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Lingkun Kong, Emmanuel Chang, Ann B. Demny, Sridevi Devaraj, Tim Stout; Bevacizumab and Angiogenesis Factors Levels in the Vitreous of Recurrent Retinopathy of Prematurity after Intravitreal Injection of Bevacizumab. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5556.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate vitreous levels of bevacizumab and angiogenesis cytokine profiles in recurrent ROP infants and to study the correlation of these levels between plasma and vitreous.
This is a prospective pilot study. Five infants and 7 eyes with recurrence of stage 4 and 5 ROP after intravitreal injection of bevacizumab or ablation laser surgery were included in this study. The ROP eyes were divided into 2 groups according to vascular activity: vascular active ROP and vascular inactive ROP. Undiluted vitreous samples were obtained from mid vitreous suing a 2-port closed vitrectomy technique with manual suction. Blood samples were collected at time type I ROP was diagnosed (T0) and time prior to vitrectomy. Plasma and vitreous levels of bevacizumab levels were measure using ELISA, and 9 cytokines from the angiogenesis growth factor panel and 7 soluble cytokine receptors were measured using magnetic multiplex assay.
Bevacizumab was detectable in the vitreous until1 month after injection. VEGFA level in the vitreous was significantly higher in all vascular active recurrent ROP patient compared to that in vascular inactive recurrent ROP vitreous. In the vitreous of vascular active ROP, in comparison to vascular inactive disease, levels of VEGF A, VEGF C, Ang-2, PLGF, sVEGFR1, sVEGFR2, sVEGFR3, sTNFR I and sTNFR II were upregulated. ET-1 and sVEGF D were not detectable in the vitreous of either group. Plasma angiogenesis cytokines level were similar between time 0 and at the time of recurrent active ROP was diagnosed, except sVEGF A which was significantly lower in the plasma of recurrent ROP infants, p=0.0001.
ROP recuured in infants who had high levels of bevacizumab, which suggests that bevacizumab as monotherapy is not effective treatment for all ROP. The results also suggested that pathogenesis of recurrent ROP is multifactorial which includes many angiogenesis factors, such as Ang-2, PLGF and VEGFA, VEGF C, Ang-2, PLGF, sVEGFR1, sVEGFR2, sVEGFR3, sTNFR I and sTNFR II.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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