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 evaluate the inhibitory effect of small interfering RNA (siRNA) targeting peroxisome-proliferator-activated receptor-γcoactivator-1α(PGC-1α) on retinal neovascularization in the mouse. MethodsEighty seven-day-old C57BL/6J mice were divided into normal group, model blank group, model control group and PGC-1αsiRNA group, twenty mice in each group. Mice in the normal group were kept in normal room air. Mice in the model blank group, model control group and PGC-1αsiRNA group were induced for retinal neovascularization by hypoxia. Liposome with PGC-1αsiRNA (1 μl) and liposome with negative control siRNA (1 μl) were injected into the vitreous in the PGC-1αsiRNA group and model control group respectively when mice were moved out to room air from the cabin (Postnatal 12). No injection were performed in the model blank group. At postnatal 17, fluorescein angiography was used to assess the vascular pattern.The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in cross-sections. PGC-1αand vascular endothelial growth factor (VEGF) level in retina were measured by real-time polymerase chain reaction (real-time PCR) and Western blot. Inhibition efficiency of PGC-1αsiRNA on PGC-1αand VEGF was calculated. ResultsMice in the normal group showed reticular distribution of retinal blood vessels. Central nonperfused retina, neovascular tufts and fluorescein leakage were seen in the model blank group and model control group. Neovascular tuft and fluorescein leakage were decreased in the PGC-1αsiRNA group compared to the model blank group and model control group. The neovascular nuclei were increased in the model blank group and model control group compared to the normal group (P < 0.05). The neovascular nuclei were decreased in the PGC-1αsiRNA group compared to the model blank group and model control group (P < 0.05). The expression of PGC-1αmRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group, while decreased 54% and 53% respectively in the PGC-1αsiRNA group as compared with model blank group and model control group (P < 0.05). The expression of VEGF mRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group, while decreased significantly in the PGC-1αsiRNA group (decreased 48% and 40% respectively) as compared with model blank group and model control group (P < 0.05). ConclusionsIntravitreal injection of PGC-1αsiRNA mediated by liposome can inhibit retinal neovascularization in the mouse effectively.
Objective To evaluate the effect of integrin-linked kinase (ILK) in the process of retinal neovascularization induced by vascular endothelial growth factor (VEGF). Methods The ILK activities of retinal choriodal endothelial cell line RF/6A were inhibited by LY294002 or siRNA knockdown. VEGF-induced changes of cell adhesion, proliferation, migration and endothelial cell tube-formation were measured then. The in-vivo effects of ILK were also assessed by intraperitoneal injection of LY294002 into an animal model of RNV. Results The cell adhesion measurements of control group, VEGF group, VEGF＋LY294002 group and VEGF＋siRNA group were 0.0726plusmn;0.01961, 0.1137plusmn;0.02631, 0.0837plusmn;0.01503 and 0.0853plusmn;0.02454 , respectively. The difference was statistically significant between VEGF group and control group（t =4.211，Plt;0.01）, and between (VEGF＋LY294002) group or (VEGF＋siRNA) group and control group (t =3.074, 2.91，Plt;0.01). The cell proliferation results of control group, VEGF group and VEGF＋LY294002 group were 0.4162plusmn;0.1392, 0.6412plusmn;0.2420, 0.4476plusmn;0.1834 , respectively. The difference was statistically significant between VEGF group and control group（t=2.608，Plt;0.05）, and between (VEGF＋LY294002) group and VEGF group（t=2.244，Plt;0.05）.The cell migration results of control group, VEGF group and VEGF＋LY294002 group were 83.66plusmn;30.283, 248plusmn;74.748, 138.5plusmn;38.167, respectively. The difference was statistically significant between VEGF group and control group（t=5.436，Plt;0.01）, and between (VEGF＋LY294002) group and VEGF group（t=3.682，Plt;0.01）. There was no obvious tube-formation after ILK activity was inhibited or knocked down. The non-perfusion areas were increased from （62798plusmn;16995.62）mu;m2 to （84722.65plusmn;10435.01）mu;m2 after intraperitoneal injection of LY294002 into animal model of RNV, the difference was statistically significant（t=3.476，Plt;0.01）. Conclusions ILK may play an important role in the process of VEGF-induced retinal neovascularization by regulating the cellular adhesion, proliferation, migration and tube-formation, as all those cellular functions were supressed obviously after the ILK activity was inhibited by LY294002 or the ILK expression was knocked down by siRNA.
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 compare the characteristics of the results of fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) in patients with classic choroidal neovasculazation (CNV). Methods The data of FFA and ICGA of 34 patients (36 eyes) with classic CNV were analyzed retrospectively and the results of the two examinations were analyzed contrastively. Results The results of FFA revealed the clew or cartheel-tike configuration of classic CNV at the early phase in 3 out of 15 eyes (20%) with age-related macular degeneration (AMD); in 5 out of 7 eyes with pathological myopia(71.4%); and in 9 out of 14 eyes with central exudative chorioretinopathy (CEC),(64.3%),In 36 eyes with classic CNV, the images of ICGA indicated CNV distinctly in 20 (55.6%) and indistinctly in 15 (41.6%); CNV was not detected by ICGA in 1 eye (2.8%); feeding blood vessels in 6 eyes (16.7%) were detected by ICGA but none by FFA. Conclusions At the early phase of FFA, the configuration of classic CNV is clew-like in eyes with pathological myopia and CEC, and erose in eyes with AMD. The image of ICGA which indicated the outline of classic CNV is not as clear as the one of FFA, but it can reveal the feeding vessels which FFA can not. (Chin J Ocul Fundus Dis, 2006, 22: 217-209)
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.
Wet age-related macular degeneration (wAMD) is caused by choroidal neovascularization (CNV), which occurs when the choroidal new capillaries reach the RPE layer and photoreceptor cell layer through the ruptured Bruch membrane, leading to neovascularization bleeding, leakage, and scarring. In view of the important role of VEGF in the development of CNV, targeted therapy with various intraocular anti-VEGF drugs is the first-line treatment for wAMD. However, the efficacy of anti-VEGF drugs in the treatment of wAMD is affected by a variety of factors, and some patients still have problems such as unresponsiveness, drug resistence, tachyphylaxis, long-term repeated injections, and severe adverse effects. It is the direction of future researches to deeply explore the physiological and pathological process of wAMD, find the cause of CNV formation, and seek better therapies.
Objective To evaluate the effects of traspupillary thermotherapy (TTT) for the treatment of central exudative chorioretinopathy (CEC). Methods Twelve eyes of 12 patients who suffered from CEC were treated by using a diode laser at 810 nm. A variable spot size of 0.5mm-2.0mm was used depending on the size of choroidal neovascularization (CNV).The treatment was initiated in one spot for 55 to 60 seconds duration at a power range between 200-350 mW, and the treated area revealed no visible color change to a light-gray appearance. Preoperative and postoperative fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in 10 of the 12 eyes. Results The visual acuity in all eyes was improved to different degree over a period of 3-10 months. Five or more lines improvement measured by Snellen chart in visual acuity was found after the treatment in 4 eyes, three to five lines in 5 eyes and one to two lines in 3 eyes. All eyes demonstrated decreased or vanished exudation in FFA. CNV disappeared or decreaced in 8 eyes and remained nochange in 2 eyes in ICGA. Conclusion TTT is obviously effective in treating CEC. (Chin J Ocul Fundus Dis, 2002, 18: 187-189)
Objective To detect expression of NF-κB in the inner retina and in vestigate the inhibitoryeffect of pyrrolidine dithiocarbamate on retinal neovascularization in rats. Methods The rat models with retinopathy were set up un der the hypoxia condition, and fluorescein fundus angiography (FFA) was used to observe the retinal neovascularization. The expressions of NF-κB in the inner retina in rats with and without neovascularization were detected by immunohisto chemical method. PDTC was intraperitoneally injected in rats with neovascularization to observe the expression of NF-κB in the inner retina and the effect on retinal neovascularization. Results Hypoxia induced NF-κB activation in the retinal glial cells and endothelial cells. But immuno-staining intensity for NF-κB and adhesion molecules were reduced by PDTC intraperitoneal injection. Retin al angiogenesis in rats were suppressed effectively (P＜0.05). Conclusions NF-κB activation correlates with retinal neovascularization closely. PDTC may inhibit the NF-κB activation and prove beneficial in the treatment of ischemic neovascularization. (Chin J Ocul Fundus Dis，2003，19：201-268)