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1、眼表疾病ocular surface diseasesDefinitionAnatomy：mucousmembraneliningtheeyelidsHistology：cornea,conjunctivaandtearfilmOcularsurfaceEpitheliumCornealepithelium:thestemcellsresideatthecorneosclerallimbusConjunctivalepithelium:theconjunctivalfornixorthejunctionbetweentheposterioreyelidandtheeyeballCONJUNCT
2、IVACORNEALIMBUSSTEMCELLSTRANSIENTAMPLIFYINGCELLSPOSTMITOTICCELLSTERMINALLYDIFFERENTIATEDCELLSLimbalstemcells n nSourceofcornealepitheliumSourceofcornealepitheliumn nIncreasedpotentialforproliferation,highcapacityofIncreasedpotentialforproliferation,highcapacityofself-renewalwithalongcellcycletimeand
3、asymmetricself-renewalwithalongcellcycletimeandasymmetriccelldivisioncelldivisionn nClassificationClassificationproliferatedcellsdifferentiatedcellsproliferatedcellsdifferentiatedcellsSCTACPMCTDCSCTACPMCTDCReproductiveactivityinfinitefiniteFissionabilitylowhighDifferentiationpotency+Characteristicso
4、flimbalstemcellsLocation:thebasementofcorneallimbusEpithelium repair when limbus defectedCornealepithelialcellsconcentricmovementConjunctivatocorneal-likeepithelium “ConjunctivalizationofthecorneawithvascularizationLimbalStemCellDeficiency Pathogenesis: Pathogenesis: lumbusepitheliumdefectedlumbusep
5、itheliumdefectedPathology: Pathology: cornealepitheliumoccupiedandcornealepitheliumoccupiedandreplacedbyconjunctivalepitheliumreplacedbyconjunctivalepitheliumManifest: Manifest: conjunctivalization,vascularization,conjunctivalization,vascularization,chronicinflammation,persistentuncle,basilarchronic
6、inflammation,persistentuncle,basilarmembranefailure,fibrocyteinvasionmembranefailure,fibrocyteinvasionTriple-symptom complexTriple-symptom complex： ConjuncivaConjuncivaepithelialcellsepithelialcellsconcentricmovement,cornealvascularization,healingdelayAmnion application in ocular surface reconstruci
7、onAmnion application in ocular surface reconstrucion羊膜的作用机制羊膜的作用机制抑制炎症反应促进上皮化抗新生血管形成抗纤维化缓解疼痛羊膜羊膜角膜缘干细胞体外培养的龛环境将角膜缘处的上皮或口腔黏膜上皮放到冷冻干燥保存的羊膜上将角膜缘处的上皮或口腔黏膜上皮放到冷冻干燥保存的羊膜上将角膜缘处的上皮或口腔黏膜上皮放到冷冻干燥保存的羊膜上将角膜缘处的上皮或口腔黏膜上皮放到冷冻干燥保存的羊膜上进行培养、扩增，并移植到眼表衰竭（角膜缘缺陷）的患眼上进行培养、扩增，并移植到眼表衰竭（角膜缘缺陷）的患眼上进行培养、扩增，并移植到眼表衰竭（角膜缘缺陷）的患眼上进
8、行培养、扩增，并移植到眼表衰竭（角膜缘缺陷）的患眼上 冷冻干燥保存羊膜冷冻干燥保存羊膜冷冻干燥保存羊膜冷冻干燥保存羊膜StemcellsofcorneallimbuscultivationandtransplantationStemcellsofcorneallimbuscultivationandtransplantation a a a a 正常人角膜正常人角膜正常人角膜正常人角膜 b b b b 正常人口腔黏膜正常人口腔黏膜正常人口腔黏膜正常人口腔黏膜 c c c c 培养的角膜上皮培养的角膜上皮培养的角膜上皮培养的角膜上皮 d d d d 培养的口腔黏膜上皮（与前者具有相似的复层上皮结
9、构）培养的口腔黏膜上皮（与前者具有相似的复层上皮结构）培养的口腔黏膜上皮（与前者具有相似的复层上皮结构）培养的口腔黏膜上皮（与前者具有相似的复层上皮结构）口腔黏膜上皮口腔黏膜上皮羊膜羊膜Rama P et alRama P et al：Transplantation 72Transplantation 72：14781478，20012001ab bcd dStemcellsofcorneallimbuscultivationandtransplantationStemcellsofcorneallimbuscultivationandtransplantationA. 对照组B. 实验组2W
10、4W眼类天疱疮眼类天疱疮眼类天疱疮眼类天疱疮 术前（术前（术前（术前（a a、b b）眼表重建眼表重建眼表重建眼表重建 术后（术后（术后（术后（c c、d d）ab bcd dShimazaki J et alShimazaki J et al：Ophthalmology 109Ophthalmology 109：12851285，20022002StemcellsofcorneallimbuscultivationandtransplantationStemcellsofcorneallimbuscultivationandtransplantation眼类天疱疮术前眼类天疱疮术前眼类天疱疮
11、术前眼类天疱疮术前（视力：（视力：（视力：（视力：0.010.010.010.01） 术后术后术后术后14141414个月个月个月个月（视力：（视力：（视力：（视力：0.60.60.60.6）Hayashida Y et alHayashida Y et al：Invest Ophthalmol Vis Sci 46Invest Ophthalmol Vis Sci 46：16321632，20052005StemcellsofcorneallimbuscultivationandtransplantationStemcellsofcorneallimbuscultivationandtran
12、splantationKeratoconjunctivitis sicca (KCS) Tear film functionn nImprove optical properties of corneaImprove optical properties of cornean nClean and dilute foreign bodies and toxinClean and dilute foreign bodies and toxinn nMoisten and lubricate ocular surface to Moisten and lubricate ocular surfac
13、e to protect epitheliumprotect epitheliumn nIntermediary agent where corneal Intermediary agent where corneal epithelium breatheepithelium breathen nDefense specificity and non-specificity Defense specificity and non-specificity inflammatoryinflammatoryThe structure of the tear-filmLipid layer produ
14、ced bymeibomian glandsAqueous layerby accessory lacrimal glandsMucin layerby goblet cellsNeuronal feedback loopLacrimalglandSecretomotorimpulseAffordocularsurfacetearNervousofocularSurfaceexcitationPathologyoftearfilmAqueous tear deficiencyMucus deficiencyLipid disorderDefinitionn nDryeyeisaDryeyeis
15、adisorderdisorderofthetearfilmduetoteardeciencyofthetearfilmduetoteardeciencyorexcessiveevaporation,whichcausesdamagetotheorexcessiveevaporation,whichcausesdamagetotheinterpalpebralocularsurfaceandisassociatedwithinterpalpebralocularsurfaceandisassociatedwithsymptomsofoculardiscomfort.symptomsofocul
16、ardiscomfort.-1995NEIReportonDryEye-1995NEIReportonDryEyen nDryeyeisaDryeyeisamultifactorialdiseasemultifactorialdiseaseofthetearsandocularofthetearsandocularsurfacethatresultsinsymptomsofdiscomfort,visualsurfacethatresultsinsymptomsofdiscomfort,visualdisturbance,andtearfilminstabilitywithpotentiald
17、amagedisturbance,andtearfilminstabilitywithpotentialdamagetotheocularsurface.totheocularsurface.ItisaccompaniedbyincreasedItisaccompaniedbyincreasedosmolarityofthetearfilmandinflammationoftheocularosmolarityofthetearfilmandinflammationoftheocularsurface.surface. -2007ReportoftheDryEyeWorkShop-2007Re
18、portoftheDryEyeWorkShop病理学机制-假说 Theearthissufferingfrom“dryeye”virgin forest desert and gobiTheinfluenceoforganicevolutionandhumanmoderncivilizationMarine life Amphibia Terrestrial animalHuman beingHuman“civilization”breakthebalanceoftheevolutionShanxiZhejiangBeijingLanzhouTheeye“workingenvironment”
19、andvisualfunctionburdenWorking face the screenVisual function burden increased TheeyesishardtodefenseduetolifestyleschangeAbout 50% female who is 35-50 years old in U.S.A. suffering from the dry eye symptomsNeurotrophy disorder SchirmerIIanddecrease,osmoticpressureoftearincrease,andallwillrecover in
20、69 months.PhysiologicalfunctionsdegenerationwithyearsPhysiologicalfunctionsdegenerationwithyearsDry eye syndromeEtiological classification：Aqueousteardeficiency（ATD）MucinteardeficiencyLipidteardeficiencyTeardynamicsdisorderMixedtypeDryeyesyndromen nVisualdisplaytermminal(VDT)n nBuildingdiseasesyndro
21、me(SBS)n nOfficeoftheeyesyndrome (OES)workresultinwinkingdecreasedenvironmentcauseoverevaporationEnvironmentalfactorsTearfunctionexaminationn nSchirmertestSchirmertest：5mm35mmfilterpaper,5mm35mmfilterpaper,measurethelengthofthemoistpartin5min.measurethelengthofthemoistpartin5min.Normalvalue:1030mmNo
22、rmalvalue:1030mm。n nBUTBUT：Normalvalue:1545s,10sistearfilmNormalvalue:1545s,312mOms/Ln nDeterminationoftearlysozyme：n nTearclearancerate：n nImpressioncytologyandbiopsy：Treatmentn nEliminate the cause of diseaseEliminate the cause of diseasen nReplacement therapy: self serum, Replacement therapy: sel
23、f serum, artificial tears without preservativesartificial tears without preservativesn nSave tearsSave tearsn nPromote tears productionPromote tears productionn nSurgerySurgery：Autologous transplantation of free submandibularTreatment protocolsClinical patternClinical patternn nLow secretionLow secr
24、etionsupply and save tears, reduce evaporation, improve supply and save tears, reduce evaporation, improve tears productiontears productionanti-inflammation and inhibit the immune responseanti-inflammation and inhibit the immune responsen nOver evaporationOver evaporationaim at MGD, anti-inflammatio
25、n, reduce evaporation, aim at MGD, anti-inflammation, reduce evaporation, clean eyelidsclean eyelidslipid replacement therapyipid replacement therapy Treatment protocolsPathogenetic conditionPathogenetic conditionmild mild only artificial tears (0.1% only artificial tears (0.1% Sodium Hyaluronate Ey
26、e Drops) )moderatemoderate main thick artificial tears without antiseptics (0.3% main thick artificial tears without antiseptics (0.3% Sodium Hyaluronate Eye Drops) ) puncta embolism puncta embolismsevere severe 0.05%CsA and puncta embolism 0.05%CsA and puncta embolism tarsorrhaphy and Submandibular
27、 gland transfer tarsorrhaphy and Submandibular gland transferCorneal disease Keratitis Etiological factorn nInfectiousInfectious： BacteriaBacteria Staphylococcus epidermidis, Staphylococcus epidermidis, Pseudomonas Aeruginosa, Staphylococcus aureusPseudomonas Aeruginosa, Staphylococcus aureus Fungus
28、 Fungus Fusarium spp. aspergillus Fusarium spp. aspergillus Viruses Viruses HSVHSV Ameba Ameban nEndogenousEndogenous：n nLocal spreadLocal spread：Keratitis Symptom： ophthalmalgia photophobia, lacrimation pink eye impaired vision secretion increaseKeratitisBasic signs： ciliary congestion corneal edem
29、a, opacity, infiltration ulceration fluorescein staining positiveKeratitisTherapeutic principle： Etiological treatmentEtiological treatment The rational use of steroidThe rational use of steroid，reduce corneal reduce corneal scarringscarring，prevent complicationprevent complication Perforation, corn
30、eal leucoma or corneal Perforation, corneal leucoma or corneal macula, then corneal transplantationmacula, then corneal transplantation Bacterial keratitispathogenic bacteria: StaphylococcusStaphylococcus Pneumococcus Pneumococcus Pseudomonas Aeruginosa Pseudomonas Aeruginosa Streptococcus Streptoco
31、ccus Gonococcus Gonococcus Pseudomonas Pseudomonas Bacterial keratitisInducement： corneal trauma corneal foreign body corneal contact lens Bacterial keratitisClinical manifestationn nAcute onset, severe symtoms, fast progress n nImpaired visionn nPurulent secretionn nEyelids and bulbar conjunctiva e
32、dema Bacterial keratitisTreatment:Treatment:n nScraping and G stainingScraping and G stainingn nbacteria and fungus cultivation and drug bacteria and fungus cultivation and drug sensitive testsensitive testn nG- : Gentamycin, TobramycinG- : Gentamycin, Tobramycinn nG+ : Ofloxacin, CiprofloxacinG+ :
33、Ofloxacin, Ciprofloxacinn nAdjust medication according to drug Adjust medication according to drug sensitive testsensitive test Bacterial keratitisTreatmentTreatment：n nAcute phase: antibiotics eye drops per 15-30min, Acute phase: antibiotics eye drops per 15-30min, drug combination per 15min in tur
34、ndrug combination per 15min in turnn nCycloplegics conventionally: 1Cycloplegics conventionally: 1 AtropineAtropinenPseudomonas aeruginosa corneal ulcer: drug discontinuance with cautionnBed isolation to inpatients Fungal keratitisInducementInducementn nVegetality trauma Vegetality trauma n nGlucoco
35、rticoid eye drops in long-term useGlucocorticoid eye drops in long-term usen nAntibiotics eye drops in long-term useAntibiotics eye drops in long-term usen nContaminative corneal contact lensContaminative corneal contact lensn nLack of specific antifungal angents, so high Lack of specific antifungal
36、 angents, so high blindness rateblindness rateFungal keratitisClinical manifestationClinical manifestationn nSlow onset, sight irritation at the beginningSlow onset, sight irritation at the beginningn nThen ophthalmalgia, photophobia and lacrimation Then ophthalmalgia, photophobia and lacrimation wi
37、th blurred visionwith blurred visionn nA corneal ulcer with satellite lesions in the A corneal ulcer with satellite lesions in the surrounding corneasurrounding corneanThick hypopyonnCorneal scraping: hyphae or spores Bacterial keratitisFungal keratitis Bacterial keratitis Bacterial keratitisFungal
38、keratitisFungal keratitisFungal keratitisFungus in general尖孢镰刀菌尖孢镰刀菌芽生菌芽生菌黄曲霉黄曲霉Chysosporium sp.Fungus microscopic characteristics茄病镰刀菌茄病镰刀菌芽生菌芽生菌弯孢霉弯孢霉黄曲霉黄曲霉HRTFungal keratitisFungal keratitisTreatmentTreatment：n nAntifungal agentsAntifungal agents： 0.25% amphotericin B eye drops0.25% amphotericin
39、B eye drops 0.5% fluconazole eye drops 0.5% fluconazole eye drops Natamycin eye drops Natamycin eye dropsnGlucocorticoid disabledn nAtropine Atropine n nCorneal transplantationCorneal transplantationCorneal transplantation indicationCCorneal transplantation indicationCorneal transplantation indicati
40、onAmeba keratitisAmoebic keratitis Ameba keratitisAmeba keratitisAmeba keratitisAmeba keratitis离体组织学检查离体组织学检查 ( (光学显微镜光学显微镜) )活体检查活体检查 (NIDEK)(NIDEK)Ameba keratitis(HRT3)Ameba keratitisLaboratory examinationn nCorneal lesion smear testn nBacteriology cultivationn nCorneal pathology examinationn nCon
41、focal microscopeHerpes simplex keratitisHerpes simplex virus infectionOften by HSV-I HSV-II by chancen nPrimary infectionn nLatent infectionn nRecurrent infectionHerpes simplex keratitisTreatmentnAntiviral drugsn nCorticosteroid drops n nSymptomatic treatmentn nLeucoma: corneal transplantationviral
42、keratitisNecroticinterstitialkeratitisviral keratitisAutoimmuneinterstitial keratitisviral keratitisviral keratitisviral keratitis Neuroparalytic keratitisNeuroparalytic keratitisTreatmentn nArtificial tears, antibiotics drops and ointment, soft contact lensesn nBlepharorrhaphyn nConsultation of neu
43、rology department Degeneration and dystrophyDegeneration: Secondary lesion on the basis of primary pathological change.Dystrophy: heredity related primary tissue change, bilateral and progressive.Cornea arcur senilisBand-shaped keratopathyBand-shaped keratopathyTerrien marginal degenerationTerrien m
44、arginal degenerationTerrien marginal degenerationGranular dystrophyFuchs endothelial dystrophy MoorensulcerDefinitionDefinition：chronic, spontaneous, peripheral, chronic, spontaneous, peripheral, progressive, painful corneal ulcerprogressive, painful corneal ulcer。EtiologyEtiology：unknowunknow It is
45、 generally agreed that it is an autoimmune It is generally agreed that it is an autoimmune condition in which the patients own immune condition in which the patients own immune system is mistakenly triggered to attack the system is mistakenly triggered to attack the cornea. No one knows what this tr
46、igger is, but cornea. No one knows what this trigger is, but suggestions have included prior eye surgery, prior suggestions have included prior eye surgery, prior eye trauma and a variety of infections. eye trauma and a variety of infections. Moorens ulcer Treatment：Glucocorticoid and collagenase in
47、hibitorImmunosuppressive agentsCorneal limbus cauterizationCorneal neoplastyLamellar KeratoplastyMoorens ulcer Moorens ulcer Moorens ulcer Moorens ulcer Moorens ulcer Keratoconus中毒性角膜炎机理机理破坏泪膜稳定性破坏泪膜稳定性破坏泪膜稳定性破坏泪膜稳定性破坏上皮细胞之间的紧密连接破坏上皮细胞之间的紧密连接破坏上皮细胞之间的紧密连接破坏上皮细胞之间的紧密连接抑制细胞的有丝分裂抑制细胞的有丝分裂抑制细胞的有丝分裂抑制细胞的有丝分裂促使结膜下的淋巴细胞向浆细胞转化和聚集促使结膜下的淋巴细胞向浆细胞转化和聚集促使结膜下的淋巴细胞向浆细胞转化和聚集促使结膜下的淋巴细胞向浆细胞转化和聚集药物作为半抗原与上皮基底膜结合药物作为半抗原与上皮基底膜结合药物作为半抗原与上皮基底膜结合药物作为半抗原与上皮基底膜结合发生发生发生发生抗原抗体复合物反应抗原抗体复合物反应抗原抗体复合物反应抗原抗体复合物反应药物作为全抗原诱发过敏反应药物作为全抗原诱发过敏反应药物作为全抗原诱发过敏反应药物作为全抗原诱发过敏反应Thank youThank you！
