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    Lorinsya Ollin
    Glaucoma is an optic neuropathy and leading cause of irreversible blindness characterized by progressive loss of visual field from the periphery to center. The major types are open-angle and closed-angle glaucoma. Treatment focuses on lowering elevated intraocular pressure (IOP) through pharmacologic agents that decrease aqueous humor production or increase outflow. Lowering IOP through medication or surgery has been shown to slow progression of visual loss in open-angle glaucoma. Understanding autonomic nervous system effects on the eye is key to rational drug treatment selection and side effect avoidance.

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    Glaucoma is an optic neuropathy and leading cause of irreversible blindness characterized by progressive loss of visual field from the periphery to center. The major types are open-angle and closed-angle glaucoma. Treatment focuses on lowering elevated intraocular pressure (IOP) through pharmacologic agents that decrease aqueous humor production or increase outflow. Lowering IOP through medication or surgery has been shown to slow progression of visual loss in open-angle glaucoma. Understanding autonomic nervous system effects on the eye is key to rational drug treatment selection and side effect avoidance.

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    Glaucoma is an optic neuropathy and leading cause of irreversible blindness characterized by progressive loss of visual field from the periphery to center. The major types are open-angle and closed-angle glaucoma. Treatment focuses on lowering elevated intraocular pressure (IOP) through pharmacologic agents that decrease aqueous humor production or increase outflow. Lowering IOP through medication or surgery has been shown to slow progression of visual loss in open-angle glaucoma. Understanding autonomic nervous system effects on the eye is key to rational drug treatment selection and side effect avoidance.

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    77 views15 pages

    Glaucome

    Uploaded by

    Lorinsya Ollin
    Glaucoma is an optic neuropathy and leading cause of irreversible blindness characterized by progressive loss of visual field from the periphery to center. The major types are open-angle and closed-angle glaucoma. Treatment focuses on lowering elevated intraocular pressure (IOP) through pharmacologic agents that decrease aqueous humor production or increase outflow. Lowering IOP through medication or surgery has been shown to slow progression of visual loss in open-angle glaucoma. Understanding autonomic nervous system effects on the eye is key to rational drug treatment selection and side effect avoidance.

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    Glaucoma

    Whatisglaucoma?
    Optic neuropathy that is the leading cause of
    irreversible blindness in the world
    Major types are open angle and closed angle
    Differences among various types of glaucoma
    complicate the nomenclature
    Glaucoma is commonly associated with elevated
    intraocular pressure (IOP), but the disease can occur in
    the context of normal IOP
    Our understanding and treatment of the disease is very
    focused on IOP

    From www.ahaf.org

    Case1
    Mr. S presents to you with diminished peripheral vision. He
    complains that he feels like the world is closing in on him. He also
    notes that he has trouble looking at lights as they all appear to be
    surrounded by halos. You perform fundoscopic and gonioscopic
    exam with tonometry and diagnose glaucoma.

    OpenAngleGlaucoma
    Obstruction at the level of the
    trabecular meshwork
    Progressive loss of visual field
    over time from periphery to
    center
    Presence of hollowed out optic
    disc (cupping) due to retinal
    ganglion cell death
    Open anterior chamber angle
    Majority of patients have IOP >
    21 mmHg, asymptomatic
    From http://www.merckfrosst.ca/e/health/glaucoma/glaucoma/classify/home.html

    Case2
    Mrs. P is a 65 yr. old female who has become acutely ill in the
    waiting room. An ophthalmologic assistant had dilated her eyes in
    preparation for examination. She is now complaining of nausea,
    diaphoresis and pain in her right eye, which is now red and swollen.

    ClosedAngleGlaucoma
    Apposition of iris and
    trabecular meshwork
    Parasympatholytics
    (pupillary dilation) can
    precipitate attack
    Increase risk with age,
    increase in volume of lens
    Acute onset, patient
    complains of nausea,
    headache (rather than eye
    ache), malaise, general
    distress
    Requires immediate

    BOTTOMLINE:IOPfromAqueousFlow,3Sites
    1.ObstructedTrabecularMesh
    OpenAngle:Agerelated,genetic
    ClosedAngle:Anatomic,
    exacerbatedby:
    2.PupillaryBlock

    Dilationofpupilirisflattens,
    flowviapupil,irisforward
    iriscorneaangle

    3.SwellingofCiliaryBody
    Modifiedfrom:Woodetal.NEJM339:1298(1998)

    SIDENOTE:
    WHYWOULDYOUWANTTODILATEMRS.PsPUPILS
    WITHPHENYLEPHRINEVS.ANANTICHOLINERGIC?

    REVIEW:AutonomicNSEffectontheEye
    RECEPTORACTIVATIONWILL:

    TOLOWERIOP,AIMFOR:

    IRIS,CircularFibers

    mAchR:ConstrictPupil

    Activity

    IRIS,RadialFibers

    1R:DilatePupil

    Activity

    CILIARYMUSCLES

    mAchR:ContractforAccomodation
    2R:RelaxforFarVision

    Activity

    Activity

    Modifiedfrom:http://pharma1.med.osakau.ac.jp/textbook/Autonomic/Autonomic.html

    TREATMENTRATIONALE

    LOWERIOPBY:
    (1) DecreasingProductionofAqueousHumor
    (2) IncreasingOutflowofAqueousHumor

    FocusonPharmacologicRx:Firstline

    DRUGSTHATDECREASEAQUEOUSPRODUCTION
    I.

    BetaBlockers[levobunolol,timolol,carteolol,betaxolol]
    Mechanism:Actonciliarybodytoproductionofaqueoushumor
    Administration:Topicaldropstoavoidsystemiceffects
    SideEffects:Cardiovascular(bradycardia,asystole,syncope),
    bronchoconstriction(avoidwith1selectivebetaxolol),depression

    II.

    Alpha2AdrenergicAgonists[apraclonidine,brimonidine]
    Mechanism:productionofaqueoushumor
    Administration:Topicaldrops
    SideEffects:Lethargy,fatigue,drymouth[apraclonidineisaderivativeof
    clonidine(antihypertensive)whichcannotcrossBBBtocause
    systemichypotension]

    III. CarbonicAnhydraseInhibitors[acetazolamide,dorzolamide]
    Mechanism:BlocksCAIIenzymeproductionofbicarbonateions

    (transportedtoposteriorchamber,carryingosmoticwaterflow),
    thusproductionofaqueoushumor
    Administration:Oral,topical
    SideEffects:malaise,kidneystones,possible(rare)aplasticanemia

    DRUGSTHATINCREASEAQUEOUSOUTFLOW
    I.

    NonspecificAdrenergicAgonists[epinephrine,dipivefrin]
    Mechanism:uveoscleraloutflowofaqueoushumor
    Administration:Topicaldrops
    SideEffects:Canprecipitateacuteattackinpatientswithnarrowiris
    cornealangle,headaches,cardiovasculararrhythmia,tachycardia

    II.

    Parasympathomimetics[pilocarpine,carbachol,echothiophate]
    Mechanism:contractileforceofciliarybodymuscle,outflowviaTM
    Administration:Topicaldropsorgel,(slowreleaseplasticinsert)
    SideEffects:Headache,inducedmiopia.FewsystemicSEfordirectacting
    agonistsvs.AchEinhibitors(diarrhea,cramps,prolongedparalysisin
    settingofsuccinylcholine).WhyisntAchused?

    III. Prostaglandins[latanoprost]
    Mechanism:Mayuveoscleraloutflowbyrelaxingciliarybodymuscle
    Administration:Topicaldrops
    SideEffects:Iriscolorchange

    LOWERINGIOPSLOWSPROGRESSIONOFVISUALLOSS
    INOPENANGLEGLAUCOMA

    Early Manifest Glaucoma Trial:


    -1st (adequately powered) randomized trial
    with untreated control arm to
    evaluate effects of IOP reduction in
    patients with open-angle glaucoma.
    -Treatment significantly delayed progression.

    RxGLAUCOMA:ADDITIONALCONSIDERATIONS
    1. Nosinglemedicationcanbeusedinallpatients
    2. Compliance

    Critical:Rxoftenrequiresseveralagents,
    multipletimesaday,everyday
    Roleofslowreleasedrugdeliverydevices(Langer)

    3. NonpharmacologicwaystolowerIOP:

    Laser(argonlasertrabeculoplasty)
    aqueousoutflow,loseseffectivenessovertime
    Surgical(trabeculectomy)
    Createsalternativepathforaqueousoutflow
    Onlydefinitivetherapyforclosedangle

    4. EffectivenessofRxmeasuredbyabilitytolowerIOP,but
    otherfactorsmaybe(more)important:
    Neuroprotection/increasedbloodflowtoopticnerve

    GLAUCOMA:KeyPoints
    Glaucoma:Visuallossfromopticneuropathy
    Openanglechronic,Closedangleacute
    Finalcommonpathway:IOP(usually)
    DrugRx:AlldirectedtowardsIOPeithervia:
    aqueousproduction:Betablockers

    Alpha2agonists
    Carbonicanhydraseinhibitors
    aqueousoutflow:(Adrenergicagonists,nonspecific)

    Parasympathomimetics
    Prostaglandins
    Treatmentslowsprogression
    UnderstandingANSeffectontheeyeiscriticalforreasoningthrough
    drugmechanismsofaction
    UnderstandingANSeffectonthewholebodyiscriticalforpredicting
    andavoidingdangeroussideeffects

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