Hideharu Funatsu

Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema

PURPOSE To investigate the relationship between diabetic macular edema and the levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in aqueous humor and plasma. DESIGN Comparative cross-sectional study. METHODS Fifty-four eyes from 54 diabetic patients were used. The concentrations of VEGF and IL-6 in undiluted aqueous specimens (obtained from the eyes during cataract surgery) and in plasma were measured by an enzyme-linked immunosorbent assay. To assess blood-aqueous barrier function, the aqueous flare intensity was measured by a laser flare-cell meter as an estimate of the aqueous protein level. RESULTS The aqueous levels of VEGF and IL-6 were significantly correlated with the severity of macular edema (rho = 0.628, P <.001 and rho = 0.517, P <.01, respectively), as well as with the aqueous protein concentration (rho = 0.618, P <.001 and rho = 0.588, P <.001, respectively). Aqueous levels of VEGF and IL-6 were significantly higher than their respective plasma levels (both P <.001). In addition, the aqueous level of VEGF was significantly correlated with that of IL-6 (rho = 0.537, P <.01). Furthermore, the status of the posterior vitreous significantly correlated with the severity of macular edema (rho = 0.618, P <.0001). CONCLUSIONS These results suggest that both VEGF and IL-6 are produced together in the intraocular tissues, and are involved in the pathogenesis of macular edema.

Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema.

PURPOSE To investigate whether interleukin-6 (IL-6) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in subjects without posterior vitreous detachment (PVD). DESIGN Retrospective case-control study. PARTICIPANTS Twenty-six subjects who had DME without PVD and 12 subjects who had nondiabetic ocular disease (the control group). METHODS Vitreous fluid samples were obtained at vitreoretinal surgery, and the IL-6 and VEGF levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES Vitreous levels of IL-6 and VEGF in DME subjects without PVD. RESULTS The vitreous levels of both IL-6 and VEGF were significantly higher in the subjects with DME than in control subjects (P<0.0001 and P<0.0001, respectively). The vitreous level of IL-6 was significantly correlated with that of VEGF (P<0.0001). Vitreous levels of both IL-6 and VEGF were significantly higher in subjects with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0008 and P = 0.0038, respectively). CONCLUSIONS We found that the levels of both IL-6 and VEGF were elevated in the vitreous fluid of subjects with hyperfluorescent DME. Our results suggest that IL-6 and VEGF may promote an increase of vascular permeability in DME subjects without PVD. Interleukin-6 may possibly induce an increase of vascular permeability through a paracrine effect on VEGF in these subjects.

Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion

BackgroundTo investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated.MethodsWe studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays.ResultsVitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P=0.0011 and P<0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P=0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P<0.0001 and P=0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P=0.0008 and P=0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044).ConclusionsThe levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

Association of vitreous inflammatory factors with diabetic macular edema.

PURPOSE To evaluate the association between vitreous inflammatory factors and the severity of diabetic macular edema (DME). DESIGN Retrospective case-control study. PARTICIPANTS Fifty-three patients with DME, 15 patients with nondiabetic ocular disease, and 8 diabetic patients without retinopathy. METHODS Vitreous fluid samples were obtained during vitreoretinal surgery, and the levels of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and pigment epithelium-derived factor (PEDF) were measured by enzyme-linked immunosorbent assay. Multivariate analysis was performed to assess the association of these factors with the severity of DME. MAIN OUTCOME MEASURES Vitreous fluid levels of inflammatory factors. RESULTS Vitreous fluid levels of VEGF, ICAM-1, IL-6, and MCP-1 were significantly higher in patients with DME than in nondiabetic patients (P<0.05, all respectively) or diabetic patients without retinopathy (P<0.05, all respectively). In contrast, the PEDF level was significantly lower in patients with DME than in nondiabetic patients (P<0.05) or diabetic patients without retinopathy (P<0.05). Vitreous levels of VEGF, ICAM-1, IL-6, and MCP-1 were significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0018, P = 0.0022, P = 0.0032, and P = 0.0053, respectively). Conversely, the vitreous level of PEDF was significantly lower in hyperfluorescent DME than in minimally fluorescent DME (P = 0.0134). Vitreous levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were significantly correlated with the retinal thickness at the central fovea (P<0.0001, P<0.0001, P = 0.0282, P = 0.0009, and P = 0.0466, respectively). VEGF and ICAM-1 had a stronger influence on the severity of DME than the other factors (P = 0.0004 and P = 0.0372, respectively). CONCLUSIONS Vitreous fluid levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were related to retinal vascular permeability and the severity of DME. VEGF and ICAM-1 had a stronger influence than the other factors. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion

AimTo investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO).MethodsAqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT.ResultsThe aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively).ConclusionOur results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.

Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients.

BackgroundCytokine levels are elevated in the ocular fluid of diabetic patients. It is unclear whether aqueous humor levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are related to the vitreous fluid levels of these substances and to the progression of diabetic retinopathy.MethodsAqueous humor and vitreous fluid samples were obtained during cataract and vitreous surgery from ten eyes of ten patients with diabetic macular edema and 26 eyes of 26 patients with proliferative diabetic retinopathy (PDR). The VEGF and IL-6 levels in aqueous humor, vitreous fluid, and plasma were measured by enzyme-linked immunosorbent assay.ResultsVEGF and IL-6 levels in aqueous humor were significantly correlated with those in vitreous fluid (ρ=0.793 and ρ=0.737, respectively). VEGF levels in aqueous humor and vitreous fluid were significantly correlated with the corresponding IL-6 levels (ρ=0.631 and ρ=0.687, respectively). The aqueous and vitreous levels of VEGF were significantly correlated with the severity of diabetic retinopathy (ρ=0.659 and ρ=0.771, respectively). Aqueous and vitreous levels of IL-6 were also significantly correlated with the severity of diabetic retinopathy (ρ=0.742 and ρ=0.746, respectively). Aqueous and vitreous levels of both VEGF and IL-6 were significantly higher in the patients with active PDR than those in quiescent PDR.ConclusionsOur results suggest that there is a significant relationship between VEGF and IL-6 levels in aqueous humor and in vitreous fluid. Measurement of the aqueous levels of VEGF and IL-6 may be useful to analyze the pathogenesis of diabetic retinopathy and to predict disease activity.

Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders

PURPOSE To investigate the correlation between angiotensin II (AII) or vascular endothelial growth factor (VEGF) levels in the vitreous fluid and the severity of diabetic macular edema (DME). DESIGN A case-control study. METHODS Vitreous fluid samples were obtained at the time of vitreoretinal surgery from 20 eyes of 20 patients with DME, 6 eyes of 6 diabetic patients without retinopathy, and 14 eyes of 14 nondiabetic patients. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay. RESULTS The vitreous concentration of VEGF was significantly higher in patients with DME than in nondiabetic patients or diabetic patients without retinopathy (P <.0001 and P <.0001, respectively). Vitreous levels of AII were also higher in patients with DME than in nondiabetic patients (P =.0082). The vitreous concentration of AII was significantly correlated with that of VEGF (P =.0022). Vitreous concentrations of both AII and VEGF were significantly higher in patients with hyperfluorescent DME than in those with hypofluorescent (P =.0228 and P =.0068, respectively). CONCLUSIONS We found that the levels of both AII and VEGF were elevated in the vitreous fluid of patients with hyperfluorescein DME. Our results suggest that both AII and VEGF are related to the increase of vascular permeability in DME.

Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion.

OBJECTIVE To investigate whether interleukin (IL)-6 or vascular endothelial growth factor (VEGF) influences macular edema in patients with central retinal vein occlusion (CRVO). DESIGN Retrospective case-control study. PARTICIPANTS Twenty-seven patients who had macular edema with CRVO and 16 patients with nonischemic ocular diseases (control group). METHODS Retinal ischemia was evaluated by measuring the area of capillary nonperfusion using fluorescein angiography and the public domain Scion Image program, and macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained at pars plana vitrectomy. VEGF and IL-6 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. MAIN OUTCOME MEASURES Vitreous fluid levels of IL-6 and VEGF. RESULTS The vitreous fluid levels of VEGF (median: 435 pg/ml) and IL-6 (median: 51.2 pg/ml) were significantly higher in the patients with CRVO than in the control group (median: 62.4 pg/ml and 1.07 pg/ml, respectively; P = 0.0046 and P<0.0001, respectively). The vitreous fluid level of VEGF was significantly correlated with that of IL-6 (P = 0.0029). Vitreous fluid levels of both VEGF and IL-6 were significantly higher in patients with CRVO who had retinal ischemia than in those without ischemia (P<0.0001 and P = 0.0003, respectively). Vitreous fluid levels of VEGF and IL-6 were also significantly correlated with the severity of macular edema (P = 0.0014 and P = 0.0047, respectively). CONCLUSIONS Both IL-6 and VEGF were elevated in the vitreous fluid of patients with ischemic CRVO and macular edema. VEGF may increase vascular permeability in patients with macular edema and CRVO, whereas IL-6 may also contribute by acting together with or via VEGF. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy

Aims: To investigate the correlation between the level of angiotensin II and vascular endothelial growth factor (VEGF) in the vitreous fluid and the severity of proliferative diabetic retinopathy (PDR). Methods: During vitreoretinal surgery at the Tokyo Womens Medical University, vitreous fluid samples were obtained from 51 eyes of diabetic patients with PDR, six eyes of diabetic patients without retinopathy, and 16 eyes of non-diabetic patients with ocular disease (controls). The VEGF levels in vitreous fluid and plasma were determined by enzyme linked immunosorbent assay, while angiotensin II levels were measured by radioimmunoassay. Results: The vitreous fluid levels of VEGF and angiotensin II were significantly higher in patients with PDR than in non-diabetic patients or diabetic patients without retinopathy (all p<0.0001). The vitreous fluid level of angiotensin II was significantly correlated with that of VEGF (p<0.0001), and the vitreous concentrations of both VEGF and angiotensin II were significantly higher in patients with active PDR than in those with quiescent PDR (p<0.0001 and p=0.0005, respectively). Conclusion: The authors found that both angiotensin II and VEGF levels were significantly higher in the vitreous fluid of patients with PDR than in that of non-diabetic patients or diabetic patients without retinopathy, and that the levels of both angiotensin II and VEGF were elevated in the active stage of PDR. These findings suggest that angiotensin II contributes to the development and progression of PDR in combination with VEGF.

Relationship between vascular endothelial growth factor and interleukin-6 in diabetic retinopathy.

Purpose To determine the relationship between the severity of diabetic retinopathy and the levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in aqueous humor and plasma. Methods Forty-four eyes of 34 diabetic patients were studied. The concentrations of VEGF and IL-6 in plasma samples and in aqueous specimens obtained from the eyes during cataract surgery were measured by enzyme-linked immunosorbent assay. Results Aqueous levels of VEGF and IL-6 were significantly correlated with the severity of diabetic retinopathy (&rgr; = 0.793 and &rgr; = 0.744, respectively). Vascular endothelial growth factor and IL-6 levels in aqueous humor were significantly correlated with the aqueous protein concentration (&rgr; = 0.641 and &rgr; = 0.646, respectively). The aqueous level of VEGF was significantly correlated with that of IL-6 (&rgr; = 0.627). Aqueous levels of VEGF and IL-6 were also significantly correlated with the grade of fundus findings. Vascular endothelial growth factor and IL-6 concentrations were higher in the aqueous than in the plasma. Conclusion The results of the current study suggest that there is a relationship between VEGF and IL-6 but the role of IL-6 in diabetic retinopathy is unclear and may warrant further investigation.