Project description:The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal-fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ?-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development.
Project description:Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
Project description:Retinopathy of prematurity (ROP) is one of the most common causes of preventable blindness in children. In spite of the availability of various treatment options, and favorable results with timely intervention, many infants present to the ophthalmologists in the advanced end stage of the disease due to lack of awareness especially in the developing nations. This blinding or Stage 5 of ROP presents with total retinal detachment and has to be managed surgically. The surgical techniques for Stage 5 ROP are unique and demanding. The successful anatomical results after surgery are only seen in 20%-50% of cases. In spite of a successful anatomical result, the visual outcome may be slow and limited. The use of newer pharmacological adjuncts has shown promising results. Because of heterogeneity of presentation of the disease severity, a genetic predisposition has also been proposed. A concerted effort from the pediatricians, ophthalmologists, and healthcare workers is required to establish effective screening and treatment guidelines to prevent blindness due to ROP. Till then surgical management has to be done. Parents must be educated regarding the limited visual benefits of surgery and the need for prolonged follow-up. This review gives a comprehensive overview of the pathogenesis, clinical aspects, surgical interventions, and their outcomes and future prospects of Stage 5 ROP.
Project description:To review findings from the authors' published studies involving telemedicine and image analysis for retinopathy of prematurity (ROP) diagnosis.Twenty-two ROP experts interpreted a set of 34 wide-angle retinal images for presence of plus disease. For each image, a reference standard diagnosis was defined from expert consensus. A computer-based system was used to measure individual and linear combinations of image parameters for arteries and veins: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis were determined for each expert. Sensitivity and specificity curves were calculated for the computer-based system by varying the diagnostic cutoffs for arterial IC and venous diameter. Individual vessels from the original 34 images were identified with particular diagnostic cutoffs, and combined into composite wide-angle images using graphics editing software.For plus disease diagnosis, expert sensitivity ranged from 0.308-1.000, specificity from 0.571-1.000, and AUC from 0.784 to 1.000. Among computer system parameters, one linear combination had AUC 0.967, which was greater than that of 18 of 22 (81.8%) experts. Composite computer-generated images were produced using the arterial IC and venous diameter values associated with 75% under-diagnosis of plus disease (ie, 25% sensitivity cutoff), 50% under-diagnosis of plus disease (ie, 50% sensitivity cutoff), and 25% under-diagnosis of plus disease (ie, 75% sensitivity cutoff).Computer-based image analysis has the potential to diagnose severe ROP with comparable or better accuracy than experts, and could provide added value to telemedicine systems. Future quantitative definitions of plus disease might improve diagnostic objectivity.
Project description: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.
Project description:BackgroundMore than 11 000 children are examined for possible retinopathy of prematurity in Germany each year, and 2-5% of them are treated for it. Even though screening and treatment programs are in place, the affected children can still suffer visual impairment.MethodsIn this article, we summarize the pathogenesis, screening, and treatment of retinopathy of prematurity on the basis of a selective review of pertinent literature, retrieved by a PubMed search. The article centers on publications from 2011 to 2015 on the new option of treatment with VEGF inhibitors and discusses it in comparison to laser therapy.ResultsAll premature neonates with a low gestational age at birth, low birth weight, or prolonged exposure to supplemental oxygen must undergo screening by an ophthalmologist. Laser therapy is effective for stages 1-3 and for aggressive posterior retinopathy of prematurity. Its disadvantages are the induction of scarring and the development of severe myopia in 17-40% of the children so treated. Anti-VEGF treatment (VEGF = vascular endothelial growth factor) does not induce any visible scarring and seems to cause less myopia, but long-term data on safety, dosing, and the choice of anti-VEGF drug are still lacking.ConclusionThe available evidence for anti-VEGF treatment is on a much lower level than the evidence for laser therapy. Anti-VEGF may be a way to avoid the disadvantages of laser therapy (scarring and severe myopia). Unlike laser therapy, however, the intravitreal injection of VEGF inhibitors may suppress systemic VEGF levels and potentially harm the developing brain, lungs, or other organs. The currently open questions about anti-VEGF treatment concern its dosing, choice of drug, and long-term safety.
Project description:To describe the clinical characteristics of intraocular hemorrhages (IOHs) in infants in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study and to evaluate their potential use for prediction of disease severity.Secondary data analysis from a prospective study.Preterm infants with birth weight (BW) ?1250 g.Infants underwent serial digital retinal imaging in both eyes starting at 32 weeks' postmenstrual age. Nonphysician trained readers (TRs) evaluated all image sets from eyes that ever had IOHs documented on image evaluation or eye examination for the presence, location, type, area, and relation of the IOH to the junction between vascularized and avascular retina. Associations of IOH with demographic and neonatal factors, and with the presence and severity of retinopathy of prematurity (ROP) were investigated by univariate and multivariate analyses. Sensitivity and specificity of the telemedicine system for detecting referral-warranted ROP (RW-ROP) were calculated with and without incorporating hemorrhage into the standardized grading protocol.Retinal and vitreous hemorrhage.Among 1239 infants (mean [standard deviation] BW = 864 [212] g; gestational age [GA] = 27 [2.2] weeks) who underwent an average of 3.2 imaging sessions, 22% had an IOH in an eye on at least 1 of the e-ROP visits. Classification of IOH was preretinal (57%), blot (57%), dot (38%), flame-shaped (16%), and vitreous (8%); most IOHs were unilateral (70%). The IOH resolved in 35% of eyes by the next imaging session and in the majority (76%) of cases by 8 weeks after initial detection. Presence of IOH was inversely associated with BW and GA and significantly associated (P < 0.0001) with the presence and severity of ROP (BW and GA adjusted odds ratios [ORs] of 2.46 for any ROP, 2.88 for stage 3, and 3.19 for RW-ROP). Incorporating IOH into the grading protocol minimally altered the sensitivity of the system (94% vs. 95%).Approximately 1 in 5 preterm infants examined had IOHs, generally unilateral. The presence of hemorrhage was directly correlated with both presence and severity of ROP and inversely correlated with BW and GA, although including hemorrhage in the grading algorithm only minimally improved the sensitivity of the telemedicine system to detect RW-ROP.
Project description:Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described.To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director.Digital retinal images.Intragrader and intergrader variability and monitoring for temporal drift.Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5% requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9% for plus disease, 12.4% for zone I ROP, and 16.9% for stage 3 or worse ROP. The weighted ? for intergrader agreement (n?=?80 image sets) was 0.72 (95% CI, 0.52-0.93) for RW-ROP, 0.57 (95% CI, 0.37-0.77) for plus disease, 0.43 (95% CI, 0.24-0.63) for zone I ROP, and 0.67 (95% CI, 0.47-0.88) for stage 3 or worse ROP. The weighted ? for grade-regrade agreement was 0.77 (95% CI, 0.57-0.97) for RW-ROP, 0.87 (95% CI, 0.67-1.00) for plus disease, 0.70 (95% CI, 0.51-0.90) for zone I ROP, and 0.77 (95% CI, 0.57-0.97) for stage 3 or worse ROP.These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.
Project description:ImportanceThe current guidelines for retinopathy of prematurity (ROP) detection programs in the United States include a range of birth weights (BWs) and gestational ages and likely require examinations of many premature infants who are at low risk for developing serious retinopathy.ObjectiveTo determine the incidence, onset, and early course of ROP in what to our knowledge is the largest cohort to date that is representative of infants who are undergoing ROP screening.Design, setting, and participantsThis secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) retrospective cohort study was conducted in 29 hospitals in the United States and Canada between January 2006 and December 2011 and included 7483 infants who underwent serial ROP examinations.Main outcomes and measuresMost severe ROP in either eye, classified as no ROP, mild ROP, type 2 ROP, or type 1 ROP (per Early Treatment for ROP Study criteria). Onset at postmenstrual age for zone I disease and stage of ROP, plus disease, and treatment.ResultsThis study included 7483 infants with a mean (SD) BW of 1099 (259) g and a mean (SD) gestational age of 28 (3) weeks who underwent ROP examinations. Of these, 3224 infants (43.1%) developed ROP, 459 (6.1%) developed type 1 and 472 (6.3%) type 2 ROP, 514 (6.9%) underwent treatment in 1 or both eyes, and 147 (2%) had zone I disease. Additionally, 98.1% of type 1 or 2 ROP cases occurred in infants with a BW of less than 1251 g. Only about half of the eyes (49.4%) were vascularized into zone III by 37 weeks postmenstrual age.Conclusions and relevanceThese findings add to our knowledge of ROP screening as they include all eligible infants, not just high-risk infants as in previous studies. More than 40% of at-risk premature infants develop some stage of ROP, and most retinopathy regresses without treatment. However, approximately 12.5% develop severe ROP, which occurs almost exclusively among infants with a BW of less than 1251 g.
Project description:Introduction:Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Areas covered:Recent methods to identify and manage treatment-warranted vascularly active ROP are recognized and being compared to standard care by laser treatment in prospective large-scale clinical studies. Pharmacologic anti-angiogenic (anti-VEGF) treatment has changed the natural history of vascularly active ROP by reducing stage 3 intravitreal neovascularization and extending physiologic retinal vascularization in many infants. Tractional retinal detachments in stage 4 ROP after treatment with anti-VEGF agents show additional fibrovascular complexity compared to eyes treated with laser only. We review current management and outcomes for vascularly active and fibrovascular retinal detachment in ROP (stages 3, 4, 5 ROP), highlighting the evidence from recent clinical studies. Included are technical details important in surgery for retinal detachment in ROP. Literature searches were employed through PubMed. Expert opinion:Methods in pediatric imaging, safer pharmacologic treatments, and surgical techniques continue to advance to improve future ROP outcomes.