10.3969/j.issn.1007-3969.2013.04.00X

Objective To investigate the clinical efficacy of intravitreal injection of conbercept on different types of macular edema (ME) induced by branch retinal vein occlusion (BRVO).Methods A prospective casecontrol study was designed.Fifty-six eyes of 56 patients diagnosed with ME secondary to BRVO in Weifang Eye Hospital between May 2016 and May 2017 were chosen for this study.According to the morphologies of ME through optical coherence tomography (OCT),patients were divided into 3 groups:15 cases 15 eyes with serous retinal detachment (SRD),19 cases 19 eyes with cystoid macular edema (CME),and 22 cases 22 eyes with mixed edema.All of the patients received intravitreal injection of conbercept using "1 +PRN" method and followed up for 6 months.When the change of central macular thickness (CMT) exceed 100 μm,repeat the injection.The best corrected visual acuity (BCVA) and CMT before and after treatment for 1 week,1 month and 6 months and the average injection times were compared among different groups and time points.This study was approved by the Ethic Committee of Weifang Ophthalmic Hospital.Informed consent was signed from each patient before any treatments were proceeded.Results The differences of BCVA (LogMAR vision) at different time points before and after treatment among the 3 groups were statistically significant (Fgroup =105.834,P =0.000;Ftime =68.070,P =0.000).One month after treatment,BCVA in SRD group was the best,the next was CME group,and BCVA in mixed edema group was the poorest,and the difference between SRD group and mixed edema group was statistically significant (P＜ 0.05).Six months after treatment,BCVA in SRD group was the best,the next was CME group,and BCVA in mixed edema group was the poorest,the differences compared with each other were statistically significant (all at P＜0.05).The BCVA after treatment were improved than those before treatment in all the three groups,BCVA in 6 months after treatment was improved than that in 1 week and 1 month after treatment in each group,the differences were statistically significant (all at P＜0.05).The differences of CMT at different time points among the 3 groups were statistically significant (Fgroup =68.640,P =0.000;Ftime =29.783,P =0.000).CMT in mixed edema group before treatment was thicker than that in the SRD group and CME group,with significant differences between them (all at P＜0.05).The CMT after treatment were thinner than those before treatment in 3 groups,with significant differences between them (all at P＜0.05).With the extension of time,CMT was thinner gradually in each group,the differences of CMT in 1 week,1 month,6 months after treatment were statistically significant (all at P＜0.05).The number of injections in 6 months was statistically different among the three groups (F =12.479,P =0.000).The number of injections in SRD group was less than that in the CME group and mixed edema group,and the differences were statistically significant (P =0.001,0.000).Among the patients who still need to be injected or laser treatment after 6 months of treatment,1 patient was SRD type ME (6.7％),3 patients were CME type ME (15.8％),and 5 patients were mixed type ME (22.7％).Conclusions The efficacy of intravitreal injection with conbercept on different types of ME induced by BRVO was definitive,which can effectively improve BCVA and reduce ME;of which,the number of average injection times in SRD group is the least and its prognosis is best,just followed by CME group,while the number of injection times in mixed edema group is the largest and its prognosis is the poorest.

Objective:To observe the effect of non-vitrectomy in the treatment of idiopathic macular epiretinal membranes (IMEM).Methods:This study is a randomized controlled trial. From December 2017 to December 2018, 60 IMEM patients (60 eyes) diagnosed in Weifang Eye Hospital were included in the study. BCVA, intraocular pressure (IOP) and OCT were performed in all patients. The BCVA examination was performed using the international standard visual acuity chart, which was converted to logMAR. The CMT was measured by OCT. According to the surgical methods, the patients were divided into non-vitrectomy group and control group, 30 patients (30 eyes) in each group. The age ( t=1.723), logMAR BCVA ( t=1.703), CMT ( t=-0.956), IOP ( t=-1.434) were not significantly different between the two groups ( P=0.090, 0.094, 0.343, 0.157). 23G vitreous cutting system was used in all eyes. The macular epiretinal membranes was removed by non-vitrectomy in the non-vitrectomy group and by vitrectomy in the control group. The relevant examination with the same equipment and methods before the operation at 1 week and 1, 3, 6 months after operation. The time of surgery, the changes of BCVA, CMT and postoperative complications in the two groups were observed comparatively. Variance analysis of repeated measurements was performed for the comparison of BCVA, CMT and IOP after surgery in the two groups. Wilcoxon rank sum test of two independent samples was performed for the degree of vision improvement. The incidence of postoperative complications was compared by χ2 test. Results:At 6 months after operation, BCVA increased in 24 eyes (80%) and unchanged in 6 eyes (20%) in the non-vitrectomy group. Compared with preoperative BCVA, the difference was statistically significant ( P<0.05). BCVA increased in 25 eyes (83.4%), unchanged in 4 eyes (13.3%) and decreased in 1 eye (3.3%) in the control group. Compared with preoperative BCVA, the difference was statistically significant ( P<0.05). There was no significant difference between the two groups in BCVA improvement degree after operation ( Z=-0.26, P>0.05). At 6 months after operation, the average logMAR BCVA was statistically significant compared with the preoperative in the non-vitrectomy group ( P=0.002, 0.005) and control group ( P=0.004, <0.001). Visual stability occurred 1 month after operation in the non-vitrectomy group and 3 months after operation in the control group. The effective operative time of the non-vitrectomy group and control group was 4.50±1.41 and 15.50±2.33 min, respectively. The difference of effective operation time between the two groups was statistically significant ( t=-22.12, P <0.05). After surgery, no significant complications were found in the non-vitrectomy group. In the control group, there were 3 eyes with low IOP and 1 eye with macular hole during operation. Conclusions:Non-vitrectomy and vitrectomy have similar effects on IMEM. Non-vitrectomy has short effective operation time, faster recovery after surgery and no obvious complications.

Objective To observe the clinical effect ofintravitreal injection of tissue plasminogen activator (t-PA),ranibizumab and C3F8 in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).Methods The clinical data of 20 eyes of 20 patients with early SMH induce to PCV were enrolled in this study.The duration of bleeding in the eye was 7 to 28 days,and the mean duration of bleeding was 14.8± 5.6 days.All eyes are measured using the Snellen chart best corrected visual acuity (BCVA),logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity.Measure central retinal thickness (CRT) and central retinal pigment epithelial detachment (PED) thickness using frequency-domain optical coherence tomography.The average logMAR BCVA of eyes was 1.73 ±0.91;the mean CRT was 620.0±275.8 μm;the average central PED thickness was 720.3±261.9 μm.All eyes receive intravitreal injection of t-PA,ranibizumab and C3F8.The intravitreal injection of ranibizumab was administered once a month for 3 consecutive months,followed by an on-demand treatment plan.Mean follow-up time was 9.9 ± 3.6 months.The changes in BCVA,CRT,central PED thickness and clearance degree of SMH at 6 months after treatment were observed.Results On the 6 months after treatment,the average logMAR BCVA,CRT and central PED thickness of the eyes were respectively 0.42 ± 0.37,290.2 ± 97.4 μmn and 41.6 ± 78.1 μm.Compared with baseline,the after treatment BCVA was significantly increased (F=38.14,P=0.000),but the CRT and central PED were significantly decreased (F=7.48,75.94;P=0.000,0.000).Among the 20 eyes,16 eyes of SMH was completely cleared,accounting for 80％;4 eyes was partially cleared,accounting for 20％.No recurrence and systemic or local complications occurred during follow-up of all eyes.Conclusion Intravitreal injection oftPA,ranibizumab,and C3F8 in the treatment of early SMH induce to PCV can effectively remove SMH,improve vision,reduce CRT and central thickness of PED.

Objective:To compare the efficacy and safety of intravitreal injection of anti-vascular endothelial growth factor drug conbercept and intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema (DME).Methods:A randomized controlled clinical study was performed.Thirty-six DME patients (36 eyes) were enrolled in Weifang Eye Hospital from March 2018 to June 2019.The patients were randomized into Ozurdex group and conbercept group via a random number table, with 18 eyes in each group.Patients received Ozurdex injection once, which was maintained for 6 months, or conbercept injection once a month for 3 times according to grouping.Before and after treatment, the best corrected visual acuity (BCVA) was examined with the International Standard Visual acuity chart and converted to logarithm of minimal angle resolution unit.The intraocular pressure (IOP) was measured using a non-contact tonometer.The central retinal thickness (CRT) was detected by optical coherence tomography (OCT).This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Weifang Eye Hospital.Results:All patients were followed up for 6 months.In Ozurdex group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection was 0.59±0.22, 0.53±0.20, 0.41±0.16, 0.38±0.19 and 0.56±0.19, respectively.The BCVA at 1 month, 3 and 4 months after the first injection were better than that before injection, and the differences were statistically significant (all at P<0.05).In conbercept group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection were 0.60±0.23, 0.51±0.17, 0.29±0.13, 0.56±0.18 and 0.60±0.18, respectively.The BCVA at 1 month and 3 months after the first injection were better than that before injection, showing statistically significant differences (all at P<0.05).The CRT at 1 month, 3 and 4 months after the first injection were significantly lower than that before treatment in both the two groups (all at P<0.05).The CRT pre-injection was (498.61±77.14)μm in Ozurdex group, which was significantly higher than (462.17±48.74)μm at 6 months after the first injection ( P<0.05).No significant difference in CRT was found between pre-injection and 6 months after the first injection in conbercept group ( P>0.05).The incidence of high IOP in Ozurdex group was 33.3%(6/18), which was higher than 5.56%(1/18) in conbercept group, with a significant difference ( χ2=4.433, P=0.035).No adverse effects such as aggravation of cataract, lens injury, endophthalmitis, vitreous hemorrhage and retinal detachment was found during the follow-up. Conclusions:For DME, both conbercept and Ozurdex can improve BCVA and reduce CRT.Ozurdex shows durable efficacy and needs fewer injections than conbercept, but conbercept has less effect on IOP and is safer than Ozurdex.

Objective To investigate the efficacy and safety of subretinal fluid extraction combined with intravitreal conbercept and gas injection in treating polypoidal choroidal vasculopathy(PCV)complicated with serous retinal pigment epithelium detachment(sPED).Methods From July 2019 to February 2021,13 patients(13 eyes)with PCV complicated with sPED who were treated with subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the Weifang Eye Hospital were selected.All affected eyes received at least 3 times(once a month)of intravitreal anti-vas-cular endothelial growth factor(VEGF)(ranibizumab)injections before the surgery,and the treatment was ineffective.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),macular foveal PED height and width before and 1 week,1 month,3 months and 6 months after the operation were observed,and the intraoperative and postop-erative complications were recorded.Results The BCVA of the affected eyes 1 week after operation was better than that before operation,and the difference was statistically significant(Z=-3.237,P=0.001).The CRT of the affected eyes at 1 week,1 month,3 months and 6 months after the operation were thinner than that before the operation,and the differ-ence was statistically significant(Z=-3.180,-3.180,-3.110 and-3.180,P=0.001,0.001,0.002 and 0.001).The height and width of PED at 1 week,1 month,3 months and 6 months after the operation were lower than those before the operation,and the differences were statistically significant(all P＜0.05).Thirteen eyes received an average of(4.15±1.40)intravitreal injections(ranibizumab)before the surgery,and the treatment duration was(5.92±3.95)months(equivalent to one injection every 6 weeks).During the 6-month follow-up,13 eyes received an average of(2.31±1.97)intravitreal injections(conbercept)(equivalent to once every 10 weeks).Partial correlation analysis showed a weak positive correla-tion between the increase in BCVA and the decrease in CRT 6 months after operation(r=0.416,P=0.203).There was no significant correlation between the increase in BCVA and the changes in PED height and width 6 months after operation(r=0.218,0.209,P=0.520,0.538).At 1 month after the operation,9 eyes had PED recurrence or different degrees of retinal nerve subepithelial effusion,and PED improved after repeated intravitreal injection of conbercept.At 6 months after opera-tion,subfoveal PED completely disappeared in 3 eyes,and the retina was completely reattached.There was still active exu-dation in the retina of 1 eye.No systemic or severe ocular complications occurred in 13 eyes during the follow-up period.Conclusion Subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the treatment of PCV complicated with sPED can safely and effectively reduce CRT,improve PED,and reduce the damage to the retina caused by long-term PED,but it has no significant effect on the improvement of BCVA at 6 months after the operation.

Objective:To observe the clinical effect of vitrectomy, inner limiting membrane (ILM) peeling, subretinal injection of compound electrolyte intraocular irrigation solution (CEIIS) and conbercept in the treatment of diabetic macular edema (DME) with hard exudate (HE) (DME-HE).Methods:A prospective clinical study. Thirty-three patients with DME-HE diagnosed by examination in Weifang Eye Hospital from June 2020 to February 2022 were included in the study. Among them, there were 15 males (16 eyes) and 18 females(20 eyes), with the mean age of (62.00±6.54) years. All patients underwent the examinations of best corrected visual acuity (BCVA), scanning laser ophthalmoscope, optical coherence tomography (OCT), and multifocal electroretinography (mf-ERG). Snellen visual acuity chart was used for BCVA examination, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for statistic analysis. Macular foveal retinal thickness (CMT) and macular volume (MV) were measured by OCT. The 1 ring P1 wave amplitude density was measured by mf-ERG. The patients were randomly divided into group A and group B, with 17 patients (18 eyes) and 16 patients (18 eyes), respectively. There were no significant differences in age, logMAR BCVA, HE area, CMT, MV, and 1 ring P1 wave amplitude density between the two groups ( t=0.403, 0.972, 0.291, 0.023, -0.268, -0.206; P>0.05). Group A was treated with vitrectomy, ILM peeling, and subretinal injection of CEIIS and conbercept (combined therapy). Group B was treated with intravitreal injection of conbercept (IVC). Follow-up was 12 months after treatment. The changes of BCVA, HE area, CMT, MV, 1 ring P1 wave amplitude density were compared between groups and groups after treatment. The times of injection and complications after treatment were observed. Independent sample t test was used for comparison between the two groups. Results:At 12 months after treatment, compared to before treatment, there were significant differences in logMAR BCVA ( F=14.837), HE area ( χ2=94.522), CMT ( χ2=199.212), MV ( χ2=81.914) and 1 ring P1 wave amplitude density ( F=8.933) in group A ( P<0.05); there were significant differences in CMT ( F=5.540) and MV ( F=7.836) in group B ( P<0.05). Compared between the two groups, logMAR BCVA: 1 week and 6 and 12 months after treatment, the difference was statistically significant ( t=2.231, -2.122, -3.196; P<0.05); HE area: except 1 week after treatment, there were statistically significant differences at other times after treatment ( t=-2.422, -3.107, -3.540, -4.119; P<0.05). CMT, MV, 1 ring P1 wave amplitude density: 12 months after treatment, the differences were statistically significant ( t=-2.653,-2.455, 2.204; P<0.05). During the follow-up period, the injection times of group A and group B were (3.06±1.89) and (5.56±2.04), respectively, and the difference was statistically significant ( t=-3.815, P<0.05). Macular hole and vitreous hematoma were found in 1 eye in group A and 1 eye in group B. Conclusion:Vitrectomy, ILM peeling, subretinal injection of CEIIS and conbercept to treat DME-HE can effectively remove HE, alleviate macular edema, improve BCVA, and reduce CMT and MV. Combination therapy can reduce the number of IVC re-treatments.

Objective:To investigate the value of nomogram predictive model established by the risk factors of upper extremity venous thrombosis risk associated with peripherally venous inserted central catheter (PICC) in cancer patients.Methods:A total of 1 032 patients who underwent PICC insertion between January 2016 and March 2017 in Zhejiang Cancer Hospital were selected by using prospective cohort study and convenience sampling. Risk factors of upper extremity venous thrombosis risk associated with PICC in cancer patients were evaluated by using Cox regression model. The nomogram predictive model of upper extremity venous thrombosis risk associated with PICC insertion was constructed. Bootstrap method was used to complete the inside check, and figure calibration was used to verify the nomogram.Results:A multivariate Cox regression analysis showed that trombosis history ( HR = 27.82, 95% CI 8.17-94.88, P < 0.01) and hyperlipidemia ( HR = 3.01, 95% CI 1.31-6.93, P = 0.009) were independent risk factors for upper extremity venous thrombosis associated with PICC. The nomogram model C-index was 0.71 (95% CI 0.63-0.80) based on the above risk factors, which indicated that the nomogram had a good differentiation. The calibration curve for predicting the probability of upper extremity venous thrombosis risk associated with PICC within one week, two weeks and one month deviated slightly from the standard curve, suggesting that the model might overestimate the risk of upper extremity venous thrombosis associated with PICC in cancer patients. Conclusions:The nomogram model has a good predictive value and strong operability, which can be used to predict the probability of upper extremity venous thrombosis associated with PICC in cancer patients after PICC insertion. It can provide a reference for identifying the high-risk cancer patients and formulating proper therapeutic strategies.

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cyclesof platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate.

Background: Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice. Methods The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC).The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival.