Risk Of Retinopathy Of Prematurity Research Articles

70740 Impact of fundus pigmentation on retinal layer visibility on investigational bedside optical coherence tomography in preterm infants

ABSTRACT IMPACT: This study helps translate investigational bedside optical coherence tomography into improved diagnosis and care of preterm infants at risk for retinopathy of prematurity. OBJECTIVES/GOALS: In retinopathy of prematurity screening, fundus photography may be of limited quality in eyes with dark fundus pigmentation (FP). The goal of this study was to evaluate the impact of FP on overall scan quality and retinal layer visibility on investigational bedside optical coherence tomography (OCT) in preterm infants. METHODS/STUDY POPULATION: We analyzed 846 OCT scans captured prospectively from 188 eyes of 94 preterm infants enrolled in the BabySTEPS study (NCT02887157). Trained ophthalmologists, masked to OCT findings, determined FP (blond, medium, or dark). Expert graders, masked to FP, evaluated OCT images for: 1) overall OCT quality (excellent, acceptable, poor, or unusable); and 2) all age-appropriate retinal layers visible (yes or no). To assess the association of FP with OCT quality (excellent/acceptable or poor/unusable) and retinal layer visibility, we performed multivariable logistic regression modeling, adjusting for biologic and demographic confounders and correlations from repeated OCT scans and paired eyes. RESULTS/ANTICIPATED RESULTS: Mean birthweight was 964 (SD=283) grams, mean gestational age was 27.8 (SD=2.6) weeks, 48 (51%) infants were male, and 51 (54%) were non-white. On exam, 72 (38%) eyes had blond FP, 92 (49%) had medium, and 24 (13%) had dark. OCT quality was excellent or acceptable in 725 scans (86%) and all age-appropriate retinal layers were visible in 781 scans (92%). Compared to eyes with blond FP, eyes with medium and dark FP did not have higher odds of poor/unusable OCT scan quality (adjusted OR 0.87 [95% CI 0.50-1.48] and 0.49 [95% CI 0.16-1.55], respectively) or not all age-appropriate retinal layers visible on OCT (adjusted OR 1.17 [95% CI 0.39-3.51] and 0.57 [95% CI 0.15-2.20], respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: Medium and dark FP did not impact overall scan quality or age-appropriate retinal layer visibility on investigational bedside OCT in preterm infants. This study supports the feasibility of using OCT to analyze retinal microanatomy in diverse populations of preterm infants with a range of FP.

Artificial Intelligence for ROP Screening and to Assess Quality of Care: Progress and Challenges.

The goal of retinopathy of prematurity (ROP) screening is to detect the constellation of clinical signs that suggest a high risk of progression to retinal detachment so that urgent treatment can be given. At each screening episode, there are 3 considerations: whether urgent treatment is needed, whether follow-up screening is needed, and whether there is no risk of sight-threatening ROP so that the screening can stop. The decisions are based on a detailed examination of the retina focused on the severity (ie, stage), location (ie, zone), and degree of dilation and tortuosity of retinal blood vessels (ie, plus disease). If ROP is not present, the peripheral retina needs to be assessed to determine the degree of maturity of the retinal vessels; if they are mature or ROP detected earlier is definitely regressing, the screening can stop.Telemedicine with artificial intelligence (AI) image analysis could transform ROP screening, especially in settings with an insufficient supply of ophthalmologists, which can happen either because of absolute workforce shortages or when ophthalmologists choose not to offer ROP screening because of the time burden or fear of litigation. Telemedicine with AI image analysis is particularly appealing for low-resource settings in which greater exposure to risk factors, such as hyperoxia, can lead to a high frequency of treatment-requiring ROP in infants born at a gestational age (GA) of <32 weeks, and severe disease can also develop in more mature infants.1 In these settings, wider screening criteria are required, which increases the screening workload.2In this issue of Pediatrics, Campbell et al3 describe a multicenter screening program in India, the Retinopathy of Prematurity Eradication Save Our Sight program, which was done in collaboration with a United States–based international group, Imaging and Informatics in Retinopathy of Prematurity (iROP). This report describes not only the diagnostic-test accuracy of the deep learning (DL) system developed by this group (iROP DL) but, also, whether the findings can be used as an indicator to assess the quality of neonatal care.iROP DL, which quantifies plus disease, performed well, with 100% sensitivity and a high specificity compared to image grading by 3 ROP experts as the gold standard. Because missing ROP that requires treatment can have serious vision consequences, a high sensitivity is essential. The low positive predictive value is not surprising because of the low prevalence of treatment-requiring ROP.The study findings related to quality of care are particularly interesting. There were highly significant associations between the mean iROP DL score and lower birth weight and whether the unit had adequate equipment to mix and monitor oxygen. A striking finding was that only 3 of the 14 study units had enough of this equipment, which is a frequent and regrettable occurrence in a large number of units in many low- and middle-income countries.There are some important limitations of this study. iROP cannot be used to assess stage or zone, only plus disease. Whether DL and AI image analysis can achieve equally high diagnostic-test accuracy for these other prognostic signs, compared to clinical examination by indirect ophthalmoscopy or image analysis by an ROP expert, remains to be seen. In India and other low-resource settings, data on GA can be unreliable because of low attendance at antenatal care, high rates of intrauterine-growth restriction, and lack of routine prenatal ultrasound. Because GA is an important risk factor for ROP, in this study, more accurate data may have attenuated the association between iROP DL scores and quality of care. The study findings might not be generalizable to other regions. For example, the degree of retinal pigmentation, which can be greater for children born in Africa, could impact the interpretation of images.Several other groups are also working on AI for ROP screening,4–7 and once systems can provide reliable information on all of the signs needed to make a management decision at each screening episode, together with the availability of lower-cost imaging devices, the door is open for a dramatic change in how ROP screening is delivered and by whom.8In 2019, the World Health Organization and United Nations Children’s Fund recommended ROP screening and treatment as standard of care in their “Survive and Thrive” policy.9 The authors correctly indicate that integrated systems will be essential before the benefits of telemedicine and AI image analysis can be fully realized. Studies of the feasibility, acceptability, and cost-effectiveness of this approach would also be required for decision-makers and policy change within countries, with allocation of resources for implementation.

Ocular Blood Flow in Preterm Neonates: A Preliminary Report.

PurposeRetinopathy of prematurity (ROP) is a vision-threatening complication occurring in pre-term neonates. The standard of care entails regular monitoring by dilated ophthalmoscopy examinations, which entail stress and potential morbidity. In this pilot study, we used plane-wave ultrasound (PWUS) to image, measure, and assess the association of blood-flow velocities in the retrobulbar vessels with ROP stages ranging from stage 0 (immature vessels without ROP) to stage 3.MethodsBoth eyes of 14 preterm neonates at risk for ROP were examined by 18 MHz PWUS. All but two subjects had a follow-up examination. PWUS was acquired for 1.5 seconds at 3000 compound B-scans/sec. Data were postprocessed to form color-flow images and spectrograms depicting flow velocity in the central retinal artery (CRA), central retinal vein (CRV), and the short posterior ciliary arteries (SPCA). Flow parameters derived from spectrograms were compared by ROP stage.ResultsROP stage was found to correlate with flow velocities. Velocities were significantly elevated with respect to non-ROP eyes in all vessels at stage 3 and in the SPCAs at stage 2.ConclusionsPWUS measurement of blood flow may provide a quantitative, clinically important, and easily tolerated means for detecting and assessing the risk of ROP in preterm neonates. We speculate that the observed increase in flow velocity results from elevated vascular endothelial growth factor (VEGF) in ROP eyes.Translational RelevancePWUS offers a gentle, nonmydriatic method for monitoring neonates at risk for ROP that would complement ophthalmoscopy.

The U.S. National Trend for Retinopathy of Prematurity.

The use of supplemental oxygen in premature infants is essential for survival. However, its use has been associated with unintended complications. The restricted use of oxygen is associated with increased mortality and necrotizing enterocolitis (NEC), whereas its liberal use is associated with increased risk for retinopathy of prematurity (ROP). Although there is no clear consensus on the acceptable oxygen saturation range, clinicians have recently become more liberal with the use of oxygen. We aim to assess (1) the national trends for ROP in very low birth weight preterm infants, and (2) the associated trends in mortality, NEC, intraventricular hemorrhage (IVH), and length of hospital stay (LOS). We analyzed deidentified patient data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) from 2002 to 2017. All infants with gestational age ≤32 weeks and birth weight <1,500 g were included. Trends in ROP, severe ROP, mortality, NEC, IVH, severe IVH, and LOS were analyzed using Jonckheere-Terpstra test. A total of 818,945 neonates were included in the study. The overall mortality was 16.2% and the prevalence of ROP was 17.5%. There was a significant trend for increased ROP over the years (p < 0.001). Severe ROP was also significantly increased (p < 0.001). This was associated with a significant trend for increased median LOS in survived infants (p < 0.001). Mortality was significantly decreased (p < 0.001), whereas NEC and severe NEC did not change over time (p = 0.222 and p = 0.412, respectively). There is a national trend for increased ROP and severe ROP over the 16 years of the study period. This trend was associated with a significant increase in the LOS in survived infants without change in NEC. · Prevalence of ROP and severe ROP has increased in VLBW infants over the 16-year study period.. · The prevalence of NEC did not change over the same time period.. · Increased ROP and severe ROP were consistent in all three GA and BW subgroups..

Screening for Retinopathy of Prematurity in Very Preterm Children: The EPIPAGE-2 Cohort Study

Introduction: Retinopathy of prematurity (ROP) is a blinding disease that requires screening by retinal examination. Screening practices are rarely evaluated. We aimed to determine the prevalence of ROP screening in very preterm infants and individual- and center-related factors associated with ROP screening. Methods: Data were extracted from the EPIPAGE-2 cohort, a French prospective population-based study of premature births in 2011. Children born before 32 weeks’ gestation (WG) without severe malformation and alive at the recommended time for ROP screening were included. Outcome measures were achievement of ROP screening and compliance with recommended screening timeline. Individual- and center-related factors associated with both measures were studied using mixed models. Results: Among 3,077 eligible infants, 2,169 (70.5%) had a ROP screening, ranging from 96% at 24 WG to 50% at 31 WG. Large variability among units was observed. Individual characteristics associated with screening were low gestational age, low birth weight, severe bronchopulmonary dysplasia or neurological lesions, and transfer between neonatal units during the screening period. Odds of screening were higher in neonatal units using wide-angle imaging (odds ratio 2.65 [95% confidence interval 1.17–6.01]) but decreased in units without a local protocol for ROP screening (0.03 [0.01–0.09]). Among screened children, 1,641/2,169 (75.7%) were screened according to recommended timeline. Delayed screening was associated with low gestational age, severe bronchopulmonary dysplasia or necrotizing enterocolitis, and absence of local protocol for ROP screening. Discussion/Conclusions: In this large cohort study of infants born very preterm, almost one-third were not screened for ROP. Children most at risk for ROP were the best screened but often with delay. The higher compliance of neonatal units using wide-angle imaging systems supports its use.

Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity

Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants. ClinicalTrials.gov Identifier: NCT03201588.

Retinopathy of prematurity screening and retinal hemorrhages - Our experience among Indian babies.

Purpose:To evaluate the clinical characteristics of intraocular hemorrhages among babies screened for retinopathy of prematurity (ROP) and thereby their additional risk to the progression of ROP.Methods:A descriptive study was conducted at a tertiary referral hospital, which included 108 eyes of 60 neonates who were discovered to have retinal hemorrhages on retinal screening of 540 babies at risk for ROP. Maternal, obstetric, and neonatal risk factors were assessed in neonates with retinal hemorrhages. Retinal hemorrhages were assessed in terms of type, area, and relation to different retinal zones.Results:Among 540 neonates who were screened, retinal hemorrhages were found in 11.2% (n = 60 babies). Elderly primigravida mothers and spontaneous vaginal deliveries with prolonged second stage of labor were a common maternal risk factors for retinal hemorrhages. Low birth weight and preterm were fetal risk factors with neonatal retinal hemorrhages. These hemorrhages were more often bilateral (no. of babies = 48, 80%). Flame-shaped hemorrhages were more common than dot and blot ones. The majority of cases (no. of eyes = 74, 65%) resolved within 4 weeks, whereas four babies (8 eyes, 7.4%) progressed to ROP were treated with laser.Conclusion:Retinal hemorrhages in neonates are commonly associated with prolonged duration of second stage of labor, advanced maternal age, and anemia. Although not all progress to ROP, recognizing preterm and low birth weight babies with junctional hemorrhages is crucial not to delay the treatment. Regular follow-up until the clearance of hemorrhages and monitoring systemic conditions in these babies of amblyogenic age-group are required.

Development and validation of education materials to reduce childhood blindness due to retinopathy of prematurity.

BACKGROUND:Timely and appropriate follow-up appointments for infants at risk for retinopathy of prematurity (ROP) are very important to prevent blindness. Caregivers are important members of the ROP team, and their involvement is essential in ensuring optimal visual outcomes. This paper aimed to develop health information materials on ROP by a systematic process for better comprehensibility by the target audience of low literacy.MATERIALS AND METHODS:It was a methodological study conducted at the neonatal intensive care unit of a tertiary care hospital, North India. The development and validation of educational materials was conducted in six steps. The study focused on both the knowledge of the target audience and on the validation of the educational materials by experts and caregivers of ROP eligible infants.RESULTS:Most of the items (content, language, layout, motivation, and cultural appropriateness) were in either a suitable or adequate category. Only one item illustration was in the nonsuitable category. The mean final score of the leaflet after revision by experts was 9 (maximum score = 10). Regarding readability, The Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and gunning fog index were found to be 72.5, 7.4, and 6.2, respectively. The leaflet was found to be suitable for the seventh grader. The mean knowledge score of the parents was 4 (maximum score-5).CONCLUSION:The study showed satisfactory acceptance of the developed ROP information materials by caregivers and experts. A similar approach could be adopted for the development of other health information materials.

Association of -634 C/G Polymorphism at Vascular Endothelial Growth Factor Gene with Risk Retinopathy of Prematurity

Background: Retinopathy of prematurity (ROP) is a major cause of blindness in newborn infants worldwide. It is well known that neovascularization of the retina is prominent in the proliferative stages of ROP. It is suggested that vascular endothelial growth factor (VEGF) may play a role in the development of ROP. The aim of this study was to evaluate the association of the VEGF -634C/G polymorphism at VEGF with risk of ROP.&#x0D; Methods: In the study 54 neonates diagnosed with ROP and 55 healthy neonates served as controls. The VEGF -634 C/G polymorphism was genotyped by restriction fragment length polymorphism (PCR-RFLP) technique.&#x0D; Results: The CC, CG, and GG genotypes of VEGF -634C/G polymorphism were found in 33.3%, 38.9%, and 27.8% of neonates with ROP, respectively. In controls, CC, CG, and GG genotypes were seen in 43.6%, 45.4%, and 10.9%, respectively. Frequency of mutant allele (C) was 52.8% in neonates with ROP and 66.4% in healthy neonates. There was a significant difference in the distribution of VEGF -634C/G polymorphisms between cases and controls. Moreover, there was a significant association between VEGF -634C/G polymorphisms and ROP risk (OR = 3.141, 95% CI 1.115-8.851, P = 0.030).&#x0D; Conclusion: This study results revealed that VEGF -634C/G polymorphism might serve as a risk factor for development of ROP. Thus, clinicians should be aware of the ROP risk in infant with the VEGF -634C/G polymorphism and ROP risk in infants. However, large sample size and well-designed studies are necessary to validate our findings.

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.

Retinopathy of prematurity (ROP) is a blinding aberrancy of retinal vascular maturation in preterm infants. Despite delayed onset after preterm birth, representing a window for therapeutic intervention, we cannot prevent or cure ROP blindness. A natural form of ROP protection exists in the setting of early-onset maternal preeclampsia, though is not well characterized. As ischemia is a central feature in both ROP and preeclampsia, we hypothesized that angiogenesis mediators may underlie this protection. To test our hypothesis we analyzed peripheral blood expression of candidate proteins with suggested roles in preeclamptic and ROP pathophysiology and with a proposed angiogenesis function (HTRA-1, IGF-1, TGFβ-1, and VEGF-A). Analysis in a discovery cohort of 40 maternal-infant pairs found that elevated HTRA-1 (high-temperature requirement-A serine peptidase-1) was significantly associated with increased risk of ROP and the absence of preeclampsia, thus fitting a model of preeclampsia-mediated ROP protection. We validated these findings and further demonstrated a dose-response between systemic infant HTRA-1 expression and risk for ROP development in a larger and more diverse validation cohort consisting of preterm infants recruited from two institutions. Functional analysis in the oxygen-induced retinopathy (OIR) murine model of ROP supported our systemic human findings at the local tissue level, demonstrating that HtrA-1 expression is elevated in both the neurosensory retina and retinal pigment epithelium by RT-PCR in the ROP disease state. Finally, transgenic mice over-expressing HtrA-1 demonstrate greater ROP disease severity in this model. Thus, HTRA-1 may underlie ROP protection in preeclampsia and represent an avenue for disease prevention, which does not currently exist.

High-Dose Erythropoietin in Extremely Low Gestational Age Neonates Does Not Alter Risk of Retinopathy of Prematurity

Introduction: The Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial sought to determine the safety and efficacy of early high-dose Epo as a potential neuroprotective treatment. We hypothesized that Epo would not increase the incidence or severity of retinopathy of prematurity (ROP). Methods: A total of 941 infants born between 24–0/7 and 27–6/7 weeks’ gestation were randomized to 1,000 U/kg Epo or placebo intravenously for 6 doses, followed by subcutaneous or sham injections of 400 U/kg Epo 3 times a week through 32 weeks post-menstrual age. In this secondary analysis of PENUT trial data, survivors were evaluated for ROP. A modified intention-to-treat approach was used to compare treatment groups. In addition, risk factors for ROP were evaluated using regression methods that account for multiples and allow for adjustment for treatment and gestational age at birth. Results: Of 845 subjects who underwent ROP examination, 503 were diagnosed with ROP with similar incidence and severity between treatment groups. Gestational age at birth, birth weight, prenatal magnesium sulfate, maternal antibiotic exposure, and presence of heart murmur at 2 weeks predicted the development of any ROP, while being on high-frequency oscillator or high-frequency jet ventilation (HFOV/HFJV) at 2 weeks predicted severe ROP. Conclusion: Early high-dose Epo followed by maintenance dosing through 32 weeks does not increase the risk of any or severe ROP in extremely low gestational age neonates. Gestational age, birth weight, maternal treatment with magnesium sulfate, antibiotic use during pregnancy, and presence of a heart murmur at 2 weeks were associated with increased risk of any ROP. Treatment with HFOV/HFJV was associated with an increased risk of severe ROP.

Retinal vascular development in an immature retina at 33\u201334\xa0weeks postmenstrual age predicts retinopathy of prematurity

In preterm birth, the immature retina can develop a potentially blinding disorder of the eye known as retinopathy of prematurity (ROP). The vaso-proliferative phase of ROP begins at an approximate postmenstrual age (PMA) of 32 weeks. There is little or no evidence of an association between ROP development and retinal status in the early vaso-proliferative phase. We aimed to evaluate the retinal vascular findings of infants at 33–34 weeks PMA to determine their risk of ROP. We reviewed 130 serial wide-field retinal images from 65 preterm infants born before the gestational age of 31 weeks. ROP occurred more frequently in infants having a leading vascular edge within posterior Zone II. This was in contrast to normal infants, who are characterized by complete retinal vascularization up to Zone II at 34 weeks PMA. The probability of ROP development in preterm infants with retinal edge hemorrhage was 24.58 times higher than in preterm infants without retinal edge hemorrhage. Eyes with ROP that required treatment showed significantly delayed retinal vascularization accompanied by pre-plus disease. In conclusion, retinal status in the early vaso-proliferation phase might determine the risk of ROP.

Risk Calculator for Retinopathy of Prematurity Requiring Treatment.

Importance: Vascular delay that occurs early in the development of retinopathy of prematurity (ROP) is a risk factor that can be compensated by ensuring a good rate of retinal vascularization to avoid ROP that requires treatment.Background: The objective of the present study was to determine the association between ROP that requires treatment and risk factors such as the extent of the temporal avascular area of the retina and the number of days of mechanical ventilation (MV).Design: Observational retrospective case-control study.Participants: Two hundred and twenty-eight premature newborns included in the screening protocol for retinopathy of prematurity.Methods: Subjects underwent retinal examination in the 4 and 6th postnatal weeks.Main Outcome Measures: The temporal avascular area was measured in disc diameters (DD), while the MV time was measured in days of treatment.Results: Patients with a longer MV time had a higher risk of treatment (R2: 24.7, p < 0.0001; increase in risk of 8.1% for each additional day), as did those who showed greater avascular area (R2: 24.7, p < 0.0001; increase in risk of 111% for each additional DD). An online calculator system and a table are presented for calculating the risk of ROP requiring treatment as a function of these two risk factors.Conclusions and Relevance: The temporal avascular area of the retina and MV time must be taken into account in the first examination of the newborn to predict the need for ROP treatment.

Trends in Retinopathy of Prematurity over 12 Years in a Colorado Cohort

ABSTRACT Purpose To determine trends in retinopathy of prematurity (ROP) in a Colorado cohort between 2006 and 2017 and compare trends in risk factors between our cohort and statewide data. Methods A retrospective cohort study was conducted by the use of records from two registry databases: 1) an academic center’s ROP registry, and 2) vital statistics birth data from the Colorado Department of Public Health and Environment (CDPHE). ROP was categorized as severe (type 1 or type 2), low grade (not type 1 or type 2), or no ROP. Other variables included in the analyses were gestational age and birth weight at delivery, and infant mortality. Trends over time were evaluated for both registry databases using generalized linear models. Results In our ROP registry cohort of 1,267 eligible infants, 134 (10.6%) developed severe ROP and 279 (22%) developed low-grade ROP. We found no overall trend in severe ROP rates (p = .23), and a decreasing trend in rates of low-grade ROP (p < .01) over the study period. Trends in gestational age, birth weight, and mortality rates remained stable during the study period in both the ROP registry and the CDPHE cohorts. Conclusion The rate of severe ROP in our ROP registry cohort did not change over time. There was evidence of a decreasing trend in low grade ROP during the 12-year study period that was not explained by a change in the primary ROP risk factors in either the ROP registry cohort or the Colorado statewide data.

Fluorescein angiographic features post-intravitreal bevacizumab for retinopathy of prematurity: can they support rescue laser photocoagulation to the avascular retina

ObjectiveTo study the fluorescein angiography (FA) features post-intravitreal bevacizumab (post-IVB) monotherapy for retinopathy of prematurity (ROP) that may pose risk for late sight-threatening ROP and support rescue laser to the avascular retina. MethodsA retrospective review of 26 infants (47 eyes) with type 1 ROP treated with IVB monotherapy. ResultsAll infants had RetCam and FA performed at an average of 68 weeks postmenstrual age (PMA), 19 at an average 98 weeks PMA, and 10 at an average of 120 weeks PMA. Average gestational age at birth and birth weight were 24.8 weeks (standard deviation [SD] 1.91 weeks) and 683 g (SD 158.85 g), respectively. Average PMA at first IVB was 37 weeks. Eight eyes of 6 infants received repeat IVB for recurrent stage 3 at an average of 46.6 weeks PMA. All infants had inhibited retinal vasculature in zone 2, and 25 of 26 had conventional FA features, which included peripheral leakage, shunts, abnormal branching, and tangles with no late reactivation of ROP until age 3 years. Only 1 infant showed diffuse hyperfluorescence along the regressed proliferation site with a late proliferation necessitating laser to preserve vision. ConclusionsConventional FA features seen in 98% post-IVB monotherapy showed no late complications without rescue laser photocoagulation to the avascular retina.

Auto-Processed Retinal Vessel Shadow View Images From Bedside Optical Coherence Tomography to Evaluate Plus Disease in Retinopathy of Prematurity

PurposeTo describe the creation of en face retinal vessel shadow view (RVSV) optical coherence tomography (OCT) images and assess the feasibility of using these for evaluating vascular disease in preterm infants at risk for retinopathy of prematurity (ROP).MethodsIn this exploratory study, we selected images from eyes with a range of ROP vascular disease, prospectively acquired from preterm infants using an investigational, noncontact, handheld, bedside swept-source OCT. We autosegmented OCT volumes using custom infant-specific software, extracted RVSV-OCT images from volumetric data bracketed around the retinal pigment epithelium, and automontaged the resulting RVSV-OCT images. Three masked ophthalmologists graded the RVSV-OCT montages as plus, pre-plus, or neither and ranked them by relative vascular disease severity.ResultsWe selected images from 17 imaging sessions (7 plus, 4 pre-plus, 6 neither on clinical examination). On review, 15/17 (88%) RVSV-OCT montages were gradable for plus, pre-plus, or neither and all 17 montages were rankable for relative severity. Intergrader agreement for plus, pre-plus, or neither grading was good (κ, 0.67; 95% confidence interval, 0.42–0.86) and for relative severity ranking was excellent (intraclass correlation coefficient, 0.98; 95% confidence interval, 0.96–0.99).ConclusionsOur novel automatic processing method can create RVSV-OCT montages optimized for retinal vessel visualization for ROP screening. Although our data support the feasibility of using RVSV-OCT montages for ranking relative vascular disease severity, there is room for improved OCT image capture and processing methods in preterm infants screened for ROP.Translational RelevanceCreation and grading of RVSV-OCT images could eventually be integrated into an alternative method for ROP screening.

Incidence and risk factors of retinopathy of prematurity in Korle-Bu Teaching Hospital: a baseline prospective study

ObjectiveTo determine the incidence of retinopathy of prematurity (ROP) and any associated risk factors among preterm infants at the Neonatal Intensive Care Unit (NICU) of Korle-Bu Teaching Hospital (KBTH).DesignProspective study.SettingLevel...

Nuevas evidencias sobre el efecto protector de la ganancia de peso en la retinopatía del prematuro

Retinopathy of prematurity (ROP) is characterised by insufficient vascular development in the retina, and requires early treatment to avoid visual disability in severe cases. ROP is currently the second leading cause of preventable child blindness in the world. This was an observational, retrospective, case-control study including 233 preterm infants examined between 1999 and 2019. Postnatal weight gain in the first 4 weeks of life, birth weight, gestational age, mechanical ventilation, transfusion, presence of sepsis, persistence of arterial ductus, necrotising enterocolitis, intraventricular haemorrhage, or periventricular leukomalacia were found to be significantly different between the ROP groups requiring and not requiring treatment. The mean postnatal weight gain in the ROP group not requiring treatment was 12.75±5.99g/day, whereas it was 9.50±5.45g/day in the ROP group requiring treatment. The risk of developing ROP that required treatment decreased with an increase in weight gain. The risk reduction was 2.76 - 8.35% in preterm infants gaining 10g/day, and 7.17 - 12.76% in infants gaining 20g/day. The risk of developing ROP requiring treatment decreased with increasing weight gain in the first 4 weeks of life. This was applicable in infants with postnatal weight gain ≥ 14g/day. However, gestational age, birth weight, time of mechanical ventilation, and comorbidity should be taken into account when evaluating the risk of ROP requiring treatment.

Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity : PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP).

Previous studies have suggested that lower mean foetal haemoglobin (HbF) levels is associated with an increased risk for developing retinopathy of prematurity (ROP). Lower HbF levels may lead to high oxygen exposure to the developing retina thereby increasing the risk of acute ROP. In this study, we characterize the temporal relationship of HbF levels and the development of ROP. This is a single institution prospective observational cohort study. Preterm infants (born <31 weeks gestational age or <1500 g) with HbF measured at birth (cord blood), 31-, 34-, and 37-weeks post menstrual age (PMA); and at least one ROP exam, were enrolled. A total of 60 preterm infants (28 females, 47%) were enrolled. At 31-, 34-, 37-weeks PMA, infants with ROP (mild = Type 2 or less severe and severe = Type 1 ROP) had statistically lower percentages of HbF than infants with no ROP (28.2 ± 15 and 9.7 ± 2.9 vs 67.1 ± 29.6; p < 0.0001; 23.3 ± 14.7 and 32.5 vs 60.1 ± 25; p < 0.005; 31.9 ± 15.8 and 41.6 vs 60.2 ± 20.0; p < 0.0019). Infants with HbF levels in the lowest tercile at 31-weeks PMA were 7.6 times more likely to develop mild and severe ROP (95% CI 2.1-24.0, p value = 0.0006) and this risk increased to 12.3 times (95% CI: 2.6-59.0, p value = 0.0017) at 34-weeks PMA. Low HbF levels at 31- and 34-weeks PMA are associated with significantly increased risk of developing ROP. The decrease in HbF precedes the development of ROP and may be important in its pathogenesis.

Influence of polymorphisms in VEGF, TNF-α, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis

Purpose To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis. Methods An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (−460 T/C, +936 C/T, −634 G/C, and −2578 C/A), TNF-α (−308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF − 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74–0.94, POR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54–0.91, POR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67–0.95, POR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59–0.94, POR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, −634 G/C, −2578 C/A, TNF-α − 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05). Conclusions VEGF polymorphism −460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP.