboptimal NICU conditions considering the development of TR-ROP in more mature and heavier preterm infants. The first ROP examination should be earlier than the fourth postnatal week. Retinopathy of prematurity (ROP) is a serious eye condition that affects premature babies, sometimes leading to blindness. Babies born at more than 32 weeks of pregnancy or weighing over 1,500 g are generally considered less at risk. However, in low- and middle-income countries where neonatal intensive care is not optimal, these bigger and more mature babies can still develop severe ROP requiring treatment (TR-ROP). This study is the first of its kind to examine how having both an eye specialist (ophthalmologist) and a baby care specialist (neonatologist) in the same hospital affects the development of TR-ROP in different regions across Turkiye. The study found that bigger babies often show signs of ROP at their first eye exam and that the condition can worsen quickly. This aggressive form of ROP, similar to a severe type called A-ROP, progresses rapidly. The findings suggest that these bigger babies need to be screened earlier than 4 weeks after birth. The study recommends expanding ROP screening programs to include larger infants, especially in developing areas of Turkiye. These recommendations could also apply to other developing countries facing similar challenges. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to determine the incidence, patterns, and risk factors for the development of retinopathy of prematurity (ROP) in infants weighing >1500 g at birth. MATERIALS AND METHODS: A retrospective analysis was done of the ROP screening records between April 2019 and March 2022. All the infants with birth weight >1500 g who underwent ROP screening were included. Data collected included demographic details, details of the risk factors (respiratory distress syndrome [RDS], hypoxia, anemia, septicemia, patent ductus arteriosus, congenital heart disease [CHD], i.e., atrial septal defects or ventricular septal defects, and multiple gestations), and ocular examination findings. Statistical analyses included calculation of mean, range, Chi-square test, and bivariate logistic regression for associations of risk factors with ROP. RESULTS: ROP was noted in 16.6% of the 336 eyes of 168 infants. The mean birth weight and mean gestational age (GA) of the infants were 1850 ± 33 g and 33.33 weeks ± 1.71 weeks, respectively. Eighteen eyes (32.1%) had Stage I, 17 eyes (30.35%) had Stage II, and 11 eyes (19.64%) had Stage III ROP in Zone II. Aggressive ROP was seen in 8 eyes (14.28%) and stage 5 ROP in two eyes (0.59%). Male gender, GA, CHD, and RDS showed a statistically significant association with the development of ROP in these infants. CONCLUSION: ROP was seen in 16.66% of our subjects. Treatment was required in 6.25% of infants. Risk factors for the development of ROP were low gestational age, male gender, the presence of RDS, and congenital heart disease. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP), a potentially blinding disease, is increasing worldwide because of the increased survival of extremely preterm and preterm infants born where oxygen monitoring and ROP screening programs are insufficient. Repeated retinal examinations are stressful for infants, and laser photocoagulation treatment for sight-threatening ROP is destructive. The use of anti-VEGF agents instead of lasers is widespread but requires a long-term follow-up because of late recurrence of the disease. In addition, the optimal anti-VEGF agent dosage and long-term systemic effects require further study. Summary: Interventions preventing ROP would be far preferable, and systemic interventions might promote better development of the brain and other organs. Interventions such as improved oxygen control, provision of fresh maternal milk, supplementation with arachidonic acid and docosahexaenoic acid, and fetal hemoglobin preservation by reducing blood sample volumes may help prevent ROP and reduce the need for treatment. Free readily available online tools to predict severe ROP may reduce unnecessary eye examinations and select, for screening, those at a high risk of needing treatment. Key Messages: Treatment warranting ROP is a sign of impaired neurovascular development in the central nervous system. Preventative measures to improve the outcomes are available. Screening can be refined using tools that can predict severe ROP. Laser treatment and anti-VEGF agents are valuable treatment modalities that may complement each other in recurrent ROP. [ABSTRACT FROM AUTHOR]

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non‐consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA‐metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC–MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12‐epoxyeicosatrienoic acid (p = 0.01), and lipid‐metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti‐inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm‐born infants. [ABSTRACT FROM AUTHOR]

This paper assesses the preferred treatment patterns for retinopathy of prematurity (ROP) and examine trends in anti-vascular endothelial growth factor (VEGF) use for ROP. Methods: A retrospective survey consisting of 14 questions was distributed to paediatric ophthalmology interest groups internationally. Main outcome measures included treatment patterns, proportion of anti-VEGF use in different stages of ROP; and comparison of first-line treatments as well as repeat anti-VEGF treatments. Results: Fifty-four ophthalmologists from 11 different countries responded to the survey. The number of respondents per question, except one, ranged between 50–54. Per annum, there was an average number of 394 infants screened by each respondent. Anti-VEGF was the preferred treatment method for aggressive (A)-ROP (64.1%), Type 1 ROP in zone 1 (71.7%), and Type 1 ROP in posterior zone 2 (56.6%). The majority used laser as the first-line treatment of Type 1 ROP in anterior zone 2 (73.6%) and Type 1 ROP in zone 3 (79.2%). Laser was the preferred treatment modality utilised in infants requiring repeat treatment following anti-VEGF injection. The preferred anti-VEGF agent was bevacizumab administered at a dose of 0.625 mg. Conclusions: Anti-VEGF as first-line therapy has been increasing. Anti-VEGF appears to be the first-line treatment of choice for A-ROP, Type 1 ROP in zone 1 and posterior zone 2 and laser for Type 1 ROP in anterior zone 2 and zone 3. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether there is a significant association between inflammatory cytokines in the tear fluid and the severity of Retinopathy of Prematurity (ROP). Study Design: Retrospective cohort study. Methods: The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment. Results: Significantly higher levels of CCL2 and vascular endothelial growth factor (VEGF) were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics' analysis. We found that combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for severe ROP (area under curve, 0.85). Conclusion: The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP. [ABSTRACT FROM AUTHOR]

To determine the effect of music applied during the ROP examination on pain, comfort, and physiological parameters in preterm infants. The sample of this prospective randomized controlled double-blind experimental study consisted of 28 preterm infants who were examined for ROP of a tertiary hospital in the Neonatal Unit. Data were collected with a Questionnaire, Physiological Parameters Observation Form (PPOF), Revised-Premature Infant Pain Profile (PIPP-R), and Premature Infant Comfort Scale (PICS). The results revealed that the crying times of the infants in the experimental group were shorter than the infants in the control group. The preterm infants in the experimental group had statistically lower PIPP-R scores during and after the procedure than the PIPP-R scores of the infants in the control group (p < 0.001) and the music applied to the preterm infants resulted in a mean decrease of 3.857 in the post-procedure and pre-procedure PIPP-R scores (p < 0.05). While there was no statistical difference between the pre-procedure and pre-procedural PICS scores of the preterm infants in the experimental and control groups (p = 0.599; p = 117), the post-procedure PICS values of the preterm infants in the experimental group were found to be lower than those of the control group (p < 0.001). It was found that the music applied to preterm infants during the ROP examination resulted in a mean decrease of 1.286 in PICS scores after the procedure and before the procedure (p < 0.05). It was determined that the music listened to during the ROP examination decreased the PIPP-R pain scores of preterm infants, had a positive effect on the PICS scores after the procedure, but did not affect the physiological parameters positively. Trial Registration: ClinicalTrials.gov Identifier: NCT05263973 [ABSTRACT FROM AUTHOR]

The purpose was to establish reference values for macular thickness, binocular vision, and stereopsis in premature infants aged 5-9 years and 10-13 years who underwent laser photocoagulation of avascular retinal zones due to retinopathy of prematurity (ROP); to assess and compare the data in an age-related perspective. Methods. Data from 24 premature infants who underwent ophthalmological examination, including optical coherence tomography, Titmus Stereo Fly Test, and the Worth 4 Dot Test, at ages 5-9 years and again at ages 10-13 years were analyzed. All children had undergone laser photocoagulation of avascular retinal zones due to ROP in infancy. Results. At ages 5-9 years, the mean central macular volume was 9.2 mm3, and the retinal thickness in the central fovea was 313.7 μm. At ages 10-13 years, the mean central macular volume was 9.1 mm3, and the retinal thickness in fovea was 320.8 μm. Normal binocular vision and stereopsis were observed in 79.2% and 33.3% of the children at the first time point, and in 87.5% and 45.8% at the second time point. Conclusions. No statistically significant difference in the central macular volume and macular thickness was detected between the two time points, (p>0.05). The thickest part of the macula was identified in the inner macula, followed by the outer macula, with the nasal quadrant being the thickest. Despite the anatomical peculiarities, high rates of binocular vision were observed at both time points, along with stereopsis at the second examination. [ABSTRACT FROM AUTHOR]

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