PURPOSE:To verify existance of a-,~-,and 3'-protein kinase C(PKC)subspecies and their localization in rabbit retina. METHODS: Using an immunohistoehemical technique with mono- elonal antibodies against PKC isozymes- I (a),-I[ (13),and -~[ (Y) to characterize the distribution of PKC in rabbit retina. RESULTS:There is a positive immunostaining for a-,13-,and ~-PKC in rabbit retina. The immunoreactivity of a-PKC was observed mainly in the bipolar cells of inner nuclear layer and the outer segments of photorecptors. The positive immunostaining of 13-PKC could be seen in the ganglion cells,inner plexiform layer,inner nuclear layer,and the outer segments of photoreceptors. A diffuse and weak staining of Y-PKC is recognized in the ganglion cell layer,inner plexifrom layer,inner nuclear layer, and the outer segments of photoreceptors. CONCLUSION:The protein kinase C sub- speeies-a,-~,and-'Y are present in retina which is a part of the central nervous system
ObjectiveTo observe the efficacy of adjuvant intravitreal injection of anti-vascular endothelial growth factor (VEGF) therapy for advanced Coats disease. MethodsThis study is a retrospective case series study. Fourteen patients (14 eyes), presenting Coats Stages 3B and 4 (8 and 6 eyes, respectively) were enrolled. All the patients were treated with adjuvant intravitreal anti-VEGF therapy. The intravitreal anti-VEGF injections varied from 1 to 7, with a median injections of 2.14. In 14 eyes, combined therapy was subretinal fluid drainage in 4 eyes, photocoagulation in 2 eyes, vitrectomy in 8 eyes. The follow-up period was ranged from 4 to 36 months, with a median follow-up of 18.8 months. Visual acuity and retinal reattachment were observed in follow up. ResultsAt last follow up, global suvival was 100.0% with no enucleation performed in any patient because of disease progression. Except for 2 children who were unable to cope with the visual acuity test, visual acuity was improved in 2 patients, stable in 8 patients, and decreased in 2 patients. 5 patients (35.7%) achieved in complete retinal reattachment, 3 patients (21.4%) were succeed in partial retinal reattachment, and the remain 6 patients(42.8%) failed in retinal reattachment. Two patients developed cataract after vitrectomy, and no other adverse reaction was observed during follow-up. ConclusionAnti-VEGF therapy combined with classic treatments in advanced Coats disease can keep or impove the visual acuity in most patients by reducing of subretinal exudation.
Objective To observe the retinal toxicity of intravitreal injection of Bevacizumab (Avastin) in albino rabbit eyes at different doses. Methods Sixteen New Zealand albino rabbits，thirty-two eyes were divided into four groups at random. Three groups were prepared for Avastin experiment, named A, B, C. Each group received intravitreal injection of Avastin at dose 1.25 mg/0.05ml，2.5 mg/0.1ml and 6.25 mg/0.25 ml respectively. The other group named D served as a control, and accepted intravitreal injection of 0.9% normal saline 0.1 ml. Then test it by electroretinagram (ERG) after 1, 2 and 4 weeks. In addition, each group was removing two rabbitprime;s eyes to observe the retinal morphology and ultra structure by light microscope and transmission electron microscopy after intravitreal injection avastin 1, 2 and 4 weeks. Results The ERG pattern and amplitude of each group were normal after intravitreal injection Avastin 1, 2 and 4 weeks. （P＞0.05）Between study and control groups, there was no significant difference in retinal morphology which was observed by light microscope at any stage of the study. By electron microscopic observation, retinal ultramicrostructure was no evident retinal toxicity being tested both at group A and B (1.25 mg/0.05 ml and 2.5 mg/0.1 ml). But at group C (6.25 mg/0.25 ml), significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors. And there was no improvement of the pathological changes in four weeks. Conclusion It is safe that intravitreal injection of Avastin in rabbitprime;s eyes at dose 1.25 mg or 2.5 mg at single time. （Chin J Ocul Fundus Dis，2008，24：193-196）
In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.
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）
Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age－related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow－up time was 6－12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow－up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P＜0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P＜0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
Objective To observe the effects of intravitreal injection of conbercept for aggressive posterior retinopathy of prematurity (AP-ROP). Methods It is a retrospective case study. Twenty-one patients (40 eyes) with AP-ROP were enrolled in this study. There were 9 males (18 eyes) and 12 females (22 eyes), with the mean gestational age of (28.30±1.79) weeks and the mean birth weight of (1 021.40±316.70) g. All the lesions of 40 eyes were located in posterior zone, with 24 eyes in zone I and 16 eyes in zone II. All the eyes were treated with intravitreal injection of conbercept 0.025 ml (0.25 mg). During follow-up, nonresponders or patients with deterioration were retreated with intravitreal injection of conbercept or photocoagulation; patients with progressive deterioration to stage 4 had received vitrectomy. At the 1, 2, 4, 8, 12, 16, 20, 24 weeks after treatments, the disappearance or decrease of retinal vessel tortuosity and neovascularization, and the growth of the normal retinal vessels toward the peripheral retina were evaluated. Results Thirty-six eyes were cured for only one injection, the cured rate was 90.00%. However, 2 eyes (5.00%) had progressed to stage 4 with contractive retinal detachment, which underwent vitrectomy. Two eyes (5.00%) had received twice injections, whose remaining avascular zone area treated by photocoagulation. No major systemic or ocular complications after injection appeared. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-up. Conclusion Intravitreal injection of conbercept is effective in the treatment of AP-ROP.
Anti-vascular dndothelial growth factor (VEGF) drugs have open up a new treatment channel for ocular neovascular diseases. A lots of clinical data has proved that anti-VEGF drugs are effective and safe. But we should also notice that long-term and excessive usage of anti-VEGF drugs brings some new problems and complications, and even affect the normal ocular physiological process of the angiogenesis and retinal blood flow. So, it is necessary to pay attention to the problems and potential risks of excessive usage of anti-VEGF therapies for ocular neovascular disease.
Objective To investigate the factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection. Methods 292 eyes of 292 patients who were diagnosed retinopathy and suitable to receive ranibizumab intravitreal injection were enrolled in this prospective clinical study. There were 157 males and 135 females. 193 patients diagnosed with age-related macular degeneration and 99 other retinopathy patients. Mean age of patients was 62.75±13.74 years. All subjects underwent systemic and comprehensive ophthalmology examinations. The mean BCVA was 0.68±0.47 logMAR. Mean basal intraocular pressure was 18.1 mmHg (1 mmHg=0.133 kPa). All patients received intravitreal injection with 0.05 ml of ranibizumab (0.5 mg). The intraocular pressure were measured by non-contact tonometer at 10, 30, 120 minutes and 1 day after injection in a sitting position. The patients were grouped by the changes of intraocular pressure 10 minutes after injection. The elevation was more than 10 mmHg as elevation group and less than 10 mmHg as stable group. Analyze the possible related factors with elevation of intraocular pressure after ranibizumab intravitreal injection by comparing the different datum of two groups. Results The mean intraocular pressure were 23.8, 20.5, 19.9 and 17.4 mmHg at 10, 30, 120 minutes and 1 day after injection. The significant elevation level were 5.8, 2.4, 1.8, −0.7 mmHg compared with basal intraocular pressure. Among 292 eyes, intraocular pressure elevation in 68 eyes and stabled in 224 eyes. The age (Z=−0.732), gender (χ2=1.929), right or left eye (χ2=2.910), BCVA (Z=−0.039), diseases (χ2=2.088) were no significant difference between two groups (P＞0.05). The injection number (Z=−2.413, P=0.001), basal intraocular pressure (Z=−3.405, P=0.016) and elevations after injection (Z=−11.501, −8.366, −5.135, −3.568; P＜0.01) were significantly different comparing two groups (P＜0.05). By logistic regression analysis, basal intraocular pressure was positively correlated with the elevation of intraocular pressure 10 minutes after injection (B=−0.844, OR=0.43, 95%CI 0.24−0.76, P=0.004). Patients with higher basal intraocular pressure may occur intraocular pressure elevation after ranibizumab intravitreal injection much probably. Conclusions The factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection were basal intraocular pressure. The higher basal intraocular pressure, the higher risk to gain elevation of intraocular pressure after injection.
Objective To investigate the influence of vascular endothelial growth factor (VEGF) antagonist bevacizumab on the growth of human choroidal melanoma (CM) OCM-1 cell xenografts in nude mice, and to explore the probable mechanism.Methods OCM-1 cells were subcutaneously implanted on 18 nude mice to establish ectopic model of human CM. The nude mice with the tumor of 5 mm in diameter were randomly divided into three groups: untreated group (group A), normal saline （NS） group (group B), drug treated group (group C). Bevacizumab was intraperitoneally injected for 14 consecutive days in group C, and the same volume of NS was used at a same way in group B. The volume and weight of implanted tumor as well as inhibitory rates of drug on tumor were calculated, ki67 and survivin proteins were measured with immunohistochemistry, and the mRNA expression of VEGF and survivin were assessed by RT-PCR.Results The volume and weight of tumor was (598.86plusmn;321.81) mm3, (0.66plusmn;0.15) g; (1 715.15plusmn;278.16) mm3, (1.54plusmn;0.39) g and (1 750.23plusmn;206.36) mm3, (1.54plusmn;0.31) g in groups C, A and B, respectively. There were significant differences between group C and A (F=34.53, P=0.00) and group C and group B (F=8.69, P=0.01). The inhibitory rate of these three groups were 57.14%, 5.31%, 6.25%, respectively, and the proliferation index (PI) of ki67 in these three groups were (51.85plusmn;1.32)%, (46.30plusmn;1.39)%, (27.90plusmn;0.90)%, respectively, there were significant differences in ki67 PI between C group and A or B group (H=15.17, P=0.00). The expression of survivin mRNA was (0.49plusmn;0.02), (0.82plusmn;0.05) and (0.61plusmn;0.05) in groupss C, A and B, respectively, there were significant differences between C group and A or B group (F=15.17, P＜0.05) . The expression of VEGF mRNA was (0.32plusmn;0.08), (0.73plusmn;0.07), (0.80plusmn;0.04) in groups C, A and B, significant difference was found between group C and A or B group (F=12.05，P＜0.05). Conclusion Bevacizumab can inhibit the growth of human CM in nude mice probably by inhibiting the activity of VEGF and downregulating survivin expression of the tumor as well as inhibiting the growth of the tumor.