CN106053615A - 人类眼部的生物标记及其方法 - Google Patents
人类眼部的生物标记及其方法 Download PDFInfo
- Publication number
- CN106053615A CN106053615A CN201510424239.6A CN201510424239A CN106053615A CN 106053615 A CN106053615 A CN 106053615A CN 201510424239 A CN201510424239 A CN 201510424239A CN 106053615 A CN106053615 A CN 106053615A
- Authority
- CN
- China
- Prior art keywords
- choroidal vasculopathy
- polypoidal choroidal
- detecting
- chinese patients
- human eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000000090 biomarker Substances 0.000 title claims abstract description 11
- 206010063381 Polypoidal choroidal vasculopathy Diseases 0.000 claims abstract description 38
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 51
- 210000004369 blood Anatomy 0.000 claims description 32
- 239000008280 blood Substances 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 28
- 108010074051 C-Reactive Protein Proteins 0.000 claims description 27
- 210000002381 plasma Anatomy 0.000 claims description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims description 16
- 231100000915 pathological change Toxicity 0.000 claims description 14
- 230000036285 pathological change Effects 0.000 claims description 14
- 238000004458 analytical method Methods 0.000 claims description 13
- 102100032752 C-reactive protein Human genes 0.000 claims description 12
- 238000007619 statistical method Methods 0.000 claims description 12
- 238000007689 inspection Methods 0.000 claims description 9
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 238000007477 logistic regression Methods 0.000 claims description 8
- 210000001367 artery Anatomy 0.000 claims description 7
- 208000029078 coronary artery disease Diseases 0.000 claims description 7
- 239000012472 biological sample Substances 0.000 claims description 6
- 230000004438 eyesight Effects 0.000 claims description 6
- 230000000391 smoking effect Effects 0.000 claims description 6
- 230000007547 defect Effects 0.000 claims description 5
- 206010059245 Angiopathy Diseases 0.000 claims description 4
- 230000035622 drinking Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 2
- 238000004611 spectroscopical analysis Methods 0.000 claims 2
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims 1
- 229960003067 cystine Drugs 0.000 claims 1
- 229960003151 mercaptamine Drugs 0.000 claims 1
- 208000033892 Hyperhomocysteinemia Diseases 0.000 abstract description 5
- 230000003225 hyperhomocysteinemia Effects 0.000 abstract description 5
- 230000002596 correlated effect Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 206010064930 age-related macular degeneration Diseases 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 6
- 208000026106 cerebrovascular disease Diseases 0.000 description 5
- 230000002207 retinal effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- YXXURDJTDAAEPH-UHFFFAOYSA-N 2-aminopropanethioic s-acid Chemical compound CC(N)C(S)=O YXXURDJTDAAEPH-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 2
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 2
- 208000008069 Geographic Atrophy Diseases 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 208000037062 Polyps Diseases 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000003161 choroid Anatomy 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 208000038015 macular disease Diseases 0.000 description 2
- 238000004848 nephelometry Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000001521 two-tailed test Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- RTDXMJJSUVCSKB-RUCXOUQFSA-N (2s)-2-azanyl-4-sulfanyl-butanoic acid Chemical compound OC(=O)[C@@H](N)CCS.OC(=O)[C@@H](N)CCS RTDXMJJSUVCSKB-RUCXOUQFSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- -1 Sulfur aminoacid Chemical class 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000005282 brightening Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000013534 fluorescein angiography Methods 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 1
- 229960004657 indocyanine green Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010202 multivariate logistic regression analysis Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000608 photoreceptor cell Anatomy 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004256 retinal image Effects 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4737—C-reactive protein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/13—Ophthalmic microscopes
- A61B3/135—Slit-lamp microscopes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6806—Determination of free amino acids
- G01N33/6812—Assays for specific amino acids
- G01N33/6815—Assays for specific amino acids containing sulfur, e.g. cysteine, cystine, methionine, homocysteine
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4737—C-reactive protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/16—Ophthalmology
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Surgery (AREA)
- Veterinary Medicine (AREA)
- Medical Informatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Ophthalmology & Optometry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明提供一种侦测及诊断人类眼部的息肉状脉络膜血管病变的生物标记,包括确定高同型半胱胺酸血症的作用程度,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。此外,本发明进一步提供一种侦测及诊断人类眼部的息肉状脉络膜血管病变的方法。
Description
技术领域
本发明涉及关于息肉状脉络膜血管病变(polypoidal choroidalvasculopathy,PCV)的侦测、预测及诊断,尤指基于高同型半胱胺酸血症(Hyperhomocysteinemia)的作用程度侦测人类眼部的息肉状脉络膜血管病变。
背景技术
眼部息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)是造成失明常见的病因,由于这类的新生血管较为脆弱,较容易破裂出血以及营养供应不良,且容易造成感光细胞的萎缩及死亡。
现今,医生诊断该病变最有效的方式是利用眼底循血绿血管摄影(indocyanine green angiography,ICGA),藉由影像的高荧光的区域,且根据其他伴随的病症或在低荧光光晕及前五分钟急遽从暗变亮上的亮度变化,来诊断息肉状脉络膜血管病变的位置。
再者,老年性黄斑部病变(age-related macular degeneration,AMD)在亚洲是造成老年失明的常见病症,其中老年性黄斑部病变可分为干性(dry,early)及湿性(wet,late),干性老年性黄斑部病变在视网膜色素上皮层(retinalpigment epithelium,RPE)上长出脉络膜玻璃膜疣(drusen)或地图状萎缩(geographic atrophy),进而慢性地导致视力衰退,湿性老年性黄斑部病变则由于脉络膜新生血管(choroidal neovascularization,CNV),容易造成血管破裂出血及养分供应不够,进而造成视网膜破坏,所以会损害视网膜视觉中心而失明,以及形成视网膜破洞。因此,老年性黄斑部病变的罹病原因一般与年龄老化、抽烟、喝酒、糖尿病、高血压、基因及曝露于蓝光有关。
高半胱胺酸(homocysteine)是蛋胺酸的代谢过程中产生的天然存在的含硫氨基酸。高半胱胺酸的高血浆程度已被确定为血管疾病的危险因子,如心血管疾病及中风、老年痴呆症及阿尔茨海默氏病症。在患者具有视网膜血管闭塞性疾病、假性青光眼及糖尿病性视网膜疾病中亦可观察到升高的血浆高半胱胺酸的程度。同样地,在具有老年性黄斑部病变的患者中也可观察到升高的血浆高半胱胺酸的程度。
C-反应蛋白(C-reactive protein,CRP)是一种全身性炎症的生物标记以及心血管疾病的一个危险因素。日本研究人员研究发现升高的高敏感度C反应蛋白(high sensitivity C-reactive protein,hsCRP)的程度与息肉状脉络膜血管病变有显著的关联,且得出炎症过程参与息肉状脉络膜血管病变的发病机制的结论。
因此,如何进一步阐明及证实息肉状脉络膜血管病变与血管疾病的危险因素有关,实为目前各界亟欲解决的技术问题。
发明内容
鉴于上述现有技术的缺点,本发明提供一种侦测或诊断人类眼部的息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)的生物标记,包括:确定高同型半胱胺酸血症(Hyperhomocysteinemia)的作用程度,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
再者,本发明进一步提供一种侦测或诊断人类眼部的息肉状脉络膜血管病变的方法,包括以下步骤:确定从该人类眼部取得的多个生物样品的高同型半胱胺酸血症的作用程度;以及将该高同型半胱胺酸血症的作用程度与高同型半胱胺酸血症的作用对照程度比较,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
较佳地,该多个生物样品的数据可包括年龄、性别、生活方式因素、吸烟、饮酒量、用药史、高血压病史、糖尿病病史、冠状动脉疾病病史、脑血管疾病病史,但本发明不限于此。
较佳地,该高同型半胱胺酸血症的作用程度可藉由以下分析方法确定:总血浆高半胱胺酸分析(total plasma homocysteine analysis)、高敏感度C反应蛋白分析(high sensitivity C-reactive protein(hsCRP)analysis)及统计分析,但本发明不限于此。
较佳地,该统计分析使用多变量逻辑回归模型(multivariable logisticregression model)判断血浆高半胱胺酸及高敏感度C反应蛋白的作用程度与该息肉状脉络膜血管病变的关联性。
较佳地,本发明的侦测或诊断人类眼部的息肉状脉络膜血管病变的方法还包括以下步骤:对该人类眼部进行最佳矫正视力检查(best-corrected visualacuity examination)、裂隙灯生物显微镜检查(slit lamp biomicroscopyexamination)及眼底镜检查(fundoscopy examination)。
具体实施方式
以下藉由特定的具体实施例说明本发明的实施方式,熟悉本领域的技术人员可由本说明书所揭示的内容轻易地了解本发明的其他优点及功效。本发明亦可藉由其他不同的具体实例加以施行或应用,本发明说明书中的各项细节亦可基于不同观点与应用在不悖离本发明的精神下进行各种修饰与变更。
以下依据本发明的实施例,描述本发明的侦测及诊断人类眼部的息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)的生物标记。
研究对象
在本发明的实施例中,确诊为PCV的患者将进行研究。除了老年性黄斑部病变(age-related macular degeneration,AMD)、视网膜血管病变、糖尿病性视网膜病变或青光眼,对照组(control group)可包括接受常规身体检查或后续的疾病,然后每一情况的年龄和性别与对照组相匹配。其中所有研究对象为中华民族患者。
在本发明的实施例中,所有参与者均接受完整的眼科检查,其中包括最佳矫正视力检查(best-corrected acuity examination)、裂隙灯生物显微镜检查(slit lamp biomicroscopy examination)及眼底镜检查(fundoscopyexamination)。再者,在本发明的实施例中,本发明通过瞳孔放大,使用眼底照相机(CF-60UD,佳能公司,日本,东京)及ICGA(海德堡视网膜血管造影II,海德堡工程,德国,海德堡)进行眼底照相及荧光血管造影(fluorescein angiography,FA)。视网膜图像均由两个视网膜专家(P.K.L.和J.H.L.)以隐密的方式进行。只有具有特征性息肉状脉络膜血管扩张(息肉样病变或息肉)的ICGA受试者被诊断为PCV,PCV的位置被分成凹外(extrafoveal),近中心凹(juxtafoveal,在200微米内凹)、凹下(subfoveal)和乳头周围区域(peripapillary area,在内视盘的盘直径内)。
在本发明的实施例中,所有受试者的数据包括年龄、性别、吸烟、饮酒、服药史的生活方式因素、高血压病史、糖尿病(diabetes mellitus,DM)疾病、冠状动脉疾病、脑血管疾病及肾功能不全等等,但不限于本发明。
总血浆高半胱胺酸分析(total plasma homocysteine analysis)
在本发明的实施例中,以坐姿方式获得空腹静脉血液样本,且收集在含有肝素的试管,接着立即将样本于4℃使用实验室离心机进行离心,以及藉由具有0.5μmol/L的灵敏度及6.8%于4.9μmol/L及3.9%于61.6μmol/L的总变异系数(coeficient of variation,CV)的自动化化学发光免疫(ADVIACentaur system,Siemens,East Walpole,MA,USA)测量血浆高半胱胺酸程度。此外,上述的测定方法亦包括荧光偏振免疫测定法(fluorescent polarizationimmunoassay)及高效液相色谱法(high-performance liquid chromatography,HPLC)。
高敏感度C反应蛋白(high sensitivity C-reactive protein,hsCRP)分析
在本发明的实施例中,本发明获得静脉血液样本,且收集在血清分离管中。藉由比率浊度测定法(rate nephelometry),利用自动化浊度计(Immage800,Beckman Coulter,Fullerton,CA,USA)测量血清hsCRP。在此hsCRP的测定法中,藉由具有0.2mg/L的分析灵敏度及5.17%于0.79mg/L及3.8%于13.4mg/L的总变异系数,已经显示出本发明的测定方法与其他常用的测定方法具有极佳的相关性。
在本发明的实施例中,高半胱胺酸血症与升高hsCRP的程度分别被定义为高于对照组的九十五百分位的百分位数(95th percentile)程度。
统计分析
在本发明的统计分析方法中,在人口和医疗方面,使用学生t检验(Student’s t-test)及皮尔森卡方检验(Pearsons’s chi-square test)分别对PCV病例和对照组之间的连续和分类变量进行比较。血浆高半胱胺酸及血清hsCRP为中位数(四分位距(interquartile range)),以及由于高半胱胺酸及hsCRP并非为常态分布(normal distribution),所以藉由Mann-Whitney U检验与对照组相比较。
在本发明的统计分析方法中,多变量逻辑回归模型(multivariable logisticregression model)被用来评估PCV是否与血浆高半胱胺酸或血清hsCRP有关。所有的胜算比(odds ratios,ORs)均依据年龄、性别、生活方式因素(吸烟和饮酒)及疾病史(高血压、糖尿病、冠状动脉疾病及脑血管疾病)进行调整。
另外,在本发明的统计分析方法中,使用SPSS的Windows版本18(SPSS公司,芝加哥,伊利诺伊州,美国)进行本发明的计算。所有的P值均基于双尾检验(two-tailed test),以及小于0.05的P值被认为是显著性差异(statistical significance)。
结果
在一百二十四名患者中,三名患者被排除由于其肾功能不全,两名患者亦被排除由于其具有AMD的CNV被诊断出。因此,最后共有一百十九名具有PCV患者与对照组相比较。
表1显示息肉状脉络膜血管病变、对照组及P值的比较。
如表1所示,在PCV组及对照组中,平均年龄分别为72.1±13.0年及69.3±10.9年,在这两个群体中,男性占优势(74.8%)。在年龄、性别、高血压、糖尿病、冠状动脉疾病、脑血管疾病及生活方式因素(包括吸烟及饮酒情况下)方面,本发明显示并无显著性差异。
表1:息肉状脉络膜血管病变、对照组及P值的比较
表2显示全体及不同性别的息肉状脉络膜血管病变、对照组及P值的比较。
如表2所示,在中位数血浆高半胱胺酸程度方面,PCV组(中位数,12.20μmol/L,四分位距,9.67-16.66μmol/L)显著地高于对照组(中位数,9.80μmol/L,四分位距,8.13-11.26μmol/L,P<0.001)。高半胱胺酸的评估可以进一步分为有糖尿病子组及无糖尿病子组。有糖尿病的PCV患者的血浆高半胱胺酸程度显著地高于有糖尿病对照组(p值=0.001)。此外,无糖尿病的PCV患者的血浆高半胱胺酸程度亦显著地高于无糖尿病对照组(P<0.001)。在中位数血清hsCRP方面,PCV组(中位数,0.16mg/dl,四分位距,0.06-0.30mg/dl)略高于对照组(中位数,0.11mg/dl,四分位距,0.06-0.25mg/dl,p值=0.07)。
此外,在对照组中,高半胱胺酸的九十五百分位的百分位数(95thpercentile)为13.26μmol/L。与对照组(P<0.001)的一百十九名患者中的五名患者(4.2%)相比较,在一百十九名PCV患者中的四十七名患者(39.5%)超过上述临界值。再者,在对照组中的hsCRP的九十五百分位的百分位数为0.70mg/dl。与对照组(p=0.12)的一百十三名患者中的六名患者(5.4%)相比较,在一百十八名患者中的十三名患者(11.1%)超过上述临界值。
表2:全体及不同性别的息肉状脉络膜血管病变、对照组及P值的比较
表3显示高半胱胺酸及高敏感度C反应蛋白的息肉状脉络膜血管病变、对照组及P值的比较。
如表3所示,在性别方面,与对照组相比较,PCV组的男性及女性具有显著地较高的血浆高半胱胺酸程度(男性,P<0.001及女姓,P=0.02)以及高同型半胱胺酸血症的比例(男性,P<0.001及女性P=0.02)。hsCRP的结果一般而言为非显著,除了升高的hsCRP在女性部分为较高比例(26.7%对比于对照组中的3.4%,P=0.01)(如表2所示)。若将高半胱胺酸程度分为三分位数(tertile),与对照组相比较(67.2%对比于对照组中的32.8%,P<0.001),PCV患者的显著较高比例在最高的前三分之一具有高半胱胺酸程度。
表3:高半胱胺酸及高敏感度C反应蛋白的息肉状脉络膜血管病变、对照组及P值的比较
关于多变量逻辑回归分析方面,在调整年龄、性别、高血压、糖尿病,冠状动脉疾病、脑血管疾病、吸烟和饮酒后,本发明指出,升高的血浆高半胱胺酸程度与PCV的增加具有显著性相关(OR,1.54;95%信赖区间(confidence interval,CI),1.33-1.79,P<0.001)。具体而言,如表3所示,在回归模型中,患者在高半胱胺酸的最高的前三分之一具有9倍增加风险的PCV(OR,8.8495%CI,3.68-21.21,P<0.001)。
因此,根据本发明的实施例,本发明的侦测或诊断人类眼部的息肉状脉络膜血管病变的生物标记可包括:确定高同型半胱胺酸血症(Hyperhomocysteinemia)的作用程度,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
再者,本发明进一步提供一种侦测或诊断人类眼部的息肉状脉络膜血管病变的方法,本发明的侦测或诊断人类眼部的息肉状脉络膜血管病变的方法包括以下步骤:确定从该人类眼部取得的多个生物样品的高同型半胱胺酸血症的作用程度;以及将该高同型半胱胺酸血症的作用程度与高同型半胱胺酸血症的作用对照程度比较,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
根据本发明的实施例,该多个生物样品的数据可包括年龄、性别、生活方式因素、吸烟、饮酒量、用药史、高血压病史、糖尿病病史、冠状动脉疾病病史、脑血管疾病病史,但本发明不限于此。
根据本发明的实施例,该高同型半胱胺酸血症的作用程度可藉由以下分析方法确定:总血浆高半胱胺酸分析(total plasma homocysteine analysis)、高敏感度C反应蛋白分析(high sensitivity C-reactive protein(hsCRP)analysis)及统计分析,但本发明不限于此。
根据本发明的实施例,该统计分析使用多变量逻辑回归模型(multivariable logistic regression model)判断血浆高半胱胺酸及高敏感度C反应蛋白的作用程度与该息肉状脉络膜血管病变的关联性。
根据本发明的实施例,本发明的侦测或诊断人类眼部的息肉状脉络膜血管病变的方法还包括以下步骤:对该人类眼部进行最佳矫正视力检查(best-corrected visual acuity examination)、裂隙灯生物显微镜检查(slit lampbiomicroscopy examination)及眼底镜检查(fundoscopy examination)。
因此,根据本发明的结果,本发明指出,升高的血浆高半胱胺酸及血清hsCRP均与PCV高度地相关联。
然而,上述实施例仅例示性说明本发明的功效,而非用于限制本发明,任何熟悉本领域的技术人员均可在不违背本发明的精神及范畴下,对上述实施例进行修饰与改变。此外,在上述这些实施例中的元件的数量仅为例示性说明,亦非用于限制本发明。因此,本发明的权利保护范围,应如以下的权利要求范围所列。
Claims (9)
1.一种侦测及诊断人类眼部的息肉状脉络膜血管病变的生物标记,其特征在于,包括:
确定高同型半胱胺酸血症的作用程度,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
2.如权利要求1所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的生物标记,其特征在于,该高同型半胱胺酸血症的作用程度藉由以下分析方法确定:总血浆高半胱胺酸分析、高敏感度C反应蛋白分析及统计分析。
3.如权利要求2所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的生物标记,其特征在于,该统计分析使用多变量逻辑回归模型判断血浆高半胱胺酸及高敏感度C反应蛋白的作用程度与该息肉状脉络膜血管病变的关联性。
4.如权利要求1所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的生物标记,其特征在于,还包括:对该人类眼部进行最佳矫正视力检查、裂隙灯生物显微镜检查及眼底镜检查。
5.一种侦测及诊断人类眼部的息肉状脉络膜血管病变的方法,其特征在于,包括以下步骤:
确定从该人类眼部取得的多个生物样品的高同型半胱胺酸血症的作用程度;以及
将该高同型半胱胺酸血症的作用程度与高同型半胱胺酸血症的作用对照程度比较,其中,该高同型半胱胺酸血症的作用程度与该人类眼部的息肉状脉络膜血管病变高度相关联。
6.如权利要求5所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的方法,其特征在于,该多个生物样品的数据包括年龄、性别、生活方式因素、吸烟、饮酒量、用药史、高血压病史、糖尿病病史、冠状动脉疾病病史、脑血管疾病病史。
7.如权利要求5所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的方法,其特征在于,该高同型半胱胺酸血症的作用程度藉由以下分析方法确定:总血浆高半胱胺酸分析、高敏感度C反应蛋白分析及统计分析。
8.如权利要求7所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的方法,其特征在于,该统计分析使用多变量逻辑回归模型判断血浆高半胱胺酸及高敏感度C反应蛋白的作用程度与该息肉状脉络膜血管病变的关联性。
9.如权利要求5所述的侦测及诊断人类眼部的息肉状脉络膜血管病变的方法,其特征在于,还包括:对该人类眼部进行最佳矫正视力检查、裂隙灯生物显微镜检查及眼底镜检查。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW104112234 | 2015-04-16 | ||
TW104112234A TWI597051B (zh) | 2015-04-16 | 2015-04-16 | 高半胱胺酸用於偵測及診斷人類眼部之息肉狀脈絡膜血管病變的用途及方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106053615A true CN106053615A (zh) | 2016-10-26 |
Family
ID=57127213
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510424239.6A Pending CN106053615A (zh) | 2015-04-16 | 2015-07-20 | 人类眼部的生物标记及其方法 |
Country Status (4)
Country | Link |
---|---|
US (2) | US20160305951A1 (zh) |
CN (1) | CN106053615A (zh) |
TW (1) | TWI597051B (zh) |
WO (1) | WO2016166582A1 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107455327A (zh) * | 2017-08-07 | 2017-12-12 | 扬州大学 | 一种仔鹅高同型半胱氨酸败血症模型及其建立方法 |
DK179993B1 (en) * | 2018-07-05 | 2020-01-14 | Region Sjælland | BIOMARKET IN POLYPOIDAL CHOROIDAL VASCULOPATHY AND APPLICATIONS THEREOF |
CN111785363A (zh) * | 2020-06-03 | 2020-10-16 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | 一种基于ai引导的慢性病辅助诊断系统 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102393373A (zh) * | 2011-10-22 | 2012-03-28 | 温州市德福泰生物科技有限公司 | 一种消除内源性胱硫醚干扰的血清同型半胱氨酸测定方法及试剂 |
WO2014074823A1 (en) * | 2012-11-08 | 2014-05-15 | Clearside Biomedical, Inc. | Methods and devices for the treatment of ocular diseases in human subjects |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPR005600A0 (en) * | 2000-09-12 | 2000-10-05 | University Of Sydney, The | Diagnostic assay |
-
2015
- 2015-04-16 TW TW104112234A patent/TWI597051B/zh active
- 2015-07-20 WO PCT/IB2015/055487 patent/WO2016166582A1/zh active Application Filing
- 2015-07-20 CN CN201510424239.6A patent/CN106053615A/zh active Pending
- 2015-09-04 US US14/845,746 patent/US20160305951A1/en not_active Abandoned
-
2016
- 2016-08-15 US US15/236,746 patent/US20160347805A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102393373A (zh) * | 2011-10-22 | 2012-03-28 | 温州市德福泰生物科技有限公司 | 一种消除内源性胱硫醚干扰的血清同型半胱氨酸测定方法及试剂 |
WO2014074823A1 (en) * | 2012-11-08 | 2014-05-15 | Clearside Biomedical, Inc. | Methods and devices for the treatment of ocular diseases in human subjects |
Non-Patent Citations (2)
Title |
---|
CHENG, HUI-CHEN; LIU, JORN-HON; LEE, SHUI-MEI: "Hyperhomocysteinemia in Patients with Polypoidal Choroidal Vasculopathy: A Case Control Study", 《PLOS ONE》 * |
卓耀,彭廷云: "启明丸治疗年龄相关性黄斑变性的临床疗效及对血浆Hcy水平的影响", 《中国中医眼科杂志》 * |
Also Published As
Publication number | Publication date |
---|---|
TWI597051B (zh) | 2017-09-01 |
WO2016166582A1 (zh) | 2016-10-20 |
US20160347805A1 (en) | 2016-12-01 |
TW201637611A (zh) | 2016-11-01 |
US20160305951A1 (en) | 2016-10-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cheung et al. | Retinal vascular fractal dimension and its relationship with cardiovascular and ocular risk factors | |
Stefánsson et al. | Retinal oximetry discovers novel biomarkers in retinal and brain diseases | |
Wu et al. | Retinal vascular geometry and glaucoma: the Singapore Malay Eye Study | |
Araszkiewicz et al. | Neurodegeneration of the retina in type 1 diabetic patients | |
Tham et al. | Relationship between retinal vascular geometry with retinal nerve fiber layer and ganglion cell-inner plexiform layer in nonglaucomatous eyes | |
EP2219511A2 (en) | Method and apparatus for detecting diseases associated with the eye | |
Hirata et al. | Relationship between the morphology of the foveal avascular zone and the degree of aniseikonia before and after vitrectomy in patients with unilateral epiretinal membrane | |
Creuzot-Garcher et al. | Comparison of two methods to measure macular pigment optical density in healthy subjects | |
Kostic et al. | Investigating the fractal dimension of the foveal microvasculature in relation to the morphology of the foveal avascular zone and to the macular circulation in patients with type 2 diabetes mellitus | |
CN106053615A (zh) | 人类眼部的生物标记及其方法 | |
Veiby et al. | Associations between macular OCT angiography and nonproliferative diabetic retinopathy in young patients with type 1 diabetes mellitus | |
Srinivas et al. | Measurement of retinal blood flow in normal Chinese-American subjects by Doppler Fourier-domain optical coherence tomography | |
Guo et al. | Parapapillary choroidal microvasculature predicts diabetic retinopathy progression and diabetic macular edema development: a three-year prospective study | |
Ozmen et al. | Retinal vessel diameters and their correlation with retinal nerve fiber layer thickness in patients with pseudoexfoliation syndrome | |
Zhang et al. | Quantitative analysis of retinal and choroidal microvascular parameters using optical coherence tomography angiography in children with nephrotic syndrome: a pilot study | |
Guo et al. | Systemic vascular dysregulation may be associated with lower peripapillary vessel density in non-glaucomatous healthy eyes: A prospective cross-sectional study | |
Yamashita et al. | Relationship between location of retinal nerve fiber layer defect and curvature of retinal artery trajectory in eyes with normal tension glaucoma | |
Uchida et al. | Macular vessel density in untreated normal tension glaucoma with a hemifield defect | |
Lei et al. | Retrospective case-control data of serum nitrotyrosine level and clinical biomedical indices in primary glaucoma patients | |
Dereci et al. | Evaluation of eye health in children with type 1 diabetes mellitus and celiac disease | |
Yan et al. | 10-year fundus tessellation progression and retinal vein occlusion | |
Tikellis et al. | Retinal vascular caliber and macular telangiectasia type 2 | |
Sheikh et al. | Risk factors of branch retinal vein occlusion (BRVO) a study at tertiary care centre | |
Elsawy et al. | Glaucoma diagnostic accuracy of ganglion cell inner plexiform layer thickness comparison with peripapillary retinal nerve fiber layer | |
Wang et al. | Macular Retinal Layer Thickness and Associated Factors. The Beijing Eye Study 2011 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161026 |