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
Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001). But the differences between two treatment groups are not statistically significant (P＞0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. （Chin J Ocul Fundus Dis，2008，24：184-188）
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）
ObjectiveTo compare the one year efficacy of intravitreal injection with ranibizumb for macular edema (ME) secondary to ischemic and non-ischemic central retinal vein occlusion (CRVO).MethodsA total of 88 patients (88 eyes) with ME secondary to CRVO were enrolled in this retrospective study. The best corrected visual acuity (BCVA) was detected by the Early Treatment Diabetic Retinopathy Study Chart. The optical coherence tomography was used to measure the foveal retinal thickness (CRT) and macular edema volume. The patients were divided into non-ischemic group and ischemic group, 44 eyes of 44 patients in each group. There was no significant differences in age (t=0.650, P=0.517) and gender (χ2=0.436, P=0.509) between the two groups. Compared with the ischemic group, the CRT was significantly decreased in the non-ischemic group (t=−2.291, P=0.024), and the edema volume in the macular area was significantly reduced (t=−2.342, P=0.022). All eyes were treated with continuous intravitreal injection of ranibizumab three times, and repeated injections were performed as needed. The patients without obvious ME regression after treatment were combined with triamcinolone acetonide injection. The patients with peripheral retinal non-perfusion area were combined with peripheral retinal laser photocoagulation. The follow-up was 1 year. The number of injections was counted. The changes of BCVA, CRT and edema volume in the macular area were compared between the two groups.ResultsDuring the 1-year follow-up period, 88 eyes were injected 1 to 10 times, with the mean of 4.51±2.33. The number of injections in the ischemic group and non-ischemic group were 4.55±1.59 and 4.48±2.91, respectively. There was no significant difference in the average number of injections between the two groups (t=0.136, P=0.892). The number of acetonide injections and laser treatment in the ischemic group was significantly higher than that in the non-ischemic group (t=3.729, 9.512; P＜0.001). At the last follow-up, compared with the ischemic group, the BCVA was increased (t=8.128), the CRT was decreased (t=−7.029) and the edema volume in the macular area was decreased (t=−7.213) in the non-ischemic group (P＜0.001).ConclusionCompared with ME secondary to ischemic CRVO, intravitreal injection of ranibizumab for ME secondary to non-ischemic CRVO has the better outcome of vision improvement and edema regression as well as less frequent of acetonide injections and laser treatment.
ObjectiveTo observe the efficacy and safety of combined photodynamic therapy (PDT) with intravitreal ranibizumab injection in patients with polypoidal choroidal vasculopathy (PCV). MethodsTwenty-four PCV patients (24 eyes) were enrolled in this retrospective case study.All patients were assessed by the examinations of Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, color fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT). The mean visual acuity was (33.41±19.43) letters; the mean macular retinal thickness was (343.63±88.60) μm. Patients received PDT first, and intravitreal injected ranibizumab 0.5 mg (0.05 ml) 72 hours later. Treatments were repeated as a single intravitreal injection of ranibizumab combined with or without PDT if the monthly follow-up indicated that it was necessary. The average follow-up period was 13.1 months. The average treatment times were analyzed for each eye. Systemic and ocular adverse events were observed. Visual acuity, macular retinal thickness and leakage of PCV before and after the treatment were analyzed. ResultsIntravitreal ranibizumab injections was repeated (2.8±1.6) times per eye on average, and intravitreal injection of ranibizumab combined with PDT was repeated (0.4±0.5) times per eye on average. No systemic and ocular adverse effects were found during and after combined therapy. In the last follow-up, the mean visual acuity of ETDRS was (44.21±17.24) letters, improved by 10.8 letters (t=-4.77, P<0.01).Visual acuity was improved in 11 eyes (45.8%) and stable in 13 eyes (54.2%). FFA and ICGA showed complete closed PCV in 17 eyes (70.8%), partial closed PCV in 7 eyes (29.2%). OCT image showed that the retinal edema was disappeared in 19 eyes (79.2%) and alleviated in 5 eyes (20.8%). The mean macular retinal thickness was (171.33±38.06) μm, which was 172.30 μm less than that of pre-treatment values (t=11.96, P<0.05). ConclusionPhotodynamic therapy combined with intravitreal ranibizumab injections for PCV is safe and effective, with visual acuity improvement, reduction of retinal edema and PCV leakage.
Objective To compare the features of OCT angiography (OCTA) between neovascular age-related macular degeneration (nAMD) and myopic choroidal neovascularization (mCNV) patients before and after intravitreal anti-VEGF treatment. Methods A prospective cohort study. Twenty-nine patients (37 eyes) with nAMD (19 males and 10 females, aged 68.20±8.76) and 31 patients (34 eyes) with mCNV (9 males and 22 females, aged 43.10±11.80, with the mean diopter of −9.71±1.20 D) from Department of Ophthalmology, West China Hospital of Sichuan University during May and December 2017 were included in this study. Ranibizumab or Conbercept (0.5 mg/0.05 ml) was intravitreally injected in all eyes. The patients were follow-up for 3−6 months. The OCTA was conducted before treatment and 1 day, 1 week, 1 month and 3−6 months after treatment. In order to ensure that the scanning position was the same, the tracking mode was adopted for each scanning. According to the OCTA images, the lesion area, parafoveal superficial vessel density and perfusion area were measured and analyzed contrastively between nAMD and mCNV patients. Results The mean lesion area before and 1 month after treatment in nAMD patients were 0.38±1.87 mm2 and 0.06±0.12 mm2, while in mCNV patients, those were 0.26±1.06 mm2 and 0.03±0.05 mm2, respectively. There were statistically significant differences (Z=4.181, 4.475; P＜0.001) in CNV lesion area before and 1 month after treatment between nAMD and mCNV patients. Compared with those before treatment, the absolute change (Z=1.853, P=0.064) and the percentage changes (t=2.685, P=0.010) of CNV lesion area 1 month after treatment in nAMD and mCNV patients show a statistical meaning. There were significantly decreases in both parafoveal superficial vessel density (F=8.997, P=0.003) and perfusion area (F=7.887, P=0.015) 3 months after treatment in nAMD patients, while decreases in parafoveal superficial vessel density (F=11.142, P=0.004) and perfusion area (F=7.662, P=0.013) could be detected 1 day after treatment in mCNV patients, before rising 1 month after treatment. Conclusions There are significantly differences in lesion area before and after the treatment of intravitreal anti-VEGF between nAMD and mCNV patients by OCTA examination. Moreover, the changes of both parafoveal superficial vessel density and perfusion area after anti-VEGF treatment are statistically different in two groups.
Neuromyelitis optica spectrum disorder (NMOSD) is a kind of demyelinating disease of central nervous system which mainly affect optic nerve and spinal cord. Because of its serious blindness and disability, how to effectively prevent relapse has become the focus of ophthalmologists. With the deep understanding of the pathogenesis and the progress of scientific and technological means, more and more monoclonal antibodies(mAb) continue to enter clinical trials. B cell surface antigen CD20 blocker, rituximab, has become a first-line drug for the treatment of NMOSD. CD19 blocker, inebilizumab, can reduce the recurrence and disability of NMOSD patients. The addition of interleukin 6 receptor blocker, satralizumab, and complement C5 inhibitor, eculizumab, reduce the recurrence. Some mAbs such as natalizumab and alemtuzumab may not be effective for the treatment of NMOSD. The expansion of mAb treatment indications and the launch of new drugs still require more clinical trials which are large-scale and international cooperation. At the same time, its potential adverse events and cost issues cannot be ignored.
ObjectiveTo observe the efficacy and safety of combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity (AP-ROP). MethodsMedical records of 70 eyes of 35 premature infants with a primary diagnosis of AP-ROP in our clinic were reviewed and analyzed retrospectively. All the lesions were located in posterior zone, with 42 eyes in zone 1 and 28 eyes in zone 2. Forty-six eyes had iris neovascularization, while 19 eyes combined with vitreous hemorrhage. All participants underwent intravitreal injection of ranibizumab as the primary treatment within 12 hours after diagnosis of AP-ROP. The systemic and ocular adverse effects were observed. The change of retinal vascular tortuosity and dilatation before and after the intravitreal injection of ranibizumab was observed one week after injection. Laser photocoagulation was used as adjuvant therapy if the plus disease persisted more than two weeks or new-onset ridge occurred after injection. The mean time interval between injection and laser therapy was (5.1±2.6) weeks (range, 1-10 weeks). Follow-up ranged from 6 to 18 months, with a mean of (10.3±3.9) months. The anatomical results and complications were evaluated after treatment. The eyes that progressed to stage 4 or 5 during the follow-ups were underwent lens-sparing vitrectomy or lensectomy combined with vitrectomy. ResultsNo major systemic or ocular complications were observed. Preretinal hemorrhages were found in 12 eyes of 8 patients (17.1%), but they were absorbed spontaneously during the follow-ups. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-ups. After the injection, the regression of iris neovascularization was observed in 46 eyes within one week, vitreous hemorrhage absorbed significantly in 16 eyes (84.2%), and plus disease disappeared completely within one week in 61 eyes (87.1%). 59 eyes (84.3%) demonstrated vascularization toward the peripheral retina after treatment. 32 out of 42 eyes (76.2%) with zone 1 demonstrated vascularization toward to zone 2, while 24 out of 28 eyes (85.7%) with zone 2 demonstrated vascularization toward to the junction of zone 2 and 3. After intravitreal injection of ranibizumab combined with laser photocoagulation, 62 of 70 eyes (88.6%) had retinal vascular ridge and plus disease regression. However, 8 eyes of 6 patients (11.4%) showed significant fibrovascular proliferation and progressed to retinal detachment after the combination treatment of intravitreal ranibizumab injection and laser photocoagulation. Four eyes underwent lens-sparing vitrectomy, while the other 4 eyes underwent vitrectomy combined with lensectomy. Five eyes achieved totally retinal reattachment after surgery, while 3 eyes achieved partially retinal reattachment. ConclusionThe combination of intravitreal injection of ranibizumab and laser photocoagulation is safe and effective in the treatment of AP-ROP.
ObjectiveTo observe the effect of intravitreal injection of conbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.MethodsA retrospective study. A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients, 30 eyes), threshold ROP (21 patients, 21 eyes) and acute aggressive posterior ROP (APROP, 6 patients, 6 eyes)) from premature infants by retinal screening in Henan Provincial People’s Hospital during October 2017 and June 2018 were enrolled in this study. All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis. Fundus examination was performed 7 days after injection. The interval of examination was 1−3 weeks according to fundus conditions. The mean follow-up was 30.1±4.6 weeks. For patients with relapse or no response to treatment, repeated intravitreal injection of conbercept or laser photocoagulation therapy was given. The retinal blood vessels of the affected eyes were observed. Logistic stepwise regression analysis was used for the correlation test of multiple factors.ResultsAmong 57 eyes, 49 eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept. After 24 weeks of treatment, in 57 eyes, 26 eyes were cured (45.6%), 22 eyes improved (38.6%), 8 eyes relapsed (14.0%), and 1 eye aggravated (1.8%). The recurrence time was 12.9±4.5 weeks after the first injection, and the corrected gestational age was 49.0±6.7 weeks. There were significant differences in initial injection time, lesion range among the cure, improved and recurrence eyes (F=5.124, 7.122; P＜0.01, ＜0.01). Parameters of ROP condition, including ROP diagnosis (pre-threshold type 1, threshold and APROP), zone (zone 1 and 2), stage (stage 2 and 3) and plus lesions, were significant different among the cure, improved and recurrence eyes (χ2=11.784, 14.100, 6.896, 9.935; P＜0.01, ＜0.01, ＜0.05, ＜0.01). Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone, more likely recurrence at zone 1 than zone 2 (Wald=9.879, OR=27.333, P=0.002). No injection-related complications such as endophthalmitis, cataract and glaucoma were found during treatment and follow-up period.ConclusionsIntravitreal injection of conbercept is effective in the treatment of ROP without obvious adverse reactions. Lesion zoning is associated with recurrence after treatment.
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.