[Off-label use of intravitreal bevacizumab for severe retinopathy of prematurity]. / Uso off-label de bevacizumab intravítreo en retinopatía del prematuro severa.

OBJECTIVE: To examine the quality of evidence and the variability in the off-label use of intravitreal bevacizumab for retinopathy of prematurity (ROP). METHODS: A wide review of the literature was performed using Pubmed, Medline, and Cochrane database, using the words vascular endothelial growth factor (VEGF), retinopathy of prematurity, treatment and bevacizumab. RESULTS: Case reports, case series, reviews, one sistematic review and one randomized controlled trial were found on the use of intravitreal bevacizumab in severe ROP, as monotherapy or combined with láser and/or vitrectomy. CONCLUSIONS: The results shown on the use of intravitreal bevacizumab in ROP stage 3+ in zone I or in aggressive posterior ROP are promising. However, uncertainty remains regarding its maximum tolerable dose in the neonatal group, its ocular and systemic safety profile, or its efficacy and bioactivity in a developing child. This report found no significant differences in the recurrence rates of ROP stage 3+ in zone II in patients treated with intravitreal bevacizumab monotherapy in comparison to láser, although the latter is the best option due to long-term safety and efficacy. The use of intravitreal bevacizumab is not indicated in stages 1 and 2 of ROP as the risk of severe visual loss is low and VEFG is necessary for normal retinal vessel development. On the other hand, the use of intravitreal bevacizumab would be contraindicated in stages 4 and 5 because the retinal detachment is accelerated.

Non-invasive monitoring of hypoxia-inducible factor activation by optical imaging during antiangiogenic treatment in a xenograft model of ovarian carcinoma.

Targeting the hypoxia response pathway and angiogenesis are two promising therapeutic strategies for cancer treatment. Their use as single strategies has important limitations. Thus, development of combined regimens has become an important step toward improving therapeutic efficacy. Also, non-invasive monitoring of the response to targeted biological therapies, as well as determination of the optimal schedule for combination regimens has become an active field of research over the last five years, with relevance for both preclinical and clinical settings. Here, we used an optical imaging method to non-invasively monitor the functional changes in HIF activity in response to antiangiogenic treatment in a xenograft model of human ovarian carcinoma. A bioluminescent reporter construct containing nine copies of the hypoxia response element upstream of the luciferase gene (9xHRE-luciferase) was characterized in vitro in a panel of tumor cell lines and in vivo in a subcutaneous xenograft model of ovarian carcinoma by means of optical imaging. We showed that in OVCAR-3 subcutaneous xenografts, the most abrupt change in the HIF functional reporter occurs before the onset of massive tumor growth. However, this system failed to detect hypoxia induced upon antiangiogenic treatment due to the compensating effects of increased hypoxia and decreased tumor cell viability caused by imbalanced neovascularization vs. tumor expansion. Therefore, the readout based on HIF functional reporter could be conditioned by the dynamics of tumor growth and angiogenesis, which is highly variable depending on the tumor type, tumor model and stage of progression.