Diabetic macular edema (DME) is one of the common causes of visual impairment. Anti-vascular endothelial growth factor (VEGF) has become the preferred therapy for DME because of significant visual improvement. Early and intensive anti-VEGF therapy combined with other individualized treatments are currently the main strategy for DME treatment. Considering the complexity of DME and limitations of anti-VEGF therapy, there are still many problems and difficulties in the treatment of DME. Optimizing treatment strategies, strengthening management of the clinical course and developing new drugs, could improve the efficacy and maintain the improvement of visual acuity and visual performance.
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 observe the efficacy of conbercept in the treatment of different types of diabetic macular edema (DME).MethodsA retrospective clinical study. From March 2019 to March 2021, 136 eyes of 136 patients with DME diagnosed in Department of Ophthalmology of Xi'an No.3 Hospital were included in the study. Among them, there were 65 males and 71 females; the average age was 56.65±8.65 years. All patients underwent best corrected visual acuity (BCVA), optical coherence tomography (OCT) examination, and glycosylated hemoglobin level (HbA1c) examination. Early Treatment Diabetic Retinopathy Study visual acuity chart was used for BCVA examination, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. An OCT instrument was used to measure the central retinal thickness (CRT) of the macula. According to the characteristics of OCT, DME was divided into diffuse retinal thickening (DRT) type, cystoid macular edema (CME) type, serous retinal detachment (SRD) type, mixed type, and grouped accordingly, respectively, about 30, 38, 33, 35 eyes. There was no significant difference in age (F=1.189), sex ratio (χ2=1.331), and HbA1c level (F=3.164) of the four groups of patients (P＞0.05). All eyes were treated with intravitreal injection of 10 mg/ml conbercept 0.05 ml (including conbercept 0.5 mg) once a month for 3 consecutive times, and then treated as needed after evaluation. BCVA and OCT examinations were performed 1, 3, and 6 months after treatment with the same equipment and methods as before treatment. The changes of BCVA and CRT before and after treatment were compared and observed. For measurement data subject to normal distribution, one-way analysis of variance was performed for comparison between groups; χ2 test was performed for comparison of count data.ResultsBefore treatment, the logMAR BCVA of the eyes in the DRT group, CME group, SRD group, and mixed group were 0.68±0.11, 0.69±0.15, 0.71±0.12, 0.73±0.14, and CRT was 631.4±50.7, 640.6±55.7, 652.3±63.4, 660.4±61.8 μm. Compared with before treatment, 1, 3, 6 months after treatment, DRT group (BCVA: t=8.139, 11.552, 11.672; CRT: t=16.163, 21.653, 25.855), CME group (BCVA: t=8.923, 9.995, 13.842; CRT: t=16.163, 21.653, 25.855), SRD type group (BCVA: t=5.171, 7.315, 6.051; CRT: t=9.099, 13.731, 21.306), mixed type group (BCVA: t=5.072, 6.939, 7.142; CRT: t=6.920, 15.352, 17.538) The BCVA of the affected eyes was significantly increased, and the CRT was significantly decreased, and the difference was statistically significant (P＜0.05). At 6 months after treatment, the differences in logMAR BCVA and CRT of the 4 groups of eyes were statistically significant (χ2=58.478, 64.228; P＜0.05). The average number of injections in the eyes of the DRT group, CME group, SRD group, and mixed group were 3.37±1.35, 3.68±1.38, 4.18±1.40, 4.13±1.50 times, respectively. Compared with the average number of injections in the eye, the difference was statistically significant (χ2=9.139, P=0.028).ConclusionsConbercept can effectively reduce CRT and increase BCVA in eyes with different types of DME. Compared with SRD type and mixed type, DRT and CME type eye are more effective in improving vision, CRT reduction degree is greater, and the number of injections is less.
ObjectiveTo observe the level of microparticles in the vitreous of patients with proliferative diabetic retinopathy (PDR), and preliminarily explore the role of microparticles in the pathogenesis of PDR.MethodsA case control study. From January to December 2018, 54 cases of 54 eyes of PDR patients (PDR group) and 20 cases of non-diabetic retinopathy patients (control group), who were diagnosed and treated with vitrectomy (PPV) in the Department of Ophthalmology, Tianjin Medical University General Hospital vitreous samples were included in the study. Among 54 eyes in the PDR group, there were 42, 21, and 17 eyes with vitreous hemorrhage (VH), traction retinal detachment (TRD), and previous intravitreal injection of drugs, respectively. Among the 20 eyes of the control group, idiopathic macular hole, idiopathic anterior macular membrane, vitreous macular traction syndrome, and complete lens dislocation were 6, 6, 2, and 6 eyes, respectively. The PDR group was divided into uncombined TRD group and combined TRD group according to PDR stage and whether TRD occurred, with 33 and 21 eyes, respectively. According to the presence or absence of VH, they were divided into groups with VH and without VH, with 42 eyes and 12 eyes, respectively. According to whether anti-vascular endothelial growth factor (VEGF) drugs were injected into the intravitreal cavity 3 days before PPV, they were divided into anti-VEGF drug group and no anti-VEGF drug group, with 17 eyes and 37 eyes respectively. The levels of retinal photoreceptor cells (RMP), platelets (PMP), endothelial cells (EMP) and phosphatidylserine (PS-MP) expressing on the membrane surface in the sample were detected by flow cytometry. The comparison between the two groups of samples was performed by t test, and the comparison between multiple groups of samples was performed by one-way analysis of variance or Mann-Whitney test.ResultsCompared with the control group, the vitreous RMP level of the PDR group was significantly decreased, and the EMP and PMP levels were significantly increased. The differences were statistically significant (t=−2.361, 5.064, 3.531; P=0.018, ＜0.001, 0.001). There was no statistically significant difference in PS-MP levels between the two groups (t=−1.617, P=0.110). Compared with the TRD group, the levels of RMP and PMP in the vitreous of the TRD group were significantly increased, and the difference was statistically significant (t=−2.221, −2.098; P=0.031, 0.041). The level of EMP in the vitreous body of the anti-VEGF drug group was significantly lower than that of the non-anti-VEGF drug group, however, it was still higher than the control group. The difference was statistically significant (Z=−2.430, −2.499; P=0.015, 0.012). The level of PMP in the vitreous body of the eye without VH was significantly higher than that in the group with VH, and the difference was statistically significant (t=−3.097, P=0.003).ConclusionsThe elevated levels of EMP and PMP in the vitreous of PDR patients may be related to the damage of retinal capillaries; intravitreal injection of anti-VEGF drugs before surgery can reduce the level of EMP. VH may be related to the procoagulant effect of PMP.
ObjectiveTo systematically review the efficacy and safety of photodynamic therapy (PDT) and intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of polypoidal choroidal vasculopathy (PCV), and to investigate the primary treatment tentatively. MethodsA systematic search of Pubmed, Embase, the Cochrane Library and the Wanfang Data was performed to identify all comparative studies that compared the outcomes of PDT alone, intravitreal VEGF inhibitors alone and combined intravitreal VEGF inhibitors and photodynamic therapy. Outcomes of interest included the regression and recurrence rate of polypoidal lesions, best corrected visual acuity (BCVA), central retinal thickness (CRT), therapeutic times, and the occurrence rate of adverse events. 2 randomized controlled trials (RCT) and 19 non-RTCs were identified. According to treatment methods, the data extracted was classified to 3 groups, analyzed with odds ratio (OR), weighted mean difference (WMD) and 95%confidence interval (95%CI). ResultsMeta-analysis suggests that the regression rate of polypoidal lesions (OR=0.34, 0.07; 95%CI=0.13-0.88, 0.02-0.36) and BCVA (WMD=0.25, 0.11; 95%CI=0.14-0.36, 0.01-0.21) in combined therapy group were significantly better than those in PDT group and intravitreal VEGF inhibitors group (P < 0.05). The recurrence rate of polypoidal lesions in PDT group was significantly lower than intravitreal VEGF inhibitors group (OR=0.35, 95%CI=0.16-0.74, P=0.006). BCVA (P=0.025) and the occurrence rate of adverse events (OR=60.36, 95%CI=6.04-603.50, P=0.000 5) in intravitreal VEGF inhibitors group were significant better than PDT group. ConclusionsCombined treatment appeared to be superior to PDT alone or intravitreal VEGF inhibitors alone. Combined treatment takes priority over all others in the primary treatment of PCV.
ObjectiveTo observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD). MethodsA retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 (IL-8), complement C3 gene (C3), complement factor H (CFH), liver lipase (LIPC), cholesterol ester transfer protein (CETP), ATP binding cassette subfamily a member 1 (ABCA1), lipoprotein lipase (LPL), fatty acid desaturation gene cluster (FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. ResultsThere were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio (OR)=0.310, 95% confidence interval (CI) 0.106-0.910, P＜0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders (OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) (OR=3.031, 95% CI 1.036-8.867, P＜0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant (t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment (IL-8 rs4073: Z=－0.198, －1.651; P=0.843, 0.099; LIPC rs2043085: Z=－0.532, －0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.
Diabetic retinopathy (DR) is a common ocular complication in diabetic patients, which is chronic and progressive and seriously impairs visual acuity. The rapid occurrence and progress of cataract in diabetic patients is also one of the important reasons for visual impairment in DR patients. Compared with non-diabetic patients, diabetic patients have higher risk of complications after cataract surgery. Studies have shown that anti-vascular endothelial growth factor (VEGF) therapy after cataract surgery can prevent the aggravation of diabetic macular edema in DR patients. However, due to the lack of systematic review of the clinical effect of anti-VEGF drugs in DR patients undergoing cataract surgery, the use of anti-VEGF drugs is relatively conservative in clinic. It is believed that with the deepening of research and the progress of clinical trials, the wide application of anti-VEGF drugs in clinical practice is expected to provide more accurate and effective treatment for DR patients in the future.
ObjectiveTo investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV). MethodsThis retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. ResultsAt baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant (Z= －3.886, －4.061; P＜0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant (t=－2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant (Z=－3.253, P＜0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up (Z=－1.342,－1.313; P=0.195, 0.195). ConclusionIntravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.
ObjectiveTo analyze the concentrations of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of patients with proliferative diabetic retinopathy (PDR) before and after intravitreal injection of ranibizumab. MethodsTwenty-five eyes of 20 PDR patients were collected as the PDR group. Twenty-five eyes of 21 senile cataract patients were collected as the control group. There were no statistical significance in gender (χ2=0.223), age (Z=-1.555) and intraocular pressure (Z=-0.225) between the two groups (P > 0.05). Samples of aqueous humor (0.1 ml) were collected just before and 7 days after the injection of ranibizumab in PDR group. Samples of aqueous (0.1 ml) humor were collected just before cataract surgery in control group. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay. ResultsThe VEGF and PEDF concentration in the aqueous humor were reduced significantly after intravitreal injection of ranibizumab in PDR group (Z=-4.072, -4.319; P < 0.05). The concentrations of VEGF and PEDF in the aqueous humor before intravitreal injection of ranibizumab in PDR group were significantly higher than the control group (Z=-5.228, 4.706; P < 0.05). The VEGF concentration in the aqueous humor after intravitreal injection of ranibizumab in PDR group were similar to control group (Z=-1.557, P > 0.05). However, the concentration of PEDF in the aqueous humor after intravitreal injection of ranibizumab in PDR group still higher than control group (Z=-2.475, P < 0.05). The ratio of VEGF/PEDF before and after intravitreal injection of ranibizumab was statistically different (Z=-2.058, P < 0.05), but was the same between PDR group and control group (Z=-0.456, -0.844; P > 0.05). The aqueous humor concentrations of VEGF and PEDF were not significantly correlated with each other, neither in PDR group (r=-0.195, -0.174; P > 0.05) nor in control group (r=-0.286, P > 0.05). ConclusionsAqueous humor concentrations of VEGF and PEDF are significantly elevated in eyes with PDR. Intravitreal injection of ranibizumab significantly decreased the VEGF and PEDF in the aqueous humor after 7 days.
Objective To compare the thickness of the macular ganglion cell inner plexiform layer (mGCIPL) in patients with a history of laser photocoagulation (LP) versus intravitreal injection of ranibizumab (IVR) for retinopathy of prematurity (ROP). MethodsA retrospective clinical study. From June 2020 to January 2021, 70 eyes of 35 children with a history of surgery for ROP in Shenzhen Eye Hospital were included in the study. Among them, 18 males had 36 eyes, and 17 females had 34 eyes. The average age was 5.54±1.04 years. There were 18 patients (36 eyes) in LP group and 17 patients (34 eyes) in IVR group. There was no significant difference in age (t=－1.956), sexual composition ratio (χ2=0.030), birth gestational age (t=－1.316) and birth weight (t=－1.060) between the two groups (P=0.059, 0.862, 0.197, 0.297). All the eyes underwent the examination of optical coherence tomography (OCT). An elliptical region of 14.13 mm2 centered on macular fovea was scanned according to the macular cube 512×128 model of the Cirrus HD-OCT 5000. The software was used to automatically divide macular fovea into six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum thickness of mGCIPL. t test was used to compared mGCIPL thickness between two groups using independent samples. Pearson correlation analysis was used to evaluate the correlation between mGCIPL thickness and age, birth gestational age, birth weight. ResultsPatients in IVR group had significantly decreased mGCIPL thickness than that in LP group in the six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum (t=6.484, 6.719, 7.682, 7.697, 5.151, 5.008, 7.148, 6.581; P＜0.05). The thickness of mGCIPL was not significantly correlated with age, birth gestational age, birth weight (P＞0.05). ConclusionThe thickness of mGCIPL in patients with IVR treatment history is thinner than that in LP treatment.