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Objective To observe the synergistic effect of metformin and anti-vascular endothelial growth factor (VEGF) in the treatment of diabetic retinopathy.Methods This study was composed of clinical data review and in vitro cell experiment.Ten patients (12 eyes) with diabetic macular edema treated with antiVEGF drugs were included in the study.Patients were randomly divided into the VEGF group (anti-VEGF drug therapy) and the combined treatment group (anti-VEGF drug combined with metformin).The changes of visual acuity and central retinal thickness (CRT) were compared between the two groups.As far as the in vitro experiment was concerned,vascular endothelial cells were divided into the control group (normal cells),the VEGF group (50 ng/ml VEGF),the anti-VEGF group (50 ng/ml VEGF+2.5 μg/ml of conbercept),and the combined group (50 ng/ml VEGF +2.5 μg/ml of conbercept +2.0 mmol/L of metforrnin).And then MTT cell viability assay,scratch assay and real-time quantitative polymerase chain reaction assay were performed to analyze the cell viability,cell migration and mRNA level of VEGFR2,protein kinase C (PKC)-α and PKC-β successively.Results Review of clinical trial shows that the CRT recovery rates in the combined treatment group were much higher than that in the VEGF group at 3 month after the operation,while the difference was statistically significant (t=-2.462,P＜0.05).In vitro cell experiment results showed that VEGF induction upregulated the viability and mobility of vascular endothelial cells obviously compared with control group,at the same time,the use of anti VEGF drugs can effectively reverse the trend,in contrast,combination of metformin and anti-VEGF showed a more superior effect to some extent (P＜0.05).In the VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-[β were significantly increased compared with the control group (P＜ 0.01);while the mRNA expression of VEGFR2,PKC-αand PKC-β in the combination group decreased significantly compared with the VEGF group and the control group (P＜0.05).However,in the anti-VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-β were decreased,but has failed to reach the level of statistical learn the difference.Conclusions The combination ofmetformin and anti-VEGF drugs can reduce the CRT of diabetic retinopathy patients and inhibit the proliferation and migration of retinal vascular endothelial cells which induced by VEGF.The synergistic mechanism may be related to the inhibitory effect of metformin on the expression of VEGFR and PKC.
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Background Vitrectomy is a primary approach to the treatment of proliferative diabetic retinopathy (PDR).However,postoperative rehaemorrhagia often occur.Ranibizumab is an effective drug of antivascular endothelial growth factor,but whether the combination of intravitreal injection of ranibizumab with vitrectomy can reduce the incidence of postoperative rehaemorrhagia in PDR patients is still unclear.Objective This study was to investigate the preventive effect of the combination of intravitreal injection of ranibizumab with 25-gauge vitrectomy on postoperative rehaemorrhagia.Methods A retrospective cohort study was perfomed.The clinical data of Ⅴ-Ⅵ stage of PDR patients who received 25-gauge vitrectomy in Peking University Interuational Hospital from January 2014 to July 2015 were collected and analyzed.The PDR patients were divided into only surgery group and drug with surgery group.The patients in the only surgery group (34 eyes of 49 patients) received 25-gauge vitrectomy,and the patients in the drug with surgery group (32 eyes of 25 patients) received the intravitreal injection of ranibizumab 0.05 ml (0.5 mg) 7 days before 25-gauge vitrectomy.The distribution of eye number in different grades of visual acuities was observed and compared between the two groups in 1 day,1 week,1 month and 3 months after surgery,and the incidence of rehaemorrhagia was intergrouply compared in 1 day,3-7 days and 1 month after surgery.Results The eye number and percentage of the different visual acuities in the drug with surgery group was not significantly different from the only surgery group in 1 day,1 week,1 month and 3 months after surgery (1 day:Z=0.673,P=0.412;1 week:Z=0.113,P=0.737;1 month:Z=1.755,P=0.185;3 months:Z=2.474.P=0.116).Rehaemorrhagia occurred in postoperative day 1 and day 3-7 was 1 eye and 1 eye respectively in the drug with surgery group,and that in the only surgery group was 9 eyes and 9 eyes respectively,showing significant difference between the two groups (all at P＜0.05).The eye number of rehaemorrhagia in postoperative 1 month was 4 in the only surgery group,and no rehaemorrhagia appeared in the drug with surgery group.Conclusions The combination of intravitreal injection of ranibizumab with 25-gauge vitrectomy can efficiently reduce the incidence of postoperative rehaemorrhagia.
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Chronic inflammation,oxidative stress and retinal ganglion cell apoptosis play important roles in the development of diabetic retinopathy.Fenofibrate,a peroxisome proliferator-activated receptor α agonist,is used for dyslipidemia.In addition to its lipid-modulating effects,fenofibrate also has antiinflammatory,antioxidant,anti-apoptotic and anti-angiogenesis properties that may be useful to delay the progression of diabetic retinopathy.Some clinical studies have already confirmed that fenofibrate has therapeutic effect on diabetic retinopathy.Further studies the application of fenofibrate in the treatment of diabetic microangiopathy to clarify the safety and efficacy of fenofibrate is of great significance.
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Laser photocoagulation,intravitreal injection of antibody against vascular endothelial growth factor (VEGF) or corticosteroids and pars plana vitrectomy are current popular therapeutic approaches for diabetic retinopathy (DR).However,some DR patients still progress to irreversible blindness even after the above treatments which do not aim at the pathological mechanisms and influence factors for DR.Thus,with the further elucidation on the molecular pathological mechanisms and overall understanding of the factors affecting DR development,more and more potential therapeutic interventions such as neuron protection,vascular reconstruction and protection,gene therapy,non-VEGF dependent antineovascularization agents have been explored.Individual precise therapy based on the potential therapeutic targets would provide the promising future for DR patients.
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Objective To observe the effect of preoperative intravitreal ranibizumab injection (IVR) on the operation duration of vitrectomy and postoperative vision for the treatment of proliferative diabetic retinopathy (PDR).Methods A prospective study was carried out with the 90 PDR patients (90 eyes) who underwent vitrectomy.The 90 patients(90 eyes)were assigned to the vitrectomy only group(43 eyes) and the IVR combined with vitrectomy group (47 eyes).The IVR was performed 5-13 days prior to vitrectomy in the IVR combined with vitrectomy group.There were 15 eyes with fibrous proliferation PDR (FPDR),16 eyes with advanced PDR (APDR) without involving the macular and 16 eyes with APDR involving the macular in the vitrectomy only group.There were 14 eyes with FPDR,15 eyes with APDR without involving the macular and 14 eyes with APDR involving the macular patients in the IVR combined with vitrectomy group.All the eyes in the two groups were regularly operated by the same doctor to complete the vitrectomy.The start and end time of vitrectomy were recorded.The average follow-up time was 10 months.The changes of best corrected visual acuity (BCVA) before and 1,3 and 6 months after surgery were compared between the two groups.Results The duration of operation of the FPDR type (t=-8.300) and the APDR involving the macular type (t=-2.418) in the IVR combined with vitrectomy group was shorter than vitrectomy only group (P＜0.05).The comparison of duration of operation of the APDR without involving the macular type in the two groups has no statistically significant difference (t=-1.685,P＞0.05).At 1 month after surgery,the comparison of BCVA of the IVR combined vitrectomy group and the vitrectomy only group in APDR involving the macular type has no statistically significant difference (t=0.126,P＞0.05).At 3,6 months after surgery,the BCVA of the IVR combined vitrectomy group in APDR involving the macular type was significantly better than the BCVA of the vitrectomy only group (t=8.014,7.808;P＜0.05).At 1,3,and 6 months after surgery,the BCVA of the IVR combined vitrectomy group in FPDR type (t=3.809,1.831,0.600) and APDR without involving the macular type (t=0.003,1.092,3.931) compared with pre-treatment,the difference were not statistically significant (P＞0.05);the BCVA in APDR without involving the macular type compared with pre-treatment,the difference was distinctly statistically significant (t=2.940,4.162,6.446;P＜0.05);the BCVA in APDR involving the macular type (t =0.953,1.682,1.835) compared with pre-treatment,the difference were not statistically significant (P＞0.05).Conclusion Preoperative IVR of PDR can shorten the operation duration and improve the BCVA of APDR involving the macular type.
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Objective To observe the clinical effect of intravitreal ranibizumab (IVR) combined with vitrectomy in treating proliferative diabetic retinopathy (PDR).Methods This is a prospective non-randomized controlled clinical study.A total of 62 patients (70 eyes) who underwent vitrectomy for PDR were enrolled and divided into IVR group (30 patients,34 eyes) and control group (32 patients,36 eyes).IVR group patients received an intravitreal injection of 0.05 ml ranibizumab solution (10 mg/ml) 3 or 5 days before surgery.The follow-up time was 3 to 18 months with an average of (4.5± 1.8) months.The surgical time,intraoperative bleeding,iatrogenic retinal breaks,use of silicone oil,the best corrected visual acuity (BCVA) and the incidence of postoperative complications were comparatively analyzed.Results The difference of mean surgical time (t=6.136) and the number of endodiathermy during vitrectomy (t=6.128) between IVR group and control group was statistically significant (P=0.000,0.036).The number of iatrogenic retinal break in IVR group is 8.8 ％ and control group is 27.8％,the difference was statistically significant (x2 =4.154,P=0.032).Use of silicone oil of IVR group is 14.7％ and control group is 38.9％,the difference was statistically significant (x2 =5.171,P=0.023).The incidence of postoperative vitreous hemorrhage in 3 month after surgery was 11.8％ and 30.6 ％ respectively in IVR group and control group.The differences were statistically significant (x2=3.932,P=0.047).The 6 month postoperative mean BCVA of IVR group and control group have all improved than their preoperative BCVA,the difference was statistically significant (t=4.414,8.234;P=0.000).But there was no difference between the mean postoperative BCVA of two groups (t=0.111,P=0.190).There was no topical and systemic adverse reactions associated with the drug after injection in IVR group.Conclusions Microincision vitreoretinal surgery assisted by IVR for PDR shorten surgical time,reduces the intraoperative bleeding and iatrogenic retinal breaks,reduces the use of silicon oil and the postoperative recurrent vitreous hemorrhage.But there was no significant relationship between vision improvement and IVR.
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Objective To 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.Methods Twenty-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 (x2 =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.Results The 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).Conclusions Aqueous 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.
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Objetivo: Avaliar o efeito preemptivo com nepafenaco 0,1% em pacientes submetidos à fotocoagulação da retina para tratamento da retinopatia diabética proliferativa. Métodos: Trinta pacientes foram submetidos à fotocoagulação com laser de argônio em ambos os olhos. O olho contralateral de cada paciente foi o controle. O nepafenaco e o placebo foram utilizados 30 minutos antes da aplicação do laser. Ambos os olhos foram fotocoagulados no mesmo dia. A intensidade da dor foi avaliada por meio da escala analógica visual e da escala descritiva de dor. Resultados: A análise da interação instilação versus nepafenaco mostrou que os pacientes do grupo placebo apresentaram níveis de dor semelhantes em ambos os olhos, e os do grupo nepafenaco apresentaram redução importante do nível de dor no olho em que foi instilado a suspensão de 0,1% quando comparado ao olho contralateral que recebeu placebo (p=0,023). Conclusão: Este estudo sugere que a suspensão de 0,1% de nepafenaco foi útil na analgesia preemptiva de pacientes submetidos à fotocoagulação de retina quando comparada ao placebo. .
Objective: To evaluate the preemptive effect of nepafenac 0,1% in patients undergoing retinal photocoagulation for the treatment of proliferative diabetic retinopathy Methods: Thirty patients underwent argon laser photocoagulation in both eyes. The contralateral eye of each patient was the control. The nepafenac and placebo were used 30 minutes before the application of the laser. Both eyes were photocoagulated in the same day. Pain intensity was assessed by visual analog scale and descriptive pain scale Results: The analysis of the interaction instillation versus nepafenac showed that patients in the placebo group had similar levels of pain in both eyes, and the nepafenac group had significant reduction in pain in the eye that was instilled suspension of 0,1% when compared to the contralateral eye which received placebo (p = 0.023). Conclusion: This study suggests that a suspension of 0,1% nepafenac helpful for preemptive analgesia in patients undergoing retinal photocoagulation compared to placebo. .
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Humans , Male , Female , Middle Aged , Pain, Postoperative/prevention & control , Phenylacetates/administration & dosage , Pain Measurement/methods , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Laser Coagulation/methods , Diabetic Retinopathy/surgery , Pain/drug therapy , Argon/therapeutic use , Preanesthetic Medication , Instillation, Drug , Random Allocation , Case-Control Studies , Double-Blind Method , Prospective Studies , Surveys and Questionnaires , Vitreoretinopathy, Proliferative/surgery , Benzeneacetamides/administration & dosage , Pain Perception/drug effects , Visual Analog Scale , Analgesia/methodsABSTRACT
Ojectvie To investigate therapeutic effect of benazepril on nonproliferative diabetic retinopathy ( NPDR) .Meth-ods Twenty nine patients with early diabetic nephropathy complicated with type 2 diabetes and NPDR were randomly divided into benazepril group ( n =12) and conventional therapy control group ( n =17).The changes of blood pressure , blood glucose, glycosy-lated hemoglobin , blood creatinine , urinary albumin , best corrected visual acuity ( BCVA ) , and fluorescein fundus angiography ( FFA) were observed before and after 3 and 6 months of treatment .Results After 3 months of treatment by benazepril , all laboratory detection parameters were no significant difference compared with before treatment and conventional therapy control group ( P >0.05);While after 6 months, compared with before treatment and control group , blood pressure, blood glucose, glycosylated hemoglo-bin, blood creatinine , and urinary albumin were significantly decreased ( P <0.05 ); According to the results of BCVA and FFA , progression of pathological changes of NPDR were significantly slower in benazepril group compared with control group ( P <0.05 ) . Conclusions Benazepril has some protection effect for NPDR to delay NPDR development and decrease serious complications .
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Objective To investigate the effects of alpha lipoic acid on patients with diabetic retinopathy (DR),explore the possible mechanisms,and provide experimental evidence for the treatment of DR with lipoic acid.Methods Totally 75 DR patients were randomly divided into control group and treatment group.Patients in control group received the standard hypoglycemic treatment,antihypertensive therapy,and other comprehensive treatment.Patients from the treatment group were treated with alpha lipoic acid 600 mg + 250 ml 0.9％ sodium chloride injection additionally,avoiding light intravenous therapy,for a total of 4 weeks.Before and after treatment,fundus fluorescein angiography and visual inspection were detected in two groups.In addition,serum level of asymmetric dimethylarginine (ADMA) were detected with high performance liquid chromatography,serum lipid peroxidation product malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected to reflect the in vivo oxidative stress before and after treatment in two groups.Results Compared to the control group,visual acuity was improved significantly (P ＜ 0.05),and total efficiency of ocular lesions-improved was increased significantly (84.21％ vs 40.54％,x2 =15.28,P ＜ 0.01).Serum levels of endogenous inhibitor of nitric oxide synthase ADMA [(0.32 ±0.13) μmol/L vs (0.51 ± 0.26) μmol/L,P ＜ 0.05] and MDA [(3.22 ± 0.90) nmol/L vs (5.13 ± 0.42) nmol/ml,P ＜ 0.05] were significantly decreased,while SOD levels [(72.68 ± 1.31) U/ml vs (53.16 ± 1.54) U/ml,P ＜0.05] were significantly increased in DR patients after alpha lipoic acid treatment.Conclusions Alpha lipoic acid had some therapeutic effects for DR patients,which mainly lied in the improvement of visual acuity and eye disease,might be related to the decrease of oxidative stress and serum level of endogenous nitric oxide synthase (NOS) inhibitor ADMA.
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Diabetic retinopathy (DR) is the leading causes of blindness in working-aged people,of which diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two main causes of vision-threatening.Through the regular screening of patients with diabetes,the risk factors of DR can be identified and proper interventions can prevent the incidence of DR.Timely retinal laser photocoagulation and application of the renin-angiotensin system inhibitors (candesartan or fibrates),lipid-lowering drug fenofibrate can inhibit DR progress.Macula local and (or) grid pattern photocoagulation or in combination with bevacizumab intravitreal injection can effectively relief DME.In regard to late PDR,vitrectomy couldrestore or retain useful vision, importantly, minimally invasive 23G vitrectomy and preoperative bevacizumab intravitreal injection greatly improved the surgical outcomes.However DR pathogenesis is not entirely clear.Also there is a lack of effective and feasible DR screening strategy in China.Furthermore existing evidence-based data of medical and surgical treatment of DR is insufficient.Therefore,the DR prevention and treatment is still a long way to go in China.
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Objective To observe the effectiveness of probucol for non-proliferative diabetic retinopathy (NPDR) with hyperlipidemia.Methods Fifty-two patients (104 eyes) of NPDR with hyperlipidemia were enrolled in this study.The patients were randomly divided into treatment group and control group,26 patients (52 eyes) in each group.Both groups received diet and exercise guidance,oral hypoglycemic agents and (or) intensive insulin therapy.After blood sugar and blood pressure were controlled,the treatment group received probucol 0.5 g,two times per day; and the control group received atorvastatin of 10 mg,one time per day.The total course was 12 months.Before and after one,three,six and 12 months,all patients underwent vision,ophthalmoscope,fundus fluorescein angiography,blood and urine tested.Variations of visual acuity,fundus condition,macular edema,triglyceride (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDLC),high-density lipoprotein cholesterol (HDLC) and 8-0HdG were observed before and after treatment.Results The total effective rate of visual prognosis were 44.23％ and 40.38％ in the treatment group and the control group,the difference had no statistical significacy (Z＝-0.335,P＞0.05).Retinal hemorrhages and microaneurysms alleviated after treatment in both groups.The total efficiency of fundus prognosis was 65.38％ in the treatment group and 36.54％ in the control group,and the difference was statistically significant (Z=-2.973,P＜0.05).Macular edema was in six and five eyes in the treatment group and the control group respectively,which were lower than before treatment,the difference was statisticaly significant (x2=4.833,4.300; P＜0.05).Between the two groups,the difference was not statistically significant (x2 =0.102,P＞ 0.05).Twelve months after treatment,TG,TC and LDLC were decreased in the treatment group (t=15.653,7.634,14.871) and control group (t=13.275,7.415,13.632),and the difference was statistically significant (P＜0.05).HDLC showed no significant difference than before in the two groups (t=0.584,0.275; P＞0.05).TG,TC,LDLC and HDLC showed no difference between the two groups (t＝1.857,0.133,1.671,0.875; P＞0.05).8-0HdG decreased gradually during the one,three,six and 12 months in the treatment group (t=7.352,15.581,27.324,28.143) and control group (t =6.877,8.672,14.671,14.855) after treatment,and the difference was statistically significant (P＜0.05).In the first month aftertreatment,8 0HdG showed no difference between the two groups (t=0.513,P＞0.05).In the 3,6,and 12 months after treatment,the 8 0HdG was lower in the treatment group than that in the control group,and the difference was statistically significant (t =3.434,5.917,5.226; P＜0.05).Conclusion In the treatment of NPDR with hyperlipidemia,probucol can reduce blood lipid,stable visual function and relieve macular edema.