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The Role Of Hemodynamic Changes In The Pathogenesis Of Polypoid Choroidal Vasculopathy

Posted on:2021-10-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:M Z YuanFull Text:PDF
GTID:1484306308488594Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
Part I Correlation between hemodynamic-related imaging changes and polypoidal choroidal vasculopathyObjective:To analyze the changes of choroidal vasculature and vortex vein-related imaging manifestations in patients with polypoidal choroidal vasculopathy(PCV)using multimodal imaging technology,and to study the correlation between the imaging features and PCV.Methods:This study was a cross-sectional study.47 PCV patients(47 eyes)and 50 healthy volunteers(50 eyes)were collected from April 1,2019 to November 28,2019.Swept source optical coherence tomography(SS-OCT),swept source optical coherence tomography angiography(SS-OCTA)and color Doppler imagining(CDI)were performed,and the results were compared and analyzed.Results:There were significant differences in subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),and choroidal capillary vessel density(CCVD)between the eyes of patients with PCV and those of the control group(P=0.002,P=0.009,P<0.001).Compared with the control group,the vortex venous blood flow velocity,short posterior ciliary artery and central retinal arterial peak systolic velocity in the eyes with PCV were significantly reduced(P<0.001,P=0.05,P=0.017),and the central retinal artery resistance index increased significantly(P<0.001),and there was no significant difference in hemodynamic parameters of the ophthalmic artery between the two groups(P>0.5).In the correlation analysis of CDI hemodynamic parameters and SFCT,CVI,and CCVD in the eyes of PCV patients,the vortex venous blood flow velocity in patients with PCV was negatively correlated with SFCT and CVI,and positively correlated with CCVD(P=0.003,P=0.004,P=0.004);peak systolic velocity of short posterior ciliary artery was negatively correlated with SFCT and CVI,and positively correlated with CCVD(P=0.021,P<0.001,P=0.001);end diastolic velocity of short posterior ciliary artery was significantly negatively correlated with SFCT(P=0.025);CDI hemodynamic parameters of the ophthalmic artery and central retinal artery were not significantly correlated with SFCT,CVI,and CCVD(P>0.05).Conclusions:PCV had the features of choroidal thickening,choroidal Haller/Sattler layer dilation,and choroidal capillary atrophy,which were associated with increased choroidal circulation resistance,decreased blood flow velocity,and choroidal blood return disorders.Part ? Correlation between cytokines in aqueous humor and vitreous fluid and polypoidal choroidal vasculopathyObjective:To study the changes of hemodynamic related cytokines in aqueous humor and vitreous fluid in patients with PCV,and to analyze the relationship between these cytokines and PCV.Methods:This study was a case-control study,divided into aqueous humor test group and vitreous fluid test group.The aqueous humor group:14 PCV patients(14 eyes)who were treated in the ophthalmology department of our hospital from September 25,2018 to August 2,2019 were selected as the experimental group.7 patients(7 eyes)with simple age-related cataract who underwent cataract surgery during the same period were selected as the control group.Aqueous humor samples were collected during treatment.Vitreous fluid group:5 PCV patients(5 eyes)who underwent vitrectomy in our ophthalmology department from August 2,2019 to October 22,2019 were selected as the experimental group,and 6 patients(6 eyes)with simple macular hole who underwent vitrectomy during the same period were selected as the control group.Vitreous fluid samples were collected during treatment.The cytokine solid-phase antibody chip technology was used to select hemodynamic related biomarkers for detection and analysis,to study the changes in hemodynamic related biomarker concentrations in aqueous humor and vitreous fluid of PCV patients,and to analyze correlation of these biomarkers with PCV.Results:There were significant differences in cytokines in the aqueous humor between PCV group and the control group:angiopoietin(ANG),angiopoietin-like protein-4(ANGPTL-4),and CXC chemokine ligand-16(CXCL-16),growth-related oncogene(GRO),hepatocyte growth factor(HGF),interleukin-10(IL-10),IL-2,interferon-inducible protein-10(IP-10),leptin(LEP),monocyte chemotactic protein-1(MCP-1),matrix metalloproteinase-1(MMP-1),MMP-9,transforming growth factor-?1(TGF-?1),tyrosine kinase receptor-2(Tie-2),matrix metalloproteinase inhibitory enzyme-1(TIMP-1),TIMP-2,TIMP-4,tumor necrosis factor-?(TNF-?),urokinase-type plasminogen activating factor(UPAR),vascular endothelial growth factor(VEGF).Significant differences in cytokines in the vitreous fluid between PCV group and the control group were:ANG-2,ANGPTL-4,neutrophil activating peptide-78(ENA-78),blisterstatin(FST),IL-12p40,HGF,IL-10,IL-6,IL-8,IP-10,LIF,MCP-1,MCP-2,MCP-3,MMP-1,Platelet-derived growth factor-BB(PDGF-BB),TGF-?,TIMP-1,uPAR.CXCL-16,GRO,and IL-2.CXCL-16,GRO and IL-2 in aqueous humor were independently related to PCV(P<0.05).The higher the level of the three cytokines,the higher the risk of PCV;IP-10 in vitreous fluid was independently related to PCV(P<0.05),The higher the level of IP-10 is,the higher the risk of PCV is,the other cytokines had no significant independent correlation with PCV(P>0.05).Conclusion:Angiogenesis-related factors and their receptors,extracellular matrix metalloproteinases and their inhibitors,inflammatory factors and chemokines participate in the pathogenesis of PCV.The possible mechanisms include the destruction of the balance between pro-angiogenic factors and anti-angiogenic factors,the induction of inflammatory responses,the changes in hemodynamics,the degradation of extracellular matrix,the induction of vascular smooth muscle cell atrophy and apoptosis,and the damage of vascular endothelial cells,which needs to be further studied.Part ? The establishment of rabbit model of obstruction in vortex venous returnObjective:To establish a vortex venous stenosis model in rabbits,to explore whether the increase of vortex venous reflux resistance can lead to PCV-related imaging findings and pathological changes,and to analyze changes in the levels of cytokines in the ocular fluid of disease animal models.Methods:Twenty livor blue rabbits were selected and divided into group 1 and group 2,10 in each group.Group 1:two eyeballs of experimental animals were stenosis group and blank control group;Group 2:two eyeballs of experimental animals were sham operation group and blank control group,respectively.The stenosis group was only partially ligated supertemporal and inferotemporal vortex veins.The sham operation group was to ligature supertemporal and inferotemporal vortex veins and cut the ligation lines immediately.The blank control group refered to the control group without any treatment.The three groups of experimental animals were examined by slit lamp,fundus photo,SS-OCT,SS-OCTA at 1 day before surgery,and 1 week,4 weeks,8 weeks,and 16 weeks after surgery;ICGA and FFA examinations were performed at 1 week,8 weeks and 16 weeks after operation to analyze the experimental animal model for PCV-related imaging findings.At 16 weeks after operation,the aqueous humor and vitreous humor of three groups of experimental animals were taken to detect related cytokines.Finally,the eyeballs of each group were removed at 16 weeks after surgery,and hematoxylin-eosin staining(HE staining)was used to observe the general morphological changes.The elastic fiber staining(verhoeff s van gieson staining,EVG staining)was used to observe the vascular elastic fibers morphology and smooth muscle cell layer changes,VEGF immunohistochemical staining to observe the destruction of vascular endothelial cells.Results:There was no statistically significant difference in choroidal thickness before operation among the three groups of experimental animals;the choroid thickness in the stenosis group was significantly higher than the other two groups at 1 week,4 weeks,8 weeks,and 16 weeks after operation.(all P values were<0.05).In the stenosis group,the choroid blood vessels were disordered,uneven in thickness,local pigmentation,the choroid thickness was significantly thickened,and the choroidal macrovascular layer was significantly expanded.Some of the stenosis groups were local neuroepithelial uplift,RPE micro-uplift,and the performance of IS/OS layer destruction,and the small dot-like and mottled high fluorescence on FFA and ICGA,the number of fluorescent spots increased and the range became larger with time.Compared with the blank control group,IL-2,IL-4,IL-8,IL-10,basic fibroblast growth factor(b-FGF),TNF-?,VEGF,MMP-9 expression increased in aqueous humor of the stenosis group,and the expression of IL-2,IL-8,IL-9,IL-10,PDGF-BB,TNF-?,VEGF,MMP-3,MMP-9,TIMP-1 increased in vitreous fluid of the stenosis group.Compared with the sham operation group,the expression of IL-2,IL-4,IL-8,IL-10,b-FGF,TNF-?,VEGF increased in aqueous humor of the stenosis group,and the expression of IL-2,IL-4,IL-8,IL-10,PDGF-BB,TNF-?,VEGF increased in vitreous fluid of the stenosis group.There was no significant difference in cytokines between the sham operation group and the blank control group.Besides,compared with the other two groups,the stenosis group may have dilated and irregular choroidal blood vessels,thinned blood vessel walls,and a vacuolar-like choroidal vascular structure.The choroidal vascular smooth muscle cells degeneration,atrophy,necrosis,and destruction of the elastic fiber layer of the choroidal vascular wall,and damage to the choroidal vascular endothelial cells and vacuolization.Conclusion:Animal models of vortex venous reflux obstruction disease may have some imaging and pathological features similar to PCV,and the increased expression of angiogenesis-related factors and their receptors,extracellular matrix metalloproteinases and their inhibitors,inflammatory factors and chemokine in intraocular fluid,which indicated that the choroidal system dysfunction and hemodynamic changes caused by obstruction of vortex vein return may be involved in the occurrence and development of PCV.
Keywords/Search Tags:polypoidal choroidal vasculopathy, optical coherence tomography angiography, color Doppler imagining, hemodynamics, aqueous humor, vitreous fluid, cytokines, polypoid choroidal angiopathy, vortex vein stenosis, disease animal model
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