The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
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 evaluate the macular visual function of patients with myopic choroidal neovascularization (MCNV) before and after intravitreal injection of conbercept.MethodsA prospective, uncontrolled and non-randomized study. From April 2017 to April 2018, 21 eyes of 21 patients diagnosed as MCNV in Shanxi Eye Hospital and treated with intravitreal injection of conbercept were included in this study. There were 9 males (9 eyes, 42.86%) and 12 females (12 eyes, 57.14%), with the mean age of 35.1±13.2 years. The mean diopter was −11.30±2.35 D and the mean axial length was 28.93±5.68 mm. All patients were treated with intravitreal injection of conbercept 0.05 ml (1+PRN). Regular follow-up was performed before and after treatment, and BCVA and MAIA micro-field examination were performed at each follow-up. BCVA, macular integrity index (MI), mean sensitivity (MS) and fixation status changes before and after treatment were comparatively analyzed. The fixation status was divided into three types: stable fixation, relatively unstable fixation, and unstable fixation. The paired-sample t-test was used to compare BCVA, MI and MS before and after treatment. The x2 test was used to compare the fixation status before and after treatment.ResultsDuring the observation period, the average number of injections was 3.5. The logMAR BCVA of the eyes before treatment and at 1, 3, and 6 months after treatment were 0.87±0.32, 0.68±0.23, 0.52±0.17, and 0.61±0.57, respectively; MI were 89.38±21.34, 88.87±17.91, 70.59±30.02, and 86.76±15.09, respectively; MS were 15.32±7.19, 21.35±8.89, 23.98±11.12, 22.32±9.04 dB, respectively. Compared with before treatment, BCVA (t=15.32, 18.65, 17.38; P＜0.01) and MS (t=4.08, 3.50, 4.26; P＜0.01) were significantly increased in the eyes 1, 3, and 6 months after treatment. There was no significant difference in the MI of the eyes before treatment and at 1, 3, and 6 months after treatment (t=0.60, 2.42, 2.58; P＞0.05). Before treatment and at 1, 3, and 6 months after treatment, the proportion of stable fixation were 28.57%, 38.10%, 38.10%, 33.33%;the proportion of relatively unstable fixation were 47.62%, 47.62%, 52.38%, 57.14% and the proportion of unstable fixation were 23.81%, 14.28%, 9.52%, 9.52%, respectively. The proportion of stable fixation and relatively unstable fixation at 1, 3 and 6 months after treatment were higher than that before treatment, but the difference was not statistically significant (x2=1.82, 1.24, 1.69; P＞0.05).ConclusionBCVA and MS are significantly increased in patients with MCNV after intravitreal injection of conbercept.
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 evaluate the efficacy and safety of photodynamic therapy (PDT) combined with intravitreal injection of bevacizumab for choroidal neovas cularization (CNV) caused by age-related macular degeneration (AMD). Methods A total of 21 eyes of 21 patients with AMD, which was diagnosed by examination of visual acuity, intraocular pressure, ocular fundus, fundus color photography, fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA)and optic coherence tomography(OCT), were underwent PDT combined with intravitreal injection of Bevacizumab. The patients, 15 males (15 eyes) and 6 females (6 eyes), aged from 56 to 78 years, with the average of 68.6 years. The best corrected visual acuity：counting fingers/10cm0.9, logMAR was 1.04 plusmn; 0.41.CNV located in below or side central fovea of macula. There was obvious leakage of fluorescein which examined by FFA and ICGA. The average of retinal thickness of macular foveal was （258.91 plusmn; 78.66）mu;m. The treatment method of PDT has to according to the way of PDT for TAP and Verteporfin PDT for VIP. Intravitreal infection with 1.5mg bevacizumab was performed after three days under surface anesthesia. Follow-up time was 1, 3, 6, 12 months after the treatment. Results At last visit, the best-corrected visual acuity：counting fingers/10 cm 1.5, logMAR was 1.04plusmn;0.41, and the differences are statistically significant compared with before. The BCVA improved four or more lines in 6 eyes (28.57%), improved two to four lines in 9 eyes (42.86%), stabilized (plusmn;1 line or no change) in 6 eyes (28.57%) and decreased in none. The average intraocular pressure was （15.20plusmn;2.41）mmHg after surgery, and the differences was not statistically significant compared with before（P＞0.05）. FFA and ICGA showed CNV complete closure in 13 eyes (61.90 %), partial closure in 8 eyes (38.10%). The average of retinal thickness of mac ular foveal was（127.38plusmn;20.14） mu;m (P＜0.01). Conclusion Combining treatment with PDT and intravitreal injection of Bevacizumab is safe and effective for CNV which caused by AMD. It has significant improvement in BCVA, leakage of CNV and retinal edema. (Chin J Ocul Fundus Dis,2008,24:164-167)
For choroidal neovascularization (CNV) secondary to pathological myopia, intravitreal injection of anti-VEGF has been widely used in clinic and achieved good outcome. However, due to the differences in the demographic characteristics, stages of disease progression and treatment procedure of CNV, the prognosis of the disease is variable. Complete ellipsoid band, smaller baseline choroidal neovascularization and better baseline vision are important predictors of good outcome of anti-vascular endothelial growth factor treatment. Chorioretinal atrophy or complications related to pathologic myopia indicate a poor prognosis. The influence of age, race, previous photodynamic therapy and early treatment on the prognosis of treatment need to be further studied.
Objective To observe the clinical effects and safety of Bevacizumab on recurrent idiopathic choroidal neoascularization(CNV). Methods To analyze retrospectively the clinical data of 21 eyes of 20 patients with recurrent idiopathic CNV who had intravitreal injection of Bevacizumab(0.05 ml 1.25 mg) after signing the letter of consent. In these patients, 12 cases (13 eyes) had been cured by photodynamic therapy (PDT), and 8 cases (8 eyes) had been cured by transpupillary thermotherapy (TTT). The follow-up periods were 2 weeks, 1 month, 3 months and 6 months after injection. The inspection findings of best-corrected visual acuity(BCVA), fundus fluorescein angiography (FFA) and optical coherence tomogr aphy (OCT) before and after the treatment were observed and analyzed. It could inject once more by the same way if there are recurrences in follow-up period. Results At the end of follow-up period, the BCVA improved obviously (gt;1 lines) in 14 eyes (66.7%)，kept stable (changed within 1 line)in 5 eyes (23.8%) and decreased (gt;1 lines) in 2 eyes(9.5%). The complete closure of CNV in 17 eyes (81.0%) and partial closure in 4 eyes (19.0%) were observed by FFA images. The thickness of retina in macular region decreased 115 micron. 3 eyes (14.3%) has inject again during follow-up period. The intraocular pressure increased in 4 eyes(19.0%) , the average intraocular pressure was 26.7 mm Hg（1 mm Hg=0.133 kPa). They have been returned to normal through the treatment. There was no serious adverse reaction in process of treatment. Conclusion Intravitreal infection of Bevacizumab can reduce the leakage of recurrent CNV and macular edema after PDT or TTT. About 2/ 3 patients can improve their visual acuity obviously. No severe complication or adverse reaction was observed in this study. (Chin J Ocul Fundus Dis,2008,24:168-171)
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 observe the inhibitory effects and characteristics of intravitreal injection with bevacizumab on laser induced choroidal neovascularization (CNV).Methods Twelve male brown norway（BN）rats were divided into the bevacizumab group and control group with six rats in each group. One eye of rats were received a series of 8 diode laser esions around optic disc to induce CNV,then the rats in bevacizumab group and control group underwent intravitreal injection with 2 mu;l bevacizumab and ringer's lactate.On days 7,14,and 21，the morphology and leakage of CNV were observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).On day 21 after photocoagulation,the photocoagulated eyes were enucleated and processed for histopathologic examination, including hematoxylin and eosin (Hamp;E) staining and immunohistochemistry staining for vascular endothelial growth factor（VEGF）.Results On day 7 after photocoagulation,ICGA showed that CNV developed in the bevacizumab group and the control group. FFA showed that leakage intensity in the bevacizumab group was significantly lower than that in the control group，but the bevacizumab group gradually increased over time. The mean thickness of CNV significantly decreased in the bevacizumab group.The CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreal injection with 2 mu;l bevacizumab can reduce the thickness of CNV and inhibit the leakage of CNV. However, bevacizumab could neither block the formation of CNV, nor suppress the permeability permanently. Combined other therapies with bevacizumab may be more potential to treat CNV effectively.
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.