MyVisionTest News Archive
Dec 17, 2009
Inverse association of VEGF and platelet-derived growth factor in wet AMD
Intravitreal Lucentis (ranibizumab) injections in patients with neovascular AMD results in decreased aqueous levels of VEGF and increased levels of platelet-derived growth factor (PDGF).
Methods and results
In this prospective clinical trial 28 eyes of patients with neovascular AMD were compared with 28 eyes of age-matched patients with cataract as control.
Lucentis was administered intravitreously once at baseline, and retreatments were given at monthly visits if optical coherence tomography (OCT) revealed macular edema or vision loss had occurred. Aqueous humor samples were taken each time intravitreal interventions were performed. Follow-up was 12 months. Luminex (Luminex Inc.) multiplex assays were used for measurement of 29 different growth factors and cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
A significantly increased expression of VEGF (P = 0.033) and a significantly decreased expression of PDGF (P = 0.038) were measured in the aqueous humor of eyes with neovascular AMD. Furthermore, a significant decrease of VEGF (P<0.001) was observed after intravitreal injection of Lucentis along with significant changes in visual acuity and central retinal thickness (P = 0.039 and P<0.001). During follow-up with a flexible regimen, a correlation was identified between increased VEGF levels and persistent or recurrent macular edema. Changes in PDGF levels were strongly associated with alterations in VEGF concentration.
Discussion and Conclusions
This study analyzed the distribution of various angiogenic and inflammatory factors in intraocular fluid of human eyes. The researchers found significantly increased concentrations of intraocular VEGF and significantly decreased concentrations of PDGF-AA compared with control eyes. These results indicate that levels of VEGF are not only increased within the CNV lesion but also measurably elevated in the human aqueous humor in vivo. These observations are especially interesting because RPE cells have been shown to secrete VEGF preferentially to their basal (choroidal) side in in vitro experiments.
After a single intravitreal injection of Lucentis, VEGF levels decreased to values below detection levels, that is, below the physiologic levels of VEGF in controls. This pronounced VEGF inhibition was measured at the time of the next consecutive injection. Thus, an intensive effect of Lucentis was still measurable as long as 4 weeks after injection.
VEGF levels increased to pathologically high levels whenever treatment was discontinued and disease activity recurred requiring reinjection. This finding provides solid evidence of an association of recurrent disease activity with recurrent increase in VEGF expression and shows that macular edema may be an appropriate biomarker for CNV activity.
This study found that concentrations of PDGF and VEGF in human eyes with CNV are inversely correlated - when VEGF is high PDGF is low, and vice versa. PDGF is a potent chemoattractant and activator of neutrophils, monocytes, and fibroblasts. Experimental inhibition of PDGF in an animal model promoted pericyte loss and angiogenesis in ischemic retinopathy. However, little is known about how VEGF and PDGF interact to influence angiogenesis in the human eye in vivo. Further investigations are needed to clarify the exact underlying mechanism of the VEGF/PDGF interaction.
The researchers conclude that VEGF and PDGF-AA seemed to be associated with disease activity of neovascular AMD. Intravitreal anti-angiogenic treatment with Lucentis resulted in significantly decreased intraocular VEGF expression below physiologic levels compared with controls. This effect was measurable as long as 4 weeks after each injection and was prolonged by consecutive retreatment. With recurrence after discontinuation of treatment, VEGF levels increased again.
Read more...
Ophthalmology. 2009 Dec;116(12):2393-9
Tags: Lucentis, PDGF, VEGF, wet AMD
Intravitreal Lucentis (ranibizumab) injections in patients with neovascular AMD results in decreased aqueous levels of VEGF and increased levels of platelet-derived growth factor (PDGF).Methods and results
Lucentis was administered intravitreously once at baseline, and retreatments were given at monthly visits if optical coherence tomography (OCT) revealed macular edema or vision loss had occurred. Aqueous humor samples were taken each time intravitreal interventions were performed. Follow-up was 12 months. Luminex (Luminex Inc.) multiplex assays were used for measurement of 29 different growth factors and cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
A significantly increased expression of VEGF (P = 0.033) and a significantly decreased expression of PDGF (P = 0.038) were measured in the aqueous humor of eyes with neovascular AMD. Furthermore, a significant decrease of VEGF (P<0.001) was observed after intravitreal injection of Lucentis along with significant changes in visual acuity and central retinal thickness (P = 0.039 and P<0.001). During follow-up with a flexible regimen, a correlation was identified between increased VEGF levels and persistent or recurrent macular edema. Changes in PDGF levels were strongly associated with alterations in VEGF concentration.
Discussion and Conclusions
This study analyzed the distribution of various angiogenic and inflammatory factors in intraocular fluid of human eyes. The researchers found significantly increased concentrations of intraocular VEGF and significantly decreased concentrations of PDGF-AA compared with control eyes. These results indicate that levels of VEGF are not only increased within the CNV lesion but also measurably elevated in the human aqueous humor in vivo. These observations are especially interesting because RPE cells have been shown to secrete VEGF preferentially to their basal (choroidal) side in in vitro experiments.
After a single intravitreal injection of Lucentis, VEGF levels decreased to values below detection levels, that is, below the physiologic levels of VEGF in controls. This pronounced VEGF inhibition was measured at the time of the next consecutive injection. Thus, an intensive effect of Lucentis was still measurable as long as 4 weeks after injection.
VEGF levels increased to pathologically high levels whenever treatment was discontinued and disease activity recurred requiring reinjection. This finding provides solid evidence of an association of recurrent disease activity with recurrent increase in VEGF expression and shows that macular edema may be an appropriate biomarker for CNV activity.
This study found that concentrations of PDGF and VEGF in human eyes with CNV are inversely correlated - when VEGF is high PDGF is low, and vice versa. PDGF is a potent chemoattractant and activator of neutrophils, monocytes, and fibroblasts. Experimental inhibition of PDGF in an animal model promoted pericyte loss and angiogenesis in ischemic retinopathy. However, little is known about how VEGF and PDGF interact to influence angiogenesis in the human eye in vivo. Further investigations are needed to clarify the exact underlying mechanism of the VEGF/PDGF interaction.
The researchers conclude that VEGF and PDGF-AA seemed to be associated with disease activity of neovascular AMD. Intravitreal anti-angiogenic treatment with Lucentis resulted in significantly decreased intraocular VEGF expression below physiologic levels compared with controls. This effect was measurable as long as 4 weeks after each injection and was prolonged by consecutive retreatment. With recurrence after discontinuation of treatment, VEGF levels increased again.
Read more...
Ophthalmology. 2009 Dec;116(12):2393-9
