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At least 1,279 records · Page 71Linked to original sources
PubMed2005

Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice.

BACKGROUND: Retinal neovascularisation occurs under the influence of angiogenic factors that are induced by hypoxia, like vascular endothelial growth factor (VEGF), which is one of the major mediators. PTK/ZK inhibits VEGF signal transduction by blocking the tyrosine kinase of all three VEGF receptors. PTK/ZK is currently being evaluated in clinical trials for angioinhibitory therapy in tumour patients. To avoid potential systemic side effects, local application would be desirable for the treatment of ischemic retinopathies in humans. We therefore investigated the effect of intravitreally applied PTK/ZK in a mouse model for ischemia-induced retinopathy. METHODS: C57BL/6J mice were placed in 75% oxygen on postnatal day 7. On day 12, they were treated with an intravitreal injection of PTK/ZK (5 microM or 40 microM) in one eye and buffer solution in the fellow eye. Afterwards, the animals were kept in room air until intracardial perfusion with fluorescein-dextran on day 17. Retinal whole mounts were prepared and ischemic retinopathy was evaluated using a standardised retinopathy score. RESULTS: A single intravitreal injection of 40 microM PTK/ZK reduced angioproliferative changes compared to the control eye of each animal (n=37). The difference in retinopathy scores was highly significant (P=0.002, Wilcoxon signed-rank test). Injection of 5 microM PTK/ZK did not show a significant antiangiogenic effect. CONCLUSIONS: Tyrosine kinase inhibitors are promising substances not only in cancer therapy, but also in the treatment of ischemic retinopathies that are mediated by VEGF. We showed that in a mouse model for ischemia-induced retinopathy a single intravitreal injection of 40 microM PTK/ZK is capable of significantly reducing angioproliferative retinopathy. The local application of PTK/ZK could be a new way to treat ischemic ocular diseases such as diabetic retinopathy in humans.

Animals↗
PubMed2004

Retinal angiomatous proliferation with a cilioretinal artery anastomosis: an unusual presentation.

PURPOSE: To report an unusual phenotype of retinal angiomatous proliferation (RAP) in age-related macular degeneration (AMD) and its short-term response to laser photocoagulation. METHODS: Case report. RESULTS: An 85-year-old woman was found to have an unusual RAP with a major feeder vessel originating from a cilioretinal artery and associated with a cilioretinal-retinal anastomosis (C-RRA). Diffuse cystoid macular edema (CME), intraretinal hard exudates in a circinate pattern, and a fibrovascular pigment epithelial detachment (PED) were present. Laser photocoagulation was performed and led to occlusion of the cilioretinal feeder vessel and angiomatous lesion, with less CME. The other (retinal) arm of the C-RRA became more engorged and a new cilioretinal feeder developed, and both were associated with intraretinal hemorrhages. Visual acuity was stable and the PED persisted throughout follow-up. CONCLUSIONS: We report an unusual phenotype of RAP that is associated with a major cilioretinal feeder vessel and comment on the possible effect of such an association on the response to laser treatment.

Aged↗
PubMed2006

Retinal angiomatous proliferation treated by intravitreal triamcinolone and photodynamic therapy with verteporfin.

PURPOSE: To examine combined treatment of intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP). METHODS: Ten eyes of eight consecutive patients with RAP underwent a single injection (about 20 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity (BCVA) was measured by standardized protocol refraction. RESULTS: Median BCVA was 20/160, 20/64, 20/98, 20/89, 20/89, 20/125 at baseline and 1, 3, 6, 9 and 12 months, respectively. Of ten eyes, six (60%) improved BCVA of at least 3 lines at 1, 3, 6 and 9 months. Four (40%) eyes improved BCVA of at least 3 lines at 12 months. Three eyes (30%) lost >3 lines at 12 months. In all patients intraocular pressure was well controlled. No endophthalmitis, retinal detachment or vitreous haemorrhage developed. CONCLUSIONS: Improvement of BCVA suggests that combination treatment with IVT and PDT for RAP merits further investigation.

Angiomatosis↗
PubMed1999

Circulating tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in proliferative diabetic retinopathy: a pilot study.

Several haemostatic abnormalities are associated with proliferative diabetic retinopathy. While abnormalities in plasma fibrinolytic activity have been described in diabetic retinopathy, platelets (a rich source of plasminogen activator inhibitor type 1, PAI-1) have received little attention. As a result, little is known about the fibrinolytic potential of circulating whole blood in diabetic retinopathy. The concentrations of tissue-type plasminogen activator (t-PA) and of its fast-acting inhibitor. PAI-1 were measured in plasma from eight patients with type 1 diabetes complicated by proliferative retinopathy, and from eight patients with type 1 diabetes and background or no retinopathy, matched for age, sex and duration of diabetes. The concentration of PAI-1 in platelets was also measured. The ratio of t-PTA to PAI-1 in plasma was significantly higher in patients with proliferative retinopathy than in those without (0.66 vs. 0.37, p < 0.02). The average quantity of PAI-1 per platelet was significantly lower in the group with proliferative retinopathy (0.33 vs. 0.50 ng/10(6) platelets, p < 0.02). These data suggest that among patients with type 1 diabetes, total circulating fibrinolytic potential is higher in those with proliferative retinopathy.

Adult↗
PubMedDate not supplied

Expression of pigment epithelium-derived factor and vascular endothelial growth factor in fibrovascular membranes from patients with proliferative diabetic retinopathy.

PURPOSE: The expression of pigment epithelium-derived factor (PEDF), a strong inhibitor of angiogenesis, has not been examined in human ocular fibrovascular membranes, to the best of our knowledge. The purpose of this study was to determine whether PEDF is expressed in the fibrovascular membranes in eyes of patients with proliferative diabetic retinopathy (PDR), and to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF). METHODS: The expression of PEDF and VEGF in the fibrovascular membranes excised during vitreous surgery in eight cases of PDR was determined by immunohistochemistry. RESULTS: VEGF was strongly expressed in the endothelial cells of newly formed vessels in the fibrovascular membranes. In contrast, PEDF was weakly expressed in the endothelial cells and was prominently expressed in the extracellular matrix and fibrous tissue surrounding the new vessels. CONCLUSIONS: Our results suggest that PEDF, along with VEGF, may modulate the formation of fibrovascular membranes in patients with PDR.

Adult↗
PubMedDate not supplied

Growth factors in retinal diseases: proliferative vitreoretinopathy, proliferative diabetic retinopathy, and retinal degeneration.

The goal of this review is to present the current knowledge on specific growth factor involvement in posterior segment eye disease. Growth factors can be defined as multifunctional signals which modify cell growth or proliferation, alone or in concert, by binding to specific cell surface receptors. Their biological effects on cells include cell adhesion, migration, survival, differentiation, extracellular matrix secretion, protease and protease inhibitor release, production of other growth activities, and angiogenesis. Growth factors couple the cell to the microenvironment. As some growth factors are soluble mediators of wound repair and angiogenesis, it seems possible that proliferative vitreoretinopathy and proliferative diabetic retinopathy are caused or aggravated by these factors. Other factors act as survival factors and can possibly prevent retinal degeneration. The multifunctional nature of growth factors makes it probable that practical uses will be found for these agents in the future.

Diabetic Retinopathy↗
PubMed1992

Patient and clinic factors predictive of missed visits and inactive status in a multicenter clinical trial. The Macular Photocoagulation Study Group.

Obtaining complete patient follow-up in clinical trials is important for the analysis of treatment results and for good patient care. Incomplete data can introduce bias into study results and can alter conclusions concerning treatment efficacy. The purpose of this study was to explore in a case-control design patient and clinic factors that may be associated with missed visits or inactive status within three clinical trials conducted as part of the Macular Photocoagulation Study. All inactive patients, all patients with any missed visits, and a random sample of patients with no missed visits were selected for interview. A total of 175 patients (60% of 292 selected) participated in the study. Two factors were found to be significantly associated (P less than .05) both with inactive status and with having any missed visits: health problems and travel costs. Several patient and clinic factors were found to be associated only with inactive status. These included change in marital status since joining the study, retirement since study entry, unsatisfactory interactions with the study physician or clinic coordinator, too little time spent with the study physician, and patient's belief that participants should be paid to participate in clinical trials. Distance from the clinic greater than 100 miles, in addition to health problems any time during follow-up and problems with travel costs, was found to be associated only with having any missed visits. This study emphasizes the importance of maintaining good patient-staff interactions and sensitivity to the events in a patient's life in order to obtain complete patient follow-up.

Bias↗
PubMed2004

Expression of ephrinB2 and its receptors on fibroproliferative membranes in ocular angiogenic diseases.

PURPOSE: To determine whether ephrinB2 plays a role in ocular angiogenesis, we investigated the expression of ephrinB2 and EphB receptors on retinal fibroproliferative membranes. DESIGN: Experimental study of the expression of ephrinB2 and EphB receptors within fibroproliferative membranes in patients with ocular angiogenic diseases collected during vitrectomy. METHODS: Fibroproliferative membranes were obtained at the time of vitrectomy from 20 patients with proliferative diabetic retinopathy (PDR) and from 40 patients who had stage 5 retinopathy of prematurity. Specimens were investigated with immunohistochemistry using polyclonal antibodies directed against ephrinB2 and the EphB2, EphB3, and EphB4 receptors. Immunoreactivity for von Willebrand factor (factor VIII) and alpha-smooth muscle actin (alpha-SMA) was also determined to confirm the identity of the target vascular endothelial cells. RESULTS: Positive staining for ephrinB2 was observed on fibroproliferative membranes that were obtained from patients with PDR (65.0%) and retinopathy of prematurity (25.0%). Specifically, ephrinB2 was found to be present on endothelial cells, as confirmed by its colocalization with factor VIII and alpha-SMA staining. EphB2 and EphB3 expression was observed on fibroproliferative membranes that were harvested from patients with PDR (EphB2, 90.0%; EphB3, 70.0%) and retinopathy of prematurity (EphB2, 35.0%; EphB3, 45.0%). However, EphB4 expression was not observed in any of the membranes derived from patients with PDR or retinopathy of prematurity. The rate of ephrinB2 expression in patients with PDR was significantly higher than that seen in patients with retinopathy of prematurity, which probably reflected differences in the vascular density of their fibroproliferative membranes. CONCLUSION: These data suggest that the ephrinB2-EphB2/B3 system may play an important role in ocular angiogenesis.

Actins↗
PubMed2005

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.

Angiopoietin-2↗
PubMed2005

Recurrent retinal angiomatous proliferation after surgical ablation.

PURPOSE: To report a case of retinal angiomatous proliferation (RAP) treated by ablation of the feeding and draining vessels that recurred by 6 months postoperatively. DESIGN: Interventional case report. METHODS: Images from fluorescein angiography, indocyanine green (ICG) angiography, and optical coherence tomography (OCT) were examined before and after ablation. RESULTS: The hot spot on late-phase ICG, the leakage on fluorescein angiography, the pigment epithelial detachment, and macular edema on OCT decreased postoperatively. However, a large hyperfluorescent lesion was detected on ICG 6 months postoperatively with recurrent cystoid macular edema. CONCLUSIONS: A new RAP lesion can develop even after the original lesion seemed to resolve after ablation.

Aged↗
PubMed2006

Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy.

PURPOSE: To determine the levels of interleukin 8 (IL-8) in the vitreous of patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational case-control study. METHODS: Vitreous fluid samples were obtained by vitreoretinal surgery from 71 eyes of patients with diabetes mellitus type 2 with PDR and from 17 eyes of nondiabetic patients with a macular hole. PDR was classified as active and inactive and subdivided according to the extent of large-vessel gliotic obliteration. The cytokine levels were measured by cytometric bead array method. RESULTS: The vitreous levels of IL-8 were significantly higher in patients with PDR in comparison with the control subjects (P < .001) and in patients with higher extent of large vessel gliotic obliteration (P < .001). A vitreous level of IL-8 was not associated with the presence of active PDR. CONCLUSION: Increased levels of IL-8 in PDR were associated with a higher extent of large-vessel gliotic obliteration.

Aged↗
PubMed2006

The activated form of gelatinase B/matrix metalloproteinase-9 is associated with diabetic vitreous hemorrhage.

We aimed to investigate the presence and activation status of matrix metalloproteinase (MMP)-2 and MMP-9 in vitreous samples from proliferative diabetic retinopathy (PDR) patients. Paired vitreous and serum samples were obtained from patients undergoing vitrectomy for the treatment of rhegmatogenous retinal detachment (RD) (65 patients) and PDR (67 patients). PDR patients were diagnosed for the presence of hemorrhage and/or patent new vessels. Quantitative assays were performed for vitreous protein content, MMP-2, MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and hemoglobin. Qualitative evaluation of the MMP-2 and MMP-9 activation status was performed by zymography. Vitreous samples contained proMMP-2 but levels were unselectively related to total protein content. ProMMP-9 and activated MMP-9 levels were significantly increased in PDR patients (p<0.001 for both comparisons). In addition, TIMP-1 levels were significantly increased in PDR patients (p=0.004) and functionally inhibited activation of MMP-9 in vitreous samples. None of the parameters significantly differed between PDR patients with patent new vessels and those with inactive disease. However, activated MMP-9 levels in vitreous samples of PDR patients with hemorrhage (75.7+/-106.3 scanning units per 2 microl) were significantly higher than those in PDR patients without hemorrhage (7.1+/-16.2 scanning units per 2 microl) (p<0.001) and strongly correlated with hemoglobin levels (r=0.7525; p<0.001). Activated MMP-9 was not detected in paired serum samples. We conclude that activated MMP-9 might be involved in hemorrhagic transformation in patients with PDR.

Collagenases↗
PubMed2002

Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the relationship between insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational case-control study. METHODS: In a prospective study, 37 consecutive diabetic patients with PDR (14 type I and 23 type II diabetes mellitus) in whom a vitrectomy was performed were compared with 21 nondiabetic patients with other conditions requiring vitrectomy (control group). Free IGF-I and VEGF were measured by ELISA. RESULTS: Vitreal levels of both free IGF-1 and VEGF were higher in diabetic patients with PDR than in control subjects (P <.01, and P <.0001, respectively). After adjusting for total intravitreous protein concentration, VEGF (ng/mg of proteins) remained significantly higher in diabetic patients with PDR than in the control group (P <.0001), whereas free IGF-I (ng/mg of proteins) was lower in diabetic patients than in control subjects (P <.0001). The vitreous concentrations of VEGF were higher in patients with active PDR than in patients with quiescent PDR (P <.005), whereas vitreous free IGF-I was not related to PDR activity. Finally, we did not observe a correlation between the vitreal levels of free IGF-I and VEGF. CONCLUSIONS: We conclude that free IGF-I and VEGF are both increased, but not related, within the vitreous fluid of diabetic patients with PDR. In addition, our results support the current concept that VEGF is directly involved in the pathogenesis of PDR, whereas the precise role of free IGF-I remains to be established.

Case-Control Studies↗
PubMed2002

Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy.

PURPOSE: To determine the levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). DESIGN: Experimental study of PEDF and VEGF levels in vitreous samples collected during vitrectomy. METHODS: The levels of PEDF and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 46 eyes of 43 patients who underwent vitrectomy with diabetic retinopathy (DR) (32 eyes of 29 patients) and an idiopathic macular hole (MH) (14 eyes of 14 patients). RESULTS: The vitreal concentration of PEDF was significantly lower at 1.11 +/- 0.14 microg/ml (mean +/- standard error) in eyes with DR than in eyes with MH at 1.71 +/- 0.22 microg/ml (P =.021). The VEGF level was 1799 +/- 478 pg/ml in eyes with DR and not detectable in MH. The PEDF level in proliferative DR (PDR) (0.94 +/- 0.12 microg/ml) was lower than that in nonproliferative DR (NPDR) (2.25 +/- 0.32 microg/ml), and that in active DR (0.85 +/- 0.14 microg/ml) was significantly lower than that in inactive DR (1.59 +/- 0.24 microg/ml; P =.01). The VEGF level was 2025 +/- 533 pg/ml in PDR and 215 +/- 201 pg/ml in NPDR and that in active DR (2543 +/- 673 pg/ml) was significantly higher than that in inactive DR (395 +/- 188 pg/ml; P =.0098). CONCLUSIONS: These results suggest that lower levels of PEDF and higher levels of VEGF may be related to the angiogenesis in DR that leads to active PDR.

Adult↗