Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.
PURPOSE:To observe the clinical features of the macular hemorrhage in myopes. METHOD:Twenty-four patients(30 eyes)with myopic macular hemorrhage were examined with slitlamp biomicroscopy,funduscope,A/B ultrasonography,and fundus fluorecein angiography(FFA). The patients were followed up for 3~18 months(average 12 months). RESULTS: Four of 26 eyes with macular hemorrhage examined with FFA were found to be due to choroidal neovaseulature,and they were associated with posterior staphyloma. The other 22 eyes without neovascular change were thought to be simple type,and 19 of them were associated with lacquer cracks. The hemorrhage in simple type cases deminished usually within 1~3 months. CONCLUSION:Myopic macular hemorrhagic eyes of neovascular type resulted usually in recurrent hemorrhage and worse prognosis in visual acuity than those of simple type. （Chin J Ocul Fundus Dis,1996,12: 220-222）
Objective To observe the effect of Chinese Herbal Preparation -Mingjing Granule on the recruitment and adhesion of bonemarrow derived cells (BMCs) to choroidal neovascu1arization (CNV) in mice induced by laser photocoagulation. Methods A total of 75 C57BL/6 mice were divided into treatment group (30 mice), control group (30 mice) and normal control group (15 mice). CNV was induced by krypton laser in the mice of treatment group and control group. BMCs from GFPtransgenic mice were injected through tail vein to those mice 0.5 -1.0 hours after laser surgery. On day one after laser surgery, the mice of treatment group were gavaged with 0.3 ml Mingjing Granule solution every day［30 g/(kg?d)］, while the control group mice were gavaged with distilled water. The mice of normal group fed with normal cereals. 7, 14, 28 days after treatment, choroidal flatmount were prepared to measure the CNV severity and BMCs recruitment. The choroidal histopathological change was observed by optical microscope. CXCR4 level in peripheral blood was measured by enzymelinked immuno sorbent assay (ELISA). Stromal cell derived factor1alpha; (SDF-1alpha;), vascular cell adhesion molecule-1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1) were detected by immunofluorescent staining. Results Choroidal flatmount showed that CNV developed in treatment group and control group, but not in normal group. On day seven and 14, CNV lesions in the treatment group showed less incorporation of BMCs and smaller CNV in size compared with the control group (t=10, 9; P=0.007, 0.024), histologic sections also showed less severe lesions in the treatment group. CXCR4 level in peripheral blood in the treatment group was less than that in the control group and normal control group on day seven and day 14（t=8.107, 2.747;P＜0.05). The expression of SDF-1alpha;, ICAM-1 and VCAM-1 in the treatment group was lower compared with the control group. Conclusions Mingjing Granule could inhibit the recruitment and adhesion of BMCs in peripheral blood to CNV at the early stage. The mechanism may be related with the action of Mingjing Granule in lowing chemokines levels in peripheral blood and expression of adhesion molecules around CNV.
Anti-vascular dndothelial growth factor (VEGF) drugs have open up a new treatment channel for ocular neovascular diseases. A lots of clinical data has proved that anti-VEGF drugs are effective and safe. But we should also notice that long-term and excessive usage of anti-VEGF drugs brings some new problems and complications, and even affect the normal ocular physiological process of the angiogenesis and retinal blood flow. So, it is necessary to pay attention to the problems and potential risks of excessive usage of anti-VEGF therapies for ocular neovascular disease.
Objective To investigate auto-cortex of crystalline lens-induced neovascular epiretinal membrane（NVERM）by micro-injuring posterior c apsule of crystalline lens. Methods twenty four C57BL/6 mouse between 4-6 weeks were selected, and divided into two groups randomly: auto-cortex of crystalline group and the control group. The auto-cortex of crystalline group was treated by penetrating the posterior capsule of lens and washing out the lens cortex into the mouse vitreous using PBS (phosphate buffered solution), while the control group were injected PBS into vitreous merely. Clinical change s were followed by slit-lamp examination and photograph. The eye balls were enu cleated at the day of 3, 7, 14 and 28 after operation. Both HE and immunohistoch emistry were used to detect the pathological changes. Results postoperative one to three days, 11 of 12 mouse in autocortex of crystalline g roup, lens appear to alba turbid at different levels one after another, and then develop into highdensity chinaware white. Postoperative (po) three days, HE s taining shows cortex of lens debris transmigrated in vitreous cavity, and some o f which approached to internal limiting membrane and lead it to rough and discon tinue; Po7-14 days, the capillary in retina expanded, migrated and broke though t internal limiting membrane which got to the pro retina and became the new ves sels. And typical NVERM were observed. Po28 days, some vascularslike structure formed in vitreous cavity. None of mouse in control group developed NVERM. Conclusion Auto-cortex of crystalline lens can induced neovascular epiretinal membrane in C57BL/6 mouse. (Chin J Ocul Fundus Dis,2008,24:118-121)
Objective To investigate the inhibitory effects and possible related mechanism of OTX008 [a selective inhibitor of galectin-1 (Galectin-1)] on retinal neovascularization (RNV) in mouse model of oxygen-induced retinopathy (OIR). Methods 7-day-old (P7) C57BL/6J mice were randomly (according to random number table) divided into 4 groups including normal group, OIR group, OIR-OTX008 group and OIR-phosphate buffered saline (PBS) group. To establish the OIR mouse model, mice from all groups except normal group were expose to (75±2)% oxygen for 5 days and then to room air. OIR-OTX008 group received an intravitreal injection of 1 μl (0.25 μg/μl) OTX008 at P12, OIR-PBS group received the equal volume (1 μl) of PBS injection. Mice from 4 groups were euthanized at P17, and retinas were collected for molecular biological analysis and morphological study. RNV was evaluated by counting the number of pre-retinal neovascular nuclei and the whole-mount immunofluorescent staining of mouse retina. Cyrosections of retinas were imaged via confocal microscopy to observe the enrichment of staining of Galectin-1. Protein levels of Galectin-1, Neuropilin-1 and phosphorylation of vascular endothelial growth factor receptor 2 (pVEGFR2) were determined with Western blot. Results At P17, Galectin-1 expressed higher in retinal ganglion cell layer, inner plexiform layer and inner nuclear layer from OIR group and OIR-PBS group than normal group. Galectin-1 expressed less in cryosection retinas from OIR-OTX008 group than OIR group and OIR-PBS group. The numbers of pre-retinal neovascular cell nuclei from OIR group and OIR-PBS group were obviously more than that from normal group (t=9.314,P＜0.05). The number of pre-retinal neovascular cell nuclei from OIR-OTX008 group were obviously lower than those from OIR group and OIR-PBS group (t=8.038, 7.774;P＜0.05). The RNV tufts area (t=13.250, 12.570), non-perfusion area (t=15.590, 12.430) and hypoxic area (t=9.542, 9.928) from OIR-OTX008 group were significantly smaller than those in OIR group and OIR-PBS group (P＜0.05). Protein levels of Galectin-1 (t=24.800, 23.060), Neuropilin-1 (t=4.120, 3.530) and pVEGFR2 (t=25.880, 15.480) in the OIR-OTX008 group were significantly down-regulated than those from OIR group and OIR-PBS group (P＜0.05). Conclusion Intravitreal injection of OTX008 inhibits RNV and ameliorates retinal hypoxia in mice model of OIR possibly through down-regulating Galectin-1, Neurolinpin-1 and pVEGFR2.
Objective To investigate the effects of celecoxib-poly lactide-co-glycolide microparticles (CEL-PLGA-MS) on rat retina after intravitreal injection. Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which received intravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. Phosphate buffer solution (PBS) was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography (OCT). The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group (F=0.12,P＞0.05). At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group (F=9.62, 46.13;P＜0.01). The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=165.15,P＜0.01). The retinal thickness was estimated equal among 40, 80, 320 mu;mol/L dosage groups in CEL-PLGA-MS group (F=4.79,P＜0.01). The retinal thickness of 160, 320 mu;mol/L dosage group were thicker than that in 40, 80 mu;mol/L dosage group in celecoxib group (F=28.10,P＜0.01). At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group (F=3.79,P＞0.05); the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the first week after injection (F=7.28, 103.99; P＜0.01). At the fourth week after injection, the retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=19.11,P＜0.01). The retinal thickness of CEL-PLGA-MS group was approximately the same to normal control group and PBS control group (F=2.02,P＞0.05). The retinal thickness of celecoxib group was thicker than that in normal control group and PBS control group. No considerable abnormality of the retina was seen by light microscope and the retinal thickness corresponded with the values measured by OCT at the first week after injection. The abnormal structures of the retina were seen in 160, 320 mu;mol/L dosage group of celecoxib group and inner changed evidently by the transmission electron microscope. Disordered arrangement of microfilaments, dilated microtubule and some mitochondria vacuolation were observed in 320mu;mol/L dosage group of celecoxib group. Others changed slightly. Conclusions CEL-PLGA-MS has less toxicity on the retina than free-celecoxib after intravitreal injection. The safety of intravitreal injection with CEL-PLGA-MS is better than celecoxib.
ObjectiveTo observe the efficacy of different administration of conbercept on choroidal neovasculature (CNV) in patients with pathological myopia (PM).MethodsA retrospective case-control study. From June 2012 to June 2017, 57 patients (61 eyes) with PM-CNV diagnosed in the Ophthalmology Department of General Hospital of Central Theater Command were included in this study. All patients underwent BCVA, intraocular pressure, refractive index, slit lamp microscope, FFA, OCT examination and axial length (AL) measurement. An international standard vision chart was used in the BCVA test, which was converted to logMAR vision. According to the initial treatment plan, the patients were divided into 1+PRN treatment group (group A) and 3+PRN treatment group (group B), with 27 patients (31 eyes) and 30 patients (30 eyes), respectively. There was no significantly statistical difference in baseline data between the two groups (P＞0.05). The eyes was injected with 10 mg/ml of conbercept 0.05 ml (including conbercept 0.5 mg). After completion of initial treatment, on-demand treatment was performed according to repeated treatment standards. The average follow-up time was 30.8 months. The time point for curative effect determination was 24 months after treatment. The frequency and recurrence rate of vitreous cavity injections in the two groups of patients and the changes of BCVA, central macular thickness (CMT), diopter and AL were compared and observed. Continuous variables were compared between groups by independent sample t test. Categorical variables were compared by χ2 test. logMAR BCVA and injection frequency were compared by Wilcoxon rank test. Comparison of CMT before and after treatment was performed by paired t test.ResultsAfter 24 months, the number of intravitreal injections in group A and group B were 3.94±1.88 and 4.83±1.72, respectively, with statistically significant difference (Z=－2.182, P=0.029). After completion of initial treatment, the number of retreatments in group A and group B were 2.94±1.88 and 1.83±1.72, respectively, with significantly statistical different (Z=－2.330, P=0.020). The CNV recurrence rates were 38.71% and 13.33%, respectively, with statistically significant difference (χ2=5.074, P=0.024). Compared with prior treatment, the average BCVA at 1, 3, 6, 12, and 24 months after treatment significantly increased in group A and B (Group A: Z=5.634, 5.367, 5.532, 6.344, 6.135l; P＜0.05. Group B: Z=5.809, 5.090, 5.341, 5.939, 8.103; P＜0.05). At 1, 3, 6, and 12 months after treatment, there was no statistically significant difference in the average BCVA of the two groups (Z=－0.966, －0.932, －0.523, －1.759; P=0.334, 0.351, 0.601,0.079); the difference was statistically significant at 24 months (Z=－2.525, P=0.012). Compared with CMT before treatment, the difference in the average CMT reduction of the eyes in groups A and B was statistically significant at 1, 3, 6, 12, and 24 months (Group A: t=4.691, 2.624, 2.121, 1.921, 2.237; P＜0.05. Group B: t=4.947, 4.554, 5.290, 5.567, 5.314; P＜0.05); the average CMT comparison between the two groups was not statistically significant (P=0.457, 0.871, 0.505, 0.333, 0.798). During the follow-up period, there were no ocular complications and systemic adverse reactions.ConclusionsDifferent administration methods for the treatment of PM-CNV by intravitreal injection of conbercept are safe and effective, which can effectively improve BCVA and reduce CMT. Total injection of 3+PRN is more than 1+PRN. However, the injections of retreatment and CNV recurrence rate is lower, and the final follow-up vision is better.
Objective To investigate the effect of photodynamic therapy (PDT) combined with intravitreal bevacizumab on wet age-related macular degeneration (AMD). Methods In this retrospective study, 34 eyes (28 cases) diagnosed with wet AMD received PDT combined intravitreal injection of bevacizumab, including 25 eyes with classic CNV and 9 eyes with minimally classic CNV by fluorescein angiography; On optical coherence tomography (OCT), 23 eyes showed intraretinal fluid (IRF) and 11 eyes presented subretinal fluid (SRF). After signing informed consent, all patients underwent initial standard PDT followed by intravitreal bevacizumab (1.25 mg) within succeeding 3 to 7 days. Best corrected visual acuity (BCVA) and OCT with routine eye examinations were evaluated monthly. Additional bevacizumab (1.25 mg) was injected intravitreally if new or increasing fluid appreciated on OCT, or BCVA lowered more than 5 letters even with stabilized fluid. Injection was discontinued if no fluid was showed on OCT (quot;dry macularquot;), or BCVA was stabilized even with fluid after two consecutive injections. BCVA and central retinal thickness (CRT) were analyzed and compared between baseline and 6 month follow-up. The correlation between parameters such as baseline BCVA, greatest linear dimension (GLD), type of CNV, SRF or IRF and posttreatment BCVA will be analyzed. The injection number of bevacizumab and complications were recorded. Results Compared to baseline, BCVA improved (9.4plusmn;10.2) letters and reach 44.9plusmn;21.3 letters (t=5.438，P＜0.01) and CRT decreased (184.6plusmn;214.6) mu;m (t=4.810，P＜0.01) at 6 month visit. The average of injection number was 1.9plusmn;0.9 (including initial injection of combination therapy). With multiple lineal regression analysis, only baseline BCVA correlated to posttreatment BCVA at 6 month visit (r=0.802.P＜0.01). The type of CNV, GLD, SRF or IRF on OCT and CRT at baseline were not associated to post-treatment BCVA (r=0.053, -0.183, 0.139 and 0.053, respectively.P＞0.05). BCVA of eyes with SRF (14.7 letters) increased more than eyes with IRF (6.9 letters) on OCT (t=-2.207，P=0.035). The change of BCVA after treatment (t=-0.076), change of CRT (t=-1.028) and number of injections (Z=-1.505) were not different between classic CNV and minimally classic CNV (P＞0.05). The change of CRT (t=-0.020) and number of injections (Z=-0.237) did not present difference between SRF and IRF (P＞0.05). The change of BCVA (t=1.159) and number of injections (Z=-1.194) were not correlated to whether residual fluid or not at 6 month visit (P＞0.05). No severe complications were noticed during follow-up.Conclusion For wet AMD patients, PDT combined intravitreal bevacizumab could improve visual acuity, reduce retinal thickness and control CNV progress in a short-term.
Objective To evaluate the inhibited effects of small interfering RNA targeting Rac1 (Rac1-siRNA) on rat retinal neovascularization in retinae. Methods Retinal vein occlusion was induced by retinal photodynamic medthod in 25 Sprague-Dawley rats. Rac1-siRNA vector DNA was injected into the vitrous of one eye of those rats (gene intervention group), and empty vector DNA was injected into the fellow eye (blank control group). Rac1-siRNA vector was injected in other 25 SD rats without retinal vein occlusion (blank intervention group). Two weeks after injection, fluorescein isothiocyanate (FITC)-dextran was perfused into the hearts of all the rats, and the retinal wholemount was made to observe the neovascularization. The numbers of endothelial cells which break through the internal limiting membrane were counted after hematoxylin-eosin staining. Results A massive of neovascularization and FITC leakage were found in blank control group. Small part of neovascularization and a little FITC leakage were observed in the gene intervention group. Retinal vessels were normal in blank intervention group. Compared with blank contrast group and blank intervention group, the difference of the mean numbers of endothelial cells which broke through the internal limiting membrane in the gene intervention group was significant（t=? P=0.000??lt;0.05）. Conclusion Rac1-siRNA can inhibit retinal neovascularization induced by retinal vein occlusion in rats.