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1.
Sci Rep ; 14(1): 15647, 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38977744

RÉSUMÉ

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.


Sujet(s)
Inhibiteurs de l'angiogenèse , Ranibizumab , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/anatomopathologie , Ranibizumab/administration et posologie , Ranibizumab/usage thérapeutique , Mâle , Femelle , Nouveau-né , Études rétrospectives , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Résultat thérapeutique , Néovascularisation rétinienne/traitement médicamenteux , Néovascularisation rétinienne/anatomopathologie , Injections intravitréennes , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Nourrisson , Prématuré
2.
Invest Ophthalmol Vis Sci ; 65(8): 10, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38958972

RÉSUMÉ

Purpose: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization. Methods: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed. Results: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.


Sujet(s)
Animaux nouveau-nés , Modèles animaux de maladie humaine , Injections intravitréennes , Souris de lignée C57BL , Oxygène , Néovascularisation rétinienne , Rétinopathie du prématuré , Animaux , Souris , Oxygène/toxicité , Néovascularisation rétinienne/métabolisme , Néovascularisation rétinienne/prévention et contrôle , Néovascularisation rétinienne/anatomopathologie , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/métabolisme , Glycoprotéines membranaires/antagonistes et inhibiteurs , Glycoprotéines membranaires/métabolisme , Glycoprotéines membranaires/génétique , Hyperoxie/complications , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Humains
3.
Int Ophthalmol ; 44(1): 305, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38954120

RÉSUMÉ

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) monotherapy and combined intravitreal bevacizumab and laser photocoagulation (LPC) therapies applied in the same session to patients with aggressive retinopathy of prematurity (A-ROP) in our clinic. METHODS: The study included 67 eyes of 37 patients diagnosed with A-ROP and treated. Forty-nine eyes treated with anti-vascular endothelial growth factor agent injection monotherapy for A-ROP treatment were included in the first group. The second group consisted of 18 eyes that received injection therapy and LPC treatment. The clinical findings of the two groups were investigated, and their treatment results were compared. RESULTS: Recurrence was observed in 19 of the 49 (38%) eyes in the first group, but there was no recurrence in any of the cases in the second group. While only IVB was applied to eight cases with recurrence, the combination of LPC and IVB treatment was applied to 11 cases. A second recurrence was detected in two of the eight cases that had received IVB monotherapy as a treatment for recurrence and in three of the 11 cases that had received LPC and IVB. The treatment outcomes of the two groups did not statistically significantly differ (P = 0.181). CONCLUSION: We consider that the combined simultaneous LPC and IVB treatment we applied in A-ROP cases is an effective approach, particularly for cases where there are concerns about the patient's ability to attend follow-up appointments.


Sujet(s)
Inhibiteurs de l'angiogenèse , Bévacizumab , Injections intravitréennes , Coagulation par laser , Rétinopathie du prématuré , Humains , Bévacizumab/administration et posologie , Bévacizumab/usage thérapeutique , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/thérapie , Rétinopathie du prématuré/diagnostic , Rétinopathie du prématuré/chirurgie , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Coagulation par laser/méthodes , Femelle , Mâle , Nouveau-né , Études rétrospectives , Résultat thérapeutique , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Association thérapeutique , Âge gestationnel , Études de suivi , Nourrisson
4.
Biol Res ; 57(1): 43, 2024 Jun 24.
Article de Anglais | MEDLINE | ID: mdl-38915069

RÉSUMÉ

BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.


Sujet(s)
Modèles animaux de maladie humaine , Hydrogène , Névroglie , Oxygène , Néovascularisation rétinienne , Rétinopathie du prématuré , Animaux , Hydrogène/pharmacologie , Néovascularisation rétinienne/traitement médicamenteux , Névroglie/effets des médicaments et des substances chimiques , Souris , Rétinopathie du prématuré/traitement médicamenteux , Souris de lignée C57BL , Rétine/effets des médicaments et des substances chimiques , Animaux nouveau-nés , Régénération/effets des médicaments et des substances chimiques , Immunohistochimie , Vaisseaux rétiniens/effets des médicaments et des substances chimiques
5.
BMJ Case Rep ; 17(6)2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38839401

RÉSUMÉ

Retinopathy of prematurity (ROP) and necrotising enterocolitis (NEC) are complications of prematurity. Despite being quite different in terms of incidence, pathogenesis and consequences, both share a pathogenic role of aberrant vascularisation: increased in ROP, deficient for NEC. Current therapy for ROP includes the use of anti-vascular endothelial growth factor (anti-VEGF) agents, which are able to interrupt retinal hypervascularity. Despite being delivered intravitreously, anti-VEGF used in ROP can be absorbed into circulation and exert systemic effects. We present here a case of an ex-27 weeks gestational age infant, presenting multiple NEC risk factors, treated at 2 months of age with low-dose ranibizumab, who developed a large bowel NEC episode in the first week after treatment. We believe that this further report of an association between anti-VEGF agents and NEC could be interesting for the identification of children at risk of severe adverse events and stimulating further research on the topic.


Sujet(s)
Inhibiteurs de l'angiogenèse , Entérocolite nécrosante , Injections intravitréennes , Ranibizumab , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/traitement médicamenteux , Entérocolite nécrosante/traitement médicamenteux , Ranibizumab/administration et posologie , Ranibizumab/usage thérapeutique , Nouveau-né , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/effets indésirables , Mâle , Prématuré , Femelle , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs
6.
BMC Ophthalmol ; 24(1): 265, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907228

RÉSUMÉ

BACKGROUND: Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms of ROP, which does not restrict the visual field in comparison to laser therapy. The present study aimed to determine and evaluate the risk factors for ROP recurrence following IVB injection. MATERIALS AND METHODS: In this retrospective study, 98 eyes of 49 infants with ROP who had received IVB injections as the primary treatment for type 1 ROP are included. RESULTS: Fifty-four eyes (55.1%) had aggressive retinopathy of prematurity (A-ROP), and forty-four (44.9%) had Stage III Plus ROP in Zone II. ROP recurred in 13 eyes (13.26%) of 8 infants. The mean period between IVB and the ROP recurrence was 8.08 (95% CI:5.32-10.83) weeks. The infants who had ROP recurrence had lower birth weight (P value = 0.002), lower postmenstrual age at IVB injection (P value = 0.001), lower IVB injection gap period from birth (P value = 0.044), higher oxygen therapy requirement rate after IVB injection (P value < 0.001, OR:19.0) and higher oxygen therapy duration (P value = 0.006). The ROP severity, gestational age at birth, and diet were not statistically different between the recurrence and complete regression groups. Out of 13 eyes treated with laser photocoagulation because of ROP relapse, macula dragging occurred in one eye, and all the cases met the complete regression. CONCLUSION: Low birth weight and oxygen therapy are the most important risk factors for ROP relapse, which requires meticulous oxygen treatment guidelines for premature infants.


Sujet(s)
Inhibiteurs de l'angiogenèse , Bévacizumab , Âge gestationnel , Injections intravitréennes , Récidive , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/diagnostic , Bévacizumab/administration et posologie , Bévacizumab/usage thérapeutique , Études rétrospectives , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Femelle , Mâle , Nouveau-né , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Facteurs de risque , Nourrisson , Études de suivi , Prématuré
7.
J Perinatol ; 44(6): 892-896, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38773216

RÉSUMÉ

OBJECTIVE: To describe the population to which we administered recombinant erythropoietin and to determine the effectiveness of this treatment as quantified by the change in hematocrit. STUDY DESIGN: This retrospective chart review study included infants who received erythropoietin for the treatment of anemia of prematurity. RESULTS: There were 132 infants representing 162 unique treatment courses included in the study. The average duration of therapy was 9 days (±7) and 6 doses (±2). The average change in hematocrit (Hct) was 6.2% (SD 3.9%, p < 0.001). Rise in Hct was associated with a higher number of rEPO doses (p < 0.001) and higher postmenstrual age (p < 0.001). In our small cohort we did not find an association between the number of rEPO doses and retinopathy of prematurity (ROP) requiring treatment. CONCLUSION: Erythropoietin is safe and effective at treating anemia of prematurity as evidenced by a clinically and statistically significant increase in Hct from baseline.


Sujet(s)
Anémie néonatale , Érythropoïétine , Prématuré , Unités de soins intensifs néonatals , Protéines recombinantes , Humains , Études rétrospectives , Nouveau-né , Érythropoïétine/usage thérapeutique , Érythropoïétine/administration et posologie , Femelle , Mâle , Protéines recombinantes/usage thérapeutique , Protéines recombinantes/administration et posologie , Anémie néonatale/traitement médicamenteux , Hématocrite , Rétinopathie du prématuré/traitement médicamenteux , Résultat thérapeutique , Âge gestationnel , Anémie/traitement médicamenteux
8.
BMC Ophthalmol ; 24(1): 220, 2024 May 24.
Article de Anglais | MEDLINE | ID: mdl-38790043

RÉSUMÉ

BACKGROUND: Retinopathy of prematurity (ROP) is a disease that affects preterm infants born younger than 30 weeks of gestation. The pathophysiology of ROP involves an initial vaso-obliterative phase followed by vaso-proliferative phase that leads to disease progression. The use of supplemental oxygen during the vaso-proliferative phase of ROP has been associated with reduced disease progression, but how this impacts the need for ROP treatment is unclear. The goal of this study was to compare the rate of laser or intravitreal bevacizumab after implementation of a new supplemental oxygen therapy protocol in preterm infants with stage 2 ROP. METHODS: This is a retrospective chart review of preterm infants diagnosed with stage 2 ROP at Riley Hospital for Children between 1/2017 and 12/2022. Patients diagnosed between 1/2017 and 6/2020 were classified as Cohort A, preprotocol implementation. Patients diagnosed from 8/2020 to 12/2022 were classified as Cohort B, postprotocol implementation. In Cohort A, oxygen saturation was kept at 91-95% through the entire hospitalization. In Cohort B, oxygen saturation was increased to 97-99% as soon as Stage 2 ROP was diagnosed. Statistical analyses were performed using chi-square and Student's T test, followed by multivariate analyses to determine the impact of the oxygen protocol on the need for ROP treatment. RESULTS: A total of 211 patients were diagnosed with stage 2 ROP between 1/2017 and 12/2022. Of those patients, 122 were before protocol implementation therapy (Cohort A), and 89 were after implementation of supplemental oxygen protocol (Cohort B). Gestational age was slightly higher in Cohort B (Cohort A 25.3 ± 1.9, Cohort B 25.8 ± 1.84, p = 0.04). There was no difference in birth weight, NEC, BPD, or survival. Cohort B had lesser need for invasive mechanical ventilation and higher days on CPAP during hospitalization. Notably, Cohort A had 67 (55%) patients treated with laser photocoagulation or intravitreal bevacizumab versus 20 (22%) patients in Cohort B (OR 0.19, 0.08-0.40). CONCLUSION: The need for laser photocoagulation or intravitreal bevacizumab was significantly decreased in high-risk patients treated with the supplemental oxygen protocol. This result supports the idea that targeted supplemental oxygen therapy to keep saturations between 97 and 99% can reduce disease progression in infants with stage 2 ROP and potentially decrease the burden of additional procedures.


Sujet(s)
Inhibiteurs de l'angiogenèse , Bévacizumab , Âge gestationnel , Prématuré , Injections intravitréennes , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/thérapie , Rétinopathie du prématuré/diagnostic , Bévacizumab/administration et posologie , Bévacizumab/usage thérapeutique , Études rétrospectives , Nouveau-né , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Mâle , Femelle , Coagulation par laser/méthodes , Oxygénothérapie/méthodes , Oxygène/usage thérapeutique , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Résultat thérapeutique
9.
BMC Ophthalmol ; 24(1): 180, 2024 Apr 19.
Article de Anglais | MEDLINE | ID: mdl-38641774

RÉSUMÉ

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.


Sujet(s)
Inhibiteurs de l'angiogenèse , Rétinopathie du prématuré , Nouveau-né , Nourrisson , Humains , Inhibiteurs de l'angiogenèse/usage thérapeutique , Rétinopathie du prématuré/chirurgie , Rétinopathie du prématuré/traitement médicamenteux , Facteur de croissance endothéliale vasculaire de type A , Études rétrospectives , Coagulation par laser/méthodes , Prématuré , Injections intravitréennes , Âge gestationnel
10.
BMC Genomics ; 25(1): 415, 2024 Apr 26.
Article de Anglais | MEDLINE | ID: mdl-38671350

RÉSUMÉ

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.


Sujet(s)
Oxygène , Protéomique , Rétinopathie du prématuré , Facteur de croissance endothéliale vasculaire de type A , Animaux , Oxygène/métabolisme , Souris , Protéomique/méthodes , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Facteur de croissance endothéliale vasculaire de type A/génétique , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Spectrométrie de masse en tandem , Gene Ontology , Chromatographie en phase liquide , Rétine/métabolisme , Rétine/effets des médicaments et des substances chimiques , Rétine/anatomopathologie
11.
JAMA Netw Open ; 7(4): e248383, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38687481

RÉSUMÉ

Importance: 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. Objective: 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). Design, Setting, and Participants: 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. Interventions: Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04015180.


Sujet(s)
Inhibiteurs de l'angiogenèse , Injections intravitréennes , Récepteurs aux facteurs de croissance endothéliale vasculaire , Protéines de fusion recombinantes , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/chirurgie , Rétinopathie du prématuré/thérapie , Rétinopathie du prématuré/traitement médicamenteux , Récepteurs aux facteurs de croissance endothéliale vasculaire/usage thérapeutique , Protéines de fusion recombinantes/usage thérapeutique , Protéines de fusion recombinantes/effets indésirables , Protéines de fusion recombinantes/administration et posologie , Femelle , Mâle , Nouveau-né , Études prospectives , Résultat thérapeutique , Inhibiteurs de l'angiogenèse/usage thérapeutique , Inhibiteurs de l'angiogenèse/effets indésirables , Thérapie laser/méthodes , Thérapie laser/effets indésirables , Nourrisson , Enfant d'âge préscolaire
12.
Surv Ophthalmol ; 69(4): 585-605, 2024.
Article de Anglais | MEDLINE | ID: mdl-38432359

RÉSUMÉ

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.


Sujet(s)
Inhibiteurs de l'angiogenèse , Bévacizumab , Injections intravitréennes , Coagulation par laser , Méta-analyse en réseau , Ranibizumab , Récepteurs aux facteurs de croissance endothéliale vasculaire , Protéines de fusion recombinantes , Rétinopathie du prématuré , Facteur de croissance endothéliale vasculaire de type A , Humains , Rétinopathie du prématuré/traitement médicamenteux , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Récepteurs aux facteurs de croissance endothéliale vasculaire/administration et posologie , Bévacizumab/administration et posologie , Bévacizumab/usage thérapeutique , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Protéines de fusion recombinantes/administration et posologie , Protéines de fusion recombinantes/usage thérapeutique , Ranibizumab/administration et posologie , Ranibizumab/usage thérapeutique , Coagulation par laser/méthodes , Nouveau-né
13.
Chem Biol Drug Des ; 103(3): e14504, 2024 03.
Article de Anglais | MEDLINE | ID: mdl-38480485

RÉSUMÉ

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.


Sujet(s)
Mélatonine , Rétinopathie du prématuré , Rats , Animaux , Mélatonine/pharmacologie , Mélatonine/usage thérapeutique , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/métabolisme , Antioxydants/pharmacologie , Antioxydants/usage thérapeutique , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Modèles animaux de maladie humaine
14.
Ophthalmic Surg Lasers Imaging Retina ; 55(4): 228-230, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38319055

RÉSUMÉ

A 33-5/7, 1570 g dichorionic diamniotic twin presented with cryptorchidism, failed hearing examination (both ears), poor feeding, profound hypoglycemia, coagulopathy, conjugated hyper-bilirubinemia, hydronephrosis, and hypotension. Microarray sent with results of whole genome SNP microgray analysis detected an interstitial duplication of the chromosomal segment 4q35 1q35.2. On this basis, telemedicine screening was performed to evaluate for ocular abnormalities in association with abnormal gene testing. Unilateral advanced retinopathy was noted affecting the right eye, with mature vascularization in the left eye. This infant was managed in concordance with retinopathy of prematurity guidelines, despite not making screening criteria. Off-label intravitreal bevacizumab injection (0.625 mg in 0.025 mL) resulted in full vascular maturation assessed by fluorescein angiography 6 months later. This represents the first description and management of retinopathy in 4q duplication syndrome. [Ophthalmic Surg Lasers Imaging Retina 2024;55:228-230.].


Sujet(s)
Inhibiteurs de l'angiogenèse , Angiographie fluorescéinique , Rétinopathie du prématuré , Humains , Rétinopathie du prématuré/diagnostic , Rétinopathie du prématuré/traitement médicamenteux , Nouveau-né , Mâle , Inhibiteurs de l'angiogenèse/usage thérapeutique , Inhibiteurs de l'angiogenèse/administration et posologie , Angiographie fluorescéinique/méthodes , Bévacizumab/usage thérapeutique , Bévacizumab/administration et posologie , Injections intravitréennes , Prématuré , Duplication chromosomique/génétique
15.
Retina ; 44(6): 1073-1082, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38346099

RÉSUMÉ

PURPOSE: To analyze the outcomes of eyes treated for retinopathy of prematurity in posterior Zone I. METHODS: In a part retrospective (9 years) and part prospective (1 year) interventional study, we analyzed eyes treated for retinopathy of prematurity in posterior Zone I with a minimum follow-up for 6 months. RESULTS: This study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) g, respectively. The treatment included intravitreal anti-vascular endothelial growth factor as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in eight eyes, either alone (n = 3) or in combination with surgery (n = 5). With anti-vascular endothelial growth factor alone, 30.68% (n = 27) eyes responded favorably, and the remaining 69.32% (n = 59) eyes needed retreatment (laser in the majority). At the final follow-up, 89.9% (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation ( P < 0.0001) and the presence of well-defined central vascular trunks ( P = 0.001). CONCLUSION: Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior Zone I retinopathy of prematurity.


Sujet(s)
Inhibiteurs de l'angiogenèse , Âge gestationnel , Injections intravitréennes , Coagulation par laser , Rétinopathie du prématuré , Facteur de croissance endothéliale vasculaire de type A , Humains , Rétinopathie du prématuré/chirurgie , Rétinopathie du prématuré/traitement médicamenteux , Rétinopathie du prématuré/thérapie , Rétinopathie du prématuré/diagnostic , Inhibiteurs de l'angiogenèse/usage thérapeutique , Inhibiteurs de l'angiogenèse/administration et posologie , Études rétrospectives , Femelle , Mâle , Inde/épidémiologie , Nouveau-né , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Études prospectives , Coagulation par laser/méthodes , Études de suivi , Vitrectomie/méthodes , Résultat thérapeutique , Bévacizumab/usage thérapeutique , Bévacizumab/administration et posologie , Poids de naissance , Nourrisson , Acuité visuelle
16.
Retina ; 44(6): 1063-1072, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38346114

RÉSUMÉ

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.


Sujet(s)
Inhibiteurs de l'angiogenèse , Bévacizumab , Choroïde , Âge gestationnel , Injections intravitréennes , Rétinopathie du prématuré , Tomographie par cohérence optique , Humains , Choroïde/anatomopathologie , Choroïde/imagerie diagnostique , Études prospectives , Mâle , Tomographie par cohérence optique/méthodes , Femelle , Rétinopathie du prématuré/diagnostic , Rétinopathie du prématuré/traitement médicamenteux , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Enfant , Bévacizumab/administration et posologie , Études de suivi , Nouveau-né , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Prématuré , Coagulation par laser/méthodes , Acuité visuelle
18.
Eye (Lond) ; 38(8): 1444-1453, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38200320

RÉSUMÉ

BACKGROUND: There are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment. METHODS: Infants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity. RESULTS: Of 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant. CONCLUSIONS: 24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity. GOV IDENTIFIER: NCT04004208.


Sujet(s)
Inhibiteurs de l'angiogenèse , Âge gestationnel , Prématuré , Injections intravitréennes , Récepteurs aux facteurs de croissance endothéliale vasculaire , Protéines de fusion recombinantes , Rétinopathie du prématuré , Facteur de croissance endothéliale vasculaire de type A , Humains , Récepteurs aux facteurs de croissance endothéliale vasculaire/administration et posologie , Rétinopathie du prématuré/traitement médicamenteux , Protéines de fusion recombinantes/administration et posologie , Nouveau-né , Mâle , Femelle , Inhibiteurs de l'angiogenèse/administration et posologie , Inhibiteurs de l'angiogenèse/pharmacocinétique , Inhibiteurs de l'angiogenèse/effets indésirables , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Coagulation par laser/méthodes
20.
Ophthalmic Surg Lasers Imaging Retina ; 55(3): 164-167, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38270566

RÉSUMÉ

A dichorionic, diamniotic twin born at 24-0/7 weeks and 740 g developed hyperbilirubinemia, necrotizing enterocolitis, and sepsis. Photographic imaging documented vitreous opacification, which was absent in the fellow twin. Retinal opacification was presumed secondary to embolic sepsis and responded to systemic antibiotics. Subsequent dropout of vascularized retina corresponded to areas of retinal opacification. Type 1 retinopathy of prematurity (ROP)-Zone I, Stage 3 ROP bilateral-demonstrated a rapid and durable response to off-label intravitreal bevacizumab 0.625 mg. Retinal opacification resolved between 39 and 40 weeks postmenstrual age. Systemic comorbidities may alter the appearance, course, and management of ROP. [Ophthalmic Surg Lasers Imaging Retina 2024;55:164-167.].


Sujet(s)
Rétinopathie du prématuré , Sepsie , Nouveau-né , Humains , Inhibiteurs de l'angiogenèse/usage thérapeutique , Rétinopathie du prématuré/diagnostic , Rétinopathie du prématuré/traitement médicamenteux , Facteur de croissance endothéliale vasculaire de type A , Âge gestationnel , Bévacizumab/usage thérapeutique , Rétine , Sepsie/traitement médicamenteux , Injections intravitréennes , Études rétrospectives
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