Features Of Retinopathy Of Prematurity Research Articles

Многофакторный анализ патогенеза ранних прогрессирующих стадий ретинопатии недоношенных

The retinopathy of prematurity (ROP) is a vasoproliferative disease causing visual impairment. Perpose. To investigate the pathogenic features of ROP. Material and methods. 1254 patients (2508 eyes), operated patients 163 (326 eyes), were included in the study; blood tests were taken from 192 patients (384 eyes). Results. Patients with lower weight, advanced stage of ROP showed greater decline in hemoglobin, lactate and thrombin time in comparison to the babies at risk; T-regulators, such as CD4+CD25highFoxp3+CD127low, correlated with gestational age and the stage of ROP; their level was increased or remained within normal range in aggressive posterior disease (AP-ROP). Serum levels of VEGFA165 and VEGFA165R1 in ROP surpassed those in babieswith congenital cataracts (p < 0.01). 19 pro-angiogenic genes (VEZF1, LTF, CSF1R, EGR1, FGF1, PTN, IFITM, HSP90AB1, HSP90B1, PRDX1, JMJD, ACTA2, XBP1, CCNG1, S100A10, IRS2, UPP1, MGP, OLFML3) and 19 antiangiogenic genes (RHBDF1, CTNNA1, F11R, PSEN2, RHBDF1, PLG, COL18A1, VHL1, EIF4A1, EIFH4, ANKRD23, MIR-16, RAB6B, TSP1, RACK1, NR2E3, TKT, VLDLR, IGFBP4) were detected. Multisensor stripping voltammetry in serum of full-term and premature babieswith ROP demonstrated significant shift of current peak height after injection of Hg (p < 0,01), Cd and Pb (p < 0,05). Conclusion. Premature patients with early stages of ROP have distinctive features of their homeostasis. Keywords: оphthalmology, CD4+CD25highFoxp3+CD127low, blood, blood serum, newborn children, cataract, retinopathy of prematurity, helth children, laboratory diagnostics, expression, antiangiogene, s factors, proangiogene, s factors, gene, multisensory inversion voltammetry, planar electrodes

Retinopathy of prematurity protection conferred by uteroplacental insufficiency through erythropoietin signaling in an experimental Murine Model.

Recent clinical studies suggest that preeclampsia, characterized by uteroplacental insufficiency (UPI) and infant intrauterine growth restriction (IUGR), may be protective against retinopathy of prematurity (ROP) in preterm infants. Experimental models of UPI/IUGR have found an association of erythropoietin (EPO) with less severe oxygen-induced retinopathy (OIR); however, it is unclear if EPO/EPO receptor (EPOR) signaling was involved. We hypothesized that maternal UPI and resultant infant IUGR would protect against features of ROP through EPO/EPOR signaling. We compared transgenic mice with hypoactive EPOR signaling (hWtEPOR) to littermate wild-type mice (mWtEpoR) in a novel combined model of IUGR and ROP. Thromboxane A2 (TXA2) was infused into pregnant C57Bl/6J dams to produce UPI/IUGR; postnatal pups and their foster dams were subjected to a murine OIR model. Following hyperoxia, hematocrits were similar between littermate wild-type (mWtEpoR) TXA2/OIR and vehicle/OIR pups. mWtEpoR TXA2/OIR had increased serum EPO, retinal EPO and VEGF, and decreased avascular retinal area (AVA) compared to vehicle/OIR pups. In comparison to the mWtEpoR TXA2/OIR pups, AVA was not reduced in hWtEPOR TXA2/OIR pups. Our findings provide biologic evidence that UPI/OIR-induced endogenous EPOR signaling confers protection against hyperoxia-induced vascular damage that may be related to pathophysiology in ROP. Maternal preeclampsia and infant growth restriction confer retinovascular protection against high oxygen-induced damage through endogenous erythropoietin signaling.

Lung and Eye Disease Develop Concurrently in Supplemental Oxygen–Exposed Neonatal Mice

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two debilitating disorders that develop in preterm infants exposed to supplemental oxygen to prevent respiratory failure. Both can lead to lifelong disabilities, such as chronic obstructive pulmonary disease and vision loss. Due to the lack of a standard experimental model of coincident disease, the underlying associations between BPD and ROP are not well characterized. To address this gap, we used the robust mouse model of oxygen-induced retinopathy exposing C57BL/6 mice to 75% oxygen from postnatal day 7 to 12. The cardinal features of ROP were replicated by this strategy, and the lungs of the same mice were simultaneously examined for evidence of BPD-like lung injury, investigating both the short- and long-term effects of early-life supplemental oxygen exposure. At postnatal days 12 and 18, mild lung disease was evident by histopathologic analysis together with the expected vasculopathy in the inner retina. At later time points, the lung lesion had progressed to severe airspace enlargement and alveolar simplification, with concurrent thinning in the outer layer of the retina. In addition, critical angiogenic oxidative stress and inflammatory factors reported to be dysregulated in ROP were similarly impaired in the lungs. These data shed new light on the interconnectedness of these two neonatal disorders, holding potential for the discovery of novel targets to treat BPD and ROP.

Automated Detection and Classification of Telemedical Retinopathy of Prematurity Images.

Background: Retinopathy of prematurity (ROP) is a retinal disorder of low birth weight infants and it is the leading cause of childhood blindness. The capability of wide field digital imaging systems to capture the clinical features of ROP has greatly helped the physicians to assess the severity of ROP and prevent childhood blindness due to ROP. Currently there is a lack of automated systems to assess the severity of ROP to assist the ROP specialist to make treatment decision. Objective: To present an automated detection and classification approach to assess the severity of ROP using wide field telemedical images. Materials and Methods: A total of 160 telemedical ROP (tele-ROP) images were collected out, of which 36 images were Normal, 79 images were Stage 2, and 45 images were Stage 3. Hessian analysis and support vector machine (SVM) classifier have been used to detect and classify the severity of ROP from tele-ROP images. Results: Classified the Normal, Stage 2, and Stage 3 images using SVM. Achieved accuracy of 91.8%, sensitivity of 90.37%, specificity of 94.65%, false positive rate of 5.35%, and false negative rate of 9.63%. Conclusions: The automated approach of detecting and classifying ROP would support pediatric ophthalmologists for early treatment decisions with optimal care.

Fluorescein angiography in the management of ROP occurred at a late postmenstrual age: our experience on seven premature infants

AbstractPurpose To report author’s management with digital camera fluorescein angiography (FA) of Type 1 retinopathy of prematurity (ROP) developed after 45 weeks of postmenstrual age (PMA).Methods Retrospective non comparative case series consisting of seven prematurely born infants with Type 1 ROP that falls outside of usual time line for the disease (PMA > 45 weeks).Results 212 premature infants with gestational age ≤ 30 weeks underwent ROP screening between January 2009 and December 2013 at Neonatal Pathology Department at San Matteo Hospital in Pavia. ROP was found in 86 babies (172 eyes, 40%) and 28 of these (56 eyes, 20.6%) were treated with laser photocoagulation. 14 eyes of 7 children developed temporal peripheral ROP (stage 2, zone 3) between 45 and 50 weeks of PMA and were included in our study. The mean gestational age for this subgroup was 27,8 weeks and mean birth weight was 864 g. Diagnosis and management were performed with indirect ophthalmoscopy, RetCam 3 and digital video FA. In 7 eyes ROP was treated with laser fotocoagulation at 47‐48 weeks PMA, while in 7 eyes regressed spontaneously with full retinal vascularisation between 48‐54 weeks PMA.Conclusion Although rare, Type 1 ROP may occur lately, after 45 weeks PMA. It is insidious because unexpected and located in extreme retinal periphery. In our experience, FA images were very useful to study the clinical features of ROP and to reveal us whether retinopathy was progressing towards threshold disease or regressing. Fluorescein Angiography lead our decisional choose: to perform laser treatment or go on with closely observation over time until the complete retinal peripheral vascularisation.

Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity: Study Design

Purpose: Detecting sight-threatening retinopathy of prematurity (ROP) relies on a diagnostic examination (DE) performed by an experienced ophthalmologist. An alternative may be a telemedicine system where retinal images of at-risk infants are graded by readers to determine features of ROP indicating the need for a DE.Methods: The multicenter Telemedicine Approaches to Evaluating Acute-phase ROP (e-ROP) Study is a cohort study of 2000 infants with birth weights <1251 g. At each visit, ophthalmologists perform DEs and non-physician imagers obtain iris and five retinal images with the disc positioned in the center, right, left, up and down. Images are uploaded to a secure server for grading by non-physician readers for the detection of plus disease, stage 3 ROP and/or zone I disease, any of which indicates “referral-warranted ROP” (RW-ROP). Images from all infants with RW-ROP and a random sample of infants without RW-ROP (based on DEs) are selected for grading. Gradings are compared to DEs to determine the validity and evaluate reliability, feasibility, safety, and cost-effectiveness of the telemedicine system.Results: e-ROP is conducted in 12 Clinical Centers in the US and Canada with Study Headquarters, the Data Coordinating Center and the Image Reading Center in Philadelphia and the ROP Data Center in Oklahoma City. A total of 27 study center coordinators, 34 ophthalmologists, 26 imagers, and 4 readers have been certified. All study data are submitted using a secure web-based system.Conclusion: The design and findings of this study will be useful to conduct other ROP studies or evaluate telemedicine for other diseases.

The Matricellular Protein Cysteine-rich Protein 61 (CCN1/Cyr61) Enhances Physiological Adaptation of Retinal Vessels and Reduces Pathological Neovascularization Associated with Ischemic Retinopathy

Retinal vascular damages are the cardinal hallmarks of retinopathy of prematurity (ROP), a leading cause of vision impairment and blindness in childhood. Both angiogenesis and vasculogenesis are disrupted in the hyperoxia-induced vaso-obliteration phase, and recapitulated, although aberrantly, in the subsequent ischemia-induced neovessel formation phase of ROP. Yet, whereas the histopathological features of ROP are well characterized, many key modulators with a therapeutic potential remain unknown. The CCN1 protein also known as cysteine-rich protein 61 (Cyr61) is a dynamically expressed, matricellular protein required for proper angiogenesis and vasculogenesis during development. The expression of CCN1 becomes abnormally reduced during the hyperoxic and ischemic phases of ROP modeled in the mouse eye with oxygen-induced retinopathy (OIR). Lentivirus-mediated re-expression of CCN1 enhanced physiological adaptation of the retinal vasculature to hyperoxia and reduced pathological angiogenesis following ischemia. Remarkably, injection into the vitreous of OIR mice of hematopoietic stem cells (HSCs) engineered to express CCN1 harnessed ischemia-induced neovessel outgrowth without adversely affecting the physiological adaptation of retinal vessels to hyperoxia. In vitro exposure of HSCs to recombinant CCN1 induced integrin-dependent cell adhesion, migration, and expression of specific endothelial cell markers as well as many components of the Wnt signaling pathway including Wnt ligands, their receptors, inhibitors, and downstream targets. CCN1-induced Wnt signaling mediated, at least in part, adhesion and endothelial differentiation of cultured HSCs, and inhibition of Wnt signaling interfered with normalization of the retinal vasculature induced by CCN1-primed HSCs in OIR mice. These newly identified functions of CCN1 suggest its possible therapeutic utility in ischemic retinopathy.

Letters to the Editor

3 May 2008 Dear Editor, RE: AP-ROP IN AN INFANT WITH MINIMAL OXYGEN EXPOSURE Buksh et al. report development of severe retinopathy of prematurity (ROP) in a 700 gm preterm baby with minimal oxygen exposure.1 The patient reported in the case is an extremely low birthweight infant (weight less than 1000 gm). Extremely low birthweight is proven to be the most important risk factor for development of ROP in various studies.2,3 The ROP disease spectrum seen in these babies is entirely different from more mature low birthweight babies. Schulenburg et al. reported variable morphological pattern of ROP seen in these extremely low birthweight infants.4 In our experience also, we found that they do not follow the typical staging pattern seen in mature babies with ROP. The specific features of ROP seen in extremely low birthweight infants are no typical demarcation line or ridge is seen between vascular and avascular retina. The shunting vessels or demarcating vessels (communication between temporal arcade vessels) are commonly seen in these babies. The site of demarcating vessel is the site of future new vessel formation. The neovascularisation seen in these babies is usually seen as filiform tangles with reduced calibre than the mature new vessels seen with ROP in mature babies. Most of these babies present with zone 1 or posterior zone 2 ROP. Flynn et al. reported two distinct pathogenetic mechanisms lying under zone 1 and zone 2 ROP.5 They described zone 1 disease as more severe form occurring frequently in low birthweight infants and as relatively insensitive to laser photocoagulation. Diagnosis of plus disease is difficult as the retinal vascular calibre is less compared with mature babies. One may observe corkscrew pattern of retinal vessels in the entire retina. This is the usual sign of plus disease, we observe in these babies. Irrespective of gestational age, we prefer initial screening for ROP at 3–4 weeks of chronological age in these extremely low birthweight babies. From then we follow them at less than 1-week intervals (3 days–1 week). We perform immediate laser photocoagulation in these babies in the presence of demarcating vessels (can term as stage I), as this is the site of future new vessel formation. We do not wait until the frank signs of plus disease like haemorrhages to appear. They usually require multiple sessions of laser photocoagulation to ablate the large avascular retina. Multiple laser sessions are also required as these babies are more prone to apnoea attacks. To conclude, we feel frequent follow up (less than a week intervals), understanding the unique disease pattern of extremely low birthweight infants and timely laser photocoagulation (usually multiple sessions) within the crucial window period are necessary to avoid the avoidable blindness of ROP.

Dynamic documentation of the evolution of retinopathy of prematurity in video format

Serial digital photographic examinations have been combined into a video format, which shows development and evolution of the disease over time. This dynamic format has changed the teaching of retinopathy of prematurity (ROP) by illustrating the subtle changes in the temporal arcade angle and choroidal vascular pattern, which can be observed over time in these videos. Consecutive weekly or biweekly images were obtained on the same infant and were captured using digital retinal photography (RetCam 120) and then archived on compact discs. Those infants that were most photographic and demonstrative of the evolution of ROP were selected for animation. The optic nerve vessels were aligned and image border blended into the previous image using a layer mask, thus creating an animation of consecutive images. The videos highlight the evolving features of ROP, such as development of arborized vessels posterior to the ridge, development of Stage 3 lesions, progression of plus disease, choroidal vascular changes accompanying the progression of ROP, dynamic changes in the temporal arcade angle, and regression of disease following last photocoagulation. The documentation of this disease as it evolves and its presentation in video format, using digital retinal photographic technology, has allowed subtle anatomical changes to be visualized and potentially studied. This process highlights a new dimension of the dynamic nature of the disease for those involved in the care of an infant with ROP.

Retinopathy of prematurity: clinical aspects

There have been many major advances recently that have improved the identification and management of retinopathy of prematurity (ROP). This chapter describes the clinical features of ROP and then considers briefly the incidence and epidemiology of acute phase disease. This is followed by a discussion of the two ROP epidemics and ROP-induced disability in high, low and middle income countries, and how this has been impacted by treatment. The principles and specifics of screening for ROP are considered, focusing on certain topical issues such as whether one screening guideline suits all populations. Treatment has undergone several advances, so that now laser therapy has overtaken cryotherapy as the preferred mode of treatment, and treatment at an earlier stage is now being considered. Finally, the authors attempt to look into the future and wonder how the criteria for treatment will change, and whether innovations in ocular imaging will impact ROP screening in both high and middle income countries.

The retinopathy of prematurity: Medicolegal aspects

The incidence of medicolegal claims based on retinopathy of prematurity (ROP) diminished in the 1960s after the role of oxygen was presumed to be understood. It has since increased again for a number of reasons. More very premature infants are being saved. The causes of ROP are multifactorial, not well understood, and the role of oxygen as a significant factor is not always clear. Morcover, the risk/benefit ratio of supplemental oxygen is not always easy to evaluate. The morphologic features of ROP are common to a number of disorders, which may be misdiagnosed as ROP. In the series of 500 medicolegal claims that I have studied, no ophthalmologists have been sued in cases concerning ROP. However, they are routinely called as expert witnesses and it is to guide them in that role that I am reviewing the subject.