Eye and BrainPub Date : 2016-05-20eCollection Date: 2016-01-01DOI: 10.2147/EB.S94449
Haibo Wang
{"title":"Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy.","authors":"Haibo Wang","doi":"10.2147/EB.S94449","DOIUrl":"https://doi.org/10.2147/EB.S94449","url":null,"abstract":"<p><p>Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD) and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV). Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR), highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"81-90"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S94449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-20eCollection Date: 2016-01-01DOI: 10.2147/EB.S95021
Anne Moskowitz, Ronald M Hansen, Anne B Fulton
{"title":"Retinal, visual, and refractive development in retinopathy of prematurity.","authors":"Anne Moskowitz, Ronald M Hansen, Anne B Fulton","doi":"10.2147/EB.S95021","DOIUrl":"10.2147/EB.S95021","url":null,"abstract":"<p><p>The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"103-111"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/8c/eb-8-103.PMC5398748.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of improved neonatal care on the profile of retinopathy of prematurity in rural neonatal centers in India over a 4-year period.","authors":"Anand Vinekar, Chaitra Jayadev, Siddesh Kumar, Shwetha Mangalesh, Mangat Ram Dogra, Noel J Bauer, Bhujang Shetty","doi":"10.2147/EB.S98715","DOIUrl":"https://doi.org/10.2147/EB.S98715","url":null,"abstract":"<p><strong>Purpose: </strong>To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices.</p><p><strong>Methods: </strong>The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015).</p><p><strong>Results: </strong>During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods (<i>P</i><0.001). The overall incidence of any stage ROP reduced significantly from 26.8% to 22.4% (<i>P</i><0.001). The incidence of treatment-requiring ROP reduced from 20.7% to 16% (<i>P</i>=0.06), and of the treated disease, aggressive posterior ROP reduced from 20.8% to 13.1% (<i>P</i>=0.23) following introduction of the guidelines.</p><p><strong>Discussion: </strong>Rural neonatal centers in middle-income countries have a large, unscreened burden of ROP. Improving neonatal care in these centers can positively impact the incidence and severity of ROP even in a relatively short period. A combined approach of a robust ROP screening program and improved neonatal care practices is required to address the challenge.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"45-53"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S98715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-20eCollection Date: 2016-01-01DOI: 10.2147/EB.S94443
D Scott McLeod, Gerard A Lutty
{"title":"Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.","authors":"D Scott McLeod, Gerard A Lutty","doi":"10.2147/EB.S94443","DOIUrl":"https://doi.org/10.2147/EB.S94443","url":null,"abstract":"<p><p>Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"55-65"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S94443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-20eCollection Date: 2016-01-01DOI: 10.2147/EB.S99038
Raffael Liegl, Ann Hellström, Lois Eh Smith
{"title":"Retinopathy of prematurity: the need for prevention.","authors":"Raffael Liegl, Ann Hellström, Lois Eh Smith","doi":"10.2147/EB.S99038","DOIUrl":"https://doi.org/10.2147/EB.S99038","url":null,"abstract":"<p><p>More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"91-102"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S99038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-20eCollection Date: 2016-01-01DOI: 10.2147/EB.S94439
Ana M Suelves, Julia P Shulman
{"title":"Current screening and treatments in retinopathy of prematurity in the US.","authors":"Ana M Suelves, Julia P Shulman","doi":"10.2147/EB.S94439","DOIUrl":"https://doi.org/10.2147/EB.S94439","url":null,"abstract":"<p><p>Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"37-43"},"PeriodicalIF":4.4,"publicationDate":"2016-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S94439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35024222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-19eCollection Date: 2016-01-01DOI: 10.2147/EB.S94436
Graham E Quinn
{"title":"Retinopathy of prematurity blindness worldwide: phenotypes in the third epidemic.","authors":"Graham E Quinn","doi":"10.2147/EB.S94436","DOIUrl":"https://doi.org/10.2147/EB.S94436","url":null,"abstract":"<p><p>Blindness due to retinopathy of prematurity (ROP) is an increasing problem worldwide as improved levels of neonatal care are provided in countries with developing neonatal intensive care units. The occurrence of ROP blindness varies dramatically with the socioeconomic development of a country. In regions with high levels of neonatal care and adequate resources, ROP blindness is largely restricted to premature infants with very low birth weight and low gestational age while in middle- and low-income countries with regional variation in technology and capacity, limited health resources may well limit the care of the premature newborn.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"31-36"},"PeriodicalIF":4.4,"publicationDate":"2016-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S94436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35023717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-19DOI: 10.2147/EB.S105319
Drs Patricia D’Amore, K. Connor, Drs Cynthia Toth
{"title":"Advances in diagnosis, clinical care, research, and treatment in retinopathy of prematurity","authors":"Drs Patricia D’Amore, K. Connor, Drs Cynthia Toth","doi":"10.2147/EB.S105319","DOIUrl":"https://doi.org/10.2147/EB.S105319","url":null,"abstract":"The appearance of retinopathy of prematurity (ROP) has changed throughout the world and since the first description of “retrolental fibroplasia” in 1942. However, despite advances in neonatal care and the abilities to improve the survival of ever younger and smaller premature infants, ROP remains a leading cause of childhood blindness worldwide. We know that ROP is complex in that it is influenced by genetic predisposition, epigenetic regulation, and environmental risks. It is strongly associated with extreme degrees of prematurity, and the “phenotype” of ROP depends on resources available to support premature infants with adequate nutrition and regulation of oxygen, as examples. New studies also suggest that what is seen in the preterm infant retina may portend later neurodevelopmental outcomes. Therefore, we believe this is a needed time to revisit ROP and provide a thematic issue focused on ROP from several perspectives.","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 1","pages":"27 - 29"},"PeriodicalIF":4.4,"publicationDate":"2016-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S105319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68359772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-05-11eCollection Date: 2016-01-01DOI: 10.2147/EB.S70822
Alice Brandli, Chi D Luu, Robyn H Guymer, Lauren N Ayton
{"title":"Progress in the clinical development and utilization of vision prostheses: an update.","authors":"Alice Brandli, Chi D Luu, Robyn H Guymer, Lauren N Ayton","doi":"10.2147/EB.S70822","DOIUrl":"https://doi.org/10.2147/EB.S70822","url":null,"abstract":"<p><p>Vision prostheses, or \"bionic eyes\", are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"15-25"},"PeriodicalIF":4.4,"publicationDate":"2016-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S70822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35023716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eye and BrainPub Date : 2016-02-19eCollection Date: 2016-01-01DOI: 10.2147/EB.S69185
Rohit Saxena, Digvijay Singh, Ravi Saklani, Suresh Kumar Gupta
{"title":"Clinical biomarkers and molecular basis for optimized treatment of diabetic retinopathy: current status and future prospects.","authors":"Rohit Saxena, Digvijay Singh, Ravi Saklani, Suresh Kumar Gupta","doi":"10.2147/EB.S69185","DOIUrl":"https://doi.org/10.2147/EB.S69185","url":null,"abstract":"<p><p>Diabetic retinopathy is a highly specific microvascular complication of diabetes and a leading cause of blindness worldwide. It is triggered by hyperglycemia which causes increased oxidative stress leading to an adaptive inflammatory assault to the neuroretinal tissue and microvasculature. Prolonged hyperglycemia causes increased polyol pathway flux, increased formation of advanced glycation end-products, abnormal activation of signaling cascades such as activation of protein kinase C (PKC) pathway, increased hexosamine pathway flux, and peripheral nerve damage. All these changes lead to increased oxidative stress and inflammatory assault to the retina resulting in structural and functional changes. In addition, neuroretinal alterations affect diabetes progression. The most effective way to manage diabetic retinopathy is by primary prevention such as hyperglycemia control. While the current mainstay for the management of severe and proliferative diabetic retinopathy is laser photocoagulation, its role is diminishing with the development of newer drugs including corticosteroids, antioxidants, and antiangiogenic and anti-VEGF agents which work as an adjunct to laser therapy or independently. The current pharmacotherapy of diabetic retinopathy is incomplete as a sole treatment option in view of limited efficacy and short-term effect. There is a definite clinical need to develop new pharmacological therapies for diabetic retinopathy, particularly ones which would be effective through the oral route and help recover lost vision. The increasing understanding of the mechanisms of diabetic retinopathy and its biomarkers is likely to help generate better and more effective medications.</p>","PeriodicalId":51844,"journal":{"name":"Eye and Brain","volume":"8 ","pages":"1-13"},"PeriodicalIF":4.4,"publicationDate":"2016-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/EB.S69185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35023718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}