Aqueous Vascular Endothelial Growth Factor Research Articles

CHANGES IN AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR AND PIGMENT EPITHELIAL-DERIVED FACTOR LEVELS FOLLOWING INTRAVITREAL BEVACIZUMAB INJECTIONS FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION OR PATHOLOGIC MYOPIA

To evaluate the changes in aqueous vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) following intravitreal bevacizumab injections for choroidal neovascularization (CNV) secondary to age-related macular degeneration or pathologic myopia. Aqueous samples were obtained at the time of injection from 51 eyes of 51 patients who underwent three monthly intravitreal bevacizumab (Avastin) injections at baseline, 1, and 2 months. Concentrations of VEGF and PEDF in the aqueous were evaluated using enzyme-linked immunosorbent assay and compared. For the 34 eyes with age-related macular degeneration CNV, the mean +/- standard deviation aqueous VEGF level reduced from 102.6 pg/mL +/- 90.6 pg/mL at baseline to 18.3 pg/mL +/- 22.5 pg/mL at 2 months (P < 0.001), whereas the mean PEDF level increased from 11.2 ng/mL +/- 10.4 ng/mL at baseline to 38.7 ng/mL +/- 47.9 ng/mL at 2 months (P = 0.001). For the 17 eyes with myopic CNV, the mean +/- standard deviation aqueous VEGF level reduced from 20.1 pg/mL +/- 28.9 pg/mL at baseline to 3.8 pg/mL +/- 5.3 pg/mL at 2 months (P = 0.016), whereas the mean PEDF level increased from 20.0 ng/mL +/- 16.3 ng/mL at baseline to 126.0 ng/mL +/- 152.0 ng/mL at 2 months (P = 0.016). Intravitreal bevacizumab injections resulted in reduced aqueous VEGF and increased PEDF levels in patients with CNV secondary to age-related macular degeneration or pathologic myopia. These changes may be favorable for the inhibition of CNV angiogenesis.

Intracameral bevacizumab effectively reduces aqueous vascular endothelial growth factor concentrations in neovascular glaucoma

Vascular endothelial growth factor (VEGF) concentrations in both the aqueous and vitreous are raised in ocular ischaemia secondary to exudative age-related macular degeneration, diabetes mellitus and other retinal vascular diseases.1...

Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Implication of VEGF as a Critical Stimulator

Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.

The Changes of Aqueous Vasopermeability Factors After Intravitreal Triamcinolone Injection for Branch Retinal Vein Occlusion

Purpose: To investigate the changes of aqueous vascular endothelial growth factor (VEGF) and interleukin (IL)-6 in patients with acute macular edema secondary to recent-onset branch retinal vein occlusion (BRVO) after a single intravitreal injection of triamcinolone acetonide (IVTA) Methods: Aqueous and plasma levels of VEGF and IL-6 were measured by ELISA in ten controls and thirty patients at the time of IVTA and 3 months afterward. We compared the aqueous levels of VEGF and IL-6 and the clinical course between responders and non-responders. Results: The aqueous levels of VEGF and IL-6 were significantly higher in non-responders than in responders at baseline measurements (495±259 pg/ml vs. 223±110 pg/ml, P

Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy

Purpose We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. Methods Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. Results The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly ( r = 0.6; p = 0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. Conclusions By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.

Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion.

To establish a role for vascular endothelial growth factor (VEGF) during the onset and clinical course of neovascularization of the iris (NVI) in ischemic central retinal vein occlusion. Sixteen patients with ischemic central retinal vein occlusion were followed up for 12 months by clinical examination, retinal and iris angiography, and serial anterior chamber sampling of aqueous humor. Aqueous VEGF level was determined by enzyme-linked immunoassay, and permeability changes were estimated by capillary zone electrophoretic assessment of aqueous albumin. A correlation was found between aqueous VEGF concentrations and the onset, persistence, and regression of NVI; extent of retinal capillary nonperfusion; and vascular permeability. The NVI occurred when aqueous VEGF concentrations were 849 to 1569 pg/mL and regressed fully when they fell below 550 pg/mL. Aqueous concentrations of serum albumin, a marker of increased permeability, correlated with increased VEGF. Placental growth factor was found at low levels only when VEGF levels exceeded 330 pg/mL. The NVI remained VEGF-dependent during the course of the disease, regressing only if VEGF concentrations were reduced after laser ablation of hypoxic retina. The close temporal correlation between aqueous VEGF levels and the course of neovascularization and permeability in human ischemic central retinal vein occlusion indicates that increased aqueous VEGF level may predict the need for treatment, and that anti-VEGF therapy at an early stage of ischemic central retinal vein occlusion may be therapeutically beneficial.

Prediction of macular edema exacerbation after phacoemulsification in patients with nonproliferative diabetic retinopathy

Purpose To ascertain whether the aqueous humor levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and protein can predict the postoperative exacerbation of macular edema in patients with nonproliferative diabetic retinopathy (NPDR) after phacoemulsification surgery for cataract. Setting Department of Ophthalmology, Diabetes Center, Tokyo Women’s Medical University, Tokyo, Japan. Methods This prospective study included 104 consecutive patients (104 eyes) with NPDR who had cataract surgery. The concentrations of VEGF and IL-6 in aqueous humor specimens obtained during cataract surgery were measured by enzyme-linked immunosorbent assay. Patients were followed for 6 months to assess the postoperative exacerbation of macular edema. Results Ninety patients (87%) achieved a visual acuity of 20/40 or better. Exacerbation of macular edema was seen in 30 eyes (29%) after 6 months. Hypertension and the aqueous levels of VEGF, IL-6, and protein were significantly correlated with the exacerbation of macular edema (odds ratio 1.16, 1.33, 1.27, and 1.28, respectively). In contrast, there was no correlation between the exacerbation of macular edema and other systemic factors. Multivariate logistic regression analysis showed that the aqueous VEGF level increase of 100 pg/mL increased the macular edema after phacoemulsification surgery (odds ratio 1.53). Conclusions A high VEGF level in the aqueous humor predicted a significant risk for the postoperative exacerbation of macular edema. A model was developed to predict the risk exacerbation.

Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus

AIMSTo determine the relation between the stages of diabetic retinopathy (DR) and the levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in aqueous fluid and serum.METHODSLevels...

Aqueous Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Decrease During Regression of Rabbit Pupillary Membrane

We studied the roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the aqueous during regression of the pupillary membrane in rabbits. Aqueous samples were obtained using a 30-gauge needle passed through the limbus in newborn rabbits. The VEGF and bFGF levels were measured by a quantitative sandwich enzyme-linked immunosorbent assay. The aqueous VEGF levels at 60 days of age (29.0–351.9 with a median of 190.5 pg/mL) decreased significantly compared with those at 12 and 20 days of age (356.7–1148.3 with a median of 752.5 pg/mL at 12 days of age and 193.5–657.7 with a median of 425.6 pg/mL at 20 days of age, Mann-Whitney U Test, P < 0.0001 and P = 0.002, respectively). The aqueous bFGF levels at 60 days of age (0.0–126.2 with a median of 63.1 pg/mL) decreased significantly compared with those at 12 days of age (33.4–301.3 with a median of 167.4 pg/mL, P < 0.0001). Light microscopically, the pupillary membrane at 12 days of age was rich with capillaries that were subsequently closed at 20 days of age, and the membrane itself disappeared at 60 days of age. The aqueous VEGF and bFGF levels decreased in the process of regression of the pupillary membrane, suggesting that VEGF or bFGF played a role in eye development such as maintenance of the pupillary membrane.

Aqueous Vascular Endothelial Growth Factor Increases in Anterior Segment Ischemia in Rabbits

Both long posterior ciliary arteries were occluded or the three extraocular muscles were tenotomized to produce anterior segment ischemia in rabbits, and the aqueous levels of vascular endothelial growth factor (VEGF) were measured. The occlusion of both long posterior ciliary arteries led to clinical and histological anterior segment ischemia in varying degrees. The aqueous VEGF levels increased significantly compared with controls on all days examined (Mann-Whitney U test: day 1, P = 0.0039; day 4, P = 0.0065; day 7, P = 0.0039; day 14, P = 0.0104), while the levels at days 7 and 14 decreased significantly compared with those at day 4 (Wilcoxon signed-rank test; day 4 to day 7 and day 4 to day 14, P = 0.0464). In contrast, tenotomy of the three extraocular muscles resulted in no histological changes. The VEGF levels increased significantly compared with controls at day 1 and day 4 after surgery (Mann-Whitney U test: day 1 and day 4, P = 0.0104), while the levels at day 14 decreased significantly compared with those at day 1 (Wilcoxon signed-rank test, P = 0.0499). Aqueous VEGF levels represent the severity of anterior segment ischemia and could be used as an indicator for the extent of ischemia.