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 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.
The introduction of anti-vascular endothelial growth factor (VEGF) therapy represents a landmark in the management of wet age-related macular degeneration (AMD). However, as a new therapy, several problems such as durability of the therapeutic effects, medication side effects, and medication selection have emerged. We should make appoint of improving the therapeutic effect and safety by realizing the limitation of the therapy, monitoring the clinical potential adverse reactions of anti-VEGF agents, and recommending individualized treatment.
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.
Objective To evaluate the clinical efficacy of intravitreal injections of antivascular endothelial growth factor monoclonal antibody ranibizumab in choroidal neovascularization (CNV) secondary to pathologic myopia (PM). Methods This is a prospective, uncontrolled, open-label study. 34 eyes of 34 patients with CNV secondary to PM were included in the study. All affected eye were treated with intravitreal ranibizumab 0.05 ml (10 mg/ml). Before the injection, bestcorrected visual acuity of early treatment of diabetic retinopathy study (ETDRS), noncontact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA) and optical coherence tomography (OCT) examination were necessary. The initial average letters of ETDRS acuity were 33.85plusmn;14.67, range from 0 to 69. The initial average central macular thickness (CMT) was（293.41plusmn;79.45） m, range from 210 m to 543 m. The patients were followed up for 3 to 12 months. Best-corrected visual acuity, OCT and ophthalmoscope examination were assessed monthly. If necessary, FFA was used. The letters of ETDRS acuity and CMT were compared before and after treatment. Results All eyes received an average of 1.68 injections, the final vision of follow-up increased （13.50plusmn;9.94） letters than before （t=7.92，P=0.00）, CMT decreased （71.14plusmn;72.26） m (t=4.62，P=0.00). There were no systemic or ocular serious side effects during the follow up. Conclusion Intravitreal ranibizumab for pathologic myopia choroidal neovascularization showed visual acuity improvement, retinal thickness reduction and safety.
ObjectiveTo evaluate the effects of intravitreal ranibizumab therapy for serous pigment epithelial detachment (sPED) secondary to exudative age-related macular degeneration(eAMD). MethodsTwenty-three eyes from 23 patients of eAMD with sPED were enrolled in this study. The best corrected visual acuity, ocular coherence tomography (OCT), maximum PED height from baseline, volume of PED and central fovea thickness(CFT)were collected monthly for these patients. And the patients were receiced intravitreal injection with ranibizumab of 0.5 mg of three consecutive monthly injections. ResultsNo complications were observed during the study period. After 6 months follow-up, 17 eyes improved, 4 eyes unchanged and only 2 eye decreased. The best corrected visual acuity was from 0.77±0.39 up to 0.61±0.27(t=2.601, P < 0.05). It was observed by OCT that the PED height was decreased from (357.2±171.9)μm (before treatment) to (247.7±171.7)μm (after treatment) (t=3.192, P < 0.05) and the volume of PED was decreased from(0.741±1.012) mm3 to (0.337±0.498) mm3 (t=2.502, P < 0.05). The central foveal thickness was decreased from (317.9±73.8)μm to (302.5±89.3)μm, but the difference were no statistically significantly (t=0.887, P > 0.05). ConclusionRanibizumab may be an effective treatment for improving vision and reducing the degree of PED in eAMD patients.
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 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)
Choroidal neovascularization (CNV) is the key characteristic of neovascular age-related macular degeneration (nAMD), and the effective therapy is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents based on clinical and basic research. In the meantime the challenge is how to further improve the inhibiting effect for CNV and visual function of anti-VEGF treatment on nAMD. The new strategy and drug delivery devices for anti-VEGF treatment will optimize the clinical scheme. From bench to bedside, the research on targeted treatment of angiogenesis brings the bloom of nAMD medical therapy.