Recurrence Of Retinopathy Of Prematurity Research Articles

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Different Retinopathy of Prematurity Severity, Onset Therapy and Outcomes in Triplet Babies: A Case Report

Introduction : Retinopathy of prematurity (ROP) is a vasoproliferative disease of the premature infants, characterized by abnormal vascularization at the junction of vascular and avascular retina. Intravitreal anti-VEGF injection is one of promising management of ROP. The aim is to present the therapy outcomes of triplet babies with different severity and onset therapy.
 Case Illustration : This case shows ROP in triplets born at 25-26 weeks gestational age. First baby, weighed 630 g with Bilateral Stage 2 Zone II Posterior with Plus Disease treated with intravitreal ranibizumab injection at 11 weeks (PMA 36-37 weeks). Second baby, weighed 620 g and get bilateral intravitreal ranibizumab injection a week after first baby, left eye got worse on first week, but getting better on the last follow up. Third Baby, weighed 750 g with bilateral Stage 3 Zone I with Plus Disease (worst eye condition), but because he had worst general condition, so the latest got screening, got no intervention. Two babies were treated with anti-VEGF therapy – bevacizumab. All babies has outcome regression, no recurrence of ROP in those short term end point, and no adverse reactions were observed until the last follow up at 27 weeks old (PMA 52-53 weeks) recorded for all babies.
 Discussion : 
 Conclusion : Primary prevention through well-managed screening programme for premature infants was the more effective way to manage the ROP. Intravitreal anti-VEGF treatment could be promising for management of ROP if it was given on the right time and early stadium.

Comparison of post-treatment recurrence between ranibizumab injection and laser photocoagulation for type 1 retinopathy of prematurity

ObjectiveTo compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors.MethodsThe clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed.ResultsOf the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence.ConclusionThere is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.

Revascularization of immature retinas with retinopathy of prematurity using combination therapy of deferred laser treatment after a single intravitreal bevacizumab injection

Background: This study aimed to observe the extent of retinal vascularization in patients with retinopathy of prematurity (ROP) who underwent deferred laser treatment (LT) after a single intravitreal bevacizumab injection (IVB).Methods: This study retrospectively evaluated 40 consecutive eyes in 21 infants who received a single IVB or LT. Deferred LT was performed in cases of ROP recurrence after a single IVB. To assess the amount of retinal vascularization between the initial IVB and deferred LT, the cases were divided into three groups based on treatment: single IVB, deferred LT after a single IVB, and prompt LT. The growth and associated complications were compared between groups.Results: There were 12, 16, and 12 eyes in the single IVB, deferred LT, and prompt LT groups, respectively. Deferred LT was performed at an average of 7.9 weeks after a single IVB. In the single IVB group, retinal vascularization proceeded to zone III, whereas the prompt LT group did not show any growth of vascularization beyond the laser scars. In the deferred LT group, during the window period before LT, retinal vascularization progressed from zone I to zone II posterior and from zone II posterior to zone II anterior, respectively, without further ROP recurrence. Conclusions: Retinal vascularization progressed during the deferred window period, thereby reducing the area of the retina ablated by LT. A single IVB followed by deferred LT can be an alternative treatment option to prevent ablation of zone I or multiple IVBs.

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.

Role of deferred retinal laser following intravitreal injection of bevacizumab in treatment of severe retinopathy of prematurity.

The purpose is to determine the advantages and role of supplemental deferred retinal laser treatment following intravitreal bevacizumab (IVB) monotherapy in cases of severe retinopathy of prematurity (ROP) requiring treatment. This is a retrospective study involving preterm infants diagnosed with treatment requiring ROP, treated initially with bevacizumab monotherapy who subsequently received deferred laser treatment during the study period from April 2019 to March 2021. Deferred laser treatment was done when recurrence of ROP or plus disease was noted or nonprogression of retinal vasculature was noted on two consecutive examinations over 2 weeks. The main outcomes measured were the ability of the treatment to prevent ROP progression or recurrence and anatomic outcome at the last follow-up visit. Twenty-three eyes of 14 neonates were treated with a deferred laser treatment following the initial intravitreal injection of Bevacizumab. The mean postmenstrual age at which IVB was given was 34+6 ± 1+3 weeks. The mean duration between IVB and retinal laser was 5+3 ± 3+4 weeks. The mean weight at the time of injection was 1317.8 ± 231.8 g. The mean weight of the infants at the time of the laser was 2050 ± 813.9 g. None of the eyes developed recurrence or adverse anatomical outcomes following laser till the last available follow-up. In our small number of subjects, blinding complications of ROP were prevented by using a deferred laser treatment protocol following initial bevacizumab therapy in treatment requiring ROP. It is better suited in cases where compliance for long-term follow-up after bevacizumab therapy cannot be ensured.

Reactivation of retinopathy of prematurity after intravitreal bevacizumab monotherapy in aggressive posterior retinopathy of prematurity

Aims: The aim of the study was to identify the risk factors and timing for the reactivation of retinopathy of prematurity (ROP) after intravitreal bevacizumab (IVB) in aggressive posterior retinopathy of prematurity (APROP). Materials and Methods: A retrospective study to analyze the outcome of 24 eyes of 12 infants treated with IVB monotherapy (0.625 mg) was done. Data were analyzed regarding the initial response to IVB, the incidence of ROP reactivation, timing, location, and stage of reactivation. Gestational age, postmenstrual age, and other neonatal comorbid risk factors were compared between the reactivation and those without reactivation after IVB. Results: The mean follow-up time was 50.2 ± 1.4 weeks after IVB. Reactivation was identified in 8 (33.3%) eyes. Reactivation in zone I was seen in only two eyes and zone II reactivation was present in six eyes. The mean postmenstrual age at the time of recurrence was 44.0 ± 1.15 weeks (range: 43–45). The mean time between initial treatment and treatment-requiring recurrence was 11.8 ± 0.9 weeks. Multiple pregnancy, low birth weight, sepsis, and necrotizing enterocolitis were significantly associated with ROP reactivation. None of our patients progressed to retinal detachment after laser treatment for reactivation. Conclusions: Although IVB treatment is effective in inducing the regression of APROP, the effect may be transient. The recurrence of ROP should be carefully watched in a long-term follow-up after IVB monotherapy, particularly in the first 12 weeks after IVB.

Comparison of intravitreal injection of ranibizumab versus bevacizumab for treatment of type 1 and aggressive retinopathy of prematurity in rural Egypt. A randomized clinical trial

ObjectiveThe objective of this study is to evaluate the efficacy of intravitreal ranibizumab (IVR) monotherapy compared with intravitreal bevacizumab (IVB) monotherapy for treatment of type 1 and aggressive retinopathy of...

Risk factors for recurrence after intravitreal anti-vascular endothelial growth factor injection for retinopathy of prematurity

To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.

Progression of retinal vascularization after intravitreal anti-vascular-endothelial growth factor therapy in retinopathy of prematurity

BackgroundAnti-vascular endothelial growth factor (Anti-VEGF) therapy is now considered as one of standard therapies in approaching infants with retinopathy of prematurity (ROP). The purpose of this study was to assess the time to full retinal vascularization in infants with ROP who were treated with intravitreal bevacizumab (IVB).MethodsThis retrospective cohort study evaluated premature infants with ROP who were treated with IVB between 2012 and 2019. Demographic and clinical data were collected from the medical records and analyzed. Main outcomes were defined as time to complete vascularization and time of zone shift.ResultsEight hundred sixty-five eyes from 441 patients were included. Average gestational age and birth weight were 28 ± 4 weeks and 1121 ± 624 g, respectively. Primary treatment failure and reactivation occurred in 35 eyes (4.0%) and 33 eyes (3.8%), respectively. Recurrent ROP occurred significantly more frequently in infants with pre-treatment zone 1 ROP compared to those with zone 2 ROP (7.6% versus 3%, p < 0.01). Patients with pre-treatment zone 2 reached zone 3 faster than those with pre-treatment zone 1 (142 ± 152 days versus 181 ± 174 days, p < 0.01); however, the time until full retinal vascularization did not significantly differ between the groups (p = 0.10).ConclusionThis study revealed that pre-treatment ROP zone was associated with ROP reactivation rate but not with time to full vascularization in those treated with IVB.Trial registration Retrospectively registered; IR.TUMS.FARABI.REC.1399.040

New trends in intravitreal anti-VEGF therapy for ROP.

Retinopathy of Prematurity (ROP) affects premature newborns, and it can cause childhood blindness and visual impairment if untreated. The understanding of the pathogenetic role of Vascular Endothelial Growth Factor (VEGF) has led to development of therapeutic strategies such as intravitreal anti-VEGF drugs. We reported drug efficacy and ROP recurrence rates, extrapolated from the reviewed studies. Association of Pegabtanib and laser photocoagulation confers efficacy in the regression of ROP stage 3 plus in zone I / II in 89.7% of treated eyes, reducing the recurrence rate to 14.6% compared to 50% of laser therapy alone. Irrespective of the dose, Ranibizumab demonstrated average efficacy greater than 75% on regression of active disease with the highest rates of the dose of 0.1 mg (92.5%). The recurrence, on the other hand, is the highest among this new anti-VEGF agents and is around an average of 41.5%, which records the highest values in the case of Aggressive Posterior Rop (APROP). Aflibercept at a dose of 1 mg demonstrated average efficacy of about 81.9% of treated infants, analyzing significantly fewer studies than Ranibizumab. The recurrence rate stands at an average of 28.9%, especially in the later forms of ROP. Using a dose of 0.25 mg of Conbercept, the disease regression rate is currently on average 83%, with an average recurrence rate of 15.24%, the peak of which was observed in cases of ROP in zone I. Further studies are needed to prove safety at long term, because,at the moment, only short-term data are available.

Treatment outcomes of central retinopathy of prematurity with localization in the Moscow regional perinatal center

BACKGROUND: Ranibizumab is widely used in retinopathy of prematurity. Therefore, it is necessary to evaluate the effectiveness, the risk of complications, and recurrence of the disease by antiangiogenic therapy.&#x0D; AIM: To demonstrate the experience of using anti-VEGF drugs in the Moscow Regional Perinatal Center and the effectiveness of different approaches to retinopathy of prematurity (ROP) treatment in the central retinal zone.&#x0D; MATERIAL AND METHODS: The case histories of 17 deeply premature infants with threshold ROP stages and localization in the posterior pole were retrospectively analyzed. Children were treated with intravitreal VEGF inhibitor (total 9 children), 5 children underwent laser coagulation of the retina, and 3 children received combined treatment (laser and intravitreal administration of a VEGF inhibitor).&#x0D; RESULTS: The average age of development of threshold stages was 35.2 weeks (range: 30.539 weeks) in our study. The frequency of promising outcomes after using anti-VEGF drugs alone or in conjunction with peripheral laser treatment was 100%. In comparison, the only laser treatment generated a promising result in 70% of the eyes. However, ROP relapses after anti-VEGF therapy developed at 37, 43, 44,5 weeks. In addition, 1 out of 9 children developed a recurrence of ROP and required laser treatment 7 weeks after using anti-VEGF.&#x0D; CONCLUSION: The use of anti-VEGF therapy is an effective method for the treatment of ROP of the posterior pole. However, there is the ambiguity of the available recommendations on the further management of children. Therefore, it is necessary to monitor the children who have received antiangiogenic therapy for as long as possible.

Comparing Recurrence and Retreatment of Three Doses of Bevacizumab in Treating Severe Retinopathy of Prematurity

Purpose: To determine recurrence and retreatment patterns after treatment of severe retinopathy of Prematurity (ROP) with either 0.5 mg, 0.25 mg, or 0.125 mg of intravitreal bevacizumab for retinopathy of prematurity.&#x0D; Methods: In this retrospective chart review, data was examined for babies who had severe ROP and were treated with intravitreal bevacizumab doses of either 0.500 mg, 0.250 mg, or 0.125 mg at Riley Hospital for Children in Indianapolis from 2014 to 2021. Data collected included demographic information, past medical history, and characteristics of ROP. The data was statistically analyzed using SPSS software.&#x0D; Results: One eye was analyzed for each baby. Out of 85 babies, 79 babies were included in the study. 26 babies were treated with 0.125 mg bevacizumab, 37 with 0.25 mg, and 16 with 0.5 mg. All babies showed initial response to the bevacizumab, with 61 babies (77.2%) receiving retreatment with laser for either recurrence or persistent avascular retina. While the babies treated with lower doses had higher percentages of retreatment (23 babies (88.5%) in the 0.125 mg, 29 babies (78.4%) in the 0.25 mg, and 9 babies (56.3%) in the 0.5 mg group), the difference was not statistically significant (p=0.069). Most of the retreatments were due to recurrence of ROP (0.125 mg: 20 (87.0%), 0.25 mg: 19 (65.5%), 0.50 mg: 8 (88.9%)) (p=0.339). On average, the babies in the 0.125 mg group were retreated with laser at 3.4 weeks earlier gestational age and 4.7 weeks sooner after initial treatment than the higher dosing groups, however, this difference was not statistically significant (p=0.181, p=0.287).&#x0D; Conclusion: The outcomes comparing three doses of intravitreal bevacizumab for severe ROP showed a slight variation in recurrence and retreatment patterns but no statistically significant difference in our study.

Epidemiology and treatment of retinopathy of prematurity. The Hannover data in the Retina.net ROP registry from 2001-2017

HintergrundDas Retina.net ROP-Register erhebt Daten von Kindern, die eine seltene behandlungsbedürftige Frühgeborenenretinopathie (Retinopathy of Prematurity, ROP) entwickeln. Ziel dieser Auswertung ist die Untersuchung der Daten zur behandlungsbedürftigen ROP, Epidemiologie, Therapie und deren Änderungen über einen Zeitraum von 15 Jahren an der Medizinischen Hochschule Hannover.MethodenAnalyse der Daten der therapiebedürftigen Fälle der ROP eines Zentrums für die Geburtsjahre 2001 bis 2016 (Therapie in 2002 bis 2017) als Gesamtzeitraum und in 5 Abschnitten.ErgebnisseEs wurden 65 Kinder behandelt (23 weiblich), davon wurden 11 (16,9 %) extern auf ROP gescreent und zur ROP-Behandlung zugewiesen. Für den Zeitraum 2006 bis 2016 lag die Inzidenz der behandlungsbedürftigen ROP unter den gescreenten Kindern bei 4,1 %. Das mittlere Gestationsalter betrug 25,7 Schwangerschaftswochen (SSW) (Standardabweichung [SA] = 1,8), das Geburtsgewicht 763 g (SA = 235), das postmenstruelle Alter bei Behandlung 38,2 Wochen (SA = 3,2), das postnatale Alter 12,4 Wochen (SA = 3,2). Über die Zeit zeigte sich kein signifikanter Unterschied der demografischen Parameter. Am häufigsten (57 Augen bei 31 Kindern) wurde eine Zone II, 3+-Erkrankung behandelt; 58 Kinder erhielten eine Laserkoagulation (N = 114 Augen), 7 Kinder bilateral eine Anti-VEGF-Therapie (Bevacizumab) (N = 14 Augen), welche ab 2014 eingesetzt wurde. Eine Wiederbehandlung bei Wiederaufflammen der behandlungsbedürftigen ROP war in einem Fall nach initialer Laserbehandlung notwendig. Kinder mit behandlungsbedürftiger ROP zeigten häufig neonatologische Komorbiditäten, in mehr als 90 % Beatmung, bronchopulmonale Dysplasie und erhielten Transfusionen.SchlussfolgerungDies ist die erste monozentrische Auswertung über 15 Jahre im Rahmen des Retina.net ROP-Registers. Ab 2014 sehen wir einen Wechsel von der Laserkoagulation zur Anti-VEGF-Therapie (Bevacizumab), während im betrachteten Kollektiv die demografischen Daten und Behandlungsparameter weitgehend konstant waren.

Comparison of 5-year safety and efficacy of laser photocoagulation and intravitreal bevacizumab injection in retinopathy of prematurity

To compare laser photocoagulation and intravitreal injection of bevacizumab (IVB) treatment for retinopathy of prematurity (ROP). The study included 52 eyes of 26 patients after ROP treatment who were observed up to 5 years of age. Twenty-eight eyes received laser photocoagulation as the initial treatment (laser group), and twenty-four eyes underwent IVB (IVB group). We collected data on gestational age, birth weight, 1- and 5-min Apgar scores, zone and stage at the time of treatment, recurrence of ROP and best-corrected visual acuity (BCVA) (logMAR), equivalent spherical value (SE), ocular complications, and developmental delay at the age of 5. More zone I low-stage eyes were treated with IVB than laser. There was no difference in BCVA (p = 0.836). Although the mean SE was not different between the groups (p = 0.280), the prevalence of myopia was significantly higher in the laser group (p = 0.020). Developmental delay was observed in 3 of 14 and 3 of 12 cases in the laser and IVB groups, respectively (p = 0.596). Retinal holes were observed in 2 eyes in the IVB group, with 1 developing localized retinal detachment. There were no significant differences between the groups in the other factors. Compared to laser for ROP, IVB was not inferior in neurodevelopment or visual outcome and was superior in refractive error. As cases in the IVB group showed retinal holes, long-term follow-up with fundus examination is recommended after IVB.

MicroRNA-126 inhibits pathological retinal neovascularization via suppressing vascular endothelial growth factor expression in a rat model of retinopathy of prematurity

Vascular endothelial growth factor (VEGF) is the principal growth factor responsible for the retinal neovascularization in the pathogenesis of retinopathy of prematurity (ROP). Current therapies for ROP include laser ablation and intravitreal anti-VEGF injection. However, these treatments either destroy the peripheral retina or associate with problems of persistent peripheral avascular retina or later recurrence of ROP. In the present study we investigated a new therapeutic approach by exploring the potential role of a specific microRNA, miR-126, in regulating VEGFA expression and retinal neovascularization in a rat oxygen-induced retinopathy (OIR) model. We demonstrated that miR-126 mimic and plasmid effectively suppresses VEGFA mRNA expression in both human and rat retinal pigment epithelium cell lines, quantified with qRT-PCR. Animal experiments on rat OIR model revealed that intravitreal injection of miR-126 plasmid efficiently downregulated VEGFA expression in the intraocular fluid and retinal tissues measured by ELISA, and significantly suppressed retinal neovascularization, which was confirmed by calculating sizes of neovascularization areas on fluorescence microscopic images of flat mounted retina stained with Alexa Fluor 594-conjugated isolectin B4 to visualize blood vessels. Together, these results showed that intravitreal injection of miR-126 plasmid could inhibit retinal neovascularization by down-regulating VEGFA expression, suggesting a potential therapeutic effect for ROP.

Update on the Use of Anti-VEGF Drugs in the Treatment of Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is one of the many significant consequences of premature birth and remains one of the leading causes of visual impairment in infants. Originally, cryotherapy was used to prevent the complications of vitreous hemorrhage and retinal detachment. Subsequently, laser photocoagulation, which is at least as effective and possibly safer than cryoretinopexy, was adopted as the primary treatment for type 1 ROP (stage 2 or 3 disease in zone II with plus disease or any stage disease in zone I with plus disease or stage 3 disease in zone I without plus disease). Laser therapy has been proven effective, and has a degree of permanence that is yet to be matched by alternative treatments, but can be associated with significant ocular side effects such as myopia. Treatment of type 1 ROP with anti-vascular endothelial growth factor (VEGF) agents seems to have fewer ocular side effects than laser ablation of the retina, particularly if used to treat type 1 ROP in zone I. However, ROP recurrence is a real threat after anti-VEGF therapy and long-term systemic side effects of this therapy remain under evaluation. This review focuses on the ophthalmic and systemic benefits and risks of anti-VEGF therapies for ROP as compared to retinal photocoagulation. Anti-VEGF therapies have dramatically altered the management of ROP and have also been shown to be beneficial with regard to the visual prognosis of patients with ROP, but patients so treated require frequent short- and long-term follow-up to detect and manage potential complications associated with this form of treatment. Such information also will allow clinicians to characterize the efficacy, side effect profile, and utility of intravitreal anti-VEGF agents for this condition. Prospective studies are needed to identify the optimum anti-VEGF drug and dose. [J Pediatr Ophthalmol Strabismus. 2020;57(6):351-362.].

RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY.

To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy. In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan. A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701). Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.

Intravitreal aflibercept injection in Indian eyes with retinopathy of prematurity.

Purpose:To study the efficacy of intravitreal Aflibercept, an anti Vascular Endothelial Growth factor, (anti-VEGF) in Retinopathy of Prematurity (ROP).Methods:This was a retrospective, interventional consecutive case series of 46 Indian eyes which received intravitreal injection of Aflibercept for High risk Prethreshold ROP, Threshold ROP, and Aggressive-Posterior ROP (AP-ROP).Results:Aflibercept was effective in achieving the primary endpoint, namely regression of ROP following the injection in all 46 eyes (100%) at one week following the injection. 32.6% (15/46) of eyes achieved secondary endpoint namely complete vascularization, with no recurrence of ROP at varying time intervals: as early as 15 weeks to as late as 29 weeks after injection, at intervals ranging from 49 to 64 weeks PCA.Conclusion:Intravitreal Aflibercept was effective in inducing complete regression of all types of ROP in all the eyes in our series. In addition, 32.6% of cases did not need a secondary intervention, with no recurrence of ROP and complete vascularization of the retina. In 81.8% of Zone I ROP eyes, Aflibercept facilitated continuation of retinal vascular development following regression of ROP, resulting in less extensive laser during treatment of ROP recurrence. This is the largest series of Aflibercept in ROP, till date as per MEDLINE search.

Commentary: Antivascular endothelial growth factor and retinopathy of prematurity.

Commentary: Antivascular endothelial growth factor and retinopathy of prematurity.