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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.

Purpose: To investigate the correlation of soluble intercellular adhesion molecule 1 (sICAM-1) and vascular endothelial growth factor (VEGF) with macular edema in patients with central retinal vein occlusion (CRVO). Methods: Twenty-nine patients who had CRVO with macular edema and 16 patients with non-ischemic ocular diseases (control group) participated. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion with fluorescein angiography and the public domain Scion Image program. Macular edema was examined by optical coherence tomography. Vitreous samples were obtained during pars plana vitrectomy. VEGF and sICAM-1 levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay. Results: The median vitreous levels of VEGF and sICAM-1 were significantly higher in the CRVO patients than in the control group [366 vs. 15.6 pg/ml ( P < 0.001) and 20.5 vs. 5.0 ng/ml ( P < 0.001), respectively]. Vitreous levels of both VEGF and sICAM-1 were also significantly higher in the CRVO patients who had retinal ischemia than in those without ischemia ( P < 0.001 and P = 0.011, respectively). Vitreous levels of VEGF and sICAM-1 were also significantly correlated with the severity of macular edema ( P = 0.004 and P = 0.012, respectively). Conclusions: VEGF and sICAM-1 may both increase vascular permeability in CRVO patients with macular edema, with sICAM-1 acting together with and/or via VEGF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influences macular edema in patients with central retinal vein occlusion (CRVO). Materials and Methods: In 27 patients who had CRVO with macular edema and 21 patients with nonischemic ocular diseases (control group), retinal ischemia was evaluated by measuring the area of capillary nonperfusion on fluorescein angiography and macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained during pars plana vitrectomy. Results: The vitreous level of VEGF was significantly higher in the CRVO patients than in the controls (median: 366 vs. 15.6 pg/ml, P < 0.0001), while the vitreous level of PEDF was significantly lower in the patients than in the controls (median: 17.5 vs. 28.4 ng/ml, P == 0.0298). Vitreous levels of VEGF were significantly higher in CRVO patients with retinal ischemia than in those without ischemia ( P < 0.0001), while PEDF levels did not show a significant difference. Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea ( P == 0.0059 and P == 0.0308, respectively). Conclusions: VEGF and PEDF may independently influence retinal vascular permeability in CRVO patients with macular edema. [ABSTRACT FROM AUTHOR]

Background: We investigated whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influence macular edema in patients with branch retinal vein occlusion (BRVO). This investigation aimed to clarify the influence of PEDF in the vitreous fluid on retinal vascular permeability in patients with macular edema secondary to BRVO. The findings were expected to be useful for the treatment of macular edema in BRVO patients. Methods: This was a retrospective cross-sectional comparative case series. Thirty-three BRVO patients with macular edema and 24 control patients with nonischemic ocular diseases were enrolled. Retinal ischemia was evaluated by measuring the area of capillary nonperfusion on fluorescein angiography with Scion Image software. Macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained via pars plana vitrectomy, and the VEGF and PEDF levels were determined by enzyme-linked immunosorbent assay. Results: The vitreous level of VEGF was significantly higher in BRVO patients than controls ( P < 0.001). The vitreous PEDF level was significantly lower in BRVO patients than controls ( P = 0.026). In BRVO patients, vitreous levels of PEDF and VEGF showed a significant negative correlation with each other ( P < 0.001). Additionally, the vitreous VEGF level had a significant positive correlation ( P < 0.001) and the vitreous PEDF level had a significant negative correlation ( P < 0.001) with the nonperfused retinal area in BRVO patients. Furthermore, vitreous levels of VEGF and PEDF showed significant positive ( P = 0.001) and negative ( P = 0.014) correlations, respectively, with macular edema in BRVO patients. Conclusions: VEGF and PEDF may inversely influence retinal vascular permeability in patients with ischemic BRVO and macular edema. However, prospective validation will be needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Background: In patients who have macular edema secondary to retinal vein occlusion, the role of vasoactive molecules such as growth factors and the influence of molecules related to leukocyte adhesion need to be investigated further. Methods: A prospective study was performed to investigate the relations between perifoveal capillary blood flow velocity and the vitreous levels of vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with macular edema and retinal vein occlusion. Undiluted vitreous specimens were obtained from 11 eyes of 11 patients with macular edema (nine had branch retinal vein occlusion and two had central retinal vein occlusion). VEGF and sICAM-1 levels were measured by enzyme-linked immunoabsorbent assay. Before vitreous sampling, perifoveal capillary blood flow velocity was measured by fluorescein angiography with a scanning laser ophthalmoscope and the tracing method. The relations between perifoveal capillary blood flow velocity and the vitreous levels of VEGF and sICAM-1 were investigated. Results: There was a significant correlation between perifoveal capillary blood flow velocity and the vitreous level of sICAM-1 ( ρ = −0.7303, p = 0.03). In contrast, there was no significant association between blood flow velocity and the vitreous level of VEGF ( ρ = −0.1458, p = 0.67). Conclusions: The vitreous level of sICAM-1 is associated with perifoveal capillary blood flow velocity in patients who have retinal vein occlusion and macular edema. [ABSTRACT FROM AUTHOR]

Purpose: To investigate perifoveal capillary blood flow velocity and retinal thickness at the central fovea in patients with branch retinal vein occlusion (BRVO) and macular edema and to assess their relation with visual acuity and visual prognosis. Methods: Eighteen patients with BRVO and 16 healthy volunteers were compared. Perifoveal capillary blood flow velocity was measured on fluorescein angiograms with a scanning laser ophthalmoscope by the tracing method. Retinal thickness was measured at the central fovea by optical coherence tomography. Best-corrected visual acuity (BCVA) was determined. Results: BCVA differed significantly between patients and controls ( P < 0.0001). Among patients, BCVA was negatively correlated with perifoveal capillary blood flow velocity by univariate analysis ( r = −0.7916, P < 0.0001), and positively correlated with retinal thickness at the central fovea ( r = 0.8970, P < 0.0001). Multivariate analysis showed that retinal thickness at the central fovea was the only independent determinant of BCVA ( P < 0.0001). Conclusions: In patients with BRVO, BCVA was more strongly influenced by retinal thickness at the central fovea than by perifoveal capillary blood flow velocity. [ABSTRACT FROM AUTHOR]

Acta Ophthalmol. 2010: 88: 646–651 Purpose: This study aimed to investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) influence macular oedema in patients with central retinal vein occlusion (CRVO). Methods: Sixteen consecutive patients with unilateral CRVO and macular oedema were studied, along with eight age- and sex-matched patients without ischaemic ocular disease. Retinal ischaemia was evaluated from capillary non-perfusion on fluorescein angiography. Macular oedema was examined by optical coherence tomography. Aqueous humour (AH) samples were obtained during combined pars plana vitrectomy and cataract surgery, and were examined by enzyme-linked immunosorbent assay. Results: Aqueous levels of VEGF and IL-6 were significantly elevated in patients compared with controls (p = 0.0142 and p < 0.0001, respectively). Aqueous levels of both molecules were significantly higher in patients with ischaemia than in those without ischaemia (p = 0.0026 and p = 0.0487, respectively). Furthermore, AH levels of VEGF and IL-6 were correlated with the severity of macular oedema (ρ = 0.7265, p = 0.0049, ρ = 0.5324, and p = 0.0392, respectively). Conclusions: Both VEGF and IL-6 were elevated in the AH of patients with macular oedema and ischaemic CRVO, suggesting that these molecules may be related to the increase in vascular permeability in such patients. [ABSTRACT FROM AUTHOR]

The changes of perifoveal capillary blood flow velocity (BFV), visual acuity, and retinal thickness after pars plana vitrectomy (PPV) have been unclear in patients with branch retinal vein occlusion (BRVO) and macular edema. In a prospective study, PPV was performed on six eyes of six consecutive BRVO patients with macular edema (two women and four men; mean age: 66.3 ± 5.0 years). Patients were examined preoperatively and 6 months postoperatively. BFV was measured by fluorescein angiography using a scanning laser ophthalmoscope and the tracing method. Macular thickness was examined by optical coherence tomography. Visual acuity was measured preoperatively and postoperatively, and data were converted to the logarithm of the minimum angle of resolution (logMAR). In all six treated eyes, the macular thickness decreased significantly compared with before PPV (464 ± 98 μm versus 224 ± 55 μm, P = 0.0082), mean BFV increased significantly compared with before PPV (1.14 ± 0.14 mm/sec versus 1.46 ± 0.21 mm/sec, P = 0.0013), and mean logMAR decreased significantly compared with before PPV (0.57 ± 0.34 versus 0.17 ± 0.21, P = 0.0036). PPV may improve perifoveal microcirculation and the visual prognosis in BRVO patients with macular edema. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Purpose: To investigate the relationship between blood flow velocity in perifoveal capillaries and retinal thickness at the central fovea in diabetic patients with clinically significant macular edema to elucidate the pathogenesis of diabetic macular edema. Design: Comparative, cross-sectional, prospective study. Participants: Participants included diabetic patients with clinically significant macular edema (n = 22), matched diabetic patients without clinically significant macular edema (n = 22), and healthy volunteers (n = 16). Methods: Perifoveal capillary blood flow velocity was measured with fluorescein angiography using a scanning laser ophthalmoscope and was analyzed by the tracing method. The severity of perifoveal capillary abnormalities among diabetic patients without clinically significant macular edema was classified by the size and outline of the foveal avascular zone and extent of foveal capillary loss at the baseline by the use of fluorescein angiograms. Retinal thickness at the central fovea was measured by optical coherence tomography. Main Outcome Measures: Relationship between perifoveal capillary blood flow velocity and retinal thickness at the central fovea. Results: Perifoveal capillary blood flow velocity was significantly slower in the patients with clinically significant macular edema (0.94±0.09 mm/second) compared with the patients without clinically significant macular edema (1.22±0.20 mm/second) and the healthy volunteers (1.49±0.11 mm/second; P<0.0001). Capillary blood flow velocity negatively correlated with retinal thickness at the central fovea (r = −0.4018, P<0.0001). Capillary blood flow velocity varied among diabetic patients without clinically significant macular edema, and there were significant negative correlations between capillary blood flow velocity and the size of the foveal avascular zone (r = −0.52, P = 0.01), the outline of the foveal avascular zone (r = −0.44, P = 0.04), and the extent of foveal capillary loss (r = −0.51, P = 0.01). Conclusions: The reduction of perifoveal capillary blood flow velocity may occur before the increase of retinal thickness at the central fovea in the diabetic patients. It is possible that long-term reduction of blood flow velocity increases retinal thickness of the macula and may play an important role in the development and the progression of diabetic macular edema. [Copyright &y& Elsevier]

Purpose: To investigate whether vitreous levels of vascular endothelial growth factor (VEGF) and pigment epithelium–derived factor (PEDF) are related to diabetic macular edema (DME). Design: Retrospective case–control study. Participants: Thirty-six patients with DME, 6 diabetic patients without retinopathy, and 13 patients with nondiabetic ocular disease. Methods: After vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. Main Outcome Measures: Correlations between vascular permeability and the vitreous fluid levels of VEGF and PEDF. Results: The vitreous level of VEGF was significantly higher in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). Conversely, the vitreous level of PEDF was significantly lower in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). The vitreous level of PEDF did not correlate significantly with that of VEGF (P = 0.1806). The vitreous level of VEGF was significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0022). Conversely, the vitreous PEDF level was significantly lower in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P<0.0001 and P = 0.0469, respectively). Conclusions: Our retrospective study suggests that VEGF and PEDF have an independent association with vascular permeability in the eye and on the DME, and we recommend that prospective validation of our findings be undertaken to confirm these observations. [Copyright &y& Elsevier]

: PurposeTo investigate whether angiotensin II (AII) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in patients with and without posterior vitreous detachment (PVD).: DesignA case-control study.: MethodsVitreous fluid samples were obtained at vitreoretinal surgery from 28 eyes of 28 DME patients without PVD, 8 eyes of 8 DME patients with PVD, 14 eyes of 14 nondiabetic patients, and 8 eyes of diabetic patients without retinopathy. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay.: ResultsThe vitreous levels of AII and VEGF were significantly higher in DME patients with or without PVD than in nondiabetic patients or diabetic patients without retinopathy (without PVD: P < .0061, P < .0001, P = .0261, and P < .0001; with PVD: P < .0012, P < .0001, P = .0473, and P < .0001, respectively). There was no significant difference in the vitreous levels of AII or VEGF between patients with or without PVD (P = .4948 and P = .6642, respectively). The vitreous level of AII significantly correlated with that of VEGF in DME patients without PVD (P = .576) or with PVD (P = .488). AII and VEGF levels in vitreous fluid were significantly higher than the respective plasma levels.: ConclusionsWe found that the vitreous levels of AII and VEGF were elevated in DME patients irrespective of the status of PVD. Angiotensin II and VEGF may be induced in the eyes and be related to the pathogenesis of DME. [Copyright &y& Elsevier]

Purpose: To investigate relationships among vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial growth factor (VEGF), and soluble intercellular adhesion molecule 1 (sICAM-1) in patients with branch retinal vein occlusion (BRVO) and macular edema or patients with idiopathic macular hole. Design: Retrospective case-control study. Methods: setting: Tokyo Women''s Medical University and Eguchi Eye Hospital. patient population: Forty-nine Japanese patients who underwent unilateral vitrectomy (27 with BRVO and 22 with macular hole). observation procedures: Vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of sVEGFR-2, VEGF, and sICAM-1. Retinal ischemia was evaluated from capillary nonperfusion on fluorescein angiography. Macular edema was examined by optical coherence tomography. main outcome measures: Vitreous fluid levels of the 3 molecules and severity of macular edema. Results: BRVO patients had a significantly higher vitreous fluid level of sVEGFR-2 (median, 1670 pg/mL; interquartile range [IQL], 1205 to 2225 pg/mL) than macular hole patients (median, 1265 pg/mL; IQR, 731 to 1800 pg/mL; P = .017), as was the case for VEGF (median, 237 pg/mL; IQR, 42.2 to 1305 pg/mL; vs median, 15.6 pg/mL; IQR, 15.6 to 15.6 pg/mL; P < .001) and sICAM-1 (median, 10.1 ng/mL; IQR, 6.3 to 22.5 ng/mL; vs median, 4.1 ng/mL; IQR, 3.3 to 6.0 ng/mL; P < .001). In BRVO patients, there was a significant positive correlation between vitreous fluid levels of sVEGFR-2 or VEGF and sICAM-1, but not between sVEGFR-2 and VEGF. Vitreous fluid levels of all 3 molecules were correlated significantly the with severity of macular edema in BRVO patients. Conclusions: sVEGFR-2 may induce an increase of vascular permeability together with or via sICAM-1, or both with and via sICAM-1, in BRVO patients with macular edema. [Copyright &y& Elsevier]