Objective To determine whether kringle 4-5 could inhibit choroidal neovascularization (CNV) in mice induced by argon laser photocoagulat ion. Methods Fundus laser photocoagulation was performed on C57BL/6J mice to induce CNV. In treatment group, 20 μg (low dosage group) and 50 μg (high dosage group) kringle 4-5 were injected retrobulbarly after photocoagulation. In control group, equilibrium liquid was injected retrobulbarly. Choroidal neovascularization was evaluated on the 7th and 14th day after photocoagulation by fundus fluorescein ang iography. The mice were killed on the 14th day after photocoagulation, the lesions were evaluated histologically and immunohistochemically, and the expression of CD105 was detected. The Expression of VEGF and bFGF was detected by immunohist ochemistry on the 4th day after photocoagulation.Results The incidence of CNV was 64.3% in control group, 51.2%（P＜0.05）in low dosage group, and 44. 1% (P＜0.01) in high dosage group. The CNV lesions were smaller in kringle 4-5 injected eyes in a dose-dependent manner and the number of proliferative vascular endothelial cells in the subretinal membrane of the treated eyes was smaller than that of the control eyes. There was no significant difference of the expression of VEGF and bFGF between the mice in control and treatment group.Conclus ions Kringle 4-5 could inhibit the development of choroidal neovascularization in the experimental mice model.(Chin J Ocul Fundus Dis，2003，19：201-268)
Pathological myopia can induce choroidal neovascularization (PM-CNV). The potential risk factors include ageing, long axial length of the eyeball, thinning of subfoveal choroidal thickness, fundus atrophy spot and lacquer crack. These factors may induce atrophy of retinal pigment epithelial cells (RPE) and hypoxia, resulting in vascular endothelial growth factors (VEGF) secretion by outer retina. The lesion type, location and activity of PM-CNV can be determined by fundus fluorescein angiography. The features of PM-CNV on optical coherence tomography include strong reflective area close to RPE with very small amount of subretinal fluid (active stage), surface strong reflection with signal attenuation area (scar stage) and flat lesion and chorioretinal atrophy (atrophy stage). Photodynamic therapy and intravitreal injection of anti-VEGF drugs are major treatments for PM-CNV, the latter is more commonly used now. However, more large randomized controlled studies are required to explore the treatment regimen (such as frequency, indications for repeated or termination of treatment) and the efficacy factors further.
ObjectiveTo observe the clinical efficacy of intravitreal Conbercept on idiopathic choroidal neovascularization (ICNV). MethodsThis is an open and prospective study without control trial. Twelve eyes from 11 patients (7 females and 4 males) with ICNV diagnosed by best corrected visual acuity (BCVA), non-contact tonometer, ophthalmoscope, fundus photography, optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) were enrolled in this study. All affected eyes were treated with intravitreal Conbercept 0.05 ml (10 mg/ml) and received an average of (1.91±1.04) injections. The initial average letters of Early Treatment Diabetic Retinopathy Study (ETDRS) chart acuity were 61.73±14.58, range from 25 to 77. The patients were followed up for 6 to 9 months.The initial average central retinal thickness (CRT) was (330.73±47.79)μm, range from 290 to 467 μm. Best-corrected visual acuity (BCVA), OCT and ophthalmoscope examination were assessed monthly. ResultsDuring the 1, 3, 6 months after treatment, themean BCVA were all improved with statistically significant difference (t=2.68, 3.80, 3.65; P < 0.05). At 1 month later after treatment, the mean BCVA was obviously improved in 1 eye (9.09%), improved in 8 eyes (72.73%), stable in 1 eye (9.09%), decreased in 1 eye (9.09%). At 6 month later after treatment, the mean BCVA was obviously improved in 3 eyes (27.27%), improved in 6 eyes (54.55%), stable in 1 eye (9.09%), decreased in 1 eye (9.09%).During the 1, 3, 6 months after treatment, the mean CRT were all decreased with statistically significant difference(t=2.44, 3.78, 4.12; P < 0.05).At latest follow up, the leakage in macula lutea disappeared in 6 eyes(58.33%), decreased in 11 eyes (25%)and increased in 3 eyes (16.67%). There were no systemic or ocular serious side effects during the follow up. ConclusionIntravitreal Conbercept for ICNV showed CNV regression, retinal thickness reduction, visual acuity improvement and safety.
Objective To investigate the inhibitory effects of IBI302 on experimental choroidal neovascularization (CNV). Methods Affinity of IBI302 to vascular endothelial growth factor (VEGF) family cytokines (including VEGF-A165, VEGF-A121 and placental growth factor PlGF) and complements (C3b, C4b) was determined by enzyme-linked immunosorbent assay (ELISA). The antagonist effect of IBI302 on VEGF was measured by proliferation, migration and tube formation tests of human umbilical vein endothelial cells (HUVEC). The anti-complement activity of IBI302 was measured by hemolysis test mediated by complement classical pathway and alternative pathway. Rhesus laser-induced CNV model was divided into 5 groups including model control group, bevacizumab group, IBI302 0.25 mg group, IBI302 0.50 mg group and IBI302 1.25 mg group. Fluorescein angiography and optical coherence tomography were performed on these monkeys at 14 and 28 days after drug delivery to observe the fluorescein leakage area and retinal thickness. The aqueous VEGF concentration was measured at 29 days after drug delivery. Results IBI302 showed good affinity to VEGF-A165, VEGF-A121 and PlGF, as well as C3b and C4b. IBI302 significantly inhibited the proliferation, migration and tube formation of HUVEC induced by VEGF-A165. IBI302 inhibited the hemolysis induced by complements obviously. At 14 and 28 days after drug delivery, the area of fluorescein leakage and retinal thickness in IBI302 0.25 mg group, IBI302 0.50 mg group, IBI302 1.25 mg group were reduced. The differences of the area of fluorescein leakage and retinal thickness in three IBI302 groups were not significant (P > 0.05). At 29 days after drug delivery, the VEGF concentration in the aqueous of rhesus monkey in bevacizumab group [(38.644±6.521) pg/ml] was decreased than that in model control group [(94.203±17.360) pg/ml], the difference was significant (P < 0.05). The VEGF concentration in the aqueous of rhesus monkey in three IBI302 groups were less than 31.300 pg/ml. Conclusion IBI302 inhibited experimental CNV through blocking the activity of VEGF and complement.
ObjectiveTo observe and classify the characteristics of optical coherence tomography (OCT) for several common diseases which could lead to submacular choroidal neovascularization (CNV), and to provide the warrant to make the differential diagnosis and treatment of CNV.MethodsThe data of OCT of 165 patients (187 eyes) with CNV due to AMD, CEC, high myopia and ICNV diagnosed by fundus photography and fundus fluorescein angiography (FFA) were retrospectively analyzed, and the images of OCT were classified considering the results of FFA, and the characteristics of different types of the images were sumerized.ResultsWell-defined fusiform thickening of retinal pigment epithelial (RPE) and choriocapillary layer in CNV with well-defined border (60 eyes), dispersed backscattering increase in poorly-defined CNV (101 eyes), optic darkspace beneath RPE layer in serous detachment of RPE layer (19 eyes), quickly decreased high backscattering region under RPE layer in hemorrhagic detachment of RPE layer (11 eyes), slight to moderate backscattering region between RPE layer in fibrovascular detachment of RPE layer (10 eyes), and detachment of neurepithelial layer from RPE layer with the optic darkspace between the layers in detachment of neurepithelial layer (45 eyes) were observed.ConclusionsThe images of OCT for the common diseases which could lead to submacular choroidal neovascularization may be divided into 6 types. Analyzing the characteristics of images of OCT is helpful in differential diagnosis and treatment of CNV. (Chin J Ocul Fundus Dis, 2005,21:69-73)
ObjectiveTo observe the expression of Rap1, guanosine triphosphate-Rap1 (GTP-Rap1), vascular endothelial growth factor (VEGF) and β-catenin in experimental choroidal neovascularization (CNV).MethodsForty-two brown Norwegian rats were randomly divided into a blank control group (7 rats) and a model group (35 rats). Both eyes were enrolled. The CNV model was established by holmium ion laser photocoagulation in the model group. At 3, 7, 14, 21, and 28 days after photocoagulation, fluorescein fundus angiography (FFA) and choroidal vascular smear were performed to observe the degree of fluorescein leakage and CNV area in rats; Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to detect the expression of Rap1, GTP-Rap1, VEGF, β-catenin and mRNA in CNV.ResultsThe results of FFA examination showed that a large disc-shaped fluorescein leaked in the photo-condensation spot 14 days after photocoagulation. Laser confocal microscopy showed that compared with 7 days after photocoagulation, CNV area increased at 14, 21, 28 days after photocoagulation, and the difference were statistically significant (t=3.725, 5.532, 3.605;P＜0.05). Western blot showed that there was no significant difference in the relative expression of Rap1 protein in CNV at different time points after photocoagulation between the two groups (P=0.156). Compared with the blank control group, the relative expression of GTP-Rap1 protein was significantly decreased, the relative expression of VEGF and β-catenin protein were significantly increased in the model group (P=0.000). The results of RT-PCR showed that there was no significant difference in the relative expression of Rap1 mRNA at different time points after photocoagulation between the two groups (P=0.645), but there were significant difference in the relative expression of β-catenin mRNA (P=0.000). At 7, 14, 21 and 28 days after photocoagulation, there were significant difference in the relative expression of GTP-Rap1 and VEGF mRNA between the two groups (P=0.000).ConclusionsThe expression of GTP-Rap1 in experimental CNV is significantly lower than that in normal rats.
Objective To investigate the related factors of effects on distant visual acuity after photodynamic therapy (PDT) for choroidal neovascularization (CNV). Methods One hundred and thirty-five cases (135 eyes ) of CNV treated with PDT were observed. The gender, preoperative distant and near visual acuity, disease course, pathogeny, area of CNV, types of CNV ascertained by fundus fluorescein angiography (FFA), and changes of CNV in FFA were recorded. Multi-factor regression analysis of visual acuity within 1 month and 3 months after PDT was performed with SPSS statistics software. Results The distant visual acuity within 1 month postoperatively was related to the preoperative distant visual acuity, the area of CNV and the changes in the FFA（P=0.000,0.030,0.062）, and 3 months after PDT, it was related to the distant and near visual acuity preoperatively and the changes in the FFA（P=0.000,0.054,0.034）. The condition of distant visual acuity within 1 month postoperatively was related to the FFA type of CNV and the disease course（P=0.018,0.08）. Conclusion The smaller the area of CNV is, the better postoperative distant visual acuity would be. The proportion of improvement of visual acuity is relatively higher in patients with classic CNV. Early treatment for the patients with the indicatio may improve the visual acuity effectively. (Chin J Ocul Fundus Dis，2004，20：292-294)
ObjectiveTo investigate the effects of transforming growth factor-β (TGF-β) in choroidal neovascularization (CNV) induced by laser in mice. Methods Eighty male C57BL/6J mice at the age of 6-8 weeks old were randomly divided into the normal control, photocoagulation model, photocoagulation with phosphate buffered saline (PBS control group) and photocoagulation with TGF-β receptor inhibitor groups (TGF-β receptor inhibitor group), twenty mice of each group. Fundus argon laser photocoagulation was performed in the photocoagulation model group, PBS control group and TGF-β receptor inhibitor group to induce CNV. One week, two, three and four weeks after the laser procedure, fundus fluorescein angiography (FFA) was carried out in the normal control or photocoagulation model groups to observe CNV formation dynamically. Western blot was used to analyze the expressions of TGF-β in the retina from the mice of normal control or photocoagulation model groups, and VEGF or TNF-α in the retina of normal control, PBS control or TGF-β receptor inhibitor groups. The CNV areas of each group were evaluated by using fluorescein stain on retinal pigment epithelium (RPE)/choroid flat mounts after two weeks of photocoagulation. ResultsThe FFA results showed the retinal vessels centered on the optic disc and arranged radially, while the choroidal vascular present network distribution in the normal control mice. Significant leakage of fluorescein showed discoid strong fluorophore in photocoagulation sites of retina at one week after photocoagulation. The quantitative analysis results of Western blot demonstrated that the TGF-β protein expression levels in retina of photocoagulation model mice gradually increased with time passing. The protein expression levels of TGF-β were significant differences in the photocoagulation model group comparing with the normal control group (F=13.042, P < 0.05). The protein expression levels of TNF-α (F=14.721, 17.509) and VEGF (F=18.890, 11.251) increased significantly in retina of PBS control or TGF-β receptor inhibitor groups when compared with that of normal control group at one week, two, three and four weeks after photocoagulation, and the differences were both statistically significant (P < 0.05). Compared with PBS control group, the protein levels of TNF-α and VEGF in retina from TGF-β receptor inhibitor group were significantly reduced, the differences was statistically significant (F=21.321, 16.160, P < 0.05). Two weeks after laser photocoagulation, a distinct reduction in CNV lesion size in the TGF-β receptor inhibitor group mice when compared to PBS or normal control groups, the differences was statically significant (F=4.482, P < 0.05). ConclusionTGF-β may promote CNV formation by up-regulating both TNF-α and VEGF protein expressions, the application of its specific inhibitor is able to reduce CNV progression.
Objective To investigate the therapeutic efficacy of transpupillary thermal therapy (TTT) for age-related macular degeneration (AMD) accompanied with subfoveal choroidal neovascularization (CNV). Methods Fifty-one eyes of 47 patients whose illness had been diagnosed as AMD by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were treated with diode 810 laser. There are 42 eyes of 39 patients had occult CNV and 9 eyes of 8 patients had classic CNV, and the average visual acuity in their fist diagnosis was 0.12. According to the focus size, the diameters of beam spot varied from 0.8, 1.2, 2.0, and 3.0 mm; and the power was 120, 160, 260 and 360mW correspondingly, with the duration of 60 seconds. The follow-up examination was performed once a month after the treatment, and repetitious treatment would be taken once to thrice if necessary. The follow-up period was 3~33 months with the mean of 10 months. Visual acuity, haemorrhage in ocular fundus, absorption of exudation, and the closure of CNV were examined in the follow-up examination. Results No immediate decrement of visual acuity or any other discomforts were found in all of the treated eyes soon after the treatment. The average visual acuity of 51 eyes was 0.16 in the last diagnosis, which remained no change in 68.62%; increased in 23.53% and decreased in 7.84% compared with that in the first diagnosis. The results of FFA and ICCG demonstrated that at the 3rd months after the treatment, the closure rate was 42.86% in occult CNV and 22.22% in classic CNV; and at the 6th month, the closure rate was 73.81% in occult CNV and 66.67% in classic CNV. The results of ophthalmoscopy showed that at the 3rd month after the treatment, partial or complete absorption of hemorrhage and/or exudates with various thickness of organized scarring tissue was found in 42 eyes with occult CNV; decrement of hemorrhage and exudates was observed in 7 out of 9 eyes with classic CNV; and new hemorrhage occurred in 1 eye. At the 6th month, in 27 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with faster absorption and remaining unchanged for 12 months; in 5 eyes with classic C NV, new hemorrhage occurred in 2, which was absorbed after treated again and remained stable in the 16-month followed-up. In 19 eyes with occult CNV which had been followed up for more than 6 months, hemorrhage disappeared in 5 and new hemorrhage occurred in 5. In the followed-up over 6 months, new hemorrhage occurred in 8 eyes with the recurrent rate of 15.6%. Conclusion TTT is effective for AMD with either classic or occult CNV. In the long-term followed-up, CNV recurs in 15.6% of the treated eyes which may be improved after the further treatment. (Chin J Ocul Fundus Dis，2004，20：280-284)
Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.