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.
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)
Objective To investigate the preoperative design and application of the minimum foveolar translocation distance and angle of macular translocation. Methods The fundus fluorescein and indocyanine green an giographies were performed on 53 eyes of 53 patients with classic subfoveal choroidal neovascularization （SCNV）, including 42 with exudative age-related macular degeneration and 11 with high myopic macular degeneration. The actual area of macular SCNV and the minimum foveolar translocation distance and angle were analyzed. Results The actual area of SCNV was 0.39~18.00 mm2 with the mean of (3.08±3.22) mm2. The designed minimum superior translocation distance was 67~2 240μm with the mean of (845.72±425.23) μm；the minimum designed minimum inferior translocation distance was 53~2 430 μm with the mean of (912.17±547.77) μm. The minimum designed superior translocation angle was 1~32°with the mean of (13.23±6.6 8)°；the minimum designed inferior translocation angle was 1~35°with the mean of (14.06±8.46)°. The individual difference of the minimum designed superior and inferior translocation distance was more than 500 μm in 16 eyes （30.19 % ）, and the difference of translocation angle was more than 10°in 11（20.75%）. Conclusion Preoperative design of minimum translocation distance and angle of macular translocation may be helpful to choose the operation program. (Chin J Ocul Fundus Dis，2004，20：75-77)
Objective To investigate the role of bone marrow-derived cells (BMC) plays in choroidal neovascularization (CNV).Methods Green fluorescent protein (GFP) chimeric mice were built by transplanting BMC from GFP transgenic mice to adult wild type C57BL/6J mice. Retinal laser photocoagulation was used to induce CNV in the chimeric mice (treated group) and adult wild type mice (control group). Four weeks later, choroidal flatmount was prepared to detect GFP positive BMC expression in the CNV lesions, and immunofluorescence stain was used to determine the expression of vascular endothelia growth factor (VEGF) and basic fibroblast cell growth factor (bFGF).Results Twenty-nine days after photocoagulation lots of GFPpositive BMC presented in the CNV area, which accounted approximate 16.22% of the total CNV area. Some BMC in the CNV area expressed VEGF and bFGF. Conclusions BMC may play an important role in CNV by forming new vessles and secreting angiogenic factors.
Myopic macularpathy is the main cause of the decline of visual function in high myopia, which including tigroid fundus, lacquer cracks, diffuse retinal choroid atrophy, plaque retinal choroid atrophy, choroidal neovascularization (CNV), Fuchs spot and posterior staphyloma. The tigroid fundus is the initial myopic retinopathy. The lacquer cracks is a special lesion in the posterior pole of high myopia. When the lacquer cracksen enlarge or lacquer cracks progress to plaque retinal choroid atrophy should be paid to monitoring the occurrence of CNV. Myopic macularpathy progression include two mode. One is from tigroid fundus——lacquer cracks——plaque retinal choroid atrophy——CNV to macular atrophy. And the other is from tigroid fundus——diffuse retinal choroid atrophy——atrophy enlarge to diffuse retinal choroid atrophy with plaque retinal choroid atrophy or plaque retinal choroid atrophy occurence on the border of posterior staphyloma. Understanding the progression patterns and natural course of these lesions will help the clinic to further understand the course of high myoipa.
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 possible relationship between choroidal neovascularization (CNV) and macular choroidal watershed zones (CWZ) in patients with age-related macular degeneration (AMD). Methods Fifty-seven selected indocyanine green video angiograms (ICGA) of 57 patients (57 eyes) with AMD were evaluated, and 35 ones of the healthy fellow eyes of 35 patients with unilateral non-AMD fundus diseases were selected as age-matched control. The video angiograms were evaluated for investigating the relationship between CNV and macular CWZ. Results In 57 eyes with AMD, 35 (61.4%) had macular CWZ, while in 35 control patients only 3 (8.57% ) had. The difference was significant (Plt;0.05). In 43 eyes with exudative AMD and CNV, 32 (74.4%) had macular CWZ, including 29 eyes (90.6%) with CNV caused by macular CWZ. Conclusion Macular CWZ could be a predilection site of CNV in exudative AMD. (Chin J Ocul Fundus Dis，2003，19：76-78)
ObjectiveTo assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).ResultsAmong the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to-IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged ＜65, and those with active CNV lesion area ＜50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions.ConclusionsThe efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before.
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 analyze the etiology of central exudative chorioretinopathy（CEC）. Methods A total of 32 CEC patients were asked the medical history, and underwent examination of purified protein derivative（PPD）test, chest Xray, blood routine test, Creactive protein, erythrocyte sedimentation rate, TORCH test and rapid plasma regain cirde card test, to determine the possible causes of CEC. Results Thirty-two patients didnprime;t have the history of tuberculosis, and no evidence of systemic active tuberculosis was found in the chest X-ray examination. the results of PPD test showed the positive rate was 37.5％. The disease condition of paitents with positive result of PPD test was stable or was alleviated after anti-tuberculosis therapy. All the results in IgM of TORCH test and rapid plasma regain cirde card test were negative. Conclusion No infectious factors related to CEC was found, thus choroidal neovascularization of CEC might be idiopathic.