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1.
BACKGROUND: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. METHOD: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined by in situ hybridization. RESULTS: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Müller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7-14 days after photocoagulation. CONCLUSION: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of CNV.  相似文献   

2.
AIMS: To investigate the longevity and reproducibility of choroidal neovascularisation (CNV) induced by krypton laser photocoagulation in the rat. The presence of cell adhesion molecules (CAMs) and vascular endothelial growth factor (VEGF) during the development of CNV was also studied. METHODS: 67 pigmented rats underwent retinal photocoagulation by krypton laser. The eyes were examined by either single or serial fluorescein angiography at 3 days, 1, 2-3, 4-5, 7-8, and 12 weeks post photocoagulation. The expression of CAMs (ICAM-1, E-selectin, and CD44) and VEGF post photocoagulation was studied by immunohistochemistry. RESULTS: CNV related fluorescein leakage appeared in 46.4% of 766 laser spots delivered to the 58 eyes that were tested at 2-3 weeks post treatment. The ratio of hyperfluorescent laser sites did not change significantly at 8 weeks post laser. The number of leaky spots was independent of the total number of lesions delivered to each eye (at 2-3 weeks post laser 10-15 spots/eye: 44% and 25-30 spots/eye: 49%; t = 0.7673; p = 0.3903). Nine eyes were followed by serial angiography between 2 and 12 weeks. The laser spots with fluorescein leakage at 2 weeks (51.5%) remained leaky at 12 weeks (51.5%). Histopathologically, macrophage accumulation peaked at 5 days and CNV was firstly observed at 1 week post photocoagulation. ICAM-1, E-selectin, CD44, and VEGF were maximally induced at 3-5 days post laser photocoagulation, and were localised to RPE, choroidal vascular endothelial, and inflammatory cells. VEGF was also detected in intravascular leucocytes at the sites of laser lesions. CONCLUSIONS: These studies demonstrated that krypton laser photocoagulation can be successfully used to produce lesions similar to those of human CNV. The response induced remained present for an extended period of time (12 weeks), thus offering a potential model to screen candidate CNV inhibitory agents. In addition, it is proposed that the expression of ICAM-1, E-selectin, CD44, and VEGF before new vessel formation might be linked to the initiation of CNV.  相似文献   

3.
BACKGROUND: Studies in corneal transplant rejection remain important because acute immunologic rejection continues to be the leading cause of human corneal transplant failure. As the permeability of vessels and the neovascularization induce cells infiltration into the graft, we considered the possibility that vascular endothelial growth factor (VEGF), a potent permeability-increasing factor and angiogenesis-mediating factor, could participate in the immune response. METHODS: As the established corneal transplant model for rejection, the corneal transplant between Lewis and Fisher rats has been reported. First, we evaluated VEGF production in the graft by immunohistochemical method in the animal model. Next, we tried to neutralize the effect of VEGF by topical administration of anti-VEGF antibody. We administered anti-VEGF antibody as eye drops for 10 days just after the transplantation of the established animal corneal transplant model. RESULTS: VEGF was strongly produced from the infiltrative cells into the graft. Anti-VEGF antibody significantly suppressed the acute rejection compared with saline or rabbit IgG. CONCLUSIONS: The inhibition of VEGF by topically applied neutralizing antibody is a new potential therapeutic strategy for the treatment of corneal transplantation.  相似文献   

4.
PURPOSE: To present the clinicopathologic features of the eyes of a patient with age-related macular degeneration (ARMD): the right eye was treated for well-defined extrafoveal choroidal neovascularization (CNV), and the left eye had an untreated disciform scar. METHODS: The patient was studied ophthalmoscopically and by fluorescein angiography at the time of presentation and on follow-up examinations up to 54 days after laser treatment, when he died. The posterior portions of both eyes (obtained postmortem), including the macula and optic nerve head, were sectioned serially for light microscopy. Tissue sections from both eyes were removed from glass slides and studied by transmission electron microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin layer of basal laminar deposit throughout the posterior pole. Two defects in Bruch's membrane without CNV were present within the area of laser photocoagulation located superior to the fovea. No CNV was present in the scar. Eleven areas of early CNV were present in the posterior pole. Histopathologic study of the left eye showed a prominent basal laminar deposit throughout the posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The clinicopathologic features of a treated eye with well-defined extrafoveal CNV, and the fellow eye with a disciform scar, both associated with ARMD, are presented. Although laser treatment obliterated a choroidal neovascular membrane, 11 additional areas of early, subclinical CNV were present.  相似文献   

5.
We compared indocyanine green (ICG) and fluorescein angiography for evaluation of choroidal neovascularization (CNV). Cast preparations of CNV induced in monkey eyes by laser photocoagulation were correlated with ICG and fluorescein angiographies of the same CNV formations. Fluorescein angiography was more effective, in general, than ICG angiography in detecting CNV; however, CNVs with subretinal hemorrhage (2 of 35 sites) were visible only with ICG angiography. In early phase ICG angiography, CNV formations that casts showed to be dense or composed of thick vessels were seen, but less dense areas were not visible. Lesions that ICG angiography revealed as leaking were not differentiated morphologically from non-leaking areas by the CNV casts. This study confirms that only ICG angiography can identify CNV hidden by subretinal hemorrhage, although fluorescein angiography is otherwise superior. Indocyanine green angiography is indicated as a valuable complement to fluorescein angiography for evaluation of CNV.  相似文献   

6.
"Classic" choroidal neovascularization (CNV) has a relatively uniform appearance in fluorescein angiography. In contrast, indocyanine green (ICG) angiography shows variable features of well-defined CNV. We examined 31 classic CNV patients secondary to age-related macular degeneration using a confocal laser scanning ophthalmoscope (Heidelberg Retina Angiograph) in order to determine ICG characteristics of classic CNV. Vascular patterns (97%), a hypofluorescent rim (84%), a hyperfluorescent margin (42%), late ICG leakage (32%) and "feeder vessels" were identified in variable frequency. Some of the ICG characteristics may correlate with histological features of the membrane and reflect proliferative activity. Extrafoveal "feeder vessels" may be amenable to laser photocoagulation in the presence of subfoveal CNV.  相似文献   

7.
BACKGROUND: Control of the natural course of choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) is difficult, and laser photocoagulation is recommended in only a subset of patients. Alternative modalities of treatment are under investigation. METHODS: We have used external beam radiotherapy (20 gray radiation units [Gy], 2 Gy fractions) to treat CNV in ARMD. A total of 111 patients have been followed for 12-30 months after radiotherapy. This study evaluates the effect of radiotherapy on the size of CNV, which was digitally measured on serial fluorescein angiograms. RESULTS: Analysis of results in the classic (or mixed classic and occult) CNV group was conclusive for fast growth of CNV and continuous increase of size during follow up. In the occult CNV group, a slowly progressive growth of CNV was demonstrated. In patients with vascularized pigment epithelium detachments, "hot spots" persisted; in a few patients, flattening of the macula was observed. Nearly all treated patients experienced further loss of vision. CNV growth in the radiotherapy treated eye was usually similar to growth in the untreated fellow eye, and in some, even worse. CONCLUSION: External beam radiotherapy (20 Gy, 2 Gy fractions) failed to control growth of CNV and was ineffective in stabilizing vision.  相似文献   

8.
Acute choroidal ischemia as a complication of photocoagulation   总被引:2,自引:0,他引:2  
Acute choroidal vascular insufficiency as a complication of photocoagulation has been little noticed. In 17 eyes of 16 patients photocoagulated with either xenon or argon sources for proliferative sickle cell retinopathy, gray lesions of the fundus developed peripheral to the photocoagulation sites. Histologic examination of similar gray lesions produced in monkeys showed necrosis and atrophy of the outer half of the retina. Intense photocoagulation of the human fundus, even with smaller spot sizes, may occlude a choroidal artery, producing separate gray lesions of distinctive shape. The lesions in both the patients and the monkeys progressed to granular hyperpigmentation by two to three weeks after photocoagulation.  相似文献   

9.
PURPOSE: To study the clinical histories and courses of six patients with choroidal neovascularization secondary to endogenous Candida albicans chorioretinitis. METHODS: The medical records, fundus photographs, and fluorescein angiograms of six patients who developed C. albicans chorioretinitis secondary to candidemia and who subsequently developed choroidal neovascularization in one or both eyes were reviewed. RESULTS: The six patients ranged in age from 18 to 79 years. Four were women and two men; all but one showed evidence of bilateral chorioretinal scarring secondary to C. albicans chorioretinitis. All patients had been treated successfully with systemic antifungal therapy (amphotericin B). Two weeks to two years after the chorioretinitis, choroidal neovascularization developed in one eye (four cases) or both eyes (two cases). The neovascularization on initial examination was subfoveal in four eyes, extrafoveal in three eyes, and juxtafoveal in one eye. Laser photocoagulation was used in four of the eight involved eyes. In these cases, the active choroidal neovascularization was brought under control. In one eye, the patient had submacular surgery for excision of the choroidal neovascular membrane. Final visual acuities ranged from 20/20 to 20/200 in treated eyes and from 20/50 to 20/400 in untreated eyes. CONCLUSION: Choroidal neovascularization is a potential cause of late visual loss in patients who have had C. albicans sepsis and endogenous C. albicans chorioretinitis. Eyes that have chorioretinal scarring from C. albicans chorioretinitis should be watched for the development of choroidal neovascularization. Laser photocoagulation or perhaps surgical excision of the neovascular complex may be of benefit in selected cases.  相似文献   

10.
OBJECTIVE: To provide long-term follow-up information on a large series of patients with choroidal osteoma. METHODS: Review of patients with a diagnosis of choroidal osteoma who had been examined at the Bascom Palmer Eye Institute, Miami, Fla, or known to one of us (J.D.M.G.). Information was obtained from hospital medical records or by a questionnaire sent to referring ophthalmologists. Life-table analysis was used to study the loss of vision and development of choroidal neovascularization. RESULTS: We followed up 36 patients, 31 (89%) were female, mean age, 21 years (range, 5-54 years) for a mean of 10 years (range, 2-22 years). Growth was observed for 9 (41%) of 22 well-documented osteomas. The probability of loss of visual acuity to 20/200 or worse was 58% by 10 years and 62% by 20 years. The probability of developing choroidal neovascularization was 47% by 10 years and 56% by 20 years. Successful treatment of the choroidal neovascularization with laser photocoagulation was performed for 5 (25%) of 20 patients. CONCLUSIONS: Most patients with choroidal osteomas maintain good vision in at least 1 eye, but they have a high risk of developing choroidal neovascularization. When this occurs, only a minority can be successfully treated with laser photocoagulation.  相似文献   

11.
Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.  相似文献   

12.
PURPOSE: To report a surgical method for translocation of the foveal retina in eyes with subfoveal choroidal neovascularization. METHODS: In three eyes of three patients, a crescent-shaped, partial-thickness scleral resection was performed near the equator at either the superotemporal or the inferotemporal quadrant. A near-total retinal detachment was created; then the edges of the resected sclera were sutured, causing shortening of the sclera with subsequent reattachment of the retina, resulting in translocation of the fovea to an area overlying nonfoveal retinal pigment epithelium and choroid. RESULTS: In three eyes of three patients, the fovea was surgically translocated to overlie retinal pigment epithelium that preoperatively was not underlying the fovea. In two patients, laser photocoagulation was applied to the choroidal neovascularization that, after translocation of the fovea, was no longer subfoveal, so that the photocoagulation was not associated with immediate visual loss. After a follow-up of 4 to 6 months, the visual acuity had improved in all patients (from 20/126 preoperatively to 20/70 in one patient, from 20/200 preoperatively to 20/70 in the second, and from 20/160 to 20/30 in the third). The patients noted distortion or tilting of the images, which improved over time. CONCLUSIONS: Limited foveal translocation may offer a therapeutic modality to preserve or improve vision in cases of subfoveal choroidal neovascularization. Additional follow-up is needed to assess the impact of potential complications associated with the surgical procedure, such as retinal detachment, proliferative vitreoretinopathy, and cataract, as well as the possibility of recurrent choroidal neovascularization.  相似文献   

13.
BACKGROUND: Fluorescein angiography (FA) is important in the diagnosis of chorioretinal diseases; however, it has some limitations. We conducted this study to evaluate whether digital indocyanine green (ICG) angiography can offer enhanced image in chorioretinal diseases. METHODS: Digital indocyanine green angiography with scanning laser ophthalmoscope (SLO) was performed in 314 patients with various chorioretinal diseases. This coupled digital imaging system can offer instant images, process and store data by computer, and give convenient hardcopy generation. RESULTS: The digital ICG angiography provided enhanced image resolution of the choroid compared with FA. The disease categories included choroidal neovascularization (CNV), choroidal tumor, inflammatory choroidal disease, ischemic choroidal disorder, idiopathic central serous chorioretinopathy and retinal macroaneurysm. CONCLUSIONS: ICG angiography is a useful adjunctive diagnostic technique to fluorescein angiography for various chorioretinal diseases. It is especially useful in the diagnosis of occult and recurrent CNV, as well as choroidal tumor and choroiditis. With greater clinical experience, ICG angiography is promising in giving additional clinical information for many other chorioretinal diseases.  相似文献   

14.
OBJECTIVE: This study aimed to use a new technique for ocular imaging, digital subtraction indocyanine green angiography (DS-ICGA), to evaluate patients with occult choroidal neovascularization (CNV). DESIGN: The design was a cross-sectional study of patients with occult CNV. PARTICIPANTS: A total of 31 eyes of 31 patients were studied. INTERVENTION: Digital subtraction of sequentially acquired indocyanine green angiographic frames was used to image the progression of the dye front in eyes with occult CNV. A method of pseudocolor imaging of the choroid was developed that allows differentiation and identification of underlying choroidal arteries and veins. RESULTS: The DS-ICGA of occult CNV showed consistent findings. Occult CNV was imaged with greater detail and in a shorter period of time than with conventional indocyanine green angiography. The fundus landmarks were retained with DS-ICGA much better than with conventional indocyanine green angiography. CONCLUSIONS: The DS-ICGA uses time to dissect the choroidal circulation. With DS-ICGA, occult CNV could be imaged more quickly and in greater detail than with conventional imaging techniques. The DS-ICGA may improve the authors ability to image, and subsequently treat, occult CNV.  相似文献   

15.
AIM: To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes. METHODS: Immunohistochemical localisation of VEGF, using antibodies raised against VEGF165 and VEGF121,165,189, was carried out on specimens of normal human retina (n = 15), diabetic retinas ((a) with no overt retinopathy (n = 19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n = 6), (c) with active proliferative retinopathy (n = 6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n = 15)), excised diabetic fibrovascular membranes (n = 19), and non-diabetic fibrocellular membranes (n = 7). The degree and pattern of immunostaining was recorded. RESULTS: In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF165 antibody was generally confined to endothelial cells adn perivascular regions while the VEGF121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined. CONCLUSIONS: This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.  相似文献   

16.
PURPOSE: To evaluate patients with unilateral occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) for the nature of the neovascularization which develops in the fellow eyes. METHODS: Patients with newly diagnosed unilateral occult CNV were followed prospectively for the development of CNV in the fellow eye. Patients were classified based on the type of occult CNV in the first eye: (1) those with associated serous pigment epithelial detachment (serous PED) and (2) those without. Demographic and clinical data, including the type of CNV in the second eyes, were compared. RESULTS: Choroidal neovascularization developed in 115 patients in the second eye. Fifty-six patients had occult CNV with a serous PED (also termed vascularized PED) in the first eye, and 59 patients had occult CNV without serous PED. The two groups did not differ significantly in the demographic and the clinical features evaluated. Well-delineated (or classic) CNV developed in the fellow eye of one patient in each group. Of the remaining 55 patients with vascularized PED in the first eye, the same type of occult CNV developed in 48 (87%) patients in the second eye. Of 58 (84%) patients in the second group, the same type of occult CNV developed in the second eye of 49 patients. This symmetric distribution of type of CNV between eyes is highly significant (P < 0.001). CONCLUSIONS: Eyes with occult CNV secondary to AMD can be classified by the presence or absence of an associated serous PED. Patients with unilateral occult CNV have a significant risk of occult CNV developing in the second eye, and the type of occult disease in the first eye is highly predictive of the type of neovascularized disease in the second eye. These findings are important with respect to natural history, and possibly to the treatment response and visual prognosis of patients with neovascularized AMD.  相似文献   

17.
PURPOSE: Surgical removal of epiretinal membranes generally leads to anatomic and functional improvement. Main complications include cataract, retinal breaks and detachment. We describe the onset of a juxtafoveal choroidal neovascularization 2 years after surgery of an epiretinal membrane. METHODS: The neovascular membrane was treated by argon laser photocoagulation. RESULTS: Complete obliteration of the neovascularization was obtained resulting in functional improvement. CONCLUSIONS: Although rare, choroidal neovascularization as a complication of epiretinal membrane surgery must be suspected in case of poor visual outcome or relapse of symptoms.  相似文献   

18.
The vascular actions of recombinant human erythropoietin (rhEPO) are of particular relevance for fully understanding rhEPO effects. This study examines the mechanisms of action of rhEPO on endothelial cells from bovine aorta (BAEC). First, the studies demonstrated that rhEPO acts on BAEC proliferation as a comitogenic growth factor in the presence of fetal calf serum (FCS). The main experimental findings disclosed that an interaction between rhEPO and vascular endothelial growth factor (VEGF) is instrumental for the growth-promoting action of rhEPO, as shown by the blockade (92.8+/-2.2% inhibition, P < 0.01) of the rhEPO-induced BAEC proliferation by a specific anti-VEGF antibody and by the capability of VEGF for substituting FCS in the induction of rhEPO-related BAEC proliferation (increase in BAEC number in the absence of FCS: 20 U/ml rhEPO alone, 0.3+/-2.8%; 5 x 10(-11) M VEGF alone, 52.9+/-3.1%; 20 U/ml rhEPO + 5 X 10(-11) M VEGF, 117.8+/-6.9%, P < 0.01 between the two agents combined with respect to each agent alone). The existence of a positive interaction between rhEPO and VEGF was further demonstrated by observing an increased cytosolic Ca2+ ([Ca2+]i) mobilization response to VEGF (10(-11)M) in BAEC pretreated or not with 20 U/ml rhEPO (delta[Ca2+]i = 704+/-111 versus 246+/-36 nM, respectively, P < 0.01). To further examine the mechanism of the potentiation of VEGF effect by rhEPO, we analyzed the mRNA expression of the VEGF receptors KDR/flk-1 and flt-1. The results disclosed that BAEC pretreatment with rhEPO upregulated the expression of both KDR/flk-1 and flt-1, therefore providing a structural basis for the aforementioned positive interactions between VEGF and rhEPO. Furthermore, inhibition by genistein suggests that tyrosine phosphorylation was involved in the VEGF receptor upregulation. The mechanisms identified in the present study disclose an interaction at the level of mRNA expression and functional effects between a hormone with predominantly hemopoietic effects, namely, erythropoietin, and an angiogenic factor, namely, VEGF. This relationship between rhEPO and VEGF might be of particular importance in neovascularization processes and in patients receiving rhEPO as a treatment.  相似文献   

19.
20.
BACKGROUND: At present no satisfying treatment for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is available. Visual results after successful surgical removal of subfoveal CNV are disappointing. This has been explained by a primary dysfunction of the retinal pigment epithelium (RPE) in the macular region and the surgical trauma to the RPE in patients with AMD. Therefore, Machemer and Steinhorst developed a technique for macular translocation after surgical removal of subfoveal CNV. We report our first experiences with this technique in patients with subfoveal CNV secondary to AMD. METHODS: Seven patients aged between 71 and 83 years with subfoveal CNV were included in the study. Visual acuity of the fellow eyes was below 20/400. All patients underwent pars plana vitrectomy. Retinal detachment was produced by subretinal infusion of balanced salt solution and a 360 degrees retinotomy at the base of the vitreous was performed. After removal of the CNV, retinal rotation and reattachment, the retina bordering the retinotomy was coagulated with endolaser photocoagulation. Silicone oil was used as temporary tamponade. RESULTS: In all patients the subfoveal CNV was removed and the macula was translocated by a 15 degrees-45 degrees rotation onto functional RPE. The mean duration of follow-up was 11 +/- 3 months. Initial visual acuity ranged from 20/80 to hand movements. Final visual acuity was 20/100 to 20/400. Initially all patients complained of tilted vision. During follow-up the rotation of the image regressed and was well tolerated by all patients. Complications included the development of retinal detachment in three patients after silicone oil removal, development of a macula pucker, and a significant increase of lens opacity in the phakic eyes. CONCLUSION: In our series rapid improvement of visual function was observed in one patient only, even if the macula appeared ophthalmoscopically and angiographically normal. Vitreoretinal complications occurred frequently during follow-up.  相似文献   

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