Retinopathy Of Prematurity Patients Research Articles

Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity.

To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. In this retrospective study, the premature children aged 4 to 9years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

Sevoflurane Insufflation Technique in Retinopathy of Prematurity Patients Underwent Intraocular Laser Photocoagulation: A Serial Case Report

Introduction: Retinopathy of Prematurity (ROP) is a developmental abnormality of the retina and vitreous due to abnormal angiogenesis. The anesthetic considerations in the preterm neonate were based on the physiological immaturity of the various organ systems, associated congenital disorders, which may result in poor tolerance to anesthetic drugs, and also considerations regarding the use of high oxygen concentrations.&#x0D; Case Illustration: We are reporting six cases of ROP patients who underwent intraocular laser photocoagulation under Volatile Induction and Maintenance Anesthesia (VIMA) using a nasal cannula. The youngest patient at the time of the procedure was 32 weeks postmenstrual age, and the oldest patient was 36 weeks postmenstrual age, with the lowest weight of 1480 grams and the highest weight of 2770 grams. A gas mixture of oxygen, nitrous oxide, and 3-5 vol% sevoflurane was delivered through a nasal cannula delivered from an anesthesia machine for anesthesia induction and maintenance throughout the procedure. The anesthesia effect was achieved less than five minutes after gas mixture delivery in all patients. Five of six patients showed satisfactory results without any serious adverse effects during and after the procedures, and one of the patients was intubated due to repeated apnea and conversion of the surgical procedure from intraocular laser photocoagulation to vitrectomy. There was no adverse event observed after the procedure.&#x0D; Conclusion: The Effective induction and maintenance of anesthesia achieved through sevoflurane insufflation via nasal cannula suggest its viability as a practical and opiod-free alternative for volatile induction and maintenance anesthesia in pediatric procedures.

Characteristics of Premature Retinopathy Patients who underwent surgery at dr. Kariadi General Hospital Semarang

Abstract&#x0D; Introduction &amp; Objectives : Introduction: Retinopathy of prematurity (ROP) represents a leading cause of childhood blindness. The management of ROP can be challenging in preterm babies, those with very low birth weight and multiple risk factors. The characteristic and risk factors of ROP is essential to acknowledge. Objective: To describe the characteristic of patients with ROP who underwent surgery in Dr. Kariadi Hospital and to identify the risk factors of the disease&#x0D; Methods : A retrospective study held from the medical record of patients with diagnosis ROP from January 2020-January 2023 in Dr. Kariadi Hospital, Semarang. The clinical characteristics: sex, gestation age, birth weight, maternal risk factors, neonatal risk factors, and ROP Stage. Type of surgery: laser, intravitreal injection, vitrectomy were also collected.&#x0D; Results : There were 19 ROP patients with 8 (42.1%) gestational age between 29-30 weeks, 8 (42.1%) birth weight 1000-1500gr, 7 (36.8%) had maternal risk: hypertension, 12 (63), 15%) of patients with ROP stage 3, 8 (42,1%) had a combined management of laser surgery and intravitreal injection. Among all the patients at risk had at least one neonatal risk factor with history of oxygenation being the most common (100%).&#x0D; Conclusion : Characteristics of ROP patients underwent surgery at Dr. Kariadi General Hospital are mostly patients with gestational age between 29-30 weeks and have the most oxygenation history factors. The most common type of surgical procedure performed is a combination of laser and intravitreal injection.

RETINOPATHY OF PREMATURITY IN TERTIARY REFERRAL EYE HOSPITAL IN INDONESIA: CHARACTERISTICS AND MANAGEMENT

Abstract&#x0D; Introduction &amp; Objectives : Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina that occurs in premature infants. Incidence of ROP is higher in middle- and lower-income countries, including Indonesia; hence information about the characteristics of the patients is essential to make strategies regarding its management. The aim of this study is to describe the characteristics and managementof patients with retinopathy of prematurity at the National Eye Center, Cicendo Eye Hospital.&#x0D; Methods : Data were obtained retrospectively from medical records from January 2018 until December 2020 using ICD-10 coding for retinopathy of prematurity. Variables include demographic data, clinical characteristics, and management.&#x0D; Results : In total, 177 patients (340 eyes) were included in this study. Demographically, 53.7% of the patients were boys; 67.8% came from West Java; 93.2% were referred; and 85.9% were health coverage users. The mean gestational age was 29.9±2.6 weeks and the mean birth weight was 1415.6±393.1 grams. Most of the patients have bilateral conditions and already have stage 5 ROP, regardless of their gestational age and birth weight. Conservative management was given to 95.5% of stage 5 ROP patients. As many as 50% of stage 4 patients underwent pars plana vitrectomy, and 85.4% stage 3 patients were managed by laser photocoagulation. Those in earlier stages were mainly observed first.&#x0D; Conclusion : Patients with ROP at Cicendo Eye Hospital mostly came in the advanced stage of the disease with conservative management. Early screening, timely referral, and prompt treatment are recommended in order to prevent blindness in premature infants.

Do intravitreal anti-VEGF injections have an effect on corneal endothelial remodeling in children with premature retinopathy?

This study was carried out to investigate the effects of retinopathy of prematurity (ROP) and intravitreal antivascular endothelial growth factor (VEGF) injections on the corneal endothelium in the childhood period of patients who have had ROP. The material of comparative case-control clinical study consisted of patients followed up with ROP between February 2013 and February 2023. The eyes in the study group were divided into two subgroups consisting of those who received intravitreal anti-VEGF injections (subgroup 1) and those who were followed up only (subgroup 2). Central corneal endothelial cell density (ECD), coefficient of variation (CV), central corneal thickness (CCT), and pleomorphism parameters in the childhood period were evaluated by corneal specular microscopy and compared with age-matched healthy control subjects. There were 84 eyes of 42 patients with ROP in the study group and 80 eyes of 40 healthy children in the control group. Mean CCT was significantly higher in subgroup 1 and the control group than in subgroup 2 (p = 0.037), and mean ECD was significantly higher in subgroup 2 than in subgroup 1 and the control group (p < 0.001). There was no significant difference between subgroup 1 and the control group in mean ECD and CCT values (p = 1.000 for both cases). Considering that ROP patients who received intravitreal anti-VEGF injections had more advanced-stage ROP than ROP patients who were followed up only, these findings suggest that intravitreal anti-VEGF applications in ROP cases may lead to corneal endothelial parameters similar to those of healthy eyes.

Choroidal measurements in decision making for retinopathy of prematurity: a decision tree analysis

BackgroundTo compare the choroidal thickness and vascular profile of premature infants with ROP (retinopathy of prematurity) using a handheld SD-OCT device.MethodsWe performed horizontal SD-OCT scans through the fovea in 115 eyes of 66 premature infants. Premature infants included 2 groups [infants with ROP requiring treatment (as treatment group) vs. infants without ROP or with ROP not- requiring treatment (as no-treatment group)] Choroidal thicknesses (CT) were measured at 5 points, including the fovea, 250 µm, and 500 µm mm nasal and temporal to the fovea. The choroidal vascularity index (CVI) and choroidal stromal index (CSI) were also calculated. The classification and regression tree (CRT) algorithm was used to predict the need for treatment based on all OCT characteristics.ResultsMean CT was higher in 500 µm nasal to the fovea compared to temporal CT (275.8 ± 64.8 and 257.1 ± 57.07, P value < 0.03). No statistically significant difference was found regarding CVI, corrected CVI, and temporal and nasal CT in the treatment group versus the no-treatment group. The foveal CT was significantly lower in ROP patients with the plus disease compared to not-plus ROP (P value = 0.03. ANOVA, Bonferroni posthoc test). CT was not significantly different between plus and pre-plus patients (P-value = 0.9, ANOVA, Bonferroni posthoc test). No significant relationship was found between the stage of ROP and choroidal thickness (P value > 0.05, GEE). The decision tree analysis showed that in infants with ROP, the most important predictor for the need for treatment is CSI.ConclusionThis study delineated the possible effectiveness of choroidal measurements as an additive to decision-making for ROP. We also demonstrated that choroidal involution is associated with the presence of plus disease, not with the stage of ROP. We demonstrated that choroidal measurements are very sensitive but not specific tools for assessing the need for treatment in ROP patients.

Vascular imaging findings in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a vascular disease among preterm infants involving incomplete or abnormal retinal vascularization and is a leading cause of preventable blindness globally. Measurements of ocular blood flow originating from a variety of imaging modalities, including colour Doppler imaging (CDI), fluorescein angiography (FA) and ocular coherence tomography angiography (OCTA), have been associated with changes in ROP patients. Herein, we discuss and summarize the relevant current literature on vascular imaging and ROP reviewed through December 2022. Differences in vascular imaging parameters between ROP patients and healthy controls are reviewed and summarized. The available data identify significantly increased peak systolic velocity (PSV) in the central retinal artery and ophthalmic artery as measured by CDI, increased vascular tortuosity as measured by FA, smaller foveal avascular zone (FAZ) as measured by FA and OCTA, and increased foveal vessel density (VD) and reduced parafoveal VD as measured by OCTA in ROP patients compared with controls. None of the above findings appear to reliably correlate with visual acuity. The studies currently available, however, are inconclusive and lack robust longitudinal data. Vascular imaging demonstrates the potential to aid in the diagnosis, management and monitoring of ROP, alongside retinal examination via indirect ophthalmoscopy and fundus photography.

Strabismus in Retinopathy of Prematurity: Risk Factors and the Effect of Macular Ectopia.

This study aimed to examine factors associated with strabismus in patients with retinopathy of prematurity (ROP) and the relationship between strabismus and macular ectopia. Patients with ROP were divided into three groups: Group 1, patients with spontaneous regression (n=45); Group 2, patients who received laser treatment (n=70); and Group 3, patients who underwent surgical treatment (n=91). Rates of anisometropia, amblyopia, nystagmus, macular ectopia, and retinal pathologies were evaluated and their impacts on strabismus development were determined. Disc-to-fovea distance (DFD) was measured from color fundus photographs and the correlation of macular ectopia with severity of strabismus was evaluated. A total of 206 patients were included. Rates of anisometropia, amblyopia, nystagmus, macular ectopia, retinal pathologies causing vision loss, and strabismus were higher in Group 3 (p=0.0001) and correlated with higher stages of ROP (p=0.0001). Macular ectopia (p=0.005), retinal pathologies (p=0.005), and amblyopia (p=0.012) had the strongest impact on strabismus development in ROP patients. DFD and strabismus severity were not significantly correlated (p=0.364). Mean visual acuity (VA) was significantly higher in orthophoric patients compared to those with esotropia and exotropia (p=0.027). Esotropic patients had lower VA compared to patients with exotropia, but this finding was not statistically significant (p=0.729). Presence of macular ectopia, retinal pathologies, and amblyopia were the most strongly correlated risk factors for strabismus development in ROP patients. DFD was not associated with severity of strabismus. Exotropia was mostly related to higher DFD and a possible relationship between esotropia and lower VA was observed.

Deep Learning-assisted Retinopathy of Prematurity (ROP) Screening

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants worldwide, particularly in developing countries. In this research, we propose a Deep Convolutional Neural Network (DCNN) and image processing-based approach for the automatic detection of retinal features, including the optical disc (OD) and retinal blood vessels (BV), as well as disease classification using a rule-based method for ROP patients. Our DCNN model uses YOLO-v5 for OD detection and either Pix2Pix or a U-Net for BV segmentation. We trained our DCNN models on publicly available fundus image datasets of size 1,117 and 288 for OD detection and BV segmentation, respectively. We evaluated our approach on a dataset of 439 preterm neonatal retinal images, testing for ROP Zone and 6 BV masks. Our proposed system achieved excellent results, with the OD detection module achieving an overall accuracy of 98.94% (when IoU 0.5) and the BV segmentation module achieving an accuracy of 96.69% and a Dice coefficient between 0.60 and 0.64. Moreover, our system accurately diagnosed ROP in Zone-1 with 88.23% accuracy. Our approach offers a promising solution for accurate ROP screening and diagnosis, particularly in low-resource settings, where it has the potential to improve healthcare outcomes.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Refractive profile of children treated with intravitreal bevacizumab for retinopathy of prematurity.

To study the refractive profile of children after they received intravitreal injection of bevacizumab for retinopathy of prematurity (ROP). The study was conducted at a tertiary eye care hospital in South India. ROP patients of more than 1 year of age, presenting to the Pediatric Ophthalmology Clinic and Retina Clinic and having history of treatment for type I ROP with intravitreal bevacizumab (IVB) or intravitreal bevacizumab and laser photocoagulation were included in the study. Cycloplegic refraction was done, and the refractive status was evaluated. The refractive status of age-matched, full-term children with uneventful perinatal and neonatal history was also recorded and compared to the study group. Among 134 eyes of 67 study subjects, the major refractive error was myopia in 93 eyes (69.4%; spherical equivalent [SE] = -2.89 ± 3.1, range = -11.5 to -0.5 D). There were 75 eyes (56%) with low-to-moderate myopia; high myopia was seen in 13.4%, emmetropia in 18.7%, and hypermetropia in 11.9% of eyes. The majority of them (87%) had with-the-rule (WTR) astigmatism. In 134 eyes, the SE was -1.78 ± 3.2 (range = -11.5 to 4 D); the SE of the 75 eyes with low-to-moderate myopia was -1.53 ± 1.2 (range = -0.50 to -5 D). In the control group, the majority had emmetropia (91.8%). There was no significant association between the age at which IVB had been injected and the development of refractive errors (P = 0.078). The prevalence of low-to-moderate myopia was more than high myopia in patients with zone I and zone II ROP before treatment (60.0% and 54.5%, respectively). Myopia was the major refractive error seen in post-IVB pediatric patients. WTR astigmatism was more commonly seen. The age at which IVB injection had been given had no effect on the development of refractive errors.

Evaluation of Oxidative Stress Levels and Dynamic Thiol-disulfide Balance in Patients with Retinopathy of Prematurity

Purpose The aim of this study is to evaluate both dynamic thiol-disulfide homeostasis and oxidative stress (OS) levels in patients with retinopathy of prematurity (ROP). Methods A total of 129 infants of <34 weeks gestational age were enrolled in the present study. The thiol-disulfide homeostasis was determined by using the new, cost-effective and fully automated colorimetric method. Total antioxidant status (TAS), Total oxidant status (TOS) and Oxidative stress index (OSI) levels were evaluated. Results We found serum TAS levels were lower while serum TOS and OSI levels were significantly higher in patients with ROP compare to the without ROP group (p < .05). However, native, total and disulfide values were not statistically significant between the groups (p > .05). In addition, we also evaluated the native, total and disulfide levels in patients with ROP according to grades and no statistically significant results were found (p > .05). Low birth weight (p = .001), gestational age (p = .001) and 5-min Apgar score were significantly lower in the ROP group. Conclusion This study revealed that dynamic thiol-disulfide homeostasis was changed in patients with ROP. Increased TOS and decreased TAS levels may be associated with functional reduction of the antioxidant system due to increased OS. This indicate that ROP patients are highly sensitive to OS. The dynamic thiol-disulfide homeostasis may conduce to the pathophysiological mechanism and disease follow-up in patients with ROP. The results of this study show that ROP patients are highly sensitive to oxidative stress.

Latest Trends in Retinopathy of Prematurity: Research on Risk Factors, Diagnostic Methods and Therapies.

Retinopathy of prematurity (ROP) is a vasoproliferative disorder with an imminent risk of blindness, in cases where early diagnosis and treatment are not performed. The doctors' constant motivation to give these fragile beings a chance at life with optimal visual acuity has never stopped, since Terry first described this condition. Thus, throughout time, several specific advancements have been made in the management of ROP. Apart from the most known risk factors, this narrative review brings to light the latest research about new potential risk factors, such as: proteinuria, insulin-like growth factor 1 (IGF-1) and blood transfusions. Digital imaging has revolutionized the management of retinal pathologies, and it is more and more used in identifying and staging ROP, particularly in the disadvantaged regions by the means of telescreening. Moreover, optical coherence tomography (OCT) and automated diagnostic tools based on deep learning offer new perspectives on the ROP diagnosis. The new therapeutical trend based on the use of anti-VEGF agents is increasingly used in the treatment of ROP patients, and recent research sustains the theory according to which these agents do not interfere with the neurodevelopment of premature babies.

Potential role of eNOS and EDN-1 gene polymorphisms in the development and progression of retinopathy of prematurity

The aim of this study was to investigate the association between selected polymorphisms of nitric oxide synthetase (eNOS) and endothelin-1 (EDN-1) with the occurrence and progression of retinopathy of prematurity (ROP). A prospective study was conducted on 90 preterm infants (44 female), comparing 39 cases with ROP and 51 controls without ROP. Patients who developed ROP were further divided into two subgroups—those with spontaneous regression of the disease and those with ROP requiring treatment. We found that preterm infants with TT genotype eNOS 894G > T had a 12.8-fold higher risk of developing ROP requiring treatment (p = 0.02). Our results showed that allele T of eNOS894G > T polymorphism was significantly more prevalent in ROP patients requiring treatment (p = 0.029). We also investigated preterm infants with TC genotype eNOS − 786 T > C and found an 8.8-fold higher risk developing of ROP requiring treatment (p = 0.021). Our results didn’t show any association between EDN-1 5665G > T polymorphism and ROP development. The eNOS polymorphisms appears to influence incidence of ROP requiring treatment in preterm infants. Future research on single nucleotide polymorphisms may provide important information about the pathogenetic mechanisms underlying the development of ROP.

Recurrence risk factors of intravitreal ranibizumab monotherapy in retinopathy of prematurity: a retrospective study at one center.

To identify risk factors of recurrence of this disorder after intravitreal ranibizumab (IVR) monotherapy. Totally 33 eyes of 19 patients who underwent initial IVR treatments for type 1 retinopathy of prematurity (ROP) at our center were retrospectively reviewed between April 1, 2016 and December 31, 2017. Patient demographics, the side of ROP, multiple gestations, Apgar scores, zone, stage, plus disease, postmenstrual age at injection, surfactant therapy, blood transfusion therapy, hemorrhage before IVR, hemorrhage after IVR, gestational diabetes mellitus, pregnancy-induced hypertension, anemia, intraventricular hemorrhage, sepsis, respiratory distress syndrome, carbohemia, and congenital heart defects were recorded. Adjusted hazard ratios (HRs) and 95% confidence intervals were determined after adjusting for potential confounders using multivariate proportional Cox regression. Of the 33 eyes, 12 (36.4%) had ROP recurrences 45.3 (5.1, 50.9)mo after initial IVR treatments. The independent risk factors for ROP recurrences were zone (II vs I, HR: 0.056, P=0.003) and gestational diabetes mellitus (no vs yes, HR: 0.095, P<0.001). The mean uncorrected visual acuity for four recurrence eyes was 0.46 logMAR (0.13, 0.70) at 55.0 (51.0, 58.9) mo after the initial IVR treatment. The mean uncorrected visual acuity for 10 eyes without recurrence was 0.46 logMAR (0.19, 0.63) at 48.0 (43.8, 58.4) mo after the initial IVR treatment. Two independent risk factors for type 1 ROP recurrence after IVR treatment involving zone I and gestational diabetes mellitus are identified, and the mean uncorrected visual acuity is 0.46 logMAR at 51.0 (44.0, 58.9)mo. The findings of this study are important for follow-up management and for improving the visual function of ROP patients.

Treatment for Nontype 1 Retinopathy of Prematurity by Intravitreal Injection of Antivascular Endothelial Growth Factor Drugs.

To explore clinical characteristics and treatment reasons for intravitreal injection of antivascular endothelial growth factor (anti-VEGF) drugs in the treatment of nontype 1 retinopathy of prematurity (ROP). A retrospective study was conducted to screen the nontype 1 ROP from the collected ROP patients who received intravitreal injections of anti-VEGF drugs in Henan Eye Hospital from September 2018 to June 2021. A total of 138 ROP cases (262 eyes) were included in this study, including 39 cases (28.3%), 65 eyes (24.8%) that were the nontype 1 ROP. Compared with the type 1 ROP group, the nontype 1 ROP group had slightly later treatment time (39.8 ± 2.7 weeks vs 38.1 ± 2.6 weeks, P < 0.05) and a higher proportion of fusion protein drugs (87.2% vs 54.5%, P < 0.05). After intravitreal injection of anti-VEGF drugs, 27 eyes (41.5%) were cured and 38 eyes (58.5%) improved in the nontype 1 ROP group, without recurrence and aggravation cases. There were more lesions in zone II (63 eyes, 96.9%), with stage 2 (40 eyes, 61.5%) and stage 3 (23 eyes, 35.4%), and 58 eyes (89.2%) showed preplus in the nontype 1 ROP group. Treatment reasons included preplus in 58 eyes (89.2%), ridge aggravation in 22 eyes (33.8%), simultaneous treatment of the contralateral eye in 9 eyes (13.8%), no regression of lesions in the persistent stage 2 or 3 over PMA 44 weeks of follow-up in 8 eyes (12.3%), and logistical considerations in 4 eyes (6.2%). Considering some peculiar clinical characteristics, treatment by intravitreal injection of anti-VEGF drugs may be considered carefully for some nontype 1 ROP in critical conditions.

Comparison in Retreatments between Bevacizumab and Ranibizumab Intravitreal Injections for Retinopathy of Prematurity: A Multicenter Study

To compare the types and dosages of anti-vascular endothelial growth factors (VEGFs) to ascertain whether specific dosages or types of injection were associated with retreatment in clinical practice in the United States. Multicenter, retrospective, consecutive series. Patients with retinopathy of prematurity (ROP) treated with anti-VEGF injections from 2007 to2021. Sixteen sites from the United States participated. Data collected included demographics, birth characteristics, examination findings, type and dose of anti-VEGF treatment, retreatment rates, and time to retreatment. Comparisons of retreatment rates between bevacizumab and ranibizumab intravitreal injections were made. Relative rate of retreatment between varying types of anti-VEGF therapy, including bevacizumab and ranibizumab, and the various dosages used for each. Data from 873 eyes of 661 patients (61% male and 39% female) were collected. After exclusion of 40 eyes treated with laser before anti-VEGF injection and 266 eyes re-treated with laser at or beyond 8 weeks after the initial anti-VEGF treatment, 567 eyes of 307 patients (63% male and 37% female) remained and were included in the primary analysis. There was no difference between the no retreatment and retreatment groups in terms of birthweight, gestational age, age at first injection, ROP stages, or number of involved clock hours. The retreatment group had a larger percentage of aggressive ROP (34% vs. 18%, P < 0.001) and greater percentage of zone 1 ROP (49 vs. 34%, P= 0.001) than the no retreatment group. Ranibizumab use was associated with a higher rate of retreatment than bevacizumab use (58% vs. 37%, P < 0.001), whereas the rate of retreatment was not associated with a specific dose of ranibizumab (R2= 0.67, P= 0.32). Meanwhile, lower doses of bevacizumab were associated with higher rates of retreatment compared with the higher doses (R2= 0.84, P= 0.01). There was a dose-specific trend with higher doses trending toward lower retreatments for bevacizumab. In a multicenter study of ROP patients initially treated with anti-VEGF therapy, ranibizumab and lower-dose bevacizumab use were associated with an increased rate of retreatment when compared with higher-dose bevacizumab. Proprietary or commercial disclosure may be found after the references.

Staged lensectomy and vitrectomy in the management of stage 5C retinopathy of prematurity with corneal opacification: long-term follow up.

To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair

Current therapies for treatment of proliferative retinopathy focus on retinal neovascularization (RNV) during advanced disease and can trigger adverse side-effects. Here, we have tested a new strategy for limiting neurovascular injury and promoting repair during early-stage disease. We have recently shown that treatment with a stable, pegylated drug form of the ureohydrolase enzyme arginase 1 (A1) provides neuroprotection in acute models of ischemia/reperfusion injury, optic nerve crush, and ischemic stroke. Now, we have determined the effects of this treatment on RNV, vascular repair, and retinal function in the mouse oxygen-induced retinopathy (OIR) model of retinopathy of prematurity (ROP). Our studies in the OIR model show that treatment with pegylated A1 (PEG-A1), inhibits pathological RNV, promotes angiogenic repair, and improves retinal function by a mechanism involving decreased expression of TNF, iNOS, and VEGF and increased expression of FGF2 and A1. We further show that A1 is expressed in myeloid cells and areas of RNV in retinal sections from mice with OIR and human diabetic retinopathy (DR) patients and in blood samples from ROP patients. Moreover, studies using knockout mice with hemizygous deletion of A1 show worsened RNV and retinal injury, supporting the protective role of A1 in limiting the OIR-induced pathology. Collectively, A1 is critically involved in reparative angiogenesis and neuroprotection in OIR. Pegylated A1 may offer a novel therapy for limiting retinal injury and promoting repair during proliferative retinopathy.

Potential biomarkers for retinopathy of prematurity identified by circular RNA profiling in peripheral blood mononuclear cells.

PurposeThis study aims to reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), and to identify potential biomarkers for ROP diagnosis.MethodsDifferentially expressed circRNAs in PBMCs of five infants with ROP and five controls were identified using microarray analysis. Twelve altered circRNAs were validated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatic analyses were conducted to predict the circRNA/miRNA interactions, competing endogenous RNA (ceRNA) network, related biological functions, and signaling pathways. Four selected circRNAs in PBMCs were verified using RT-qPCR in another cohort, including 24 infants with ROP and 23 premature controls, and receiver operating characteristic (ROC) curves were used to estimate their potential as diagnostic biomarkers of ROP.ResultsA total of 54 and 143 circRNAs were significantly up- and down-regulated, respectively, in the PBMCs of patients with ROP compared with controls. Twelve of the significantly altered circRNAs were preliminarily validated by RT-qPCR, which confirmed the reliability of the microarray analysis. The circRNA/miRNA interactions and ceRNA network were displayed according to the altered circRNAs. Three circRNAs (hsa_circRNA_061346, hsa_circRNA_092369, and hsa_circRNA_103554) were identified as potential diagnostic biomarkers for ROP with certain clinical values.ConclusionsCircRNAs were significantly altered in PBMCs of treatment-requiring ROP patients. CircRNAs may be used as potential biomarkers and possible therapeutic targets for ROP.