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