ABSTRACT
Intravitreal injection of antiangiogenic agents is widely used to treat retinal vascular disease.This therapy can induce regression of neovascular vessels; reduce intraocular inflammation and retinal vascular permeability,and control macular edema.However the action period of these agents is short,and thus this therapy need repeated injections which cause higher operation risk and cost.Retinal laser photocoagulation therapy can close retinal capillary non-perfusion area and neovascular vessels,reduce macular edema caused by vascular leakage.However,as its therapeutic effect is based on the destruction of the retinal tissues in the lesion area,this therapy need longer time to show its effects.When the disease is controlled by this method,it may already induce some structural irreversible damages to the retina,especially the macular.This is why the visual acuity is not satisfactory in some patients,even though the disease get controlled,macular edema gets disappeared and anatomical structure of retina get improved.Properly evaluating all the pros and cons of retinal photocoagulation and intravitreal injection of antiangiogenic agents,will allow us to explore a better way to combine these two therapies to treat retinal vascular diseases.
ABSTRACT
BackgroundHypoxia-inducible factor-1 α (HIF-1α) specific double-stranded RNA ( dsRNA ) mediated by liposome inhibit reinal neovascularization in mice at dose-dependent manner. ObjectiveThe present study was to investigate the inhibitory effect of dsRNA targeting HIF-1α on retinal neovascularization in mice.MethodsModels of oxygen-induced retinal neovascularization were set up in C57BL/6J mouse through exposure of postnatal day 7 ( P7 ) to (75±3) ％ oxygen for 5 days.Fluorescein conjugated Dextran angiography of retinal vascular was performed to identify the retinal neovascularization.The 8 mice of the normal group were raised in the room air.Fifty-one P7 mice exposed to(75±3)％ oxygen for 5 days and then returned to the room air and assigned to control group ( 3 mice),empty vector group( 3 mice) and gene therapy group (45 mice),and the latter were medially divided to 9 groups randomly according to dose-ratio ( liposomes ∶ plasmid).The pSilencer 2.1-U6 hygro was injected in the model mice of empty vector group,and different dose-ratios of pSilencer2.1-U6 hygro-HIF-1α dsRNA were injected respectively in the model mice of various gene therapy groups.Fluorescein conjugated Dextran angiography of retinal vascular was performed to observe the morphology of new blood vessels,and retinal slides were prepared to score the numbers of nuclei extending beyond the inner limiting membrane( ILM ),and expression of vascular endothelial growth factor(VEGF) was detected in the retina by immunohistochemistry.Results The retinal blood vessels of the normal group formed a fined radial branching pattern.The retinal vascular patterns in the control group and the empty vector group were characterized by decreased central perfusion in both the superficial and the deep layers.The abundant vessels were distorted and irregular in the control group and empty vector group,and the obstructed capillary and lots of neovascular tufts were seen.The retinal neovascularization and non-perfusion distraction in the every gene therapy group were reduced markedly with the most severe appearance in 1 ∶ 1 ( liposomes ∶ plasmid) dose-ratio group.Few vascular endothelial cell nucleus extending beyond the ILM were found in the normal group;while a large number of vascular endothelial cell nucleus were showed in the control group and empty vector group with the occurring rate 100％.Statistically,no significant difference was seen in the number of nuclei extending beyond the ILM between the control group and the empty vector group(11.57±5.85 vs 11.53±6.15),however,that in 1∶1 (liposomes∶plasmid) group was reduced markedly ( 2.17 ± 4.23 ) ( P ＜ 0.01 ).Immunohistochemistry revealed that VEGF was faintly expressed in the normal group but strongly expressed in the control group and the gene therapy group.VEGF expressions of various gene therapy groups were weaker than ones of the control group and the empty vector group.ConclusionsRetinal neovascularization can be efficiently inhibited by intravitreal injection of the pSilencer2.1-U6 hygro-HIF-1α dsRNA mediated by liposome.Proportion of 1 ∶ 1 (liposomes ∶ plasmid)has a maximized efficiency.
ABSTRACT
Up-regulation of vascular endothelial growth factor(VEGF)is demonstrated to be a key role in formation process of intraocular neovascularization.Anti-VEGF treatment is the breakthrough of intraocular neovascular diseases therapy.Intravitreal injection of anti-neovascularization drug looks to be an effective method on ocular neovascular diseases which with the advantages of good biocompatibility,low prices and longer intravitreal half-time etc.However,at present,it lack of multi-center study;the long-term efficacy and the systematic safety needs the further clinicsl verification.Various types of CNV showed the different therapeutic reactions to either PDT or Anti-VEGF agent,the treatment methods for exudative AMD include laser,PDT,and drug like Triamcinolone Acetonide,several anti-VEGF preparations.Therefore.understanding the pathogenesis of neovascular AMD and choosing a reasonable therapeutic methods are necessary.We should try to explore a safe,effective,economic,new approach.
ABSTRACT
Objective To investigate the therapeutic efficacy of transpupillary thermal therapy (TTT) for age-related macular degeneration (AMD) accompanied with subfoveal choroidal neovascularization (CNV). Methods Fifty-one eyes of 47 patients whose illness had been diagnosed as AMD by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were treated with diode 810 laser. There are 42 eyes of 39 patients had occult CNV and 9 eyes of 8 patients had classic CNV, and the average visual acuity in their fist diagnosis was 0.12. According to the focus size, the diameters of beam spot varied from 0.8, 1.2, 2.0, and 3.0 mm; and the power was 120, 160, 260 and 360mW correspondingly, with the duration of 60 seconds. The follow-up examination was performed once a month after the treatment, and repetitious treatment would be taken once to thrice if necessary. The follow-up period was 3~33 months with the mean of 10 months. Visual acuity, haemorrhage in ocular fundus, absorption of exudation, and the closure of CNV were examined in the follow-up examination. Results No immediate decrement of visual acuity or any other discomforts were found in all of the treated eyes soon after the treatment. The average visual acuity of 51 eyes was 0.16 in the last diagnosis, which remained no change in 68.62%; increased in 23.53% and decreased in 7.84% compared with that in the first diagnosis. The results of FFA and ICCG demonstrated that at the 3rd months after the treatment, the closure rate was 42.86% in occult CNV and 22.22% in classic CNV; and at the 6th month, the closure rate was 73.81% in occult CNV and 66.67% in classic CNV. The results of ophthalmoscopy showed that at the 3rd month after the treatment, partial or complete absorption of hemorrhage and/or exudates with various thickness of organized scarring tissue was found in 42 eyes with occult CNV; decrement of hemorrhage and exudates was observed in 7 out of 9 eyes with classic CNV; and new hemorrhage occurred in 1 eye. At the 6~(th) month, in 27 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with faster absorption and remaining unchanged for 12 months; in 5 eyes with classic CNV, new hemorrhage occurred in 2, which was absorbed after treated again and remained stable in the 16-month followed-up. In 19 eyes with occult CNV which had been followed up for more than 6 months, hemorrhage disappeared in 5 and new hemorrhage occurred in 5. In the followed-up over 6 months, new hemorrhage occurred in 8 eyes with the recurrent rate of 15.6%. Conclusion TTT is effective for AMD with either classic or occult CNV. In the long-term followed-up, CNV recurs in 15.6% of the treated eyes which may be improved after the further treatment.