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Objective:To investigate the effect of vascular endothelial growth factor-A ( VEGF- A) gene mutation to neovascular age-related macular degeneration (nAMD) and the response to ranibizumab with this mutation in Chinese. Methods:This was a case-control study.We recruited 127 cases (diagnosed as nAMD) and 101 ethical, age and geographical area matched unrelated healthy controls in Beijing Hospital from February 2017 to January 2018.The patients with nAMD were divided into two subgroups: good response to intravitreal ranibizumab (IVR) and poor response to IVR based on whether gain 5 letters 3 months after therapy.Phenol chloroform method was used in purification of genomic DNA in the peripheral venous blood of each individual.All exons and 2 kb upstream and downstream sequence of VEGF-A was sequenced by using Sanger Sequenced method, and candidate variations were screened out.Restriction fragment length polymorphism (RFLP) method was used in genotyping of the case-control study.Hardy-Weinberg equilibrium was used to test the representativeness of the sample group.The differences of allele distribution frequency and genotype distribution frequency between the case group and control group, good response group and poor response group were compared.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Beijing Hospital (No.2017S-012).Results:The mutation (rs3025018) was located in 7th intron of VEGF-A.The allele were C, G, T and the genotype were CC, CT, CG, TT and TG.The allele distribution frequency between the case and control group were significantly different ( χ2=7.492, P=0.024). The allele G vs. C+ T distribution frequency between the case and control group were significantly different ( χ2=7.490, P=0.006). The genotype distribution frequency between the case group and control group were significantly different ( χ2=13.376, P=0.010). The genotype (CG+ GT vs. CC+ CT+ TT) distribution frequency between the case group and control group were significantly different ( χ2=8.335, P=0.004). The allele frequencies or genotype frequency were not significantly different between the good response group and poor response group (all at P>0.05). Conclusions:G allele of VEGF- A (rs3025018) carriers were less possible to occur nAMD compared with C and T allele.However, there is no effect of VEGF- A gene mutations (rs3025018) on response to ranibizumab for nAMD.
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Objective To compare the efficacy of intravitreal dexamethasone implant (OZURDEX（R）) in the treatment of macular edema (ME) caused by central retinal vein occlusion (CRVO) in different ages.Methods A retrospective case observation study was performed.Forty eyes of 40 patients diagnosed with ME secondary to CRVO were enrolled in the study.According to patient's age,all of the 40 eyes were divided into ＜40 years old group (20 eyes) and ≥40 years old group (20 eyes).All eyes went through best corrected visual acuity (BCVA),intraocular pressure (IOP) and optic coherence tomography (OCT) examinations.Early Treatment Diabetic Retinopathy Study chart was used to test visual acuity,and central macular thickness (CMT) was measured by OCT.Fundus fluorescein angiography (FFA) was proceeded selectively.All eyes went through intravitreal injections off intravitreal dexamethasone implant and BCVA,IOP,OCT were tested 1 month,2,3,6,9 and 12 months after injection.After 3 months follow-up,intravitreal dexamethasone implant or ranibizumab would be injected again for patients with ME recurrence or poor treatment effects.Changes of BCVA,IOP and CMT before and after injection were observed.Results BCVA and CMT in the ＜40 years old group and ≥40 years old group were compared at different time points,and the differences were significantly different (BCVA:Fgroup =2.071,P =0.044;Ftimc.=9.551,P ＜ 0.001.CMT:Fgroup =2.402,P=0.034;Ftime =13.175,P＜0.001),compared with before injection,the BCVA at each time point of post-injection was improved,and CMT was thinner than that before injection;at 2 months after injection,the BCVA was improved and CMT was thinner than those 1 month after injection,the differences were statistically significant (all at P＜0.05);at 12 months after injection,the BCVA in the ＜40 years old group was obviously better than that in the ≥40 years old group,the CMT was much thinner than that in the ≥40 years old group,the differences were statistically significant (both at P＜0.05).Compared with before injection,the IOP at 1 month,2 and 3 months after injection was increased,the IOP at 2 months after injection was higher than that at 1 month after injection,the differences were statistically significant (both at P＜0.05).The mean number of injections was (1.8±0.9) times in the ＜40 years old group and (2.7±1.4)times in the ≥40 years old group,with a statistical difference between them (t =2.569,P =0.014).Conclusions In different age groups,patients with ME caused by CRVO can be effectively treated by intravitreal dexamethasone implant,the therapeutic effect is significant at 1 month post-injection and most improvement is shown at 2 months post-injection.Compared with patients over 40 years of age,patients under 40 years of age have better long-term results,better visual improvement,thinner CMT and less intravitreal injections.
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Objective To investigate the factors associated with short-term elevation ofintraocular pressure after ranibizumab intravitreal injection.Methods 292 eyes of 292 patients who were diagnosed retinopathy and suitable to receive ranibizumab intravitreal injection were enrolled in this prospective clinical study.There were 157 males and 135 females.193 patients diagnosed with age-related macular degeneration and 99 other retinopathy patients.Mean age of patients was 62.75 ± 13.74 years.All subjects underwent systemic and comprehensive ophthalmology examinations.The mean BCVA was 0.68± 0.47 logMAR.Mean basal intraocular pressure was 18.1 mmHg (1 mmHg=0.133 kPa).All patients received intravitreal injection with 0.05 ml of ranibizumab (0.5 mg).The intraocular pressure were measured by non-contact tonometer at 10,30,120 minutes and 1 day after injection in a sitting position.The patients were grouped by the changes ofintraocular pressure 10 minutes after injection.The elevation was more than 10 mmHg as elevation group and less than 10 mmHg as stable group.Analyze the possible related factors with elevation of intraocular pressure after ranibizumab intravitreal injection by comparing the different datum of two groups.Results The mean intraocular pressure were 23.8,20.5,19.9 and 17.4 mmHg at 10,30,120 minutes and 1 day after injection.The significant elevation level were 5.8,2.4,1.8,-0.7 mmHg compared with basal intraocular pressure.Among 292 eyes,intraocular pressure elevation in 68 eyes and stabled in 224 eyes.The age (Z=-0.732),gender (x2=1.929),right or left eye (x2=2.910),BCVA (Z=-0.039),diseases ((2=2.088) were no significant difference between two groups (P＞0.05).The injection number (Z=-2.413,P=0.001),basal intraocular pressure (Z=-3.405,P=0.016) and elevations after injection (Z=-11.501,-8.366,-5.135,-3.568;P＜0.01) were significantly different comparing two groups (P＜0.05).By logistic regression analysis,basal intraocular pressure was positively correlated with the elevation of intraocular pressure 10 minutes after injection (B=-0.844,OR=0.43,95％CI 0.24-0.76,P=0.004).Patients with higher basal intraocular pressure may occur intraocular pressure elevation after ranibizumab intravitreal injection much probably.Conclusions The factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection were basal intraocular pressure.The higher basal intraocular pressure,the higher risk to gain elevation of intraocular pressure after injection.
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Objective To evaluate the efficacy and safety of dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO).Methods Thirty-nine patients (39 eyes) with ME secondary to RVO were enrolles in this study.Of the patients,27 were male and 12 were female.The mean age was (41.9 ± 16.3) years.The mean course of disease was (5.0± 5.3) months.The best corrected visual acuity (BCVA),intraocular pressure and optical coherence tomography (OCT) were performed.BCVA was measured by Early Treatment Diabetic Retinopathy Study charts.Central macular thickness (CMT) was measured by OCT.The mean BCVA was (13.4± 15.3) letters.The mean intraocular pressure (IOP) was (14.1 ±2.8) mmHg (1 mmHg=0.133 kPa).The mean CMT was (876.1 ±437.9) μm.Of the 39 eyes,33 were central RVO,6 were branch RVO.Patients were categorized into ischemic (18 eyes)/non-ischemic (21 eyes) groups and previous treatment (22 eyes)/treatment naive (17 eyes) groups.All eyes underwent intravitreal 0.7 mg Ozurdex injections.BCVA,IOP and CMT were assessed at 1,2,3,6,9,12 months after injection.Three months after injection,intravitreal injections of Ozurdex,triamcinolone acetonide or ranibizumab could be considered for patients with ME recurrence or poor treatment effects.Change of BCVA,IOP and CMT were evaluated with paired t test.The presence of ocular and systemic adverse events were assessed.Results BCVA,IOP significantly increased and CMT significantly decreased at 1 month after injection compared to baseline in all groups (t=3.70,3.69,4.32,3.08,4.25,6.09,6.25,4.02,5.49,8.18,6.54,5.73;P＜0.05).Two months after injection,change of BCVA,IOP and CMT was most significant (t=4.93,6.80,6.71,5.53,4.97,5.89,5.13,7.68,7.31,8.67,8.31,5.82;P＜0.05).Twelve months after injection,there was no statistical difference regarding BCVA of ischemic RVO group and previous treatment group,compared to baseline (t=1.86,0.67;P＞0.05);BCVA ofnon-ischemic RVO group and treatment naive group significantly increased compared to baseline (t=2.27,2.30;P＜0.05);IOP significantly increased and CMT significantly decreased in all groups (t=0.30,0.13,4.60,3.26,0.64,1.53,3.00,4.87;P＜0.05).Twenty-seven eyes (69.2％) experiences ME recurrence (4.5± 1.5) months after injection.Most common side-effect was secondary glaucoma.41.0％ eyes had IOP more than 25 mmHg,most of which were lowered to normal range with use of topical IOP lowering drugs.Four eyes (10.3％) presented with significant cataract progression and needed surgical treatment,all were central RVO eyes.No serious ocular or systemic adverse events such as vitreous hemorrhage,retinal detachment or endophthalmitis were noted.Conclusions Intravitreal injection of Ozurdex for patients with ME secondary to RVO is effective in increasing BCVA and lowering CMT in the first few months.Significant treatment effect could be seen at 1 month after injection and was most significant at 2 months after injection.The long-term vision of eyes in non-ischemic RVO group and treatment naive group are better.69.2％ eyes experience ME recurrence at 4 months after injection.Short term adverse events were mostly secondary glaucoma and long term adverse events are mostly cataract progression.
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Objective To investigate the factors associated with vision and hole closure for idiopathic macular hole (IMH) after vitrectomy surgery.Methods Eighty-nine eyes of 89 patients with IMH were enrolled in this retrospective study.There were 15 males and 74 females.The patients aged from 42 to 82 years,with the mean age of (64.13 ± 7.20) years.All subjects underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations.The BCVA ranged from 0.01 to 0.4,with the mean BCVA of 0.12 ± 0.09.The MH stages was ranged from 2 to 4,with the mean stages of 3.56 ± 0.77.The basal diameter ranged from 182 μm to 1569 μm,with the mean basal diameter of (782.52± 339.17) μm.The treatment was conventional 25G pars plana vitrectomy combined with phacoemulsification and intraocular implantation.Fortyone eyes received internal limiting membrane peeling and 48 eyes received internal limiting membrane grafting.The follow-up ranged from 28 to 720 days,with the mean follow-up of (153.73 ± 160.95) days.The visual acuity and hole closure were evaluated on the last visit and the possible related factors were analyzed.Results On the last visit,the BCVA ranged from 0.02 to 0.8,with the mean BCVA of 0.26±0.18.Among 89 eyes,vision improved in 45 eyes (50.56％) and stabled in 44 eyes (49.44％).Eighty-six eyes (96.63％) gained MH closure but 3 eyes (3.37％) failed.By analysis,patients of early stages of MH and smaller basal diameter of MH will gain better vision outcome (t=2.092,2.569;P＜ 0.05) and patients of early stage MH will gain high hole closure rate after surgery for IMH (t=-5.413,P＜0.05).However,gender,age,duration,preoperative BCVA,surgery technique,gas types and follow-up time had no relationship with the effect after surgery for IMH (P＞0.05).Conclusions Stages of MH and basal diameter of MH may be the factors associated with the visual outcome for idiopathic macular hole after surgery.However,age,gender,duration,surgery patterns,gas types and followup time showed no effects on operational outcomes.
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Exudative age-related macular degeneration (AMD) is the leading cause of central vision loss in elderly population,and its primary pathological mechanism is the formation of choroidal neovascularization (CNV).Recently,it is found that the balance of angiogenesis and antiangiogenic factors plays an important role in the formation of CNV,and the main factors are vascular endothelial growth factor (VEGF) and pigment epitheliumderived factor (PEDF).The targeting therapy for these cytokines provides a new approach to the treatment of exudative AMD.Anti-VEGF therapy is of great effect on controlling CNV and improving visual acuity in exudative AMD patients.The purpose of this review was to summarize current advance in the study of cytokines associated with the pathogenesis of exudative AMD and its targeting therapy.