Potential Role of Bilirubin in Preventing Retinopathy of Prematurity.

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

Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP: a substudy of the Mega Donna Mega trial.

Objective: The current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales (original: ROP-ActS and modified: mROP-ActS), describing increasing severity of ROP, versus the categorical variables severe ROP, stage, zone and plus disease were evaluated as discriminators of the effect of an ROP preventive treatment. Methods and analysis: The Mega Donna Mega trial investigated ROP in infants born <28-week gestational age (GA), randomised to arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation or no supplementation. Of 207 infants, 86% with finalised ROP screening were included in this substudy. ROP-ActS versus standard variables were evaluated using Fisher's non-parametric permutation test, multivariable logistic and linear regression and marginal fractional response models. Results: The AA:DHA group (n=84) and the control group (n=93) were well balanced. The maximum ROP-ActS measurement was numerically but not significantly lower in the AA:DHA group (mean: 4.0 (95% CI 2.9 to 5.0)) versus the control group (mean: 5.3 (95% CI 4.1 to 6.4)), p=0.11. In infants with any ROP, the corresponding scale measurements were 6.8 (95% CI 5.4 to 8.2) and 8.7 (95% CI 7.5 to 10.0), p=0.039. Longitudinal profiles of the scale were visually distinguished for the categories of sex and GA for the intervention versus control. Conclusions: The preventive effect of AA:DHA supplementation versus no supplementation was better discriminated by the trial's primary outcome, severe ROP, than by ROP-ActS. The sensitivity and the linear qualities of ROP-ActS require further validations on large data sets and perhaps modifications. Trial registration number: NCT03201588.

Accidentally diagnosed ocular abnormalities identified during close screening for retinopathy of prematurity.

PURPOSE: To report the variety of ocular findings which have been identified serendipitously during the screening for retinopathy of prematurity (ROP) in a tertiary referral center during seven-year period. METHODS: The charts of 1568 preterm infants who screened for ROP were reviewed retrospectively. Any ocular lesion except for ROP were noted. All infants had undergone routine ocular examination of the external eye, pupillary light reflex, anterior and posterior segment. Wide-angle digital retinal image acquisition system for any vitreoretinal pathology requiring a close follow-up had been utilized. RESULTS: Abnormal ocular findings other than ROP were diagnosed in 296 infants (19.2%). Tunica vasculosa lentis was the most common finding (25%) followed by vitreous or retinal hemorrhages (17.2%) and retinal white lesions (16.6%). Retina was the most frequently involved anatomic site. Other frequent ocular findings included optic disc cupping, congenital cataract, optic nerve hypoplasia, choroidal nevus, persistent fetal vasculature, lid hemangioma, and tilted disc. However, life-threatening pathologies such as lipemia retinalis and even retinoblastoma were also diagnosed. CONCLUSION: A duly ophthalmologic examination is mandatory in premature infants for ROP screening. During such examinations, ophthalmologists must be aware of coexisting ocular findings; which could be sight-threatening or even life-threatening.

Intravitreal bevacizumab to treat retinopathy of prematurity in 865 eyes: a study to determine predictors of primary treatment failure and recurrence.

PURPOSE: This study aimed to evaluate the rate and risk factors for primary failure and recurrence after intravitreal anti-VEGF injection in retinopathy of prematurity (ROP). METHODS: This retrospective study was performed on 865 eyes from 441 patients with retinopathy of prematurity receiving intravitreal bevacizumab from 2012 to 2019. Medical records of patients were evaluated. RESULTS: Mean gestational age (GA) and birth weight of patients were 28 ± 2 weeks and 1121 ± 312 g, respectively. Thirty-five eyes (4.04%) had a primary failure, including 18 eyes from 187 eyes in zone 1 (9.6%) and 17 eyes from 678 eyes in zone 2 (2.5%). The mean time of retreatment was 16.64 ± 13.68 days in eyes without regression ROP. The remaining 830 eyes (95.95%) were included in recurrence analysis. The recurrence occurred in 33 eyes (3.97%) of them in 20 patients, with the meantime of 77.52 days after the first treatment (IVB). The presence of plus disease, history of oxygen therapy or phototherapy, and GA less than 32 were associated with significantly increased prevalence of treatment failure. The risk factors predicting recurrence are lower birth weight, zone 1 pretreatment, history of intubation, anemia, and sepsis. CONCLUSION: Intravitreal anti-VEGF is a successful treatment for ROP with a low rate of primary failure and recurrence. Awareness of risk factors for treatment failure and recurrence may help clinicians to schedule more vigilant approach in susceptible cases.

Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial.

Importance: Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). Objective: To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03201588.

Music therapy and retinopathy of prematurity screening: using recorded maternal singing and heartbeat for post exam recovery.

OBJECTIVE: Explore a music therapy (MT) intervention to support infant recovery post retinopathy of prematurity (ROP) exam. STUDY DESIGN: Prospective, double-masked, randomized, parallel group study of 100 preterm infants exposed to MT (recorded maternal singing/heartbeat) or standard care (SC). Premature Infant Pain Profile (PIPP) measured at: baseline, during the exam, and 1 and 5 min post exam. RESULTS: Recovery PIPP scores were less with MT vs. SC, but statistical significance not achieved (Mean ± sd: MT 1 min [5.81 ± 2.93] and 5 min [3.91 ± 1.73] vs. SC 1 min [6.40 ± 2.78] and 5 min [4.76 ± 2.07], p = 0.07). Recovery PIPP sores were significantly higher with SC compared to MT when eye exams were longer (p = 0.049) or when exams were more painful (p = 0.04). CONCLUSION: Recorded maternal singing and heartbeat can support recovery post ROP exam. For longer/more painful ROP exams, MT may be more effective than SC promoting recovery post exam.

Retinopathy of prematurity: Overview and highlights of an initiative to integrate prevention, screening, and management into the public health system in India.

Purpose: In India, more than 800 special newborn care units (SNCUs) have been established since 2008 in government facilities. More preterm infants are now surviving and blindness from retinopathy of prematurity (ROP) is increasing. The aim of the Queen Elizabeth Diamond Jubilee Trust's initiative (2012-1019) was to improve the quality of neonatal care and integrate ROP services into the government health system using expertise in the government and nongovernment sector in four states in a sustainable and scalable manner. Methods: State Ministries of Health were engaged and collaboration was established between three government programs (Ministry of Health and Family Welfare, Rashtriya Bal Swasthya Karyakram, and blindness prevention) and relevant professionals. Extensive training took place and equipment was provided. Implementation was guided by a multidisciplinary National Task Force and was monitored by state coordination committees. The Task Force appointed technical expert groups to support implementation through advocacy, information, education and communication materials, operational guidelines, a competency-based training curriculum, and an online database and website. Results: Twenty-two ophthalmologists in government facilities were trained to screen for ROP and nine to treat ROP. Almost 13,500 preterm infants were screened in 17 SNCUs and 86% of the 456 infants with sight-threatening ROP were treated. An educational resource using latest pedagogy based on key domain areas for best practices for small and preterm neonates including ROP has been developed and pilot tested and is being evaluated and scaled up. Conclusion: All four states are scaling up services or have plans to scale up, and several other states have started the initiatives.

EARLY VITAMIN A SUPPLEMENTATION IMPROVES THE OUTCOME OF RETINOPATHY OF PREMATURITY IN EXTREMELY PRETERM INFANTS.

PURPOSE: This study assessed the efficacy and safety of early vitamin A (VA) supplementation to improve outcomes of retinopathy of prematurity in extremely preterm infants. METHODS: A total of 262 eligible extremely preterm infants underwent randomization; of these, 132 were assigned to the VA group and 130 to the control group. The infants were administered a solution of VA (1,500 IU/day), added to their enteral feeds as soon as minimal feeding was introduced and continued for 28 days or until discharge. RESULTS: With no adverse effects occurring, serum VA of the VA-supplemented infants on Days 14, 28, and postmenstrual 36 weeks was higher than that of the placebo group (P < 0.001). No signs of VA toxicity or increased intracranial pressure were reported. The VA group had lower unadjusted rates of Type 1 retinopathy of prematurity (1.6 vs. 6.9%, P = 0.030) and bronchopulmonary dysplasia (18.9 vs. 33.8%, P = 0.008) than the control group. Regression analysis revealed an association between serum VA levels and risk of Type 1 retinopathy of prematurity (beta = -2.37). CONCLUSION: Vitamin A supplementation reduced VA deficiency in extremely preterm infants; it was associated with a decreased incidence of Type 1 retinopathy of prematurity and may also have a positive impact on reducing bronchopulmonary dysplasia.

A pilot randomised clinical trial of 670 nm red light for reducing retinopathy of prematurity.

BACKGROUND: Photobiomodulation by 670 nm red light in animal models reduced severity of ROP and improved survival. This pilot randomised controlled trial aimed to provide data on 670 nm red light exposure for prevention of ROP and survival for a larger randomised trial. METHODS: Neonates <30 weeks gestation or <1150 g at birth were randomised to receive 670 nm for 15 min (9 J/cm2) daily until 34 weeks corrected age. DATA COLLECTED: placental pathology, growth, days of respiratory support and oxygen, bronchopulmonary dysplasia, patent ductus arteriosus, necrotising enterocolitis, sepsis, worst stage of ROP, need for laser treatment, and survival. RESULTS: Eighty-six neonates enrolled-45 no red light; 41 red light. There was no difference in severity of ROP (<27 weeks-p = 0.463; ≥27 weeks-p = 0.558) or requirement for laser treatment (<27 weeks-p = 1.00; ≥27 weeks-no laser treatment in either group). Survival in 670 nm red light treatment group was 100% (41/41) vs 89% (40/45) in untreated infants (p = 0.057). CONCLUSION: Randomisation to receive 670 nm red light within 24-48 h after birth is feasible. Although no improvement in ROP or survivability was observed, further testing into the dosage and delivery for this potential therapy are required.

Periventricular Leukomalacia in Patients With Pseudo-glaucomatous Cupping.

PURPOSE: Periventricular leukomalacia (PVL) is a structural loss of white matter pathways that carry visual information from the lateral geniculate bodies to the visual cortex. It is observed radiologically in patients with a history of prematurity and is associated with visual field (VF) defects and optic disc cupping. Advances in perinatal care have improved survival for premature babies, so many now present as adolescents and adults to comprehensive eye doctors who are unaware of the relationship of cupping, field defects, and prematurity and who may diagnose manifest or suspected normal tension glaucoma. We describe 2 such patients to raise awareness of this entity. DESIGN: Case series. METHODS: Review of clinical information of 2 patients identified during clinical practice. Charts were reviewed for gestational age, optic nerve appearance, intraocular pressure (IOP), and sequelae of prematurity. Magnetic resonance imaging (MRI), optical coherence tomography (OCT), VF, and optic disc photographs were reviewed. RESULTS: Two young patients with a history of prematurity presented with enlarged cup-to-disc ratio and normal IOP. OCT thinning was most prominent superiorly, with VF defects more notable inferior and homonymous. No progression on VF or OCT was noted in the index case over almost 4 years. CONCLUSIONS: Periventricular leukomalacia should be added to the differential diagnosis of normal tension glaucoma (NTG) when there is a history of prematurity. Careful examination of the optic nerve will assist in differentiating from NTG. Specifically, horizontal cupping with minimal or no nasal displacement of vessels, and superior optic nerve thinning with inferior VF defects, suggest PVL.

Band keratopathy in children previously treated with diode laser for type 1 retinopathy of prematurity.

Band keratopathy is a corneal degeneration caused by chronic inflammation, systemic abnormalities, or, rarely, a primary biallelic SLC4A4 mutation leading to calcium hydroxyapatite deposition in Bowman's layer. We report a series of 16 eyes of 10 children with a remote history of diode laser treated retinopathy of prematurity who developed late-onset band keratopathy without evidence of other prior risk factors. The majority of patients developed band keratopathy bilaterally. Five eyes had visually significant central band keratopathy that required treatment with disodium ethylenediaminetetracetic acid (EDTA) chelation or phototherapeutic keratectomy. Band keratopathy may be an underreported late ophthalmic complication of diode-laser treated retinopathy of prematurity.

Alteration of erythrocyte membrane polyunsaturated fatty acids in preterm newborns with retinopathy of prematurity.

Extremely preterm infants are at high risk for retinopathy of prematurity (ROP), a potentially blinding disease characterized by abnormalities in retinal vascularization. Whereas animal studies revealed that n-3 polyunsaturated fatty acids (PUFAs) may be of benefit in preventing ROP, human studies conducted on preterm infants during the 1st weeks of life showed no association between blood n-3 PUFA bioavailability and ROP incidence and/or severity, probably because of the influence of nutrition on the lipid status of infants. In the OmegaROP prospective cohort study, we characterized the erythrocyte concentrations of PUFAs in preterm infants aged less than 29 weeks gestational age (GA) without any nutritional influence. We show that GA is positively associated with the erythrocyte n-6 to n-3 PUFA ratio, and particularly with the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA), in infants with ROP. A time-dependent accumulation of AA at the expense of DHA seems to occur in utero in erythrocytes of preterm infants who will develop ROP, thus reinforcing previous data on the beneficial properties of DHA on this disease. In addition, preliminary data on maternal erythrocyte membrane lipid concentrations suggest modifications in placental transfer of fatty acids. Documenting the erythrocyte AA to DHA ratio at birth in larger cohorts might be useful to set up new prognostic factors for ROP.

Non-invasive assessment of oxidative stress in preterm infants.

Preterm newborns have an immature antioxidant defense system and are especially susceptible to oxidative stress. Resuscitation, mechanical ventilation, intermittent hypoxia and apneic episodes require frequently oxygen supplementation which leads to oxidative stress in preterm newborns. The consequences of oxidative damage are increased short and long-term morbidities, neurodevelopmental impairment and increased mortality. Oxidative stress biomarkers are determined in blood samples from preterm children during their stay in neonatal intensive care units especially for research purposes. However, there is a tendency towards reducing invasive and painful techniques in the NICU (Neonatal Intensive Care Unit) and avoiding excessive blood extractions procedures. In this paper, it has been described some studies that employed non-invasive samples to determine oxidative stress biomarkers form preterm infants in order to perform a close monitoring biomarker with a significant greater predictive value. Among these methods we describe a previously developed and validated high-performance liquid chromatography tandem mass spectrometry method that allow to accurately determine the most reliable biomarkers in biofluids, which are non-invasively and painlessly obtained.

Resultados del Programa Nacional de Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro en Argentina (2004-2016) / Results of the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity in Argentina (2004-2016)

Introducción. El Grupo ROP Argentina,a cargo del "Programa Nacional para la Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro" (ROP), se creó en 2003. Objetivos. Describir la implementación y resultados alcanzados por el programa en la efectividad, acceso y calidad en la atención de la ROP (2004-2016). Población y métodos. Estudio descriptivo, retrospectivo, de una cohorte dinámica, en instituciones adheridas al registro. Población elegible: la totalidad de recién nacidos prematuros con factores de riesgo para desarrollar ROP. Resultados. Los servicios incorporados aumentaron de 14 a 98; cubrieron 24 provincias. Los niños < 1500 g registrados en 2004fueron 956, y 2739 en 2016. El 22,7 % de estos presentó algún grado de ROP y el 7,8 % requirió tratamiento (ROP grave). La pesquisa superó el 90 % y aumentaron los tratamientos en el lugar de origen (57 %-92 %). La incidencia de casos inusuales sigue siendo elevada (17,3 % de los tratados) y aún se registran oportunidades perdidas. El uso de drogas antiangiogénicas se triplicó desde su inicio en 2011. Conclusiones. Se observan logros significativos en términos de representatividad, alcance y adherencia al programa, también en el acceso a la pesquisa y tratamiento en el lugar de origen; sin embargo, la incidencia de ROP es aún elevada. La subraya la necesidad de fortalecer aún más las acciones del programa en cuanto a servicios.

Introduction. The ROP Argentina Group was created in 2003 and is responsible for the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity (ROP) in Argentina. Objectives. To describe the program implementation and results achieved in relation to ROP care in terms of effectiveness, access, and quality (2004-2016). Population and methods. Descriptive, retrospective study with a dynamic cohort carried out in facilities that are part of the registry. Eligible population: All preterm newborn infants with risk factors for ROP. Results. Participating health care services increased from 14 to 98 and covered the 23 provinces and the Autonomous City of Buenos Aires. A total of 956 infants were born with < 1500 g in 2004 and 2739, in 2016. Of these, 22.7 % had some degree of ROP and 7.8 % required treatment (severe ROP). Vision screening exceeded 90 %, and treatments at the place of origin increased (57 %-92 %). The incidence of unusual cases is still high (17.3 % of treated cases), and missed opportunities are still recorded. The use of anti-angiogenic drugs trebled since 2011, when they started to be used. Conclusions. Significant achievements were observed in terms of program representativeness, scope, and adherence, and also in relation to screening access and treatment at the place of origin; however, the incidence of ROP is still high. The persistence of unusual cases and missed opportunities evidences deficiencies in the quality of health care and outpatient followup and underlines the need to strengthen the program actions in relation to services.

Results of the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity in Argentina (2004-2016). / Resultados del Programa Nacional de Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro en Argentina (2004-2016).

INTRODUCTION: The ROP Argentina Group was created in 2003 and is responsible for the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity (ROP) in Argentina. OBJETIVES: To describe the program implementation and results achieved in relation to ROP care in terms of effectiveness, access, and quality (2004-2016). POPULATION AND METHODS: Descriptive, retrospective study with a dynamic cohort carried out in facilities that are part of the registry. Eligible population: All preterm newborn infants with risk factors for ROP. RESULTS: Participating health care services increased from 14 to 98 and covered the 23 provinces and the Autonomous City of Buenos Aires. A total of 956 infants were born with < 1500 g in 2004 and 2739, in 2016. Of these, 22.7 % had some degree of ROP and 7.8 % required treatment (severe ROP). Vision screening exceeded 90 %, and treatments at the place of origin increased (57 %-92 %). The incidence of unusual cases is still high (17.3 % of treated cases), and missed opportunities are still recorded. The use of anti-angiogenic drugs trebled since 2011, when they started to be used. CONCLUSIONS: Significant achievements were observed in terms of program representativeness, scope, and adherence, and also in relation to screening access and treatment at the place of origin; however, the incidence of ROP is still high. The persistence of unusual cases and missed opportunities evidences deficiencies in the quality of health care and outpatient followup and underlines the need to strengthen the program actions in relation to services.

Introducción. El Grupo ROP Argentina,a cargo del "Programa Nacional para la Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro" (ROP), se creó en 2003. Objetivos. Describir la implementación y resultados alcanzados por el programa en la efectividad, acceso y calidad en la atención de la ROP (2004-2016). Población y métodos. Estudio descriptivo, retrospectivo, de una cohorte dinámica, en instituciones adheridas al registro. Población elegible: la totalidad de recién nacidos prematuros con factores de riesgo para desarrollar ROP. Resultados. Los servicios incorporados aumentaron de 14 a 98; cubrieron 24 provincias. Los niños < 1500 g registrados en 2004fueron 956, y 2739 en 2016. El 22,7 % de estos presentó algún grado de ROP y el 7,8 % requirió tratamiento (ROP grave). La pesquisa superó el 90 % y aumentaron los tratamientos en el lugar de origen (57 %-92 %). La incidencia de casos inusuales sigue siendo elevada (17,3 % de los tratados) y aún se registran oportunidades perdidas. El uso de drogas antiangiogénicas se triplicó desde su inicio en 2011. Conclusiones. Se observan logros significativos en términos de representatividad, alcance y adherencia al programa, también en el acceso a la pesquisa y tratamiento en el lugar de origen; sin embargo, la incidencia de ROP es aún elevada. La subraya la necesidad de fortalecer aún más las acciones del programa en cuanto a servicios.

Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs ω-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of ω-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. Objective: To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating ω-3 and ω-6 LC-PUFAs. Design, Setting, and Participants: This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in Göteborg, Sweden. Main Outcomes and Measures: Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. Results: Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20:4 ω-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. Conclusions and Relevance: Low postnatal levels of the ω-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction. Trial Registration: clinicaltrials.gov Identifier: NCT02760472.

Monitoring neovascularization in aggressive posterior retinopathy of prematurity using optical coherence tomography angiography.

We describe the use of optical coherence tomography angiography (OCTA) in detecting and monitoring regression of the neovascular complex (NVC) in a case of aggressive posterior retinopathy of prematurity (AP-ROP). A premature Asian Indian girl with AP-ROP underwent laser photoablation at 26 days of life. Persistent NVC at the posterior border of the lasered retinal bed was detected clinically. On en face spectral domain optical coherence tomography (SD-OCT) and OCTA, the NVC appeared as an arborizing vascular net in the superficial capillary plexus. The deep capillary plexus and outer retinal layers showed corresponding flow outlines that suggested deeper extensions of the lesion. Supplemental laser treatment of the NVC was performed. Ten days later repeat en face SD-OCT and OCTA of the identical retinal location revealed that the vascular tortuosity and dilatation had reduced and that the flow lesions in the deeper layers were undetectable. Our findings in this case suggest that the NVC in AP-ROP extends beyond the superficial retina.

Adequacy of published screening criteria for retinopathy of prematurity.

BACKGROUND: Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria. DESIGN: We collected retrospective data at a tertiary level neonatal nursery. PARTICIPANTS: Our participants were 1007 babies, born between 1997 and 2011, at <32 weeks gestational age or <1500 g birth weight (as recommended by the National Health and Medical Research Council in 1996), who had completed follow-up to full retinal vascularization, with defined presence or absence of retinopathy of prematurity. METHODS: We determined whether disease would be detected using an alternative Australian screening model (gestational age <30 weeks or birth weight <1250 g) or screening criteria utilized in developed countries with similar standards of neonatal care. MAIN OUTCOME MEASURES: Detection of retinopathy of prematurity is our main outcome. RESULTS: Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of <30 weeks gestational age or <1500 g birth weight as the criteria would still have screened these infants but would have reduced the number of infants screened by 24.9%. CONCLUSIONS: Some commonly utilized international screening criteria for retinopathy of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and '<30 weeks gestational age and/or <1500 g birth weight' appears a viable option.

[Screening ROP in the University Hospital Ostrava]. / Screening ROP ve FN Ostrava.

OBJECTIVE: To analyze the group of premature infants who were examined by an ophthalmologist in screening for ROP (retinopathy of prematurity) at the University Hospital in Ostrava. METHODS: A retrospective observational case series. We reviewed and analyzed clinical records of all the premature infants born before the 32nd gestational week examined by ophthalmologist in ROP screening at the University Hospital in Ostrava in the period from 1. 9. 2011 to 31. 8. 2012. Childrens gestational age at birth, birth weight, postconceptional age (PCA) of the child at the time of the first ocular inspection, at the time of diagnosis ROP and at the time of any intervention, possible risk factors of ROP (Apgar score in the 1st minute, duration of oxygen therapy, FiO2 (%) (percentage fraction of oxygen in the inspired gas mixture), duration of mechanical ventilation, transfusion of erythrocytes (resuspended leukodepleted), presence of sepsis / infection in the perinatal period and duration of phototherapy) were evaluated. Eye examination was performed in local anesthesia with the use of an eyelid retractor, in artificial mydriasis, using an indirect ophthalmoscope and digital imaging system RetCam 3. RESULTS: 138 premature infants with an average gestational age at birth of 29.8 weeks, average birth weight 1385 g, were included in this study. Thirty-four children (24.6 %) were diagnosed with ROP, in all cases 1st stage at the time of diagnosis. An ophthalmologist indicated and subsequently implemented intervention (cryotherapy / laser treatment) in the case of five children (14.7 %) with ROP under general anesthesia. Average duration of oxygen therapy at infants with ROP was 371 hours, in the group without ROP 84 hours. The difference between the average values was statistically significant [t (37) = -3.69, P <= 0.0007]. Average time of mechanical ventilation in the case of children with ROP were 229 hours, in the group without ROP 41 hours [t (35) = -2.99, P <0.005]. In the case of children with ROP, we noticed on average 3 transfusions of erythrocytes, in the group without ROP 1 transfusion [t (40) = -3.94, P <= 0.0003]. The average value of the Apgar score in the 1st minute of children with ROP group was 6.3 and children without ROP 7.8. The difference between the average values of Apgar score in the 1st minute was between both groups statistically significant [t (136) = 4.06, P <= 0.00008]. Sepsis / infection in the perinatal period occurred in 30 (88.2 %) children with ROP, in comparison with 46 (44.2 %) children with sepsis / infection without ROP. Average duration of phototherapy in infants with ROP was 42.4 hours, in the group without ROP 53.6 hours [t(136) = 1,21, P<= 0,2]. CONCLUSION: This study demonstrated statistically significant correlation of Apgar score in the 1st minute, duration of oxygen therapy, duration of mechanical ventilation, transfusion of erythrocytes and presence of sepsis / infection on the onset and progression of ROP at premature infants in our group. No effect of FiO2 (%) and duration of phototherapy on the onset and progression of ROP was demonstrated.

Analysis of continuous oxygen saturation data for accurate representation of retinal exposure to oxygen in the preterm infant.

Maintaining blood oxygen saturation within the intended target range for preterm infants receiving neonatal intensive care is challenging. Supplemental oxygen is believed to lead to increased risk of retinopathy of prematurity and hence managing the level of oxygen within this population is important within their care. Current quality improvement activities use coarse hourly spot readings to measure supplemental oxygen levels as associated with targeted ranges that vary based on gestational age. In this research we use Artemis, a real-time online healthcare analytics platform to ascertain if the collection of second by second data provides a better representation of retinal exposure to oxygen than an infrequent, intermittent spot reading. We show that Artemis is capable of producing more accurate information from the higher frequency data, as it includes all the episodic events in the activity of the hour, which provides a better understanding of oxygen fluctuation ranges which affect the physiological status of the infant.