Retinopathy of prematurity shows alterations in Vegfa164 isoform expression

Mezu‐Ndubuisi, Olachi J.; Song, Yong; Macke, Erica L.; Johnson, Hailey; Nwaba, Ginika; Ikeda, Akihiro

doi:10.1038/s41390-021-01646-9

Cited by 3 publications

(2 citation statements)

References 48 publications

(46 reference statements)

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“…Previous studies reported conflicting results of VEGFR2 expression in OIR. Whereas several studies showed no upregulation of VEGFR2 in OIR retinas of mice and rats [42][43][44], other groups reported significant induction of the receptor in OIR retinas [41,45]. Our in vivo ligand binding assay detected equivalent VEGF binding activities to retinal vessels in OIR and healthy mice, suggesting that VEGFR2 was unlikely upregulated in the disease condition [18].…”

Section: Discussioncontrasting

confidence: 47%

Safety and Efficacy of Systemic Anti-Scg3 Therapy to Treat Oxygen-Induced Retinopathy

Dai¹,

Tian²,

Bhatt³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim of this study is to investigate the safety and efficacy of a humanized anti-Scg3 antibody via systemic administration. Methods: We analyzed the safety and efficacy of a humanized anti-Scg3 antibody Fab fragment (hFab) delivered by intraperitoneal injection in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP. Results: The results showed that systemic anti-Scg3 hFab effectively alleviated pathological retinal neovascularization in OIR mice with similar efficacy to the anti-VEGF drug aflibercept. Systemic aflibercept conferred significant adverse side effects in neonatal mice, including reduced body weight, abnormalities in retinal and renal development, and retarded physiological neovascularization, whereas systemic anti-Scg3 hFab elicited no such side effects. Conclusions: The findings suggest that systemic anti-Scg3 hFab is a safe and effective therapy for OIR and support further development for ROP treatment.

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Section: Discussioncontrasting

confidence: 47%

Safety and Efficacy of Systemic Anti-Scg3 Therapy to Treat Oxygen-Induced Retinopathy

Dai¹,

Tian²,

Bhatt³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…Vascular endothelial growth factor (VEGF) 3 , 4 , one of the angiogenic factors, plays an important role in retinal vascular development. High levels of VEGF in the vitreous cavity are closely related to the development of ROP.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab

Jang

2024

Sci Rep

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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.

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Characteristics of retinal vascularization in reactivated retinopathy of prematurity and clinical outcome after reinjection of ranibizumab

Jang

2024

Preprint

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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 recurrence of retinopathy of prematurity (ROP) and whether repeated injection treatment will be effective in case of recurrence. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-reactivated ROP or reactivated 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 retinal vascularization was measured with serial RETCAM™ fundus images using disc-fovea distance (DF) unit. ROP reactivation occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean reactivation interval after the initial injection was 9.0 ± 3.3 weeks (range 4–16). In the reactivated ROP group, the time required for the resolution of plus disease after 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 reactivated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with reactivated 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. 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 ROP recurrence. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating ROP recurrence.

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Retinopathy of prematurity shows alterations in Vegfa164 isoform expression

Cited by 3 publications

References 48 publications

Safety and Efficacy of Systemic Anti-Scg3 Therapy to Treat Oxygen-Induced Retinopathy

Safety and Efficacy of Systemic Anti-Scg3 Therapy to Treat Oxygen-Induced Retinopathy

Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab

Characteristics of retinal vascularization in reactivated retinopathy of prematurity and clinical outcome after reinjection of ranibizumab

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