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 inhibitory effect of endostatin (ES) on oxygen-induced retinal neovascularization.MethodsThirtyfour 7-day-old C57BL/6J mice were randomly divided into 3 groups: oxygen-exposed group (12 mice), ES group (12 mice) and the control group (8 mice). The mice in oxygen-exposed and ES group were exposed to (75±5)% oxygen for 5 days and then back to the normal air. In ES group, 1 μg ES endostatin were injected into vitreous in one eye, while PBS was injected into the other eye as the control 12 and 36 hours after being exposed to oxygen. The mice in the control group were fed in normal circumstance. The changes of retinal neovascularization was examined by fluorescence angiography with fluorescein isothiocyanatedextran. The number of endothelial cells breaking through the internal limiting membrane (ILM) was counted and the inhibitory effects of ES on retinal neovascularization was observed.ResultsCompared with the oxygen-exposed group, the branches of retinal vessels went normal without any un-perfused area in ES group. The number of nuclei of endothelial cells breaking through ILM on each retinal crosssection decreased to (5.39±1.52), which differed much from that in the oxygen-exposed group (22.56±2.13) (plt;0.001).ConclusionES can effectively inhibit the formation of retinal neovascularization in rats and might be a new path of the treatment for proliferative retinopathy.(Chin J Ocul Fundus Dis, 2005,21:314-317)
Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age-related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow-up time was 6-12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow-up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P<0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P<0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
Objective To determine the effect of posterior vitreous detachment on the prognosis of branch retinal vein occlusion (BRVO). Methods One hundred and sixteen patients (116 eyes) with BRVO who underwent vitreous examination were retrospectively studied.The relati onship of vitreous conditions to posterior segment neovascularization and macular edema was statistically investigated. Results In 40 ischemic cases,12 of 25 eyes (48.0%) with no posterior vitreous detachme nt (PVD) or partial PVD developed retinal or optic disc neovascularization ,or both,but only one of the 15 eyes (6.7%) with complete PVD developed neovasculariz ation during a mean follow-up period of 10.7plusmn;2.2 months (Plt;0.05) . Diffuse macular edema was found in 45 eyes (38.8%).The incidence o f macular edema was significantly higher in eyes with vitreomacular attachment (51.5%) than in those with vitreomacular separation (22.0%) (Plt;0.01). Conclusion It was suggest ed that compl ete PVD may play a role in protecting eyes with BRVO from posterior segment neov ascularization and macular edema. (Chin J Ocul Fundus Dis, 2001,17:2-4)
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.
Two-hundred and forty-five eyes of 240 cases of branch retinal vein occlusion (BRVO) were analysed to determine the risk factors influencing the development of retinal neovascularization (NV).There were 208 eyes with major BRVO, 37 eyes with macular BRVO, 79 eyes with major BRVO developed NV, and the incidence of NV in this series was 37.9%.The incidence of vitreous hemorrhage in these eyes was 15.9%(39 eyes). The risk factors influencing the development of retinal NV in BRVO seem as follows: (]) the extent of retinal capillary nonperfusion area, (2)inefficiency of arterial infusion, (3) the extent of venous block at the arteriovenous crossing, (4) the duration of follow-up since onset of BRVO, and (5) the lack of collateral formation, Because BRVO has a long natural history, it is recommended that the patients should be followed-up for a long time If the vessels at peripheral retina closed, fluorescein angiography should be performed without hesitation and if the nonperfusion area is greater than 20-30 disc area, one should follow the patient carefully.As soon as the new vessels appear, laser photocoagulation should be applied without delay. (Chin J Ocul Fundus Dis,1994,10:67-70)
Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P<0.001). But the differences between two treatment groups are not statistically significant (P>0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P>0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. (Chin J Ocul Fundus Dis,2008,24:184-188)
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
Objective To analyze the pathogenesis of cystoid macular edema (CME) secondary to exudative age-related macular degeneration (AMD). Methods From October 2000 to December 2003, OCT images of 171 eyes of 140 patients with exudative AMD were evaluated. The CNV types were classified according to its location (above or below the RPE), and the correlation between the types of CNV and the development of CME were analyzed. Results Of the 171 eyes with AMD, 89 eyes (52.0%) had CME, and 82 eyes (48.0%) had no CME. Among the 89 eyes with CME, 76 eyes (85.4% ) had an active CNV lesion, and 13 eyes (14.6%) had a disciform scar. Among the 82 eyes without CME, 69 eyes (84.1%) had an active CNV lesion, and 13 eyes (15.9 %) had a disciform scar. In the 76 eyes with both CME and active CNV, 75 eyes (9 8.7%) had a subretinal CNV, which included 61 eyes (80.3%)with a combined CNV complex and 14 eyes (18.4%) with a Gass 2 type CNV, only 1 eye (1.3%) had a Gass 1 type CNV. Whereas, in the 69 eyes with active CNV but without CME, 57 eyes (82.6%) had a Gass 1 type CNV, only 12 eyes (17.4%) had a subretinal CNV. There was a significant difference in the incidence of subretinal CNV between eyes with or without CME (χ2=99.5838, P=0.0000). Conclusions CME formation was highly corre lated with the invasion of CNV into the subretinal space. Subretinal CNV might be the direct cause of CME secondary to exudative AMD.(Chin J Ocul Fundus Dis,2004,20:299-302)
Retinal neovascularization is a complicated pathophysiological process as a result of imbalance between angiogenic and antiangiogenic factors. Correct understanding of the signaling pathways, exploring the critical factors involved in retinal angiogenesis, looking for new strategies by reconstructing the new vessels are helpful for knowing the mechanism of the occurrence and development of reitnal neovascularization, which would be good for preventing and treating retinal neovascularization diseases.