Objectives To explore intraocular drug concentration changes and the pharmacokinetics after topically applied of bevacizumab with annexin A5-associated liposome on rabbit eyes. Methods A total of 105 healthy New Zealand white rabbits were selected and divided randomly into 3 groups (group A, B and C), and each group had 35 rats. Bevacizumab with annexin A5-associated liposome, bevacizumab liposome and bevacizumab were topically applied 50 μl respectively on right eyes of rabbits in group A, B and C, respectively. Aqueous, vitreous body and retina/choroid were obtained at 5, 15, 30 minutes and 1, 2, 4, 8 hours and the free bevacizumab concentrations in these ocular tissues were measured by ELISA (enzyme linked immunosorbent assay). DAS 2.1.1 software was used to fit the pharmacokinetic parameters. Results The peak drug concentrations in aqueous humor of the eyes in group A, B, C were at 15 minutes after topical administration and the difference was statistically significant (F=301.061,P＜0.01). The peak drug concentrations in vitreous of the eyes in the group A, B, C were at 2 hours after topical administration and the difference was statistically significant (F=885.997,P＜0.01). The peak drug concentrations in retina/choroid of the eyes in the group A, B, C were at 1 hour after topical administration and the difference was statistically significant (F=644.908,P＜0.01). Least significant difference pair-wise test found that the drug concentrations in aqueous humor, vitreous and retina/choroid of group A was higher than that of the group B and C respectively (P＜0.05), while that of the group B and C had no significant different (P＞0.05). Pharmacokinetic fitting analysis found that the half-life (t½) of bevacizumab in aqueous humor were 1.14, 1.29, 1.29 hours, the distribution t½ were 1.40, 1.50, 1.42 hours and the eliminated t½ were 2.62, 2.84, 2.73 hours in vitreous, the distribution t½ were 2.61, 2.99, 2.70 hours and the eliminated t½ were 2.61, 2.99, 2.70 hours in retina/choroid respectively for the 3 groups. Changes of bevacizumab concentration in aqueous humor of rabbit eyes for 3 groups was complied with one compartment model, and that in vitreous body and retina/choroid complied with two compartment model. Conclusions Topically applied annexin A5-associated liposome has higher ocular concentrations of bevacizumab than those of controls. Changes of bevacizumab concentration in aqueous humor of rabbit eyes was complied with one compartment model, and that in vitreous body and retina/choroid complied with two compartment model.
ObjectiveTo observe the effect of non-vitrectomy in the treatment of idiopathic macular epiretinal membranes (IMEM).MethodsThis 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.ResultsAt 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.ConclusionsNon-vitrectomy and vitrectomy have similar effects on IMEM. Non-vitrectomy has short effective operation time, faster recovery after surgery and no obvious complications.
ObjectiveTo observe the efficacy and safety of individual dose of intravitreal conbercept (IVC) in the treatment of retinopathy of prematurity (ROP) before type 1 threshold.MethodsA retrospective case study. From January to July, 2019, 23 cases (46 eyes) of children with type 1 pre-threshold ROP were included in the study. Among them, 14 cases (28 eyes) were male and 9 cases (18 eyes) were female. The mean gestational age at birth was 28.06±1.73 weeks. The average birth weight was 1.14±0.19 kg. The mean corrected gestational age was 34.38±1.41 weeks at the time of first intravitreal injection of IVC. The axial length (AL) of children was measured by A-mode ultrasound before IVC for the first time. According to the calculation of AL, the corresponding injection dose range was 14.23-16.19, 16.20-17.57, 17.58-18.63 mm and the injection dose of IVC was 0.015, 0.020, 0.025 ml (including IVC was 0.15, 0.20, 0.25 mg, respectively). The first IVC dose was 0.015 ml. On the first day before IVC and on the first and seventh days after IVC, 2 ml of arterial blood was taken from children, serum vascular endothelial growth factor (VEGF) concentration was detected. The follow-up time after treatment was ≥1 year. After one year of follow-up, the effective rate and recurrence rate of IVC for the first time were tested by χ2 tests. The short-term changes of injection times, injection intervals, retinal vascularization time and serum VEGF concentration in children were tested by t test.ResultsRetinal neovascularization subsided and vascular buckling decreased in all eyes. Iris neovascularization subsided, 1-3 weeks after IVC for the first time. Within one year after the first IVC, 16 eyes underwent IVC twice with or without new blood vessels at the junction of the vascular area. The average corrected gestational age was 40.56±3.81 weeks. The injection dose of IVC was 0.015 ml and 0.020 ml for 2 eyes and 14 eyes, respectively.The mean interval from IVC for the first time was 40.89±8.99 days. Of the 16 eyes who underwent IVC twice, 8 eyes showed neovascularization again in the retinal area with or without blood vessels. The average corrected gestational age was 43.00±1.41 weeks. The injection dose of IVC was 0.020 ml and 0.025 ml for 3 eyes and 5 eyes, respectively. The mean interval of the second IVC was 28.60±6.07 days. The mean interval from the first IVC was 69.20±12.40 days. At the end of follow-up, all eyes were treated effectively (100%, 46/46). The mean time of retinal vascularization was 46.31±3.42 weeks. The average number of injections was 1.52±0.76. On the first day before IVC and on the first and seventh days after IVC, the average serum VEGF concentrations were 111.21±148.71, 25.60±27.71 and 42.99±38.01 pg/ml, respectively. Serum VEGF concentration was significantly lower than that before IVC on the 1st and 7th day after IVC (Z=−4.054, −2.779; P＜0.05). Serum VEGF concentration was higher 7 days after IVC than 1 day after IVC, and the difference was statistically significant (Z=−2.505, P＜0.05). All eyes were not treated by laser photocoagulation or vitrectomy. No eye complications such as lens opacification, endophthalmitis and retinal detachment related to drugs or treatment methods were found in all patients.ConclusionIntravitreal injection of individualized dose of IVC is effective in the treatment of type 1 pre-threshold ROP. Seven days after treatment, serum VEGF concentration of patients’serum decreases.
ObjectiveTo evaluate macular microvessel changes in familial exudative vitreoretinopathy (FEVR) by optical coherence tomography angiography. MethodsCross-sectional clinical case-control study. From November 2019 to November 2020, 21 FEVR patients (41 eyes) from Weifang Eye Hospital were selected; 17 healthy volunteers (28 eyes) with the same age and gender as FEVR group were selected as normal control group. According to the best corrected visual acuity (BCVA) 1.0 and ＜1.0, FEVR group was divided into normal visual acuity group (27 eyes) and visual acuity decreased group (14 eyes). All enrollees received BCVA and OCTA. BCVA was performed with an international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) vision. The OCTA instrument was used to scan the macular area of all the examined eyes in the range of 3 mm×3 mm, 6 mm×6 mm, and the blood vessel density (VD) and blood perfusion density (PD) within the range of 3 mm×3 mm, 6 mm×6 mm were measured and the area, circumference, and morphological index of the foveal avascular zone (FAZ) within the range of 6 mm×6 mm. Quantitative data were compared between groups by independent sample t test. Statistical data were compared by χ2 test. The area under curve (AUC) of each index was determined according to receiver operating characteristic curve (ROC curve), and the predictive value of each index was evaluated. ResultsIn the macular area of 6 mm×6 mm, VD, PD, FAZ area and FAZ perimeter of FEVR group were all lower than those of normal control group, and the differences were statistically significant (t=−3.350, −2.387, −3.519, −3.029; P＜0.05). In macular area of 3 mm×3 mm and 6 mm×6 mm, compared with normal vision group and vision loss group, both VD and PD decreased. The differences were statistically significant (t=2.088, 2.114, 2.160, 2.545; P＜0.05). In the macular area of 6 mm×6 mm , the FAZ morphological index of the two groups was significantly different (t=2.409, P＜0.05). ROC curve analysis showed that all the indicators had low diagnostic value for FEVR (AUC＜0.5). ConclusionThere are microvascular abnormalities in macular area in FEVR patients, and the decrease of blood vessels and the change of FAZ shape may be related to the loss of visual acuity.
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). MethodsA 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. ResultsAt 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. ConclusionVitrectomy, 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.
ObjectiveTo observe the clinical effect of intravitreal injection of tissue plasminogen activator (t-PA), ranibizumab and C3F8 in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).MethodsThe 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.ResultsOn 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 μm 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.ConclusionIntravitreal injection of t-PA, 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.