Objective To evaluate the safety repeated intravitreal injection of bevacizumab (Avastin) with different dosage in rabbitsprime;eyes. Methods Fourteen chinchilla rabbits were randomly divided into 3 groups, including both eyes of 2 rabbits in the control group,the right eyes of the other 12 rabbits in the experimental group,and the left eyes of the 12 rabbits in the experimental control group. The eyes in the experimental group underwent intravitreal injection of bevacizumab with the dosage of 2.5 mg/0.1 ml and 5.0 mg/0.2 ml of bevacizumab; the eyes in the experimental control group underwent intravitreal injection of normal saline with the same dosage as in the experimental group. Injections were performed every two weeks and lasted six weeks. Clinical observation and retinal function tests were performed before and two days after every injection. The eyes were sacrificed 1 week and 4 weeks after last intravitreal injection respectively.Electron and optical microscope and TUNEL were performed.Results After intravitreal injection,no obvious anterior chamber flare, abnormal change of the ocular fundus, or vitreous opacity and hemorrhage was observed in all of the eyes.No change was found by indirect ophthalmoscope,Bultrasonic inspection, ultrasound biomicroscopy and optical coherence tomography. The number of anterior chamber flare before and after the injection with the dosage of 2.5 and 5.0 mg, the difference among the 3 groups didnprime;t differ much from each other (Pgt;0.05).Amplitude and pattern of ERG responses and flash VEP were similar between the control and experimental groups (Pgt;0.05). Some inflammatory cells were found in the some bevacizumabinjected eyes 1 week after injection, and vanished 3 weeks later. The histological configuration of the retina didnprime;t change in both experimental control and the control group. Electron microscopy showed that plasma cells were presented and vacuolelike change was observed in part of the photoreceptor cells in 5.0 mg experimental group 1 week after injections.Cellular apoptosis was observed in the photoreceptor cell layer. The number of apoptotic cells was more in 5.0 mg experimental group than that in the control and experimental control group 1 week after injections (Plt;0.01). Conclusion Multiintravitreal injection with 5.0 mg bevacizumab may have mild toxicity to the retina in the rabbits.
OBJECTIVE:To evaluate the toxicity of retinoic acid in silicone oil to the retinal tissue.
METHOD:Twelve New Zealand white rabbits(24 eyes)were divided into three grorps at random. Three days after gas-compression vitrectomy,24 eyes were unedrgone gas/silicone oil exchange. The silicone oil 0.5 ml was injected intravitreally in 4 eyes as controls ,and 5mu;g/ml retinoic acid silicone oil 0.5ml in 10 eyes and 10 mu;g/ml retinoic acid silicone oil 0.5 ml in 10 eyes respectively as 2 study groups. After intravitrea[ injections, all the eyes were examined by ophthalmoscopy on the 1st, 3rd, 7th, 14th, 21st and 28th day. The retinas of the enucleated eyes on the 28th day were then examined by light microscopy and transmission electrone microscopy.
RESULT: No evidence of toxicity was found in retinas after intravitreal injections of silicone oil with 5 mu;g/ml or 10 mu;g/ml retinoic acid.
CONCLUSION :There was no toxic effect on the retinas by using 5 mu;g/ml or 10 mu;g/ml retinoic acid in intravitreal silicone oil tamponade operation.
（Chin J Ocul Fundus Dis,1997,13: 81-82）
ObjectiveTo observe the effect of epinephrine in intraocular irrigation solution on retinal vascular caliber and macular thickness.
MethodsA prospective control study. 32 eyes of 32 patients with macular hole who underwent vitrectomy were enrolled in this study. The patients including 14 males (14 eyes) and 27 females (18 eyes), with the average age of (64.0±4.5)years. Uncorrected visual acuity, corrected visual acuity, slit lamp biomicroscopy, indirect ophthalmoscopy, fundus color photography and optical coherence tomography were performed in all patients. Retinal vascular caliber located in 0.5-1.0 disc diameter from optic disk was measured from digital fundus photographs and summarized as central retinal artery (CRAE) and vein (CRVE) equivalents in all eyes at baseline and at the 1 month, 3 months follow-up visit. The macular thickness is the distance from retinal interface of inner plexiform layer to retinal pigment epithelium layer. The macula was divided into inner ring ( < 3 mm) and outer ring (3-6 mm) according to the distance from the fovea. The patients were divided into experiment group (include epinephrine in intraocular irrigation solution, 1:1000) and control group (without epinephrine in intraocular irrigation solution), 16 eyes in each group. The difference of CRAE and CRVE between two groups was not significant (P > 0.05). The difference of macular thickness between inner ring and outer ring was not significant (P > 0.05). The average follow-up was 3.5 months. CRAE, CRVE and macular thickness in inner ring and outer ring before and 1 month, 3 months after surgery were comparatively analyzed.
ResultsThe differences of CRAE and CRVE before and 1, 3 months after surgery both in experiment group (tCRAE=0.322, 0.148; tCRVE=0.317, 0.005) and control group (tCRAE=0.226, 0.137; tCRVE=0.284, 0.151) were not significant (P > 0.05). The differences of CRAE (t=0.624, 0.424) and CRVE (t=0.015, 0.041) between experiment group and control group also were not significant (P > 0.05). The differences of macular thickness in inner ring and outer ring before and 1, 3 months after surgery both in experiment group (tinner=0.322, 0.148;touter=0.317, 0.005) and control group (tinner=0.226, 0.137;touter=0.284, 0.151) were not significant (P > 0.05). The differences of macular thickness in inner ring (t=1.568, 0.373) and outer ring (t=-1.697, 0.536) between experiment group and control group also were not significant (P > 0.05).
ConclusionEpinephrine (1:1000) in intraocular irrigation solution has no effect on retinal vascular caliber and macular thickness in patients with macular hole.
Objective To investigate the feasibility of a new kind of porous β tricalcium phosphate (β-TCP) as a scaffold for the bone tissue engineering Methods The inverted phase contrast microscope was used to observe the growth of the marrow mesenchymal stem cells (MSCs) in the experimentalgroup and the control group at 10 days.In the experimental group, the MSCs were cultured with β-TCP(3 mm×3 mm×3 mm) in the 24-hole cultivation board, and in the control to control group, only MSCs were cultivated. The scanning electron microscope was used to observe growth of MSCs at 6 days. Cultivated with β-TCP at 3, 6, 9, 12 days, the MTT assay was used to judge the biocompatibility. The cytotoxicity was analyzed with the method that used the different density(100%， 50%， 10%， 1%，0%) leaching liquor gained from β-TCP to raise MSCs. MSCs were induced into the osteoblasts and were mixed with β-TCP, and the composite was used to repair a large radius bone defect in the rabbit. The specimens were made at 2,6,12 weeks. The histology imageology, and the radionuclide bone scan were used to analyze the bone formation. Results Some MSCs had a good adherence 4 hours after MSCs were inoculated and had a complete adherence at 12 hours. The cells were shaped like polyangle, spindle or converge monolayer after 8-10 days. The cells in the two groups had no difference. The cell adhesion was good, when observed by the inverted phase contrast microscope and the scanning electron microscope at 6 days. MTT showed that the absorbance (A)was not statistically different between the experimental group and the control group (P＞0.05); the different density leaching liquor had no cytotoxicity at the different time points. Histology, X-ray, and CT tomograph showed that itcould repair the large radius bone defect in the rabbit and its in vivo degradationrate was the same as the bone formation rate. Conclusion The new porous β-TCP has a unique three dimensional (3D) stereochemical structure and superordinary physicochemical property, and so it is a good scaffold for the bone tissue engineering.
Objective
To investigate the retinal toxicity and verify the safe dose of intravitreal injecting fluconazole.
Methods
Twelve healthy adult white rabbits were divided at random into 6 groups：a normal control group and 5 groups received intravitreal injection of a single dose of fluconazole ranging from 10 to 200 mu;g respectively.Retinal toxicity was examined by ophthalmoscopy, electroretinography, light and transmission electron microscopy (TEM) on the third and fourteenth day after injection.
Results
The ultrastructures of the retinal tissues of the normal control group and fluconazole 10～150 mu;g groups were normal on the third and fourteen day after injection.The light microscopy and TEM showed that cells of all the retinal layers in the 200 mu;g group revealed apparent degenerative changes on the fourteenth day after injection, and the light microscopic picture showed the vacuolar degeneration of outer segments of photoreceptors, the nuclei in outer nuclear layer drop out into inner segments, the vacuolar degeneration of nerve fiber layer, and the proliferation of pigment epithelium. TEM revealed expansion of paranucl eus space and karyopyknosis of the bipolar cells, the swelling of nerve fibers and disappearance of the synapses in the inner plexiform layer, the vacuolation and disappearance of microvilli of the pigment epithelium cells.
Conclusion
The safe dose of fluconazole injected intravitreally should be 100～150 mu;g.
(Chin J Ocul Fundus Dis，2000，16：139-212)
Anti-vascular endothelial growth factor (VEGF) drugs have been widely used in clinic by inhibiting angiogenesis to treat ocular diseases such as malignant tumors and diabetic retinopathy. However, recent studies have shown that intravitreal injection of anti-VEGF drugs may have significant systemic absorption, leading to a series of renal damages such as worsening hypertension, proteinuria, new glomerular disease, and thrombotic microangiopathy. This article reviews the renal toxicity of intravitreal injection of anti-VEGF drugs in the treatment of diabetic retinopathy and other ocular diseases, aiming to provide recommendations for clinicians.
Objective
To investigate the effect of tetrandrine (Tet) on experimental choroidal neovascularization and the effect of Tet on retinal structure and function.
Methods
Choroidal neovascularization was induced in 20 Brown Norway (BN) rats (40 eyes) by diode laser (wavelength: 810 nm; exposal time: 0.1 second; facular diameter:100 mu;m; energy: 120 mW), and the rats were divided randomly into experimental and control group with 10 rats (20 eyes) in each group. In experimental group, 0.05 ml Tet with the concentration of 3.21 mu;mol/L was injected intravitreously 0 and 3 days after laser photocoagulation; in the control group, the rats underwent an intravitreous injection with the same volume of sodium chloride solution. The incidence of CNV was evaluated by fundus fluorescein angiography (FFA) 14 days after laser photocoagulation. Five right eyes of another Five healthy BN rats underwent intravitreous injection with 0.05 ml Tet with the concentration of 3.21 mu;mol/L, and an intravitreous injection with the same volume of sodium chloride solution was performed on the left eyes. Before injection, 1 hour, and 1 day after the first injection, and 1 hour, 1 day, 7 days, 14 days after e second injection the electroretinography (ERG) was performed on these 5 rats; 14 days after the second injection, the retinae were examined by light microscopy and transmission electron microscopy.
Results
The incidence of CNV was 23.26% in experimental group，which was obviously lower than that in the control group (63.33%) (Plt;0.01). The ratio of amplitude of b wave of ERG in the rats undergone intravitreous injection with 3.21 mg/ml Tet didnprime;t differ much from which before the injection (Pgt;0.05). There were no structural changes of retinal tissues examined by light and electron microscopy.
Conclusion
Tet may inhibit choroidal neovascularization in rats; there isnprime;t any significant toxic effect of intravitreous injection with Tet on retina at the dosage of 3.21 mu;mol/L.
(Chin J Ocul Fundus Dis, 2006, 22: 242-244)
Objective To observe the effects of structure and function of cornea, chamber angle and retina of varying doses of Bevacizumab which was injected intravitreally in rabbits. Methods Twenty-four New Zealand albino rabbits were divided into three groups randomly, the right eyes in three groups received int ravitreal injection Avastin at dose 1.25 mg，2.5 mg and 5 mg respectively as experimental eye, the left eyes accepted intravitreal injection 0.9% normal saline at the same volume as a control eye. The anterior segment of eye and ocular fundus were examined and intraocular pressure was measured by slit-lamp microscope and direct ophthalmoscope before and after injection. It was tested by Electroretino gram (ERG) before and after injection 1, 4, 8 weeks. At the 8th week, it carried out corneal endothelium counting; then enucleated eyes to observe by the light microscope and transmission electron microscope. Results No statistically significant difference regard to IOP,corneal endothelium counting, a-and b-waves of ERG at any stage of study in every group（P＞0.05）. No obvious change at cornea, chamber angle, retinal structure and retinal ultrastructure in every group under light microscope. Conclusion This study indicated that there is no obvio us toxicity of intravitreal injection with Avastin 1.25~5.0 mg in normal rabbit eyes. （Chin J Ocul Fundus Dis，2008，24：189-192）
Heart failure is a progressive disease with high readmission rate and long treatment duration, which impose a heavy financial burden on patients and their families. The resulting financial toxicity can also affect the health outcomes of patients. This article provides an in-depth analysis of the concept, evaluation tools, research status, hazards, influencing factors, and coping strategies of financial toxicity in patients with heart failure. Suggestions are put forward for the development of evaluation tools and the improvement of coping strategies for financial toxicity, aiming to provide a reference for the development of more scientific and effective systematic intervention strategies.
