Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys

Purpose. To evaluate the effect of vitrectomy on the concentration of vascular endothelial growth factor (VEGF) and the pharmacokinetics of intravitreally injected bevacizumab in the aqueous humor in cynomolgus macaques. Methods. Pars plana lensectomy and a standard three-port vitrectomy were performed in one eye each of six macaques. After a minimal 12-week healing period, the vitrectomized eyes received an intravitreal injection of bevacizumab (1.25 mg/50 μL). Aqueous humor and venous blood samples were obtained from the macaques just before vitrectomy, just before injection of bevacizumab, on days 1, 3, and 7, and during weeks 2, 4, 6, and 8 after the injection. The bevacizumab and VEGF concentrations were measured by using enzyme-linked immunosorbent assay. Results. The VEGF concentrations in the aqueous humor ranged from 52.6 to 113.9 pg/mL (mean ± standard deviation [SD], 81.7 ± 27.0 pg/mL) before vitrectomy and 20.7 to 72.7 pg/mL (mean ± SD, 51.4 ± 20.5 pg/mL) 3 months after vitrectomy, a difference that reached significance (P = 0.03). The aqueous VEGF concentrations decreased to less than 9.0 pg/mL, the lower limit of detection, in all eyes between 1 and 7 days after injection of bevacizumab. The mean half-life of 1.25 mg intravitreally injected bevacizumab was 1.5 ± 0.6 days (range, 1.0-2.4 days) in the aqueous humor. Conclusions. The VEGF concentration in the aqueous humor decreased and the half-life of the intravitreally injected bevacizumab was shorter in vitrectomized eyes.     

Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab

Purpose  Bevacizumab is a human monoclonal IgG1 antibody that blocks the action of vascular endothelial growth factor (VEGF). The purpose of this study was to determine the level of VEGF and pigment epithelium-derived factor (PEDF) in eyes with proliferative diabetic retinopathy (PDR) before and after an intravitreal injection of bevacizumab. Methods  Eleven eyes of ten patients were studied. Patients were included if they had neovascular glaucoma, rubeosis of the iris with PDR, or aggressive PDR. Samples of aqueous humor were collected just before the injection of bevacizumab and the vitrectomy. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay, and the effects of bevacizumab on PDR were evaluated. Results  The free VEGF concentration before the injection was 676.5 ± 186.7 pg/ml (mean ± SEM, n = 11). Seven days later, it was significantly reduced to 7.1 ± 7.1 pg/ml (P < 0.005, n = 9). The PEDF concentration before the injection was 2.32 ± 0.49 μg/ml (n = 11), and 7 days later, it was 3.23 ± 0.76 μg/ml (P = 0.33). During the vitrectomy, patients had less intraoperative bleeding when the neovascular tissues were cut. Conclusions  An intravitreal injection of bevacizumab significantly decreased the free VEGF in the aqueous humor by 7 days, indicating that the clinical effects of bevacizumab appear rapidly. However, intravitreal bevacizumab did not affect the level of intraocular PEDF.     

Concentrations of unbound bevacizumab in the aqueous of untreated fellow eyes after a single intravitreal injection in humans

Purpose: To determine the concentration of unbound bevacizumab in untreated fellow eyes after contralateral intravitreal injection of bevacizumab. Methods: A total of 18 eyes received intravitreal injections of 1.5 mg bevacizumab. Nine probes were obtained in the injected eye and nine in the fellow eye. Each group contained three individual eyes. Aqueous humour samples were obtained during uneventful phacoemulsification at three intervals 1–7 days (group a), 8–12 days (group b) or 13–28 days (group c). Results: In untreated fellow eyes, the concentration of unbound bevacizumab was below the detectable limit of the ELISA (5 ng/ml in all samples). The mean concentration of unbound bevacizumab in the injected eye declined from 28.6 μg/ml (group a), 16.5 μg/ml (group b) to 7.4 μg/ml (group c). Conclusions: There are no pharmacological indications for a significant concentration of unbound bevacizumab in the anterior chamber of contralateral eyes in humans.     

Concentration of Vascular Endothelial Growth Factor After Intracameral Bevacizumab Injection in Eyes With Neovascular Glaucoma

Purpose

To study the concentration of vascular endothelial growth factor (VEGF) in the aqueous humor before and after intracameral injection of bevacizumab in eyes with neovascular glaucoma, and to detect the duration of an anti-VEGF effect of bevacizumab in the anterior chamber.

Methods

In this prospective interventional case series, 1.25 mg of bevacizumab was injected into the anterior chamber of five eyes in five neovascular glaucoma patients. Aqueous humor samples were obtained just before intracameral injection of bevacizumab and two weeks after injection. The concentrations of VEGF in the aqueous humor were measured using ELISA. To investigate corneal endothelial damage after intrecameral bevacizumab injection, specular microscopy was performed before injection and two weeks after injection. Slit lamp photo and iris fluorescent angiography was performed to determine the regression of iris neovascularization.

Results

After injection, substantial regression of neovascularization or fluorescein leakage was seen in all treated eyes. The VEGF concentrations in the aqueous humor in eyes with NVG were 1181.8±1248.3 pg/mL before intracameral injection of bevacizumab. Two weeks after injection, the VEGF concentrations decreased to 33.2±12.2 pg/mL (p=0.04, Wilcoxon signed rank test). There were no significant changes in IOP or corneal endothelial cells.

Conclusions

Intracameral bevacizumab injection can remarkably reduce iris neovascularization in neovascular glaucoma patients. VEGF levels were significantly decreased two weeks after injection and corneal toxicity was not observed during short term follow-up.     

Vascular endothelial growth factor plasma levels before and after treatment of neovascular age‐related macular degeneration with bevacizumab or ranibizumab

Purpose:  To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age‐related macular degeneration (AMD). Methods:  Forty‐three patients with exudative AMD and 19 age‐ and sex‐matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4‐weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. Results:  At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty‐eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab‐treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab‐treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. Conclusions:  Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time‐point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.     

Intravitreal anti‐vascular endothelial growth factor therapy with bevacizumab for tuberous sclerosis with macular oedema

Purpose: To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC) who were treated with intravitreal bevacizumab injection. Methods: Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC‐associated macular oedema / exudative retinal detachment. Vascular endothelial growth factor (VEGF) concentration in the vitreous fluid was measured by enzyme‐linked immunosorbent assay (ELISA) in one of these patients. Results: Patient 1: a 22‐year‐old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars‐plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema disappeared by intravitreal injection of bevacizumab. Patient 2: a 32‐year‐old woman with TSC‐associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size reduced markedly with regression of neovascularization. Conclusion: These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC.     

Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes

PURPOSE: To determine the intravitreal concentration and clearance of triamcinolone acetonide at various intervals after intravitreal injection into nonvitrectomized eyes. METHODS: Six participants were administered 4 mg (0.1 cc) of triamcinolone acetonide ophthalmic suspension. All six eyes underwent therapeutic pars plana vitrectomy with membranectomy at various post injection intervals ranging from 1.25 to 5 months from the intravitreal injection. Undiluted specimens of vitreous overlying the macula and of aqueous humor were submitted for analysis. Vitreous and aqueous humor concentrations of triamcinolone were measured by high performance liquid chromatography. RESULTS: Four eyes demonstrated detectable intravitreal concentrations of triamcinolone acetonide between 1.25 and 2.75 months after a single injection. Two eyes had an undetectable level of triamcinolone in both the vitreous and aqueous at 3 and 5 months post single injection. CONCLUSIONS: The intravitreal concentration of triamcinolone acetonide is detectable up to 2.75 months post a single 4 mg injection in nonvitrectomized eyes. A reinjection interval of 3 months may be needed to achieve sustained measurable levels of triamcinolone in nonvitrectomized patients.     

Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

AIM:To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.METHODS:Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.RESULTS:The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.CONCLUSION: The result of this study shows the beneficial effects of PLGA in prolonging the residency of bevacizumab in the vitreous. And the drug delivery system may have potential as a treatment modality for related disease.     

Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes

PURPOSE: To assess the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor in eyes with and without glaucoma. METHODS: Concentrations of VEGF were measured using a sandwich ELISA kit in aqueous humor aspirates taken during anterior segment surgery from 87 patients, of whom 54 had glaucoma (27 primary open-angle glaucoma, 8 angle-closure glaucoma, 16 exfoliative glaucoma) and 33 had cataract only. RESULTS: Vascular endothelial growth factor was detected in all samples. The concentration in eyes with cataract only without glaucoma was 102.4 +/- 29.7 pg/mL (mean +/- SD), which was significantly lower than that from eyes with glaucoma (146.7 +/- 51.8 pg/mL). There were no significant differences between primary open-angle glaucoma (140.4 +/- 51.0 pg/mL), angle-closure glaucoma (142.8 +/- 40.2 pg/mL), and exfoliative glaucoma (158.6 +/- 58.9 pg/mL). An unusually high VEGF concentration was detected in one eye with neovascular glaucoma (759 pg/mL) and two eyes with uveitic glaucoma (322 pg/mL). No effect of age, gender, or previous history of medical, laser, or surgical treatment of the aqueous humor VEGF concentration could be detected ( > 0.05). Aqueous humor and plasma VEGF concentrations were measured and compared in 46 patients. The aqueous humor VEGF concentration (144.2 +/- 107.9 pg/mL) was significantly higher ( < 0.01) than the plasma concentration (79.2 +/- 46.1 pg/mL). No significant correlation was found between aqueous humor and plasma VEGF concentrations. CONCLUSION: Aqueous VEGF concentration is increased in eyes with glaucoma.     

Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized eyes

PURPOSE: To report the visual acuity (VA) and foveal thickness (FT) changes after intravitreal bevacizumab for diabetic macular edema (DME) in previously vitrectomized eyes. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Medical records of 11 eyes of 10 patients who underwent intravitreal bevacizumab injection for persistent DME were reviewed. This retrospective study included eyes that had persistent DME despite prior pars plana vitrectomy with internal limiting membrane removal at our institution with optical coherence tomography (OCT) assessment of DME. All eyes received three intravitreal injections of bevacizumab 1.25 mg/0.05 ml monthly. RESULTS: Mean FT was 408 +/- 77 microm at baseline, 453 +/- 97 microm at three months, and 454 +/- 101 microm at six months (P = .172). Mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores were 59 +/- 15 (20/80) at baseline, 59 +/- 16 (20/80) at three months, 57 +/- 15 (20/80) at six months (P = .398). CONCLUSION: No change in VA and FT was observed in the short-term after intravitreal bevacizumab for DME in previously vitrectomized eyes.     

Ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade

Purpose. We characterized the ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade. Methods. A total of 18 pigmented rabbits underwent vitrectomy and silicone oil tamponade before an intra-silicone oil injection of 1.25 mg bevacizumab. At post-injection days 1, 7, 14, 28, 42, and 56, 3 rabbits were sacrificed and enucleated, and bevacizumab concentrations were measured in various ocular tissues and plasma. Results. The bevacizumab peak concentration was reached at day 14 in the aqueous humor (4030.70 ng/mL), retina (42,171.7 ng/g), and choroid (56,243.33 ng/g). In the iris/ciliary body and plasma, the peak concentration was reached at day 7 with 52,648.30 ng/g and 197.70 ng/mL, respectively. The choroid had the maximum exposure to bevacizumab with an area under the curve calculated from time zero to the last observed time (AUC(last)) of 1,151,633.40 ng/day/g and the aqueous humor had the minimum exposure (AUC(last) = 74,611.28 ng/day/g) among the ocular tissues, while the drug exposure to the plasma was the smallest of all tissues studied (AUC(last) = 3795.17 ng/day/g). The terminal half-lives and the mean residence time of bevacizumab in the ocular tissues ranged from 3-5 and 10-13 days, respectively. Conclusions. The peak concentration of bevacizumab in various ocular tissues and plasma was delayed and lower than that found in normal rabbit eyes; however, the terminal half-lives were similar to those found in the eyes with native vitreous following an intravitreal injection. Oil may have impacted the distribution of bevacizumab and led to an altered profile of drug level in the ocular tissues.     

Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

Background

Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data.

Methods

Twenty-two (22 eyes) were included in this study, and divided into four groups: eight patients received topical bevacizumab and aqueous samples were obtained 1 hour later during cataract extraction surgery (group 1), eight patients received topical bevacizumab and vitreous samples were obtained 1 day later during pars-plana vitrectomy (PPV) (group 2), three patients received intravitreal bevacizumab and vitreous samples were obtained during PPV (group 3). Vitreous samples from three patients who received no bevacizumab served as controls (group 4). All samples underwent enzyme-linked immunosorbent assay to detect bevacizumab.

Results

No bevacizumab was detected in the aqueous or vitreous of any topically treated eyes. The mean vitreal half-life for intravitreally injected bevacizumab was 4.9 days in four non-vitrectomized eyes and 0.66 days in one previously vitrectomized eye.

Conclusions

Topically administered bevacizumab does not penetrate the cornea into the anterior chamber and vitreous cavity, indicating that topical use for treating corneal neovascularization has minimal risk of intraocular penetration and adverse events related to intraocular vascular endothelial growth factor inhibition. The half-life following intravitreal bevacizumab injection measured in this study is comparable to that of previous reports, and includes the first demonstration of a significantly reduced half-life following intravitreal injection in a previously vitrectomized eye.     

玻璃体腔注射贝伐单抗Avastin后糖尿病视网膜患者血清中VEGF含量的变化研究

目的研究玻璃体腔注射贝伐单抗Avastin后增生性糖尿病视网膜病变（PDR）患者血清中血管内皮细胞生长因子（VEGF）的变化。方法收集玻璃体腔注射Avastin后PDR患者血清样本（注射前当天,注射后1 d,注射后7 d,注射后28 d）,并以注射前当天的血清样本为基准值作为对照,用ELISA方法测定血清中VEGF的含量。结果玻璃体腔注射Avastin术后,所有样本血清中VEGF含量都降低,降低幅度在术后7 d达到最大峰值,术后28 d VEGF有所上升,但仍未达到术前水平。结论一次玻璃体腔注射Avastin术后,血清中VEGF含量降低并且维持相当时间,说明Avastin进入到血液循环中,因此有必要密切关注Avastin玻璃体腔注射后的系统性影响和对未注射眼的影响。     

Safety of intravitreal injection of bevacizumab in rabbit eyes

PURPOSE: To evaluate the safety of intravitreal injection of bevacizumab in rabbits using electrophysiological testing and histopathologic analysis. METHODS: New Zealand albino rabbits were injected in one eye with control antibody (n = 2), 0.05 mL of bevacizumab (n = 3), or 0.2 mL of bevacizumab (n = 3). Electroretinograms were obtained 1 week and 4 weeks after injection. Histologic analysis was performed after completion of the electroretinographic studies. RESULTS: No statistical differences were seen in scotopic and photopic a- and b-wave amplitudes between untreated control and bevacizumab-injected eyes. No histopathologic differences were identified between untreated control and bevacizumab-injected eyes. CONCLUSION: Our study did not find evidence of retinal toxicity from a single intravitreal injection of bevacizumab in rabbits.     

药物辅助下玻璃体切除术治疗增生性糖尿病视网膜病变

目的:探讨曲安奈德联合Bevacizumab(Avastin)辅助玻璃体切除术治疗严重糖尿病视网膜病变的临床应用价值。方法:回顾性分析药物辅助下玻璃体切除治疗的严重增生性糖尿病视网膜病变13例15眼,15眼均于术前3~14d行Bevacizumab(Avastin)1.25mg/0.05mL玻璃体腔注射,常规玻璃体切除术中使用曲安奈德辅助切除残留的玻璃体皮质、视网膜增殖膜,其中9例合并牵拉性视网膜脱离及黄斑水肿者硅油填充并留置4mg/0.1mL曲安奈德,4眼未使用硅油填充眼因合并黄斑水肿大量硬性渗出予曲安奈德留置。2眼单纯玻璃体积血者未注射曲安奈德。结果:除1例玻璃体腔注射Avastin 3d后术中出血较多特别是在剥离纤维新生血管膜过程中,其余病例术中出血很少,并能迅速自凝。联合曲安奈德辅助可清晰地辨别残留皮质、视网膜前膜甚至内界膜,黄斑水肿术后明显减轻,所有病例术后炎症反应轻,眼压控制良好,硅油眼中留置曲安奈德无明显并发症。结论:严重的增生性糖尿病视网膜病变玻璃体切除术前7~14d玻璃体腔注射Bevacizumab(Avastin),明显减少术中出血,术中使用曲安奈德辅助可视性良好。术毕留置4mg曲安奈德可有效减轻黄斑水肿及术后反应。     

Intravitreal triamcinolone will cause posterior subcapsular cataract in most eyes with diabetic maculopathy within 2 years

PURPOSE: To determine the incidence of cataract following intravitreal triamcinolone (IVTA) for diabetic macular oedema. METHODS: Prospective, non-randomised, interventional cohort case series. A total of 27 eyes of 27 patients with diabetic macular oedema received an intravitreal injection of 4 mg (0.1 ml) of triamcinolone acetonide inferotemporally through the pars plana under direct vision. In 20 patients the fellow eye served as control, whereas seven patients had both eyes injected (not simultaneously). Seven patients had a repeat (second) injection in the same eye. The main outcome measures were cataract and intraocular pressure (IOP) rise of at least 5 mmHg (IOP responder). RESULTS: The mean follow-up time was 18.9 months (range 13-29 months). A total of 22 (81%) of 27 eyes developed cataract during the follow-up period, of which 20 (74%) were posterior subcapsular in nature. None of the 20 uninjected fellow eyes developed posterior subcapsular cataract. Mean time to cataract formation was 16.2 months. In the seven patients who had both eyes injected, mean time to cataract formation was 16.5 and 17.1 months in the first and second eye, respectively. Mean time to cataract formation in seven eyes receiving a repeat second injection was 17.9 months. There was no significant difference in cataract formation between IOP responders (85%) and non-responders (79%) (P=1.00, Fisher's exact test). Uneventful cataract surgery was performed in six eyes of five patients. CONCLUSION: This study demonstrates that given appropriate long-term follow-up, the majority of patients, even after a single IVTA injection, will go on to develop cataract, of which posterior subcapsular will be by far the most common.     

The effects of indocyanine green and endoillumination on rabbit retina: an electroretinographic and histological study

AIM: To evaluate the functional and morphological retinal toxicity associated with intravitreal injection of indocyanine green (ICG) dye in rabbit eyes during vitrectomy with endoillumination. METHODS: 20 eyes of 10 New Zealand pigmented rabbits were used in the study. All eyes underwent pars plana vitrectomy and removal of posterior vitreous cortex under endoillumination. In one eye of each rabbit, intravitreal injection of 0.1 ml of 2.5 mg/ml ICG was applied for 30 seconds followed by 10 minutes of endoillumination. The control eye had endoillumination only without ICG injection. Dark adapted and light adapted electroretinograms (ERGs) were performed before the surgery and 1 week after surgery for serial comparisons. Rabbits were killed 1 week after surgery and eyes were enucleated for histological examination. RESULTS: Serial ERG comparisons showed significant reduction in the light adapted a-wave amplitude (p = 0.037) and significant delays in the dark adapted and light adapted b-wave latencies (p = 0.020 and p = 0.038, respectively) in the ICG treated eyes. Histological examinations demonstrated loss of photoreceptor outer segments with focal absence of photoreceptors in some areas in the ICG injected eyes. CONCLUSIONS: Vitrectomy followed by intravitreal injection of 2.5 mg/ml ICG for 30 seconds with endoillumination may result in retinal toxicity causing functional and morphological retinal damages in rabbit eyes. The lowest concentration of ICG should be used if necessary for intraocular use to prevent potential retinal toxicity.     

BMP-6与新生血管性年龄相关性黄斑变性的相关性

目的：探讨新生血管性年龄相关性黄斑变性(nARMD)患者房水中骨形态发生蛋白6(BMP-6)、白细胞介素-6(IL-6)及血管内皮生长因子(VEGF)的变化及其与黄斑区视网膜厚度的相关性。

方法：收集2015-06/2017-03于我院眼科就诊的nARMD患者34例35眼作为nARMD组,选取同期于我院住院行白内障手术的年龄相关性白内障患者20例20眼作为对照组。采用光学相干断层扫描(OCT)测量两组患者黄斑区1mm范围内的平均视网膜厚度(CSMT)。通过ELISA法检测房水中BMP-6的浓度,流式微球技术(CBA)测量IL-6和VEGF的浓度。

结果：nARMD组患者房水中BMP-6水平(35.29±4.27pg/mL)明显低于对照组(62.04±2.78pg/mL),而VEGF水平(93.13±47.25pg/mL)明显高于对照组(69.21±13.40pg/mL),差异均有统计学意义(P<0.05),两组患者房水中IL-6的水平差异无统计学意义(P>0.05)。Spearman相关性分析表明,nARMD组患者房水中BMP-6含量与CSMT呈负相关(r_s=-0.409,P=0.015)。

结论：nARMD患眼房水中BMP-6浓度下降,而VEGF浓度升高,BMP-6含量与CSMT呈负相关,其可能参与nARMD的发病过程。     

4期早产儿视网膜病变玻璃体视网膜手术前玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab的安全性和有效性

目的 观察4期早产儿视网膜病变（ROP）玻璃体视网膜手术前玻璃体腔注射抗 血管内皮生长因子单克隆抗体bevacizumab（商品名Avastin）的安全性和有效性。 方法 回顾性病例研究。临床确诊为4期ROP并接受玻璃体腔注射bevacizumab治疗的8例患儿16只眼纳入本研究。所有患儿于表面麻醉下给予双眼玻璃体腔注射bevacizumab 0.625 mg。注药后第5天,采用间接检眼镜和二代广角数码视网膜成像系统（RetCam Ⅱ）观察并记录患眼眼底情况,评估血管活动性;观察有无与玻璃体腔注射bevacizumab相关的不良反应。所有患儿在全身麻醉状态下行玻璃体切割手术;其中,14只眼行保留晶状体的玻璃体切割手术,2只眼行晶状体切除联合玻璃体切割手术。玻璃体切割手术后3个月,观察所有患眼视网膜复位情况以及行保留晶状体玻璃体切割手术的14只眼的晶状体透明度。结果注药后第5天,所有患眼视网膜动脉纡曲及静脉扩张程度明显减轻,新生血管膜变白并有不同程度萎缩。无1例患儿发生眼内炎、眼内压增高、眼内新鲜出血、胃肠道反应等与玻璃体腔注射bevacizumab相关的不良反应。玻璃体切割手术后3个月,视网膜完全复位15只眼,占93.75%;视网膜部分复位1只眼,占6.25%。所有保留的晶状体都保持透明。结论4期ROP患儿玻璃体视网膜手术前行玻璃体腔注射bevacizumab能安全、有效地减轻ROP血管活动性。     

Induction of posterior vitreous detachment in rabbits by intravitreal injection of tissue plasminogen activator following cryopexy

The purpose of this study was to generate intravitreal plasmin after intravitreal injection of tissue plasminogen activator (TPA) and cryopexy, and to assess its proteolytic effect on the vitreoretinal border region.Twenty-four hr after a mild cryopexy, 25 microg recombinant tissue plasminogen activator (TPA) was injected into the vitreous cavity, the fellow eye received an intravitreal injection of the same volume of buffered salt solution. Light, scanning and transmission electron microscopy was performed in 24 eyes that underwent vitrectomy 1 week later. Plasmin was measured prior and 2 hr after intravitreal TPA injection (4 eyes). Hyaluronic acid (8 eyes) and vitronectin (4 eyes) were measured 1 week after TPA- or BSS-injection and compared to untreated controls.In all eyes treated with TPA, histopathologic examination by scanning and transmission electron microscopy demonstrated a complete detachment of the vitreous from the surface of the retina as well as from the posterior surface of the lens. After BSS-injection, vitreous cortex attachment to the retina was demonstrated in all eyes. Two hr after TPA-injection, plasmin increased to 9.75 mU ml(-1)(s.d.+/-2.3). Neither a decrease of hyaluronic acid nor an increase of transglutaminase, that might alter the vitreous structure leading to a collapse of the vitreous, were detected in treated eyes. There was no increase of vitronectin indicating proliferative activity.A temporary breakdown of the blood-retinal barrier by cryopexy combined with intravitreal injection of TPA is a sufficient technique to induce a posterior vitreous detachment enzymatically. The method may be useful prior to mechanical vitrectomy.