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.
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.
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.
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 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 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.
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)
Objective To observe the inhibition effect of selective cyclooxygenase2 inhibitor（celecoxib）on the experimental choroidal neovascularization（CNV）. Methods Thirty 8-10 weeks old healthy male Brown-Norway（BN）rats were randomly divided into the control, laser and celecoxib group,with 10 rats in each group. At the dosage of 50 mg/kg, celecoxib was gavaged twice per day. After 7 days, experimental CNV was induced by Krypon laser on laser group and celecoxib group. Fundus fluorescein angiography (FFA) was performed on days 3, 7,14,21,30 after laser photocoagulation.On days 21 after photocoagulation, 5 rats in each group were sacrificed and the relative thickness of CNV membranes, the expression of COX-2, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2(MMP-2) were studied by histopathologic or immunohistochemistry examination.Results On days 21 after photocoagulation, the incidence of CNV in the celecoxib group is significantly lower than that in the laser group (chi;2=7.1068,P=0.0077); the relative thickness of the CNV membranes in the celecoxib group is reduced 41.38% compared to the laser group, the difference is statistically significant (t=16.760 0，P=0.0000).COX-2,VEGF and MMP-2 expression in the CNV membrane of celecoxib group were significantly lower than in control group (t=5.710 0,5.840 0, 8.020 0; P=0.000 0); the COX-2, VEGF and MMP-2 expressions in choroid and retina of control group were weak. Conclusion Prophylactic celecoxib can reduce the expression of VEGF and MMP-2 by inhibiting COX-2, and prevent the CNV induced by laser photocoagulation.
ObjectiveTo observe the changes in choroidal characteristics of polypoid choroidal vascular disease (PCV) eyes after intravitreal injection of anti-VEGF drugs, and to preliminarily evaluate its predictive effect on the response of PCV anti-VEGF drugs.MethodsA retrospective clinical study. From January 2015 to May 2020, 63 eyes (63 PCV patients) diagnosed in NanJing Medical University Eye Hospital were included in the study. There were 39 eyes (39 males) and 24 eyes (24 females); all were monocular, with the average age of 62.53±6.05 years old. All eyes were treated with intravitreal injection of ranibizumab, and those with poor response after treatment were treated with photodynamic therapy (PDT) combined with anti-VEGF drugs. Among the 63 eyes, 38 eyes did not respond or responded poorly after treatment, and 25 eyes responded well. Based on response results, patients were divided into the poor response group and the good response group. The confocal laser synchronous angiography system (HRA+OCT) enhanced depth scanning technology of Herdelberg (Germany) was used to measure the foveal choroid thickness (SFCT) and the choroidal large vessel thickness (LCVT). The choroidal hyperpermeability (CVH) was judged based on the ICGA inspection results. CVH: In the middle and late stages (10-15 min after indocyanine green injection), the choroid of the posterior pole can be seen with multifocal strong fluorescence with blurred edges. The SFCT and LVCT changes of the two groups of eyes before treatment and 6 months after treatment in the good response group, and 6 months after the treatment of the poor response group combined with PDT were observed. SFCT and LCVT were compared with t test before and after treatment.ResultsBefore treatment, of the 63 eyes, 38 eyes (60.3%) with CVH manifestations, of which 5 eyes (20.0%, 5/25) and 33 eyes (86.8%, 33/ 38). The SFCT and LCVT of the good response group and the poor response group were 244.16±23.74, 152.76±22.70 μm and 367.34±35.21, 271.84±35.42 μm, respectively. The comparison of SFCT and LVCT between the two groups of eyes before treatment showed statistically significant differences (t=7.24, 6.87; P=0.01, 0.01). Six months after treatment, the SFCT and LVCT of the eyes in the good response group were 241.04±32.56 and 150.44±23.45 μm, respectively; compared with those before treatment, the difference was not statistically significant (t=5.35, 8.64; P=0.08, 0.07). Six months after the poor response group combined with PDT treatment, SFCT and LCVT were 311.63±25.36 and 220.11±41.30 μm respectively; compared with those before treatment, the difference was statistically significant (t=6.84, 9.23; P=0.02, 0.01). After treatment, the CVH manifestations of all the eyes did not change significantly, but the eyes of the poor response group were treated with PDT, and the multifocal strong fluorescence was significantly weakened.ConclusionsPCV thick choroid is mostly caused by abnormal thickening of choroidal large vessels. Eyes with thick choroid and CVH have poor response to anti-VEGF drug therapy alone, and combined PDT therapy may be more suitable for this type of patients.