Partners
Eye Care Specialists
GlaucomaGlaucoma
Dr. David GosiengfiaoDr. David Gosiengfiao
Dr. Ernesto PangalanganDr. Ernes...
Partners
Eye Care Specialists
What is Glaucoma?What is Glaucoma?
A family of diseases having in commonA family of diseases...
Partners
Eye Care Specialists
Why is Glaucoma important?Why is Glaucoma important?
Potentially blindingPotentially blindin...
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Eye Care Specialists
Visual pathwayVisual pathway
Photoreceptor cellsPhotoreceptor cells
Bipolar cellsBipolar cel...
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Eye Care Specialists
Changes in glaucomaChanges in glaucoma
Normal Glaucomatous
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Eye Care Specialists
ApoptosisApoptosis
Programmed cell deathProgrammed cell death
Cell shrinkageCell shrinkage
C...
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Eye Care Specialists
ApoptosisApoptosis
SignalSignal

Neurotrophin deprivationNeurotrophin deprivation

Glutama...
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Eye Care Specialists
ApoptosisApoptosis
Activation caspacesActivation caspaces

Digest cellular componentsDigest...
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Eye Care Specialists
NeurotrophinsNeurotrophins
BDNFBDNF

<50% in acute glaucoma<50% in acute glaucoma

Upregul...
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Eye Care Specialists
ExcitotoxicityExcitotoxicity
May trigger cell death in adjacent cellsMay trigger cell death ...
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Eye Care Specialists
Reduction of blood flowReduction of blood flow
Depletion of cellular energy storesDepletion ...
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Eye Care Specialists
Role of glial cells and ECMRole of glial cells and ECM
Glial cellsGlial cells

AstrocytesAs...
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Eye Care Specialists
Role of IOPRole of IOP
Direct effect on retinal ganglion cellsDirect effect on retinal gangl...
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Eye Care Specialists
Direct effect on RGCDirect effect on RGC
Somatic shrinkageSomatic shrinkage
Dendritic change...
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Eye Care Specialists
Mechanical effect on optic nerveMechanical effect on optic nerve
headhead
Optic nerve head i...
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Eye Care Specialists
Effect on blood flowEffect on blood flow
PP = MAP – IOPPP = MAP – IOP
PP:PP: Perfusion press...
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Eye Care Specialists
Mechanisms of elevated IOPMechanisms of elevated IOP
IOP = F / C + PIOP = F / C + Pee
F = aq...
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Eye Care Specialists
Anataomy and physiology ofAnataomy and physiology of
aqueous flowaqueous flow
Produced via a...
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Eye Care Specialists
Primary open angle glaucomaPrimary open angle glaucoma
SenescenseSenescense

Decreased numb...
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Eye Care Specialists
Steroid induced glaucomaSteroid induced glaucoma
Myocilin / Tigr protein expressionMyocilin ...
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Eye Care Specialists
Pseudoexfoliative glaucomaPseudoexfoliative glaucoma
Basement membraneBasement membrane
dise...
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Eye Care Specialists
Pigmentary glaucomaPigmentary glaucoma
Reverse pupillary blockReverse pupillary block
Poster...
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Eye Care Specialists
Increased episcleral resistanceIncreased episcleral resistance
Sturge WeberSturge Weber
synd...
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Eye Care Specialists
Angle closure glaucomaAngle closure glaucoma
AcuteAcute

SymptomaticSymptomatic
PainPain
Re...
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Eye Care Specialists
Pupillary block glaucomaPupillary block glaucoma
Resistance at irido-Resistance at irido-
le...
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Eye Care Specialists
Plateau irisPlateau iris
Central iris flatCentral iris flat
centrally and convexcentrally an...
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Eye Care Specialists
Supraciliary effusionsSupraciliary effusions
UveitisUveitis
Drug effectDrug effect

SulfaSu...
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Eye Care Specialists
Role of ocular blood flow andRole of ocular blood flow and
oxygenationoxygenation
IschemiaIs...
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Eye Care Specialists
Immunologic mechanismsImmunologic mechanisms
T cell mediated modulation of glutamateT cell m...
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Eye Care Specialists
ConclusionConclusion
Glaucoma is a multi-faceted and multi-Glaucoma is a multi-faceted and m...
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Glaucoma dr.gosiengfiao dr.pangalanan

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  • Please not that elevated intraocular pressure is no longer part of the definition of glaucoma.
  • 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
  • Autoregulation
    BP
    PP
    Dysregulation
    OAG
    OHT
    NTG
  • Glaucoma dr.gosiengfiao dr.pangalanan

    1. 1. Partners Eye Care Specialists GlaucomaGlaucoma Dr. David GosiengfiaoDr. David Gosiengfiao Dr. Ernesto PangalanganDr. Ernesto Pangalangan
    2. 2. Partners Eye Care Specialists What is 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. 3. Partners Eye Care Specialists Why is 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. 4. Partners Eye Care Specialists Visual pathwayVisual 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. 5. Partners Eye Care Specialists Changes in glaucomaChanges in glaucoma Normal Glaucomatous
    6. 6. Partners Eye Care Specialists ApoptosisApoptosis Programmed cell deathProgrammed cell death Cell shrinkageCell shrinkage Chromatin clumpingChromatin clumping DNA fragmentationDNA fragmentation
    7. 7. Partners Eye Care Specialists ApoptosisApoptosis SignalSignal  Neurotrophin deprivationNeurotrophin 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. 8. Partners Eye Care Specialists ApoptosisApoptosis Activation caspacesActivation caspaces  Digest cellular componentsDigest cellular components Cellular debris phagocytosed by glial cellsCellular debris phagocytosed by glial cells
    9. 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. 10. Partners Eye Care Specialists ExcitotoxicityExcitotoxicity May trigger cell death in adjacent cellsMay trigger cell death in adjacent cells
    11. 11. Partners Eye Care Specialists Reduction of 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. 12. Partners Eye Care Specialists Role of 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. 13. Partners Eye Care Specialists Role of 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. 14. Partners Eye Care Specialists Direct effect on RGCDirect effect on RGC Somatic shrinkageSomatic shrinkage Dendritic changesDendritic changes Heat shock responseHeat shock response
    15. 15. Partners Eye Care Specialists Mechanical effect 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. 16. Partners Eye Care Specialists Effect on 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. 17. Partners Eye Care Specialists Mechanisms of 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. 18. Partners Eye Care Specialists Anataomy and 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. 19. Partners Eye Care Specialists Primary open 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. 20. Partners Eye Care Specialists Steroid induced 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. 21. Partners Eye Care Specialists Pseudoexfoliative glaucomaPseudoexfoliative glaucoma Basement membraneBasement membrane diseasedisease Exfoliated materialExfoliated material obstruct TMobstruct TM
    22. 22. Partners Eye Care Specialists Pigmentary glaucomaPigmentary 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. 23. Partners Eye Care Specialists Increased episcleral resistanceIncreased episcleral resistance Sturge WeberSturge Weber syndromesyndrome AV fistulaAV fistula Orbital floor fracture IOP + 6 mmHg
    24. 24. Partners Eye Care Specialists Angle closure glaucomaAngle closure glaucoma AcuteAcute  SymptomaticSymptomatic PainPain RednessRedness Blurred visionBlurred vision HaloesHaloes Nausea or vomitingNausea or vomiting ChronicChronic  May be asymptomaticMay be asymptomatic
    25. 25. Partners Eye Care Specialists Pupillary block 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. 26. Partners Eye Care Specialists Plateau irisPlateau iris Central iris flatCentral iris flat centrally and convexcentrally and convex peripherallyperipherally Angle closes onAngle closes on dilationdilation
    27. 27. Partners Eye Care Specialists Supraciliary effusionsSupraciliary effusions UveitisUveitis Drug effectDrug effect  SulfaSulfa  TopiramateTopiramate Malignant glaucomaMalignant glaucoma
    28. 28. Partners Eye Care Specialists Role of 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. 29. Partners Eye Care Specialists Immunologic mechanismsImmunologic 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. 30. Partners Eye Care Specialists ConclusionConclusion Glaucoma is 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

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