Changes in components of the neurovascular unit in the retina in a rat model of retinopathy of prematurity.

An impairment of cellular interactions between the elements of the neurovascular unit contributes to the onset and/or progression of retinal diseases. The present study aims to examine how elements of the neurovascular unit are altered in a rat model of retinopathy of prematurity (ROP). Neonatal rats were treated subcutaneously with the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8 to induce ROP. Morphological assessments were performed of blood vessels, astrocytes and neuronal cells in the retina. Aggressive angiogenesis, tortuous arteries and enlarged veins were observed in the retinal vasculature of KRN633-treated (ROP) rats from P14 to P28, compared to age-matched control (vehicle-treated) animals. Morphological abnormalities in the retinal vasculature showed a tendency toward spontaneous recovery from P28 to P35 in ROP rats. Immunofluorescence staining for glial fibrillary acidic protein and Pax2 (astrocyte markers) revealed that morphological changes to and a reduction in the number of astrocytes occurred in ROP rats. The developmental cell death was slightly accelerated in ROP rats; however, no visible changes in the morphology of retinal layers were observed on P35. The abnormalities in astrocytes might contribute, at least in part, to the formation of abnormal retinal blood vessels and the pathogenesis of ROP.

In-utero ultrasonography detection of fetal retinoblastoma and neonatal selective ophthalmic artery chemotherapy.

We report a case of non-familial, sporadic fetal retinoblastoma (RB) that was accidently detected at 39 weeks of gestation on pre-natal ultrasonography in left eye (OS). Post-natal examination revealed Group A and, Group D RB in right eye (OD) and OS, respectively. At 35 days, selective ophthalmic artery intra-arterial chemotherapy (IAC) was performed in OS and laser for OD. Pre-natal ultrasound and its application in RB are limited to those cases with a strong genetic predisposition. Our case was accidently detected at late gestation with no familial or genetic predisposition. In addition, this was the youngest reported case that received IAC on literature review.

Guía de práctica clínica retinopatía del prematuro / Retinopathy of prematurity clinical practice guide

Generar recomendaciones basadas en la mejor evidencia disponible acerca del manejo de personas con Retinopatía del prematuro.

Retinopatía del prematuro / Retinopathy of prematurity

INTRODUCCIÓN: después de un parto pretérmino, múltiples factores pueden provocar, primero una detención, y luego un crecimiento anormal de los vasos de la retina, y producir la retinopatía del prematuro. OBJETIVO: caracterizar el patrón clínico epidemiológico de la retinopatía del prematuro en recién nacidos menores de 35 semanas de gestación y peso al nacer inferior o igual a 1 700 g. MÉTODOS: estudio observacional, descriptivo, transversal y retrospectivo de los nacidos con menos de 35 semanas de edad gestacional y peso inferior o igual a 1 700 g, en el período comprendido entre 2006 y 2011, ambos inclusive, en el Hospital General Universitario "Dr. Enrique Cabrera Cossío". Se analizaron como factores de riesgo asociados a la retinopatía del prematuro: la edad gestacional, el peso, el sexo, la apariencia racial, la oxigenoterapia, el método de administración del oxígeno, la sepsis, el distrés respiratorio, la administración de esteroides, las transfusiones de sangre, la apnea y la hemorragia intraventricular. Se utilizó el estadígrafo chi cuadrado para verificar la posible asociación entre las variables y la presencia de retinopatía. RESULTADOS: se incluyeron en el estudio 89 pacientes. Presentó retinopatía el 20,2 % de la muestra, y el 72,2 % de los que desarrollaron retinopatía nació antes de las 32 semanas de gestación; con mayor frecuencia el peso al nacer osciló entre 1 000 y 1 500 g, y predominó el sexo masculino. En los menores de 1 000 g el 66,6 % presentó retinopatía. El 88,2 % de los que desarrollaron retinopatía recibieron ventilación con presión positiva intermitente como método de la oxigenoterapia. Un paciente (5,6 %) no recibió oxígeno y desarrolló retinopatía. Las afecciones que más se presentaron relacionadas con la prematuridad fueron el síndrome de distrés respiratorio y las infecciones. CONCLUSIONES: los factores de riesgo asociados fueron la edad gestacional, la utilización de oxígeno, el número de días con oxigenoterapia, el método de administración de este y la presencia de 2 afecciones perinatales (distrés respiratorio e infecciones).

INTRODUCTION: after a preterm delivery, a number of factors may cause first detention and then abnormal growth of the retinal vessels and give rise to retinopathy of prematurity. OBJECTIVE: to characterize the clinical and epidemiological pattern of the retinopathy of prematurity in newborns aged less than 35 weeks of gestation and birthweight equal or under 1 700 g. METHODS: retrospective, observational, descriptive and cross-sectional study of newborns with less than 35 weeks of gestational age and weighing 1 700g or less in the period of 2006 through 2011, including both years, at "Dr Enrique Cabrera Cossio" general university hospital. Risk factors associated to retinopathy of prematurity were analyzed such as gestational age, weight, sex, racial appearance, oxygen therapy, method of oxygen administration, sepsis, respiratory distress, steroid administration, blood transfusions, short of breath and intraventricle hemorrhage. Chi square statistic was used to verify the possible association between the variables and the presence of retinopathy. RESULTS: eighty nine patients were included in the study. Retinopathy affected 20.2 % of the sample and 72.2 % of those who developed retinopaty were born before 32 weeks of gestation; their birthweight frequently ranged from 1 000 to 1 500 g and boys predominated. In those neonates weighing less than 1 000 g, 66.6 % presented with retinopathy. In the group of neonates that developed retinopathy, 88.2 % were ventilated with intermittent positive pressure as method of oxygen therapy. One patient (5.6 %) did not receive oxygen and suffered retinopathy. The most frequent prematurity-related conditions were respiratory syndrome distress and infections. CONCLUSIONS: the risk factors were gestational age, oxygen supply, number of days with oxygen therapy, oxygen administration method and the existence of two perinatal conditions such as respiratory distress and infections.

Fluorescein angiography and retinal vascular development in premature infants.

OBJECTIVE: To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. METHODS: An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. RESULTS: There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. CONCLUSIONS: RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

The premature retina: a model for the in vivo study of molecular genetics?

Retinopathy of prematurity is a disease of developing blood vessels. Although it is seen predominantly in premature infants requiring life support systems to survive, it does occur in full-term infants, infants with hypoxia, cyanotic heart disease and in stillborn infants. Although oxygen has been considered to be the prime aetiologic agent, evidence for this, particularly in recent years, is not compelling. The timing of the occurrence of the disease is closely related to the conceptional age of the infant rather than weeks post birth, birth weight, gestational age at birth. In addition, the case to case similarity of the disease, as well as the diverse cell types produced in unfavourable outcomes (cicatricial ROP), point to the possibility of an in utero insult to the clone of cells giving rise to the vascular endothelium providing blood supply to the neural retina.

Retinopathy of prematurity.

ROP is a challenging disease of the decade of the 1980s. Answers, even partial answers, to many of its questions may provide information bearing on those same questions in other blinding vascular retinopathies, such as diabetes and sickle cell disease. Answers more clearly defining the role of oxygen, ventilation, antioxidants, blood transfusions, and a host of diseases of the premature infant will lead to better care of that infant. I have tried in this article to present the boundaries of the problem, a theory of its genesis and progression, and a review of the major issues to be confronted by the pediatric, ophthalmologic, and basic science communities through its recurrence today. I have tried to make it clear to the reader when I was so doing. I have used information liberally from studies both under way and in the planning stages to make the reader aware of what is being done, even if these have not yet reached fruition, for the field is a rapidly growing one. Finally, I have tried to point out directions that I believe clinical and experimental work should take on certain critical issues.

A model for the pathogenesis of retrolental fibroplasia based on the metabolic control of blood vessel development.

We postulate that the pathogenesis of retrolental fibroplasia (RLF) is related to the disruption of the normally coordinated ocular development and maturation in which there is an interplay between function, metabolism, and blood vessel development. The normal retina is avascular until the fourth month of gestation, at which time vascularization proceeds from the optic disk towards the peripheral retina. Until this time, the underlying choroidal circulation provides for full-thickness retinal oxygenation. We hypothesize that the centrifugal maturation of the retina, including the retinal photoreceptors (the major oxygen-consuming cell type of the adult retina), precedes this vascular outgrowth. The maturation of the photoreceptors and the concomitant increased oxygen consumption would make it impossible for the choroid to provide adequate full-thickness retinal oxygenation. The resulting progressive change in the inner retinal metabolism thus provides an orderly, controlled stimulus for the subsequent progression of retinal vascularization from the optic disk to the peripheral retina. Exposure of the premature neonate to abnormal oxygen levels would selectively retard inner retinal blood vessel development while the photoreceptors continue to mature and increase their oxygen consumption. Thus, when the infant is removed from abnormal oxygen, a neovascular proliferative stimulus will develop in direct relation to the mass of non-vascularized but metabolically active retina, initiating uncoordinated vessel growth in the inner retina.