RESUMEN
This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.
Asunto(s)
Inhibidores de la Angiogénesis , Ranibizumab , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/patología , Ranibizumab/administración & dosificación , Ranibizumab/uso terapéutico , Masculino , Femenino , Recién Nacido , Estudios Retrospectivos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Resultado del Tratamiento , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/patología , Inyecciones Intravítreas , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Lactante , Recien Nacido PrematuroRESUMEN
BACKGROUND: Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly. Utilizing mouse models of both oxygen-induced retinopathy (OIR) and BPD, this study was designed to test the hypothesis that hyperoxia induces ASC speck formation, which leads to microglial activation and retinopathy, and that inhibition of ASC speck formation by a humanized monoclonal antibody, IC100, directed against ASC, will ameliorate microglial activation and abnormal retinal vascular formation. METHODS: We first tested ASC speck formation in the retina of ASC-citrine reporter mice expressing ASC fusion protein with a C-terminal citrine (fluorescent GFP isoform) using a BPD model that causes both lung and eye injury by exposing newborn mice to room air (RA) or 85% O2 from postnatal day (P) 1 to P14. The retinas were dissected on P14 and retinal flat mounts were used to detect vascular endothelium with AF-594-conjugated isolectin B4 (IB4) and citrine-tagged ASC specks. To assess the effects of IC100 on an OIR model, newborn ASC citrine reporter mice and wildtype mice (C57BL/6 J) were exposed to RA from P1 to P6, then 75% O2 from P7 to P11, and then to RA from P12 to P18. At P12 mice were randomized to the following groups: RA with placebo PBS (RA-PBS), O2 with PBS (O2-PBS), O2 + IC100 intravitreal injection (O2-IC100-IVT), and O2 + IC100 intraperitoneal injection (O2-IC100-IP). Retinal vascularization was evaluated by flat mount staining with IB4. Microglial activation was detected by immunofluorescence staining for allograft inflammatory factor 1 (AIF-1) and CD206. Retinal structure was analyzed on H&E-stained sections, and function was analyzed by pattern electroretinography (PERG). RNA-sequencing (RNA-seq) of the retinas was performed to determine the transcriptional effects of IC100 treatment in OIR. RESULTS: ASC specks were significantly increased in the retinas by hyperoxia exposure and colocalized with the abnormal vasculature in both BPD and OIR models, and this was associated with increased microglial activation. Treatment with IC100-IVT or IC100-IP significantly reduced vaso-obliteration and intravitreal neovascularization. IC100-IVT treatment also reduced retinal microglial activation, restored retinal structure, and improved retinal function. RNA-seq showed that IC100 treatment corrected the induction of genes associated with angiogenesis, leukocyte migration, and VEGF signaling caused by O2. IC100 also corrected the suppression of genes associated with cell junction assembly, neuron projection, and neuron recognition caused by O2. CONCLUSION: These data demonstrate the crucial role of ASC in the pathogenesis of OIR and the efficacy of a humanized therapeutic anti-ASC antibody in treating OIR mice. Thus, this anti-ASC antibody may potentially be considered in diseases associated with oxygen stresses and retinopathy, such as ROP.
Asunto(s)
Oxígeno , Retinopatía de la Prematuridad , Animales , Retinopatía de la Prematuridad/patología , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/metabolismo , Ratones , Anticuerpos Monoclonales Humanizados/farmacología , Ratones Endogámicos C57BL , Animales Recién Nacidos , Modelos Animales de Enfermedad , Humanos , Hiperoxia/patología , Hiperoxia/complicaciones , Retina/patología , Retina/metabolismo , Retina/efectos de los fármacos , Proteínas Adaptadoras de Señalización CARD/metabolismo , Ratones Transgénicos , Neovascularización Retiniana/patología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/tratamiento farmacológico , Microglía/patología , Microglía/metabolismo , Microglía/efectos de los fármacosRESUMEN
Retinopathy of prematurity (ROP) is a retinal disease-causing retinal neovascularization that can lead to blindness. Oxygen-induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti-oxidative and anti-inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood-retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT/mTOR/HIF1α pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA-induced AKT/mTOR/HIF1α pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2-dependent manner, implicating ICA as a potential therapeutic agent for ROP.
Asunto(s)
Modelos Animales de Enfermedad , Flavonoides , Hexoquinasa , Microglía , Oxígeno , Neovascularización Retiniana , Retinopatía de la Prematuridad , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Hexoquinasa/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Oxígeno/metabolismo , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/metabolismo , Retinopatía de la Prematuridad/patología , Ratones , Humanos , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Endogámicos C57BL , Movimiento Celular/efectos de los fármacosRESUMEN
Macrophages form a crucial component of the innate immune system, and their activation is indispensable for various aspects of immune and inflammatory processes, tissue repair, and maintenance of the balance of the body's state. Macrophages are found in all ocular tissues, spanning from the front surface, including the cornea, to the posterior pole, represented by the choroid/sclera. The neural retina is also populated by specialised resident macrophages called microglia. The plasticity of microglia/macrophages allows them to adopt different activation states in response to changes in the tissue microenvironment. When exposed to various factors, microglia/macrophages polarise into distinct phenotypes, each exhibiting unique characteristics and roles. Furthermore, extensive research has indicated a close association between microglia/macrophage polarisation and the development and reversal of various intraocular diseases. The present article provides a review of the recent findings on the association between microglia/macrophage polarisation and ocular pathological processes (including autoimmune uveitis, optic neuritis, sympathetic ophthalmia, retinitis pigmentosa, glaucoma, proliferative vitreoretinopathy, subretinal fibrosis, uveal melanoma, ischaemic optic neuropathy, retinopathy of prematurity and choroidal neovascularization). The paradoxical role of microglia/macrophage polarisation in retinopathy of prematurity is also discussed. Several studies have shown that microglia/macrophages are involved in the pathology of ocular diseases. However, it is required to further explore the relevant mechanisms and regulatory processes. The relationship between the functional diversity displayed by microglia/macrophage polarisation and intraocular diseases may provide a new direction for the treatment of intraocular diseases.
Asunto(s)
Microglía , Retinopatía de la Prematuridad , Recién Nacido , Humanos , Microglía/patología , Retinopatía de la Prematuridad/patología , Retina/patología , Macrófagos , FenotipoRESUMEN
Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.
Asunto(s)
Proteína ADAM17 , Proteínas Proto-Oncogénicas c-fos , Neovascularización Retiniana , Animales , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Neovascularización Retiniana/genética , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Ratones , Humanos , Retinopatía de la Prematuridad/metabolismo , Retinopatía de la Prematuridad/patología , Retinopatía de la Prematuridad/genética , Ratones Endogámicos C57BL , Transcripción Genética , Regulación de la Expresión Génica , Vasos Retinianos/metabolismo , Vasos Retinianos/patología , Células Fotorreceptoras Retinianas Bastones/metabolismo , Células Fotorreceptoras Retinianas Bastones/patología , Modelos Animales de Enfermedad , AngiogénesisRESUMEN
PURPOSE: Experimental studies provide evidence that regulation of VEGF receptor-2 signaling in endothelial cells orders cell divisions and extends developmental angiogenesis while inhibiting pathologic intravitreal angiogenesis and has relevance to retinopathy of prematurity (ROP). We tested the hypothesis that intravitreal anti-VEGF would extend vascularization into peripheral avascular retina in human type 1 ROP compared with controls. DESIGN: Retrospective, nonrandomized treatment comparison. METHODS: The study was conducted at an academic institution, with the study population comprising all premature infants screened for ROP from January 2019 through December 2022. The experimental group included type 1 ROP treated with bilateral bevacizumab (0.25 mg) and had adequate fundus imaging by a certified ophthalmic photographer at 2 examinations: within 2 weeks of treatment and 1-3 weeks later. A control group included gestational age- and birthweight-matched infants with ROP less severe than type 1 ROP. The main outcome measure was extent of temporal retinal vasculature measured by a masked analyst between treated and control eyes. Paired and nonpaired t tests were used. RESULTS: Of 382 screened infants, 34 developed type 1 ROP; 11 comprised the experimental group and 11 the control group. At baseline, there was a trend toward shorter temporal vascular extent in treatment compared with control groups (3667±547 vs 4262±937 pixels, 95% CI -1277, 88; P = .084) but no difference between groups at follow-up (P = .945). Vascular extension was significantly greater in the treatment than control (872±521 vs 253±151 pixels, 95% CI 262, 977; P = .003), showing catch-up growth. CONCLUSIONS: This clinical evidence supports laboratory-based studies that regulation of VEGF using an intravitreal anti-VEGF agent increases developmental angiogenesis into the peripheral avascular retina while inhibiting pathologic intravitreal angiogenesis in ROP.
Asunto(s)
Neovascularización Retiniana , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/patología , Células Endoteliales/patología , Estudios Retrospectivos , Inyecciones Intravítreas , Bevacizumab/uso terapéutico , Recien Nacido Prematuro , Edad Gestacional , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/tratamiento farmacológico , Retina/patologíaRESUMEN
Purpose: To determine the horizontal corneal diameter, central corneal thickness, and axial length in premature infants. Methods: Infants with a birth weight of less than 2,500 g or with a gestation period of less than 36 weeks were included in the study. Infants with retinopathy of prematurity (ROP) were allocated to Group 1 (n=138), while those without ROP were allocated to Group 2 (n=236). All infants underwent a complete ophthalmologic examination, including corneal diameter measurements, pachymetry, biometry, and fundoscopy. Between-group comparisons of horizontal corneal diameter, central corneal thickness, and axial lengths were performed. Independent sample t-tests were used for statistical analysis. Results: Data was obtained from 374 eyes of 187 infants (102 female, 85 male). The mean gestational age at birth was 30.7 ± 2.7 weeks (range 25-36 weeks), the mean birth weight was 1,514 ± 533.3 g (range 750-1,970 g), and the mean postmenstrual age at examination was 40.0 ± 4.8 weeks. The mean gestational age and the mean birth weight of Group 1 were statistically lower than Group 2 (p<0.05). There were no significant differences in horizontal corneal diameter, central corneal thickness, and axial length between the two groups (p>0.05). Conclusions: The presence of ROP in premature infants does not alter the horizontal corneal diameter, central corneal thickness, or axial length. .
Objetivo: Determinar o diâmetro horizontal corneano, a espessura corneana central e o comprimento axial de prematuros. Métodos: Crianças com peso de nascimento menor que 2.500 g ou idade gestacional menor que 36 semanas foram incluídas no estudo. Recém-nascidos com retinopatia da prematuridade (ROP) foram alocados no Grupo 1 (n=138), sem ROP foram alocados no Grupo 2 (n=236). Todos os bebês foram submetidos a exame oftalmológico completo, incluindo medida do diâmetro corneano, paquimetria, biometria e fundoscopia. O diâmetro horizontal corneano, a espessura corneana central e o comprimento axial dos grupos foram comparados. Teste de "Student" para amostras independentes foi utilizado na análise estatística. Resultados: Os dados foram obtidos a partir de 374 olhos de 187 crianças (102 meninas, 85 meninos). A idade gestacional média ao nascer foi de 30,7 ± 2,7 semanas (variação de 25 a 36 semanas). O peso médio ao nascer foi de 1.514 ± 533,3 g (variação de 750 a 1.970 g). A idade pós-menstrual média de exame foi de 40,0 ± 4,8 semanas. A idade gestacional e o peso médio do Grupo 1 eram estatisticamente inferiores aos do Grupo 2 (p<0,05). Não houve diferenças significativas no diâmetro horizontal da córnea, espessura corneana central e medidas de comprimento axial entre dois grupos (p>0,05). Conclusões: A presença de ROP em prematuros não altera o diâmetro da córnea horizontal, espessura corneana central e o comprimento axial. .
Asunto(s)
Femenino , Humanos , Recién Nacido , Masculino , Córnea/anatomía & histología , Recien Nacido Prematuro , Peso al Nacer , Estudios de Casos y Controles , Edad Gestacional , Retinopatía de la Prematuridad/patologíaRESUMEN
OBJETIVO: Comparar a estrutura retiniana da mácula e fóvea entre prematuros com retinopatia da prematuridade (ROP) estágios II e III pós-tratamento, com ROP estágios II e III regredida espontaneamente e sem ROP, através de exames de tomografia de coerência óptica (OCT) e da oftalmoscopia binocular indireta (OBI). MÉTODOS: Estudo do tipo transversal, observacional e não cego. Foram incluídas crianças prematuras nascidas entre 06/1992 e 06/2006 e examinadas entre 06/2009 e 12/2010; idade gestacional menor ou igual a 32 semanas e peso ao nascer menor ou igual a 1.599 g; com mínimo de três consultas durante o período de seleção; sem retinopatia da prematuridade ou com diagnóstico de ROP estágios II ou III em pelo menos um dos olhos com regressão espontânea ou após tratamento; máximo de seis meses de idade cronológica para o primeiro exame no serviço; idade cronológica mínima de quatro anos no período da reavaliação. Foram excluídas crianças prematuras que não compareceram ou que não tinham condições clínicas para a realização dos exames de reavaliação. Os prematuros foram divididos em três grupos: G1- com ROP pós-tratamento; G2- com ROP pós-regressão espontânea; e G3- sem ROP. Os exames realizados foram OBI e OCT. RESULTADOS: Vinte e quatro prematuros (48 olhos) apresentaram os critérios exigidos para a pesquisa, com idade média cronológica entre 5 e 6 anos. À OBI, houve diferença estatística significativa para a presença de alterações na retina dos prematuros do grupo G1. No entanto estas alterações corresponderam às lesões cicatriciais deixadas pelo tratamento da ROP, sem comprometimento visível da região macular. À OCT houve diferença estatística significativa para a maior espessura foveal para os prematuros do grupo G1. Considerando-se o olho esquerdo, não houve diferença estatística significativa relacionada à espessura da fóvea entre G1 e G3. Não houve diferença entre os três grupos estudados quanto às alterações encontradas nas camadas da retina ao OCT. CONCLUSÃO: Os prematuros com ROP pós-tratamento apresentaram espessura foveal maior que os prematuros com ROP pós-regressão espontânea e espessura foveal semelhante aos prematuros sem ROP em relação à avaliação do olho esquerdo. Em relação às alterações das camadas da retina detectadas ao OCT, os três grupos foram semelhantes, sem expressão de diferença para o grupo tratado neste estudo.
PURPOSE: Compare the retinal structure of the macula and fovea among premature infants with retinopathy of prematurity (ROP) stages II and III post treatment, premature infants with ROP stages II and III with spontaneous regression and premature infants without ROP, through optical coherence tomography (OCT) and binocular indirect ophthalmoscopy (BIO) examinations. METHODS: Cross-sectional observational and not-blinded study. There were included premature infants born between 06/1992 and 06/2006 and examined between 06/2009 and 12/2010; gestational age less than or equal to 32 weeks and birth weight less than or equal to 1,599 g; with a minimum of three visits during the selection period; without retinopathy of prematurity, or with the diagnosis of ROP stages II or III in at least one eye with spontaneous regression or after ROP treatment; maximum of six months of chronological age for the first examination at the service; minimal chronological age of four years old in the reassessment period. There were excluded premature infants who did not attend or did not have clinical conditions for the reassessment examination. The premature infants were divided into three groups: G1 - with ROP post-treatment; G2 - with ROP post-spontaneous regression; and G3 - without ROP. The exams performed were BIO and OCT. RESULTS: Twenty-four premature infants (48 eyes) presented the criteria required for the research, chronological age ranging from 5 to 6 years. At BIO, there was a statistically significant difference for the presence of alterations in the retina of premature infants from group G1. However these changes corresponded to the cicatricial lesions left by the ROP treatment, without visible impairment to the macular region. At OCT there were statistically significant differences for the greatest foveal thickness between premature infants from groups G1 and G2. Considering the left eye, there was no statistically significant difference related to the thickness of the fovea between G1 and G3. There was no difference among the three groups studied in relation to the changes of the retinal layers at OCT. CONCLUSION: Premature infants with ROP post-treatment showed foveal thickness greater than premature infants with ROP post-spontaneous regression; and foveal thickness similar to premature infants without ROP in relation to assessment of the left eye. Regarding the changes of the retinal layers detected at OCT, the three groups were similar, without expression of difference for the treated group in this study.
Asunto(s)
Preescolar , Femenino , Humanos , Masculino , Mácula Lútea/patología , Retinopatía de la Prematuridad/patología , Estudios Transversales , Recien Nacido Prematuro , Oftalmoscopía/métodos , Retina/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
La incidencia de la Retinopatía del Prematuro (ROP) se asocia con las tasas de supervivencia y con la gravedad del proceso sistémico en elrecién nacido pretérmino y está influenciada por diversos factores. 1- Conocer la incidencia actual y la gravedad de la ROP. 2- Determinar la frecuencia según el sexo y edad gestacional. Estudio descriptivo, de diseño longitudinal. Se analizó una población de 363 prematuros, quienes fueron explorados secuencialmente enbúsqueda de ROP, de acuerdo al protocolo estandarizado de dicha condición. La severidad de ROP fue estimada según la extensión de la lesión. Del total de los 363 prematuros evaluados en la primera consulta, 214 presentaron ROP en la primera evaluación, y de estos 102 (28%) mantuvieron un diagnóstico definitivo a través del seguimiento. No hubo diferencia de incidencia entre varones y hembras. 40,65% tuvo un peso entre 1001-1499 gramos. 97 casos (45,32%) ocurrieron en niños entre 35 y 37 semanas. La ROP extendida a zona II fue la modalidad más común (88,23%). 28% de los prematuros estudiados desarrolló definitivamente la enfermedad. La mayoría de niños afectados tuvo ROP extendida a zona II. Hubo una alta incidencia de niños prematuros tardíos afectados por la complicación
Incidence of Retinopathy of Prematurity (ROP) is associated with survival rates and severity of systemic disease in premature newborns and is influenced by several factors. To determine the incidence and severity of ROP, and its frequency by gender and gestational age. Descriptive, longitudinal study. The analyzed population included 363 premature infants, who were evaluated for ROP, according to a standardized protocol. Type of ROP was defined by extent of the lesion. 214 out of the 363 infants had ROP at the first exam, and 102 (28%) had a definitive diagnosis on follow-up. There were no differences in incidence for males and females. 40% had a birth weight between 1001 and 1499 grams. 45,33% of cases occurred in preemies between 35 and 37 weeks gestational age. 88% of affected children had a zone II ROP. 28% of the infants had definitive diagnosis of ROP. Zone II ROP was the most common variant. There was a high incidence of ROP in late preterm newborns
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Oftalmopatías , Recién Nacido de Bajo Peso/fisiología , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/patología , Oftalmología , PediatríaRESUMEN
La retinopatía del prematuro es una de las complicaciones de la prematurez, numerosos factores influyen en la prevalencia y la gravedad deeste cuadro. Se revisan aspectos nutricionales y de crecimiento que se han asociado a mayor o menor incidencia y gravedad de la retinopatía.Esta información puede permitir una mejor predicción del riesgo de retinopatía y un manejo clínicoque contribuya a minimizar el daño visual.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Fórmulas Infantiles , Inositol/uso terapéutico , Lactancia , Leche Humana , Nutrición Prenatal , Retinopatía de la Prematuridad/etiología , Retinopatía de la Prematuridad/patología , Vitamina ERESUMEN
Objectives: This paper aims to evaluate the overall incidence of retinopathy of prematurity (ROP), the rate of treatment in severe ROP, and the six-month outcomes in all preterm infants screened for ROP at Hospital de Clínicas de Porto Alegre, Brazil, between October 2002 and October 2006, Methods: A prospective cohort study included all premature children born with birth weight *1,500 grams or a gestational age at birth *32 weeks. All patients were examined by indirect binocular ophthalmoscopy between the 4th and the 6th week of life. The examinations were repeated depending on the disease classification according the International Classification of ROP. Results: Three hundred-twenty-two preterm infants were included in this study. ROP occurred in 82 infants (25.5%). Severe ROP occurred in 18 patients (5.6%). Seventeen of these were treated by diode laser photocoagulation. Three of the treated children needed a second laser session. One patient of the re-treated group needed scleral buckling surgery with an equatorial silicon band after progression for stage 4 of ROP. One patient missed the opportunity for laser and the disease progressed to stage 5 of ROP and blindness. Conclusions: The incidence of retinopathy at our institution was similar to international results as well the as percentage of severe disease needing treatment. Laser photocoagulation was effective to stabilize the disease among 17 treated patients
Objetivos: Avaliar a incidência geral da Retinopatia da Prematuridade (ROP) e a incidência da ROP em forma severa necessitando tratamento, assim como a evolução aos seis meses de idade nos nascidos pretermo admitidos na Unidade de Terapia Intensiva Neonatal do Hospital de Clínicas de Porto Alegre entre outubro de 2002 e outubro de 2006. Métodos: Estudo de coorte, prospectivo, incluindo todos os pretermos com peso de nascimento *1.500 gramas ou com idade gestacional *32 semanas que sobreviveram até o momento do exame oftalmológico inicial. Todos foram examinados por oftalmoscopia binocular indireta entre a 4ª e a 6ª semana de vida com reavaliações periódicas de acordo com os achados baseados na Classificação Internacional da ROP. Resultados: A ROP afetou 82 pacientes (25,5%). A doença severa necessitando tratamento ocorreu em 18 pacientes (5,6%). Dezessete pacientes realizaram tratamento de fotocoagulação por laser diodo. Três das crianças tratadas necessitaram uma segunda sessão de tratamento. Um dos pacientes re-tratados evoluiu com progressão necessitando cirurgia de retinopexia com banda de silicone epi-escleral. Um paciente perdeu a oportunidade do tratamento e desenvolveu cegueira total bilateral. Conclusões: A incidência da doença bem como o percentual de crianças necessitando tratamento na instituição foi similar ao encontrado em outros centros internacionais. O tratamento foi eficiente para estabilizar e evitar a progressão para cegueira em 17 pacientes admitidos no hospital durante o período do estudo
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Retinopatía de la Prematuridad/prevención & control , Resultado del Tratamiento , Estudios de Cohortes , Incidencia , Estudios Prospectivos , Retinopatía de la Prematuridad/patología , Retinopatía de la Prematuridad/terapiaRESUMEN
PURPOSE: To describe morphological features of the macula in patients with retinopathy of prematurity. METHODS: Twelve premature babies with retinopathy of prematurity grades I, II and III underwent dilated fundus examination and optical coherence tomography evaluation. RESULTS: In all thirteen eyes of the twelve premature patients optical coherence tomography revealed a condensed retinal pigmented epithelial layer in the macular-foveal area shown by increased reflectivity. In these eyes the retinal layers were not well differentiated. Foveal depression was clearly evident in 23 percent. CONCLUSIONS: In premature patients with retinopathy of prematurity, optical coherence tomography revealed poorly differentiated layers in the macular region with increased reflectivity in retinal pigmented epithelial-choriocapillaris zone.
OBJETIVO: Descrever os aspectos morfológicos da mácula em pacientes com retinopatia da prematuridade (ROP). MÉTODOS: Doze pacientes com retinopatia da prematuridade graus I, II and III foram submetidos a mapeamento de retina e avaliação por tomografia de coerência óptica. RESULTADOS: Em todos os treze olhos de 12 pacientes a tomografia de coerência óptica mostrou a camada do epitélio pigmentar hiperrefletiva, sendo a área macular com maior intensidade. Nesses olhos as camadas da retina não estavam totalmente diferenciadas. A depressão foveal ficou claramente evidente pela tomografia de coerência óptica em 23 por cento. CONCLUSÃO: Nos pacientes prematuros com retinopatia da prematuridade, a tomografia de coerência óptica mostrou as camadas da retina pouco diferenciadas com aumento da refletividade na área macular do complexo epitélio retiniano pigmentar-coriocapilar.
Asunto(s)
Humanos , Recién Nacido , Mácula Lútea/patología , Retinopatía de la Prematuridad/diagnóstico , Tomografía de Coherencia Óptica , Edad Gestacional , Recién Nacido de muy Bajo Peso , Estudios Retrospectivos , Retinopatía de la Prematuridad/patología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the prevalence of retinopathy of prematurity and the risk factors affecting very low birth weight infants at a neonatal intensive care unit. METHODS: A cross-sectional study investigating all newborn infants with birth weights > 1,500 g and/or gestational ages > 32 weeks, admitted to the Neonatal ICU at the Hospital de Clínicas de Porto Alegre, from October 2002 to March 2004. Patients underwent indirect binocular ophthalmoscopy of the fundus at six weeks postpartum. Infants who progressed to threshold disease were given laser therapy. RESULTS: One hundred and fourteen newborn infants were studied. Eighty-three patients were not diagnosed with retinopathy of prematurity, 18 had stage I retinopathy of prematurity, seven stage II retinopathy of prematurity and six patients had threshold retinopathy of prematurity. The prevalence of retinopathy of prematurity was 27.2% (95% CI: 19.28-36.32) affecting 31 newborn infants, and the prevalence of retinopathy of prematurity progressing to threshold disease was 5.26% (95% CI: 1.96-11.10), affecting six patients. Retinopathy of prematurity was confirmed in 50% of the patients with weights below 1,000 g and 71.5% of newborn infants born at gestational ages of less than 28 weeks. Gestational age and birth weight were significantly lower among patients with retinopathy of prematurity than among those without. CONCLUSIONS: Although the results of this study demonstrate that the observed prevalence was similar to that described in literature, this ROP frequency remains elevated among very low birth weight infants. The development of retinopathy of prematurity was inversely proportional to weight and gestational age at birth.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Recién Nacido de muy Bajo Peso , Recien Nacido Prematuro/fisiología , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Retinopatía de la Prematuridad/epidemiología , Puntaje de Apgar , Brasil/epidemiología , Métodos Epidemiológicos , Edad Gestacional , Oftalmoscopía , Retinopatía de la Prematuridad/patologíaRESUMEN
In order to evaluate the effect of postnatal hyperoxia on retinal structure, newborn rats were exposed to different oxygenation intervals (80 ± 1%) with three interruptions of 21% (30 min each). Four groups of rats were exposed from birth to the 6th, 9th, 12th and 14th postnatal day, respectively and another group was placed under normoxia. After this period all oxygenated groups and the controls remained under normoxia until they were 30 days old for the structural analysis of retina. Retinal histology was carried out using conventional techniques for transmission electron microscopy (TEM). In the ganglion cell layer of the retina from rats exposed for 9 days to hyperoxia, capillaries with large projections toward the lumen, were observed as a possible consequence of cellular edema of endothelium. The most severe damage was observed in rats exposed to hyperoxia during 12 and 14 days, showing mitochondrias swollen up and without crests in the areas surrounding the capillaries, necrosis and apoptosis processes, dense bodies, cells with swollen cytoplasms and rupture of the plasmatic membrane. The results suggest that postnatal hyperoxia causes severe damages to the retina in developing rats with a direct relationship between the time exposed to oxygen and ultra structural damages.
Con el propósito de evaluar el efecto de la hiperoxia posnatal sobre la estructura retiniana se analizaron retinas de ratas recién nacidas expuestas a diferentes periodos de oxigenación (80 ±1%), con tres interrupciones de 21% (30 min c/u). Cuatro grupos de ratas fueron expuestas desde su nacimiento hasta el 6to, 9no, 12mo y 14to días de vida y otro grupo fue mantenido en normoxia. Después de este periodo tanto los grupos expuestos a la hiperoxia como los controles permanecieron en normoxia hasta una edad de 30 días para el análisis estructural de la retina. La histología se hizo usando técnicas convencionales para microscopía electrónica de transmisión (MET). En la capa de células ganglionares de la retina de ratas expuestas a nueve días de hiperoxia, se observaron capilares con notables proyecciones hacia la luz, posiblemente como consecuencia de edema celular del endotelio. El daño más intenso fue observado en las ratas expuestas a hiperoxia durante 12 y 14 días, mostrando mitocondrias hinchadas y sin crestas en las áreas circundantes a los capilares, procesos de necrosis y apoptosis, cuerpos densos, células con citoplasmas hinchados y con ruptura de la membrana plasmática. Los resultados sugieren que la hiperoxia posnatal causa graves daños a la retina en las ratas en desarrollo, con una relación directa entre el tiempo de exposición al oxígeno y los daños ultraestructurales.
Asunto(s)
Animales , Humanos , Recién Nacido , Ratas , Oxígeno/toxicidad , Retina/ultraestructura , Retinopatía de la Prematuridad/patología , Factores de Edad , Animales Recién Nacidos , Capilares/ultraestructura , Membrana Celular/ultraestructura , Modelos Animales de Enfermedad , Endotelio Vascular/ultraestructura , Eritrocitos/química , Glutatión/sangre , Glutatión/química , Mitocondrias/ultraestructura , Vaina de Mielina/ultraestructura , Oxidación-Reducción , Ratas Sprague-Dawley , Retina/crecimiento & desarrollo , Células Fotorreceptoras Retinianas Bastones/ultraestructuraRESUMEN
Se realizó una revisión de la literatura acerca de la retinopatía del prematuro (RDP), su definición, epidemiología, factores de riesgo de presentación, clasificación internacional, cuadro clínico, patogénesis, diagnóstico, historial natural, pronóstico y tratamiento. Se revisaron también los reportes del estudio multicéntrico de tratamiento con crioterapia de la RDP. Se concluye que es de gran importancia conocer las alteraciones provocadas por este padecimiento, así como realizar el diagnóstico y tratamiento oportunos, para así evitar las secuelas que muchas veces llevarán al paciente a la ceguera
Asunto(s)
Humanos , Recién Nacido , Crioterapia , Enfermedades del Prematuro , Pronóstico , Retinopatía de la Prematuridad/clasificación , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/patología , Retinopatía de la Prematuridad/terapiaRESUMEN
O presente trabalho por objetivo discutir os aspectos mais importantes e atuais com relaçäo à etiologia, fatores de risco, classificaçäo, problemas associados e tratamento da ROP, especialmente questionando o uso de vitaminas E
Asunto(s)
Humanos , Recién Nacido , Retinopatía de la Prematuridad/etiología , Vitamina E/uso terapéutico , Ceguera/fisiopatología , Retinopatía de la Prematuridad/clasificación , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/patologíaRESUMEN
La Retinopatía del Prematuro continúa siendo una importante causa de ceguera en infantes. La terapia con vitamina E aparenta ser de utilidad en la disminución de la severidad en los pacientes afectados. La mejor terapia para el manejo de la Fibroplasia Retrolental Cicatricial es la vitrectomía a cielo abierto