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Glaucoma dr.gosiengfiao dr.pangalanan
- 1. Partners Eye Care Specialists GlaucomaGlaucoma Dr.David GosiengfiaoDr. David Gosiengfiao Dr. Ernesto PangalanganDr. Ernesto Pangalangan
- 2. Partners Eye Care Specialists Whatis Glaucoma?What is Glaucoma? A family of diseases having in commonA family of diseases having in common characteristic progressive optic neuropathy andcharacteristic progressive optic neuropathy and an associated visual field lossan associated visual field loss Retinal ganglion cell lossRetinal ganglion cell loss Characteristic optic nerve head changesCharacteristic optic nerve head changes Characteristic visual field changesCharacteristic visual field changes
- 3. Partners Eye Care Specialists Whyis Glaucoma important?Why is Glaucoma important? Potentially blindingPotentially blinding Causes irreversible optic nerve damageCauses irreversible optic nerve damage Largely manageable when caught earlyLargely manageable when caught early
- 4. Partners Eye Care Specialists VisualpathwayVisual pathway Photoreceptor cellsPhotoreceptor cells Bipolar cellsBipolar cells Retinal ganglion cellsRetinal ganglion cells Nerve fiber layerNerve fiber layer Optic nerve headOptic nerve head Optic nerveOptic nerve Optic chiasmOptic chiasm Lateral geniculate bodiesLateral geniculate bodies Optic radiationsOptic radiations Occipital cortexOccipital cortex
- 5. Partners Eye Care Specialists Changesin glaucomaChanges in glaucoma Normal Glaucomatous
- 6. Partners Eye Care Specialists ApoptosisApoptosis Programmedcell deathProgrammed cell death Cell shrinkageCell shrinkage Chromatin clumpingChromatin clumping DNA fragmentationDNA fragmentation
- 7. Partners Eye Care Specialists ApoptosisApoptosis SignalSignal NeurotrophindeprivationNeurotrophin deprivation Glutamate toxicityGlutamate toxicity Activation p53Activation p53 bcl-2 (inhibits apoptosis)bcl-2 (inhibits apoptosis) bax (promotes apoptosis)bax (promotes apoptosis) Activation cytochrome cActivation cytochrome c
- 8. Partners Eye Care Specialists ApoptosisApoptosis ActivationcaspacesActivation caspaces Digest cellular componentsDigest cellular components Cellular debris phagocytosed by glial cellsCellular debris phagocytosed by glial cells
- 9. Partners Eye Care Specialists NeurotrophinsNeurotrophins BDNFBDNF <50%in acute glaucoma<50% in acute glaucoma Upregulated Trk B receptor in chronic glaucomaUpregulated Trk B receptor in chronic glaucoma bFGFbFGF NT-3,4NT-3,4 NGFNGF CNTFCNTF InterruptionInterruption Mechanical obstructionMechanical obstruction Impaired transport mechanismImpaired transport mechanism
- 10. Partners Eye Care Specialists ExcitotoxicityExcitotoxicity Maytrigger cell death in adjacent cellsMay trigger cell death in adjacent cells
- 11. Partners Eye Care Specialists Reductionof blood flowReduction of blood flow Depletion of cellular energy storesDepletion of cellular energy stores NaNa++ /K/K++ pump failurepump failure AcidosisAcidosis Membrane depolarizationMembrane depolarization Opening of voltage-operatedOpening of voltage-operated calcium channelscalcium channels Elevation of intracellular CaElevation of intracellular Ca2+2+ Activation of:Activation of: lipaseslipases NO synthaseNO synthase proteases - calpainsproteases - calpains endonucleasesendonucleases Releases of glutamate Activation of NMDA, AMPA, kainate and metabotropic receptors NO Free radical formation Cell death Reperfusion Inflammation Glutamate cascadeGlutamate cascade
- 12. Partners Eye Care Specialists Roleof glial cells and ECMRole of glial cells and ECM Glial cellsGlial cells AstrocytesAstrocytes Muller cellsMuller cells Have glutamate transporters that bufferHave glutamate transporters that buffer extracellular glutamateextracellular glutamate GLT-1GLT-1 GLASTGLAST Modulate ECMModulate ECM
- 13. Partners Eye Care Specialists Roleof IOPRole of IOP Direct effect on retinal ganglion cellsDirect effect on retinal ganglion cells (RGC)(RGC) Mechanical effect on optic nerve headMechanical effect on optic nerve head Blood flow effectBlood flow effect
- 14. Partners Eye Care Specialists Directeffect on RGCDirect effect on RGC Somatic shrinkageSomatic shrinkage Dendritic changesDendritic changes Heat shock responseHeat shock response
- 15. Partners Eye Care Specialists Mechanicaleffect on optic nerveMechanical effect on optic nerve headhead Optic nerve head is weakest point in eyeOptic nerve head is weakest point in eye Greatest stressGreatest stress Astrocyte remodeling and migrationAstrocyte remodeling and migration Elastin depositionElastin deposition Posterior bowing and thinning of cribriformPosterior bowing and thinning of cribriform plateplate
- 16. Partners Eye Care Specialists Effecton blood flowEffect on blood flow PP = MAP – IOPPP = MAP – IOP PP:PP: Perfusion pressurePerfusion pressure MAP:MAP: Mean arterial blood pressureMean arterial blood pressure IOP:IOP: Intraocular pressureIntraocular pressure Decrease PPDecrease PP PP dependent axonal transport of BDNFPP dependent axonal transport of BDNF
- 17. Partners Eye Care Specialists Mechanismsof elevated IOPMechanisms of elevated IOP IOP = F / C + PIOP = F / C + Pee F = aqueous flowF = aqueous flow (uL/min)(uL/min) C = outflow facilityC = outflow facility (uL/min/mmHg)(uL/min/mmHg) PPee = episcleral venous pressure= episcleral venous pressure (mmHg)(mmHg) Increased aqueousIncreased aqueous productionproduction Impaired aqueousImpaired aqueous outflowoutflow Elevated episcleralElevated episcleral venous pressurevenous pressure
- 18. Partners Eye Care Specialists Anataomyand physiology ofAnataomy and physiology of aqueous flowaqueous flow Produced via activeProduced via active transport in non-transport in non- pigmented epithelium ofpigmented epithelium of the ciliary processesthe ciliary processes OutflowOutflow TrabecularTrabecular UveoscleralUveoscleral Elevated IOPElevated IOP Open angleOpen angle Closed angleClosed angle
- 19. Partners Eye Care Specialists Primaryopen angle glaucomaPrimary open angle glaucoma SenescenseSenescense Decreased number of pores in TMDecreased number of pores in TM Decreased cellularity of TMDecreased cellularity of TM Helicobacter pyloriHelicobacter pylori 88% in POAG88% in POAG Treatment associated with + responseTreatment associated with + response OptineurinOptineurin VasoregulationVasoregulation apoptosisapoptosis
- 20. Partners Eye Care Specialists Steroidinduced glaucomaSteroid induced glaucoma Myocilin / Tigr protein expressionMyocilin / Tigr protein expression Increased aqueous viscosityIncreased aqueous viscosity Triggered by Myoc/Tigr geneTriggered by Myoc/Tigr gene
- 21. Partners Eye Care Specialists PseudoexfoliativeglaucomaPseudoexfoliative glaucoma Basement membraneBasement membrane diseasedisease Exfoliated materialExfoliated material obstruct TMobstruct TM
- 22. Partners Eye Care Specialists PigmentaryglaucomaPigmentary glaucoma Reverse pupillary blockReverse pupillary block Posterior bowing of irisPosterior bowing of iris Pigment epithelium contact with lensPigment epithelium contact with lens Pigment released causing Krukenberg spindlesPigment released causing Krukenberg spindles Pigment phagocytosed by TM causing decreased TMPigment phagocytosed by TM causing decreased TM functionfunction
- 23. Partners Eye Care Specialists Increasedepiscleral resistanceIncreased episcleral resistance Sturge WeberSturge Weber syndromesyndrome AV fistulaAV fistula Orbital floor fracture IOP + 6 mmHg
- 24. Partners Eye Care Specialists Angleclosure glaucomaAngle closure glaucoma AcuteAcute SymptomaticSymptomatic PainPain RednessRedness Blurred visionBlurred vision HaloesHaloes Nausea or vomitingNausea or vomiting ChronicChronic May be asymptomaticMay be asymptomatic
- 25. Partners Eye Care Specialists Pupillaryblock glaucomaPupillary block glaucoma Resistance at irido-Resistance at irido- lenticular interfacelenticular interface Pressure bows irisPressure bows iris anteriorlyanteriorly Dilation causes angleDilation causes angle to closeto close May be lens / cataractMay be lens / cataract inducedinduced
- 26. Partners Eye Care Specialists PlateauirisPlateau iris Central iris flatCentral iris flat centrally and convexcentrally and convex peripherallyperipherally Angle closes onAngle closes on dilationdilation
- 27. Partners Eye Care Specialists SupraciliaryeffusionsSupraciliary effusions UveitisUveitis Drug effectDrug effect SulfaSulfa TopiramateTopiramate Malignant glaucomaMalignant glaucoma
- 28. Partners Eye Care Specialists Roleof ocular blood flow andRole of ocular blood flow and oxygenationoxygenation IschemiaIschemia triggers glutamate cascadetriggers glutamate cascade May impair axonal transportMay impair axonal transport Impaired compensation in OAGImpaired compensation in OAG Dysautoregulation in NTGDysautoregulation in NTG Nocturnal hypotension and NTGNocturnal hypotension and NTG Sleep apnea and NTGSleep apnea and NTG Migraine and NTGMigraine and NTG
- 29. Partners Eye Care Specialists ImmunologicmechanismsImmunologic mechanisms T cell mediated modulation of glutamateT cell mediated modulation of glutamate toxicitytoxicity Cop-1 induced immunityCop-1 induced immunity C-terminal cross reactivityC-terminal cross reactivity CaspacesCaspaces HspHsp
- 30. Partners Eye Care Specialists ConclusionConclusion Glaucomais a multi-faceted and multi-Glaucoma is a multi-faceted and multi- factorial diseasefactorial disease Can occur at any intraocular pressureCan occur at any intraocular pressure Misdiagnosis can be visually devastatingMisdiagnosis can be visually devastating A high index of suspicion is necessaryA high index of suspicion is necessary
Editor's Notes
- #3 Please not that elevated intraocular pressure is no longer part of the definition of glaucoma.
- #14 Most commonly recognized Pathophysiology Direct effect on RGC Mechanical effect on optic nerve head Effect on blood flow Classes ACG Lens induced OAG POAG Childhood and juvenile glaucomas
- #29 Autoregulation BP PP Dysregulation OAG OHT NTG