Course Of Retinopathy Of Prematurity Research Articles

Predictive Role of Fluorescein Angiography in Retinopathy of Prematurity.

Fluorescein angiography (FA) has been a pivotal tool for studying the pathophysiology of retinopathy of prematurity (ROP) in vivo. We examined the course of ROP using FA to assess the predictive value of angiographic features. This is an observational retrospective cohort study of eyes screened for ROP with a binocular indirect ophthalmoscope and FA. RetCam fundus imaging and video digital fluorescein angiography were performed in the neonatal intensive care unit of Santa Maria Hospital of Perugia. The masked grading of the FA images was retrospectively conducted by two ROP expert ophthalmologists. A total of 80 eyes of 40 patients were included for this study. Among the angiographic features evaluated, leakage, shunts, and tangles were predictive of the development of treatment-requiring ROP (p < 0.05). FA can add to our understanding of the evolution of vascular abnormalities in the course of ROP and can help predict which eyes will go on to treatment.

The state of ocular arterial blood flow in active retinopathy of prematurity

Purpose: to study the state of blood flow in the ocular arteries of patients with various forms, stages and course types of active retinopathy of prematurity (ROP). Material and methods. Colour duplex scanning was performed by colour Doppler mapping and pulsed Doppler sonography for 55 premature babies (55 eyes) with active ROP and 8 premature babies (8 eyes) without ROP signs. The children’s gestation age was 25 to 32 weeks, and the body weight at birth was 680 to1760 g. Blood flow was examined in the ophthalmic artery (OA), the central retinal artery (CRA) and the medial and lateral posterior short ciliary arteries (PSCA). Results. The ophthalmic artery revealed no significant differences between the children with ROP and without ROP, except for a significant increase in the peak systolic velocity (Vsyst) in an unfavorable course of stage III of ROP. The development of aggressive posterior ROP is accompanied by a statistically insignificant decrease in blood flow velocity of OA. Hemodynamic parameters of CRA indicate an increase in peripheral vascular resistance in children with an unfavorable course of ROP. A significant increase of Vsyst in the posterior short ciliary arteries was revealed in children with an unfavorable course of stages I–III of ROP and Vsyst, and Vdiast (diastolic blood flow velocity) in children with aggressive posterior ROP as compared with children without ROP. A pronounced impact of the ROP course (favorable or unfavorable) on the Vsyst, Vdiast, and PI indicators in the posterior short ciliary arteries was revealed. The most informative hemodynamic parameters in predicting the course of active ROP are Vsyst and Vdiast values in the ophthalmic artery and Vsyst in the posterior short ciliary arteries. The least informative were the hemodynamic parameters of the central retinal artery. Conclusion. The assessment of hemodynamic changes in eye arteries may be used as an additional diagnostic criterion in the early diagnosis of ROP.

Advances in retinopathy of prematurity imaging

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3). ROP imaging has also allowed the real-world adoption of telemedicine- and artificial intelligence (AI)-based screening. Recent study demonstrated proof of concept that AI has a high diagnostic performance for the detection of ROP in a real-world screening. Here, we summarize the recent advances in ROP imaging and their application for screening, diagnosis, and management of ROP.

Role of studying the pathogenesis of retinopathy of prematurity in optimizing disease screening

Background: The efficiency of treatment and prevention of retinopathy of prematurity (ROP) has improved. In addition, the development of a disease screening system to reduce the incidence of disability resulting from this pathology is important.&#x0D; Aim: This study aimed to determine new laboratory criteria for screening and predicting the ROP course through in-depth investigation of the molecules participating in the pathogenesis of ROP.&#x0D; Material and methods: A comprehensive clinical and experimental study was performed to assess the local and systemic levels of 49 cytokines with various biological effects, four monoamines, and angiotensin-II (AT-II) at different stages of the pathological process. In the clinical analysis, 165 preterm infants at risk of ROP development were examined. For the experimental part, the disease course of 145 Wistar infant rats in the developed model of experimental ROP was analyzed.&#x0D; Results: Among cytokines, the seven most promising potential laboratory markers of ROP development and adverse course were as follows: MCP1 95 pg/mL, IGF-II 140 pg/mL, TGFbeta1 18000 pg/mL, and IGF-I 24 pg/mL in the blood serum of preterm infants before the first signs of ROP and VEGF-A 108 pg/mL, TGF-beta2 100 pg/mL, and PDGF-BB 1800 pg/mL at ROP manifestation. Among monoamines, serotonin (17.0 pg/mL) and L-DOPA indicated their prognostic value in the clinical and experimental settings. Moreover, a possible prognostic role of AT-II was found.&#x0D; Conclusion: In this study, methods to improve the ROP screening system are outlined, but further work is necessary to assess the possibility of implementing the results in clinical practice

Clinical profile on incidence and course of Retinopathy of Prematurity in a tertiary care hospital of Northern India

Background: Retinopathy of prematurity (ROP) is a vaso-proliferative disorder of retina of preterm infants. It remains the leading cause of childhood blindness worldwide. Aggressive posterior retinopathy of prematurity (APROP) is rapidly progressive severe form of ROP.&#x0D; Aims and Objectives: The present study was done to assess incidence and evaluate course of ROP in preterm babies born before 34 weeks and birth weight &lt;1750 grams.&#x0D; Material and Methods: The current study was a two year prospective observational study. Screening of all neonates born with gestational age ≤34 weeks and birth weight &lt;1750 grams was done for ROP at 4 weeks of their postnatal age by indirect ophthalmoscopy and followed up till vascularization was complete. All neonates identified with APROP and ROP with plus disease was treated with double-frequency Nd YAG laser.&#x0D; Results: Of 318 neonates screened, 34.9% neonates (111) were observed to have ROP. 2.5% (8/318) neonates diagnosed with APROP and 4.4% neonates (14/318) having ROP with plus disease including pre-threshold and threshold ROP were treated with double frequency Nd Yag laser. All 14 treatment requiring ROP babies and 6 APROP babies showed total regression while one neonate with APROP succumbed to septicaemia during follow up and one APROP baby had to be referred to higher centre after he developed partial retinal detachment (RD) (Stage 4a).&#x0D; Conclusion: 34.9% had ROP, only 6.28% needed intervention. Laser monotherapy even when administered early has lesser favorable structural and functional outcome in APROP as compared to classical ROP.

Spontaneous regression of the retinopathy of prematurity

Retinopathy of prematurity (ROP) has become the leading cause of childhood blindness worldwide. It is the key point of ROP prevention and treatment to screen out and deal with severe ROP that require treatment. However, more than 70% ROP regressed spontaneously without treatment. It is useful in deeply understanding the natural course of ROP and is helpful to develop strategies of ROP screening and prevention, that the characteristics of spontaneous regression of ROP are investigated comprehensively. The epidemic characteristics, clinical features, time course, related factors and visual impairment of ROP regression will be systematically summarized in this review.(Chin J Ophthalmol, 2021, 57: 150-155).

Early angiographic signs of retinopathy of prematurity requiring treatment.

Fluorescein angiography (FA) has been a pivotal tool to study the pathophysiology of retinopathy of prematurity (ROP) in vivo. We examined the course of ROP using FA in order to assess the predictive value of angiographic features. This is an observational retrospective cohort multi-center study of eyes screened for ROP with binocular indirect ophthalmoscope and with FA. All infants undergoing screening examination for ROP who had retinal vasculature limited to Zone I and posterior Zone II vascularization underwent FA between 31 and 34 weeks postmenstrual age. RetCam fundus imaging and video digital fluorescein angiography were performed in the neonatal intensive care units. Masked grading of the FA images was retrospectively conducted by two ROP expert ophthalmologists. Ten criteria that describe retinovascular and choroidal features on FA were used to assess their predictive value for development of treatment-requiring ROP. A total of 98 eyes of 56 patients were included for this study. FAs of eyes of premature infants show a wide range of features either at the junction between the vascular and avascular retina and posteriorly to that. Among the angiographic features evaluated, leakage, shunts and hyperfluorescent lesions at the junction between vascular and avascular zone were predictive of the development of treatment-requiring ROP (p < 0.05), but findings in the posterior vascularized retina were not. FA can add to our understanding of the evolution of vascular abnormalities in the course of ROP and can help predict which eyes will go on to treatment.

Retinopathy of prematurity and neonatal gut microbiome: An interview with Professor Dimitra Skondra, Associate Professor of Ophthalmology and Vitreoretinal Surgeon at The University of Chicago (USA).

Retinopathy of prematurity (ROP) is a sight-threatening disorder of the retina affecting neonates of very low birth weight and gestational age, and is characterized by the development of abnormal blood vessel growth. According to Dr Dimitra Skondra, Associate Professor of Ophthalmology and Vitreoretinal Surgeon at the University of Chicago School of Medicine in Chicago, USA, the neonatal gut microbiome may be implicated in the neoangiogenesis process in the neonatal retina and this role may be one of the missing links in the pathogenesis of ROP. The human gut microbiome consists of bacteria, viruses, protozoa and fungi, which colonize the sterile fetal intestine, and differ depending on gestational age, mode of delivery, type of neonatal feeding, the usage of antibiotics and the requirement of neonatal intensive care. To date, it has been related to multiple nutritive, metabolic and immunological functions and has been implicated in the pathogenesis of several human diseases, such as the inflammatory bowel diseases, autoimmune and neurogenerative disorders, metabolic syndrome, cardiovascular diseases and various types of malignant neoplasias. Recent research has proposed that the neonatal gut microbiome profile in high-risk neonates who develop ROP is significantly enriched with Enterobacteriacaea species several weeks prior to the diagnosis of ROP. Further research using animal models is required to prove the causative or secondary role of the microbiome composition in the development and clinical course of ROP. If this role is proven, the gut microbiome could then be a target of intervention for personalized medicine in the prevention and therapeutic management of ROP in neonates.

Incidence and Early Course of Retinopathy of Prematurity

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new. insight into the development of ROP.

Inflammation-associated gene polymorphisms and clinical variables in the incidence and progression of retinopathy of prematurity.

IntroductionA growing body of evidence shows that genetics plays a vital role in the development and progression of retinopathy of prematurity (ROP). Perinatal inflammation is also considered an important risk factor of ROP. Therefore, understanding the interplay of genetics and susceptibility to inflammation might shed light on the pathogenesis of ROP and make its screening and treatment more effective in preventing visual impairment in premature infants.Material and methodsThis study investigated the correlation of inflammation-associated gene polymorphisms: IL-1β +3953 C>T, IL-1RN VNTR 86 bp, IL-6 -174 G>C, IL-6 -596 G>A, and TNF-α -308 G>A as well as demographic and clinical characteristics of ROP in preterm infants (n = 90).ResultsOur results demonstrate that IL-1RN rs2234663 1/1 genotype prevails in infants with ROP that regresses without intervention, when compared to those requiring laser photocoagulation/anti-VEGF injection (p = 0.031). Genotype 2/2 of IL-1RN occurs more frequently in children with severe ROP (28.6%) than in the group in which ROP regressed spontaneously (4.0%). The analysis revealed also differences between the genotypes of IL-1RN in ROP patients with intrauterine infection and in patients who had ROP without intrauterine infection; however, this was not statistically significant. Other studied polymorphisms were not associated with ROP development or its progression.ConclusionsThese results suggest that different genotypes of IL-1RN might have an impact on the course of ROP. Genotype 2/2 of IL-1RN gene may predispose to ROP progression.

New modifications of Swedish ROP guidelines based on 10-year data from the SWEDROP register

Background/aimsDuring the last decade, improved neonatal care has resulted in increased survival of the most immature infants and improved health of more mature infants. We hypothesise that this has affected...

The Thiol-Disulfide Homeostasis and Coenzyme Q10 in Conjunction with Vitamin E Effect on Retinopathy Prematurity

Purpose: This study was performed to determine whether one drop of topical administration of Coqun® (Coenzyme Q10 and Vitamin E)-a potent antioxidant-twice a day has any effect on the thiol-disulphide homeostasis-a novel oxidative stress marker in the Retinopathy Of Prematurity (ROP) disease course. Methods: This was a prospective observational study comprising 28 infants with ROP at stage 2 and higher who followed up at the paediatric intensive care unit. Ferric reducing power of plasma (FRAP), albumin, ischemia-modified albumin (IMA) and thiol disulphide homeostasis levels were studied in the infants before and two weeks after Coqun® treatment. Results: The mean gestational age was 27 (24–32) weeks, the mean birth weight was 1,012±326 g and the mean duration of care in an incubator was 64±23 days. FRAP levels were 0.91±0.17 μmol/L, IMAs were 0.85±0.29, native thiols were 248±38.9 μmol/L and total thiols were 284±39.2 μmol/L, respectively, at the beginning of therapy. FRAP levels 0.79±0.21(p= 0.006) μmol/L, IMAs 0.73±0.36(p = 0.096), native thiols 262±42.6(p = 0.164) μmol/L and total thiols 291±43.6(p = 0.344) μmol/L showed no difference after two weeks of therapy. Conclusion: Thiol disulphide homeostasis levels do not change with Coqun® therapy during ROP course.

Artificial Reproductive Technology - A Risk Factor for Retinopathy of Prematurity.

BACKGROUND:Retinopathy of Prematurity (ROP) is a potentially blinding vasoproliferative disease in premature babies. The presentation and course of ROP are determined by a complex interaction of a series of risk factors, including artificial reproductive technology (ART).AIM:To analyse and combine the information relating ART as an independent risk factor for retinopathy of prematurity.METHODS AND MATERIAL:The article is systematic review and meta-analysis using RevMan 5. Pubmed, Scopus and Medline were searched for articles from 1990 to 2018.RESULTS:Studies suggest that ROP is observed more frequently in ART children. They are more likely to be premature and of low birth weight than those conceived naturally. Results vary from just a tendency to a five-fold increase in risk to develop ROP in ART babies. At the same time, they might develop ROP later, and more mature newborns might be affected.CONCLUSION:The data relating ART as a risk factor for ROP is inconclusive, but most studies show at least a tendency. The ART newborns need to be considered as a risk group for ROP and observed with greater suspicion. Even more mature ART newborns might need to be screened in order not to miss any significant pathology.

Fluorescence Angiography to Determine the Features of Active Retinopathy of Prematurity Course

The purposeis to determine the features of different stages of active retinopathy prematurely according to fluorescent angiography data.Patients and methods. In 2011–2017, 271 angiographic studies were performed in 207 premature infants born at 25– 33 weeks of gestation with 710–1980 grams weight at birth, with different stages of active ROP in age of live 3–12 weeks (30– 39 weeks of post-conceptual age). A voluntary informed consent to perform the examination was received from the legal representatives of all patients. FAG was performed using retinal pediatric digital video system «RetCam-3» with built-in angiographic unit under mask anesthesia, in the presence of anesthesiologist-resuscitator, under the monitor control of the respiratory and cardiovascular systems of the child.Results. Unfavorable types of active ROP are characterized by the specific manifestations that are not defined by the standard ophthalmologic methods: early flat neovascularization, the presence of small tortuous peripheral vessels with signs of leakage, reperfusion areas with an apparent lack of capillaries and shunts. This opens up the opportunities for early detection of stages of the disease requiring therapeutic measures. The aggressive posterior ROP is distinguished by a variety of angiographic patterns, the most important feature is the massive loss of the retinal capillary bed in the vascularized retina. FAG data about latent neovascularization and ischemic zones of the retina represent the particular value in the prediction of active ROP course.Conclusion. The obtained results could allow to make the most differentiated approach to the management of children with active ROP, timely and effectively predict the course of the disease and to performed adequate treatment based on objective indications.

Iridofundal colobomas may lower severity of retinopathy of prematurity

We report a case where unilateral iridofundal coloboma (IFC) was observed with asymmetric retinopathy of prematurity (ROP). Associated ocular abnormalities with IFC are present in nearly 15% of the cases; however its implications on course of ROP have not been reported thus far. IFC, damaging in its own respect, may be protective against disease progression in ROP.

Variation in the vitreoretinal configuration of Stage 4 retinopathy of prematurity in photocoagulated and treatment naive eyes undergoing vitrectomy.

Purpose:We sought to document the difference in the vitreoretinal configuration of Stage 4 retinopathy of prematurity (ROP) in photocoagulated and treatment naive eyes undergoing vitrectomy and to correlate it with surgical complexity.Methods:Consecutive eyes posted for vitrectomy with Stage 4 ROP were documented preoperatively using a RetCam for the presence of peripheral traction (PT), presence of central traction just outside the arcades, and presence of traction extending to the lens. A note was made of the following intraoperative events: lensectomy, intraoperative bleeding, and iatrogenic breaks. Wilcoxon rank-sum test was used for analysis.Results:From a total of 46 eyes, 16 and 30 eyes were from the treated and treatment naive group, respectively. More eyes in the treated group had central (P < 0.0001) and lenticular traction (P = 0.022). More eyes in the untreated group had PT (P < 0.0001). A significant number of eyes without photocoagulation needed lensectomy (P = 0.042), and no difference in intraoperative bleeding (P = 0.94) was demonstrable. Iatrogenic retinotomy occurred in three eyes, all naive. Notably, age at surgery was more in the untreated group (P = 0.00008).Conclusion:Vasoproliferative activity in all retinopathies occurs at the junction of the ischemic and nonischemic retina. In the natural course of ROP, this takes place peripherally, at the ridge. In photocoagulated eyes, this junction is displaced posteriorly due to peripheral ablation. Treated eyes manifested with posterior proliferative changes and were more amenable to lens-sparing vitrectomy. Naive eyes were older when they underwent surgery to relieve PT with greater chances of lensectomy and iatrogenic breaks.

Changes in Course of Retinopathy of Prematurity from 1986 to 2013: Comparison of Three Studies in the United States

To compare infant and retinopathy of prematurity (ROP) characteristics from 3 clinical studies conducted over a 27-year period in the United States. Secondary analysis of results of 3 clinical studies. Infants with birth weight (BW) <1251 g. Analysis of data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) and Early Treatment for Retinopathy of Prematurity (ETROP) trials and the primary data from the Telemedicine Approaches for the Evaluation of Acute-Phase Retinopathy of Prematurity (e-ROP) study. Infant characteristics and onset, severity, and time course of ROP. Across the 3 studies, mean (standard deviation) BW and mean gestational age (GA) decreased over time from CRYO-ROP (954 g [185 g], 27.9 weeks [2.2 weeks]) to ETROP (907 g [205 g], 27.4 weeks [2.2 weeks]) to e-ROP (864 g [212 g], 27.0 weeks [2.2 weeks]), with an increase in the percentage of infants enrolled weighing <750 g (15.8% CRYO, 24.9% ETROP, 33.4% e-ROP; P<0.0001). The percentage of infants who developed ROP varied only minimally (65.8% CRYO, 68.0% ETROP, 63.7% e-ROP; P= 0.003). Moderately severe ROP (defined as prethreshold or referral warranted) varied (17.8% CRYO, 12.3% ETROP, 19.4% e-ROP; P<0.0001), whereas the time of onset of any ROP did not vary (34.3 weeks CRYO, 34.1 weeks ETROP, 34.8 weeks e-ROP). The BW and GA of infants enrolled in ROP studies in the United States have decreased over the past 27 years, whereas ROP prevalence and onset of disease are stable.

Predictive Value of Pre-plus Disease in Retinopathy of Prematurity

To investigate prospectively whether the presence of pre-plus disease predicts progression to severe retinopathy of prematurity (ROP) requiring laser treatment. Posterior retinal video recordings were obtained during 710 indirect ophthalmoscopy examinations of 214 premature infants over a period of 5 years. Two masked experts reviewed short video recordings and determined whether there was plus disease, pre-plus disease, or neither. The primary analysis included results of one examination of the right eye at 33 to 34 weeks' postmenstrual age. The primary outcome was a comparison of the proportion of eyes subsequently requiring laser treatment between the group graded as having pre-plus disease vs the group graded as having neither plus disease nor pre-plus disease. Of 10 eyes with pre-plus disease at 33 to 34 weeks' postmenstrual age, 7 (70%) subsequently required laser treatment; of 154 eyes without pre-plus disease or plus disease at 33 to 34 weeks' postmenstrual age, 14 (9%) subsequently required laser treatment (risk ratio, 7.7; 95% confidence interval, 4.1-14.8; P<.001). The mean time between the examination diagnosing pre-plus disease and laser treatment was 1.6 weeks (range, 1.0-2.4 weeks). When adjusting for birth weight, gestational age, ROP location (zone), and ROP severity (stage), the presence of pre-plus disease at 33 to 34 weeks' postmenstrual age independently predicted the need for laser treatment (adjusted odds ratio, 7.6; 95% confidence interval, 1.4-42.3; P=.02). Pre-plus disease observed early during the course of ROP is strongly associated with the development of severe ROP requiring laser treatment. The diagnosis of pre-plus disease has prognostic value beyond that already provided by birth weight, gestational age, ROP zone, and ROP stage. Eyes with pre-plus disease should be closely observed to allow optimal timing of intervention.

Profile of asymmetrical retinopathy of prematurity in twins

Background:In twin births, both babies have the same gestational age and pre-natal conditions. However, twins may develop a varied retinopathy of prematurity (ROP) course depending on birth weight and other systemic factors.Objective:To study the profile of asymmetric ROP in twinsDesign:Retrospective studySetting:Tertiary ROP referral eye hospital.Materials and Methods:The profile of 56 pairs of twins with ROP were studied and analyzed for differences in zone or need for treatment, while studying possible causes for the varied outcome.Results:In 45 pairs of twins (80%) the disease progressed identically in both eyes, while in 11 pairs (20%) the ROP showed differences in zone or need for treatment. Four of these pairs were discordant. In 3 of these 4 pairs, the heavier birth weight twin had a more severe ROP course.Conclusions:Twins can present with asymmetric ROP course, and it is therefore essential to examine both twins as per screening protocols.

Biomarkers of oxidative stress in babies at high risk for retinopathy of prematurity

Oxygen-induced oxidative stress (OS) has damaging effects in the perinatal period. For now there is a lake of evidence that OS occurs in babies with retinopathy of prematurity (ROP) We tests the hypothesis that a strict oxygen policy may minimize postnatal OS reducing severity of ROP. Multicenter prospective cohort study (72 newborns), using a common clinical management protocol with a strict control of oxygen administration. Assessment of biochemical markers of OS in blood samples at birth and on days 7, 14, and 21. Sixteen babies (22.2 per cent) developed ROP stage 1-2. No severe form of ROP was observed. Birth weight and O2 administration in delivery room were the factors significantly associated with the development of ROP stage 1-2. Prematurity and O2 administration in delivery room are the main factors coming into play in the course of ROP. Because room air is richer in oxygen than intrauterine environment, higher OS can be minimized, as well as incidence and severity of ROP, using standardized management with a restricted oxygen breathing policy.