RESUMEN
Purpose: To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP). Methods: This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. Results: Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0-3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1-3.9) and funisitis (OR = 1.8; 95% CI, 1.0-3.1). Conclusions: Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible.
Asunto(s)
Edad Gestacional , Placenta , Retinopatía de la Prematuridad , Humanos , Femenino , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/diagnóstico , Embarazo , Recién Nacido , Estudios Retrospectivos , Placenta/irrigación sanguínea , Masculino , Factores de Riesgo , Estudios Prospectivos , Adulto , Recién Nacido Pequeño para la Edad Gestacional , Peso al Nacer , Circulación Placentaria/fisiologíaRESUMEN
PURPOSE: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: â¯Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. STUDY POPULATION: Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. INCLUSION CRITERIA: participation in an ongoing neuropediatric study (EpoKids), written informed consent. EXCLUSION CRITERIA: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. INCLUSION CRITERIA: term birth, informed consent. EXCLUSION CRITERIA: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. OBSERVATION PROCEDURES: The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. MAIN OUTCOME MEASURES: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). RESULTS: No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups. CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.
Asunto(s)
Electrorretinografía , Eritropoyetina , Edad Gestacional , Proteínas Recombinantes , Retina , Retinopatía de la Prematuridad , Agudeza Visual , Humanos , Niño , Método Doble Ciego , Femenino , Masculino , Adolescente , Electrorretinografía/efectos de los fármacos , Agudeza Visual/fisiología , Eritropoyetina/administración & dosificación , Estudios de Seguimiento , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/tratamiento farmacológico , Retina/fisiopatología , Recién Nacido , Proteínas Recombinantes/administración & dosificación , Recien Nacido Extremadamente Prematuro/fisiología , Recien Nacido PrematuroRESUMEN
PURPOSE: To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. STUDY POPULATION: extremely or very preterm born children aged 7-15 years from an ongoing neuropediatric study (EpoKids). These had been previously randomized to receive either high-dose rhEPO or placebo perinatally. INCLUSION CRITERIA: participation in the EpoKids Study, written informed consent (IC). EXCLUSION CRITERIA: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Term-born children of comparable age were enrolled as a healthy control (HC) group. INCLUSION CRITERIA: term birth, IC. EXCLUSION CRITERIA: any ocular or visual abnormality, high refractive error. Examiners were blinded regarding intervention status until completion of all analyses. (Participants/guardians remain blinded). OBSERVATION PROCEDURES: Spectral-domain OCT scans (Heidelberg Spectralis system) and OCTA imaging (Zeiss PlexElite 9000) were obtained. Ophthalmological and orthoptic examinations excluded ocular comorbidities. MAIN OUTCOME MEASURES: OCT (central retinal thickness, CRT; total macular volume, TMV), superficial plexus OCTA (foveal avascular zone, FAZ; vessel density, VD; vessel length density, VLD) parameters and foveal hypoplasia grade according to published criteria. RESULTS: Macular vessel density parameters (VD and VLD) were significantly lower (p =0.015, CI-95: 0.01 to 0.06 and p=0.015, CI-95: 0.74 to 3.64) in the EPO group (n= 52) when compared to placebo (n=35). No other significant differences were observed between the EPO and placebo group. When comparing the intervention subgroups to HC we found six significant differences in OCT and OCTA parameters (FAZ, VD, VLD and CRT comparing HC and EPO group; FAZ and CRT when comparing HC and placebo group). CONCLUSIONS: Early high-dose rhEPO in infants born extremely or very preterm affects macular vessel density parameters compared to placebo. Premature birth (regardless of intervention status) affects retinal structure and vascular development. Our findings on macular vascular development do not contraindicate the administration of early high-dose EPO in preterm infants. For further understanding of the role of EPO on macular development and its clinical significance, future studies are needed.
Asunto(s)
Eritropoyetina , Edad Gestacional , Vasos Retinianos , Retinopatía de la Prematuridad , Tomografía de Coherencia Óptica , Humanos , Niño , Femenino , Masculino , Método Doble Ciego , Adolescente , Vasos Retinianos/diagnóstico por imagen , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/fisiopatología , Estudios de Seguimiento , Eritropoyetina/administración & dosificación , Recién Nacido , Agudeza Visual/fisiología , Proteínas Recombinantes/administración & dosificación , Recien Nacido Prematuro , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/efectos de los fármacosRESUMEN
Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.
Asunto(s)
Bevacizumab , Desarrollo Infantil , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/terapia , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/cirugía , Masculino , Femenino , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Preescolar , Estudios Transversales , Niño , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Recién Nacido , Recien Nacido Prematuro , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Destreza Motora/fisiología , Inyecciones IntravítreasRESUMEN
BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) shunt may predispose infants to retinopathy of prematurity (ROP) because of its higher preductal cardiac output and blood oxygen content, which may augment ocular oxygen delivery. METHODS: A retrospective cohort study of preterm infants, born at <27 weeks' gestation and admitted at <24h postnatal age to a large quaternary referral was conducted. The primary composite outcome was death at <32 weeks or moderate-to-severe ROP (≥stage 2 or requiring treatment) in either eye. Secondary outcomes included ROP requiring treatment, and any ROP. Univariate analysis of patient characteristics and outcomes was performed as well as logistic regression. A receiver operating characteristics curve was generated for the outcome of ROP ≥stage 2 or requiring treatment. RESULTS: A total of 91 patients were screened, of whom 86 (54 hsPDA, 32 controls) were eligible for inclusion. hsPDA patients were younger and lighter at birth and had a higher burden of hyperglycemia and respiratory illness. The rates of the composite outcome (death <32 weeks or moderate-to-severe ROP) and of any ROP were more frequent in the hsPDA group. hsPDA shunt exposure was independently associated with development of any ROP among survivors to assessment (P = 0.006). PDA cumulative exposure score of 78 (clinical equivalent = 7 days high-volume shunt exposure) predicts moderate-to-severe ROP with 80% sensitivity and 78% specificity. CONCLUSIONS: Among infants <27 weeks, hsPDA shunt is associated with increased risks of a composite outcome of death or moderate-to-severe ROP, as well as ROP of any stage. Shunt modulation as a strategy to reduce ROP represents a biologically plausible avenue for investigation.
Asunto(s)
Conducto Arterioso Permeable , Edad Gestacional , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/fisiopatología , Conducto Arterioso Permeable/fisiopatología , Estudios Retrospectivos , Recién Nacido , Femenino , Masculino , Hemodinámica/fisiología , Factores de Riesgo , Recien Nacido Prematuro , Curva ROCRESUMEN
PURPOSE: To examine potential changes in the foveal avascular zone (FAZ) during adulthood due to prematurity and retinopathy of prematurity (ROP), as assessed by measurements of the FAZ area and circularity. METHODS: The Gutenberg Prematurity Eye Study is a retrospective German cohort study with a prospective ophthalmologic examination of adults aged 18 years to 52 years, born either preterm or full-term, using spectral-domain optical coherence tomography angiography. Participants were categorized into groups based on gestational age and postnatal ROP status. The study conducted multivariable linear regression analyses to explore associations with the FAZ. RESULTS: The study cohort comprised 380 right eyes from individuals born both preterm and full-term, with an average age of 28.4 years ± 8.6 years, including 214 women. The FAZ area decreased as gestational age decreased: FAZ was 0.28 mm 2 ± 0.12 mm 2 in the control group, 0.21 ± 0.10 mm 2 at GA 33 weeks to 36 weeks, 0.18 mm 2 ± 0.10 mm 2 at GA 29 weeks to 32 weeks, 0.11 mm 2 ± 0.10 mm 2 at GA ≤28 weeks, 0.11 mm 2 ± 0.10 mm 2 in ROP without treatment, and 0.11 mm 2 ± 0.10 mm 2 in those requiring ROP treatment. In the multivariable analyses, smaller FAZ was independently associated with gestational age ( P < 0.05), increased foveal retinal thickness ( P < 0.05), and foveal hypoplasia ( P < 0.05). Moreover, no association was seen between visual acuity and FAZ. CONCLUSION: The main perinatal factor associated with a smaller FAZ in this German cohort is preterm birth, while ROP, ROP treatment, or other perinatal factors do not affect FAZ observed in adulthood. A smaller FAZ shape in preterm individuals might be an indicator of foveal hypoplasia.
Asunto(s)
Angiografía con Fluoresceína , Fóvea Central , Edad Gestacional , Vasos Retinianos , Retinopatía de la Prematuridad , Tomografía de Coherencia Óptica , Humanos , Femenino , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/fisiopatología , Masculino , Fóvea Central/patología , Fóvea Central/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Adulto Joven , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Persona de Mediana Edad , Adolescente , Recién Nacido , Agudeza Visual/fisiología , Estudios Prospectivos , Alemania/epidemiología , Recien Nacido PrematuroRESUMEN
PURPOSE: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. METHODS: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. RESULTS: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. CONCLUSIONS: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity.
Asunto(s)
Percepción de Profundidad , Edad Gestacional , Recien Nacido Prematuro , Retinopatía de la Prematuridad , Agudeza Visual , Humanos , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/cirugía , Percepción de Profundidad/fisiología , Masculino , Femenino , Estudios Transversales , Preescolar , Niño , Agudeza Visual/fisiología , Estudios de Seguimiento , Recién Nacido , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Visión Binocular/fisiología , Inyecciones Intravítreas , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Coagulación con Láser/métodosRESUMEN
PURPOSE: This study was carried out to investigate the effects of retinopathy of prematurity (ROP) and intravitreal antivascular endothelial growth factor (VEGF) injections on the corneal endothelium in the childhood period of patients who have had ROP. METHODS: The material of comparative case-control clinical study consisted of patients followed up with ROP between February 2013 and February 2023. The eyes in the study group were divided into two subgroups consisting of those who received intravitreal anti-VEGF injections (subgroup 1) and those who were followed up only (subgroup 2). Central corneal endothelial cell density (ECD), coefficient of variation (CV), central corneal thickness (CCT), and pleomorphism parameters in the childhood period were evaluated by corneal specular microscopy and compared with age-matched healthy control subjects. RESULTS: There were 84 eyes of 42 patients with ROP in the study group and 80 eyes of 40 healthy children in the control group. Mean CCT was significantly higher in subgroup 1 and the control group than in subgroup 2 (p = 0.037), and mean ECD was significantly higher in subgroup 2 than in subgroup 1 and the control group (p < 0.001). There was no significant difference between subgroup 1 and the control group in mean ECD and CCT values (p = 1.000 for both cases). CONCLUSIONS: Considering that ROP patients who received intravitreal anti-VEGF injections had more advanced-stage ROP than ROP patients who were followed up only, these findings suggest that intravitreal anti-VEGF applications in ROP cases may lead to corneal endothelial parameters similar to those of healthy eyes.
Asunto(s)
Inhibidores de la Angiogénesis , Bevacizumab , Endotelio Corneal , Inyecciones Intravítreas , Retinopatía de la Prematuridad , Factor A de Crecimiento Endotelial Vascular , Humanos , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/diagnóstico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Masculino , Femenino , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Endotelio Corneal/patología , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Estudios de Casos y Controles , Preescolar , Recuento de Células , Estudios de Seguimiento , Lactante , Recién Nacido , Niño , Edad Gestacional , Ranibizumab/administración & dosificación , Ranibizumab/uso terapéuticoRESUMEN
There is limited information on functional low vision (FLV) in Latin America, especially in individuals under 50 years of age. In the present study, we retrospectively evaluated the medical records of 1393 consecutive subjects seen at a Brazilian tertiary rehabilitation service, from February 2009 to June 2016. We collected sociodemographic, clinical data, and information on optical aids and spectacle prescription. Subjects were divided into three age groups: 0 to 14 years old (children), 15 to 49 years old (young adults), and 50 years or older (older adults). The main etiologies leading to FLV in children were cerebral visual impairment (27.9%), ocular toxoplasmosis (8.2%), and retinopathy of prematurity (7.8%). In young adults, retinitis pigmentosa (7.4%) and cone/rod dystrophy (6.5%) were the most frequent, while in older adults, age-related macular degeneration (25.3%) and diabetic retinopathy (18.0%) were the leading causes. Our results indicate that preventable diseases are important causes of FLV in children in the area, and proper prenatal care could reduce their burden. The increasing life expectancy in Latin America and the diabetes epidemic are likely to increase the demand for affordable, people-centered rehabilitation centers, and their integration into health services should be planned accordingly.
Asunto(s)
Retinopatía de la Prematuridad/epidemiología , Toxoplasmosis Ocular/epidemiología , Trastornos de la Visión/epidemiología , Baja Visión/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Niño , Preescolar , Distrofias de Conos y Bastones/epidemiología , Distrofias de Conos y Bastones/fisiopatología , Retinopatía Diabética/epidemiología , Retinopatía Diabética/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Degeneración Macular/epidemiología , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Retinitis Pigmentosa/epidemiología , Retinitis Pigmentosa/fisiopatología , Retinopatía de la Prematuridad/fisiopatología , Centros de Atención Terciaria , Toxoplasmosis Ocular/fisiopatología , Trastornos de la Visión/fisiopatología , Baja Visión/fisiopatología , Adulto JovenRESUMEN
Importance: Children born preterm (<37 weeks' gestation) have a higher risk of visual impairment and ocular morbidities compared peers born at full term. However, the long-term ocular sequelae in adulthood for those born extremely preterm (EP), who have the highest risk of neonatal retinopathy, are unknown. Objective: To evaluate visual function and ocular morbidity in young adults born EP compared with controls born full term. Design, Setting, and Participants: This prospective cohort study of a geographically based birth cohort in the UK and Ireland born from March 1 through December 31, 1995, included 128 participants aged 19 years (born at 22-25 weeks' gestation) and 65 age-matched controls born at full term. Statistical analysis was performed from March 1, 2020, to November 26, 2021. Exposures: Participants underwent eye examinations as part of a comprehensive outcome evaluation. Main Outcomes and Measures: Best-corrected visual acuity, refractive status, contrast sensitivity, color vision, prevalence of strabismus and nystagmus, and patient-reported visual function, measured using the Health Utilities Index Mark 3. Results: The study comprised 128 participants (256 eyes; 68 female participants [53%]; mean [SD] age, 19.3 [0.5] years) and 65 age-matched controls born at full term (130 eyes; 40 female participants [62%]; mean [SD] age, 19.2 [0.5] years). Compared with control eyes, the mean (SD) best-corrected visual acuity among eyes in the EP group was significantly worse (monocular vision: -0.06 [0.14] logMAR in the control group vs 0.14 [0.38] logMAR in the EP group; P < .001; binocular vision: -0.14 [0.15] logMAR in the control group vs 0.06 [0.37] logMAR in the EP group; P < .001). Participants in the EP group had a significantly higher prevalence of strabismus (36% [46 of 127] vs 0%; P < .001), abnormal ocular motility (15% [19 of 125] vs 0%; P < .001), and nystagmus (13% [16 of 127] vs 0%; P < .001) than the control group. No significant differences between participants in the EP group and controls were observed for refractive error, contrast sensitivity, color vision, or patient-reported visual function. Among the participants in the EP group, 48% of eyes (120 of 250) had no retinopathy of prematurity (ROP), 39% (98 of 250) had ROP not requiring neonatal treatment, and 13% (32 of 250) received cryotherapy or laser ablation for ROP. Within the EP group, there was no significant difference in binocular visual function parameters, prevalence of ocular morbidity, and patient-reported visual function by neonatal ROP status. Conclusions and Relevance: Extreme prematurity is associated with an increased prevalence of visual and ocular deficits in young adulthood; this study suggests that, for individuals born EP, visual and ocular deficits appear to be partially independent of ROP status in the neonatal period but reports similar overall visual function.
Asunto(s)
Oftalmopatías/epidemiología , Recien Nacido Extremadamente Prematuro , Estudios de Casos y Controles , Ojo/fisiopatología , Oftalmopatías/etiología , Femenino , Edad Gestacional , Humanos , Irlanda/epidemiología , Masculino , Medición de Resultados Informados por el Paciente , Prevalencia , Estudios Prospectivos , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/fisiopatología , Reino Unido/epidemiología , Pruebas de Visión , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety. METHODS: The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. RESULTS: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. CONCLUSION: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.
Asunto(s)
Bevacizumab/administración & dosificación , Coagulación con Láser/métodos , Trastornos del Neurodesarrollo/diagnóstico , Ranibizumab/administración & dosificación , Retinopatía de la Prematuridad/terapia , Inhibidores de la Angiogénesis/administración & dosificación , Método Doble Ciego , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Recién Nacido , Inyecciones Intravítreas , Masculino , Estudios Prospectivos , Retinopatía de la Prematuridad/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Factor A de Crecimiento Endotelial VascularRESUMEN
Throughout the central nervous system, astrocytes adopt precisely ordered spatial arrangements of their somata and arbors, which facilitate their many important functions. Astrocyte pattern formation is particularly important in the retina, where astrocytes serve as a template that dictates the pattern of developing retinal vasculature. Thus, if astrocyte patterning is disturbed, there are severe consequences for retinal angiogenesis and ultimately for vision - as seen in diseases such as retinopathy of prematurity. Here we discuss key steps in development of the retinal astrocyte population. We describe how fundamental developmental forces - their birth, migration, proliferation, and death - sculpt astrocytes into a template that guides angiogenesis. We further address the radical changes in the cellular and molecular composition of the astrocyte network that occur upon completion of angiogenesis, paving the way for their adult functions in support of retinal ganglion cell axons. Understanding development of retinal astrocytes may elucidate pattern formation mechanisms that are deployed broadly by other axon-associated astrocyte populations.
Asunto(s)
Astrocitos/fisiología , Retina/crecimiento & desarrollo , Retina/fisiología , Animales , Axones/fisiología , Muerte Celular , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Humanos , Neovascularización Fisiológica , Fibras Nerviosas/fisiología , Retina/citología , Retina/embriología , Células Ganglionares de la Retina/fisiología , Vasos Retinianos/embriología , Vasos Retinianos/crecimiento & desarrollo , Vasos Retinianos/fisiología , Retinopatía de la Prematuridad/patología , Retinopatía de la Prematuridad/fisiopatologíaRESUMEN
Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease, initiated by delayed retinal vascular growth after premature birth. In the majority of cases, ROP resolves spontaneously; however, a history of ROP may increase the risk of long-term visual problems. In this study, we evaluated the endothelial function of retinal blood vessels in adult rats with a history of ROP. ROP was induced in rats by subcutaneous injection of a vascular endothelial growth factor receptor tyrosine kinase inhibitor (KRN633) on postnatal day (P) 7 and P8. On P56, vasodilator responses to acetylcholine, GSK1016790A (an activator of transient receptor potential vanilloid 4 channels), NOR3 (a nitric oxide [NO] donor), and salbutamol (a ß2-adrenoceptor agonist) were assessed. Compared to age-matched controls, retinal vasodilator responses to acetylcholine and GSK1016790A were attenuated in P56 rats with a history of ROP. No attenuation of acetylcholine-induced retinal vasodilator response was observed under inhibition of NO synthase. Retinal vasodilator responses to NOR3 and salbutamol were unaffected. These results suggest that the production of and/or release of NO is impaired in retinal blood vessels in adult rats with a history of ROP. A history of ROP might increase the risk of impaired retinal circulation in adulthood.
Asunto(s)
Endotelio Vascular/fisiopatología , Vasos Retinianos/fisiopatología , Retinopatía de la Prematuridad/fisiopatología , Vasodilatación , Acetilcolina/farmacología , Albuterol/farmacología , Animales , Animales Recién Nacidos , Circulación Sanguínea/efectos de los fármacos , Femenino , Leucina/análogos & derivados , Leucina/farmacología , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Embarazo , Ratas Sprague-Dawley , Sulfonamidas/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.
Asunto(s)
Plaquetas/metabolismo , Retinopatía de la Prematuridad/fisiopatología , Anemia/complicaciones , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Inflamación/fisiopatología , Masculino , Recuento de Plaquetas/métodos , Estudios Retrospectivos , Trombocitopenia/complicacionesRESUMEN
To study the anatomical success rate of light amplification by stimulated emission of radiation (LASERS) as first line of management in stage 4A retinopathy of prematurity (ROP). Observational, prospective case series of 14 eyes of 7 babies (males: 3, females: 4) with stage 4A ROP who underwent LASERS for stage 4A between January 2018 and July 2019. Gestation age (GA), birth weight (BW), and post-menstrual age (PMA) at which laser was done were noted in all cases. A number of clock hours of detachment at the time of presentation were noted in all babies. All babies were followed up up to 6 months after laser for any recurrence. Success was defined as complete regression of disease without the need of any other modality of treatment like anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy. A total of 92.85% (13/14) showed complete regression of disease. One eye progressed to stage 4B ROP warranting lens-sparing vitrectomy (LSV). LASERS is an effective method of management without any need of anti-VEGF or surgical intervention even in babies with stage 4A ROP.
Asunto(s)
Retinopatía de la Prematuridad/cirugía , Peso al Nacer , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Cristalino/cirugía , Masculino , Retinopatía de la Prematuridad/fisiopatología , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual , VitrectomíaRESUMEN
PURPOSE: To report anatomical and visual outcomes and potential prognostic factors with microincision vitrectomy surgery in Stage 5 retinopathy of prematurity. METHODS: The medical records of premature babies who underwent microincision vitrectomy surgery for Stage 5 retinopathy of prematurity using 23G, 25G, or 27G instrumentation and had a minimum follow-up of 6 weeks were, retrospectively, analyzed. Primary outcome measures were anatomical success at last follow-up defined as retinal attachment at the posterior pole and visual outcomes. Potential risk factors and complications influencing anatomical outcomes were also analyzed. RESULTS: One hundred seventy eyes of 115 infants underwent lensectomy and vitrectomy with microincision vitrectomy surgery. After a mean follow-up of 30.59 ± 33.24 weeks, anatomical success was achieved in 56 eyes (33.7%) of 166 eyes that had a minimum follow-up of 6 weeks. Occurrence of vitreous hemorrhage was more with 23 gauge (62.27%) as compared to 25 gauge (37.73%) (P = 0.024). With increase in age with each week, the probability of achieving anatomical success was found to be significantly more (odds ratio 1.030; confidence interval = 1.010-1.060; P = 0.008). Presence of anterior segment pathology was associated with poor anatomical outcomes (odds ratio 2.480; confidence interval = 1.190-5.160; P = 0.010). Seventeen children with attached retina had a follow-up of 14 months-5 years, of which ambulatory vision was recorded in five eyes and the ability to identify objects close to face in 12 eyes. CONCLUSION: Although surgery for Stage 5 retinopathy of prematurity is challenging, anatomical success can be seen in one-third of cases with microincision vitrectomy surgery. Visual prognosis may be limited but still beneficial.
Asunto(s)
Microcirugia/métodos , Retinopatía de la Prematuridad/diagnóstico , Agudeza Visual , Vitrectomía/métodos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: To assess the association between glycemic variability (GV) and Type 1 retinopathy of prematurity (ROP) in infants with birth weights of less than 1,251 g. METHODS: A case-control study of infants with birth weights of less than 1,251 g who developed Type 1 ROP (n = 20) was conducted. Controls had a less severe ROP or no eye disease and were individually matched for gestational age and birth weight (n = 40). Odds ratios of ROP were calculated based on multiple factors including oxygen exposure, respiratory support, incidence of hyperglycemia, and GV. For glucose measurements, a continuous glucose monitoring system was used. RESULTS: There were no significant differences in gender, antenatal steroid administration, severity of illness, and Apgar score. Univariate analyses suggest increased risk for the development of Type 1 ROP based on incidence of intraventricular hemorrhage Grade 3 or 4 (P = 0.048), duration of oxygen exposure (P = 0.003), incidence of hyperglycemia over 150 mg/dL (P = 0.01), and GV according to significantly higher SD (P = 0.002), coefficient of variation (P = 0.001), and mean amplitude of glucose excursion (P = 0.008). Using a multiple regression model, increased risk of Type 1 ROP was only found to be associated with duration of oxygen exposure and higher GV. CONCLUSION: Our study demonstrates a relationship between GV and the development of severe ROP.
Asunto(s)
Glucemia/metabolismo , Índice Glucémico/fisiología , Retinopatía de la Prematuridad/fisiopatología , Peso al Nacer , Automonitorización de la Glucosa Sanguínea , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Coagulación con Láser , Masculino , Oportunidad Relativa , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/cirugía , Factores de RiesgoRESUMEN
INTRODUCTION: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. OBJECTIVE: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. METHODS: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. RESULTS: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. CONCLUSIONS: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.
Asunto(s)
Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Retina/fisiopatología , Retinopatía de la Prematuridad/tratamiento farmacológico , Agudeza Visual , Inhibidores de la Angiogénesis/administración & dosificación , Animales , Modelos Animales de Enfermedad , Inyecciones Intravítreas , Ratones , Ratones Endogámicos C57BL , Oxígeno/toxicidad , Retina/efectos de los fármacos , Retinopatía de la Prematuridad/inducido químicamente , Retinopatía de la Prematuridad/fisiopatología , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To evaluate foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity who had laser treatment in one eye and spontaneously regressed retinopathy of prematurity in the fellow eye. METHODS: Totally, 17 children (34 eyes) with a history of asymmetric course of acute Zone II retinopathy of prematurity were assessed. Data on best-corrected visual acuity, refractive status, axial length, anterior chamber depth, and optical coherence tomography angiography findings were analyzed between treated and non-treated fellow eyes. RESULTS: Treated eyes were more myopic than non-treated eyes (mean, -0.09 ± 1.86 diopters vs mean, 0.07 ± 0.98 diopters, p = 0.026). Compared to non-treated eyes, treated eyes had shallower anterior chamber depth (mean, 3.27 ± 0.24 mm vs mean, 3.55 ± 0.19 mm, p = 0.02). No significant difference was observed regarding optical coherence tomography angiography parameters between two eyes of the children. The mean central foveal thickness was found to be higher in treated eyes than in non-treated eyes (297.46 ± 22.03 vs 275.55 ± 18.45, p = 0.009). Higher number of laser spots were associated with decreased parafoveal superficial capillary plexus vessel density (r = -0.56, p = 0.02) and increased central foveal thickness (r = 0.62, p = 0.008). CONCLUSION: Our results revealed no difference in optical coherence tomography angiography parameters between laser-treated and non-treated eyes in children with asymmetric involvement of Zone II retinopathy of prematurity except for a higher central foveal thickness in laser-treated eyes. Treated eyes were more myopic than the non-treated eyes. Number of laser applications during treatment had an impact on parafoveal superficial capillary plexus vessel density.
Asunto(s)
Fóvea Central/diagnóstico por imagen , Miopía/diagnóstico , Refracción Ocular/fisiología , Retinopatía de la Prematuridad/diagnóstico , Agudeza Visual , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Recién Nacido , Masculino , Microvasos/diagnóstico por imagen , Miopía/etiología , Miopía/fisiopatología , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/fisiopatología , Tomografía de Coherencia Óptica/métodosRESUMEN
Purpose: Retinopathy of prematurity (ROP) is a severe complication of premature infants, leading to vision loss when untreated. Presently, the molecular mechanisms underlying ROP are still far from being clearly understood. This study sought to investigate whether thyroid hormone (TH) signaling contributes to the neuropathology of ROP using the mouse model of ROP to evaluate longitudinal photoreceptor function. Methods: Animals were exposed to hyperoxia from P7 to P12 to induce retinopathy, thereafter the animals were returned to room air (normoxia). The thyroid-activating enzyme type 2 deiodinases (Dio2) knockout (KO) mice and the littermate controls that were exposed to hyperoxia or maintained in room air and were then analyzed. The retinal function was evaluated using electroretinograms (ERGs) at three and seven weeks followed by histologic assessments with neuronal markers to detect cellular changes in the retina. Rhodopsin protein levels were measured to validate the results obtained from the immunofluorescence analyses. Results: In the ROP group, the photoreceptor ERG responses are considerably lower both in the control and the Dio2 KO animals at P23 compared to the non-ROP group. In agreement with the ERG responses, loss of Dio2 results in mislocalized cone nuclei, and abnormal rod bipolar cell dendrites extending into the outer nuclear layer. The retinal function is compromised in the adult Dio2 KO animals, although the cellular changes are less severe. Despite the reduction in scotopic a-wave amplitudes, rhodopsin levels are similar in the adult mice, across all genotypes irrespective of exposure to hyperoxia. Conclusions: Using the mouse model of ROP, we show that loss of Dio2 exacerbates the effects of hyperoxia-induced retinal deficits that persist in the adults. Our data suggest that aberrant Dio2/TH signaling is an important factor in the pathophysiology of the visual dysfunction observed in the oxygen-induced retinopathy model of ROP.