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Glaucoma
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What is glaucoma?
Optic neuropathy that is the leading cause ofirreversible blindness in the world
Major types are open angle and closed angle
Differences among various types of glaucomacomplicate the nomenclature
Glaucoma is commonly associated with elevated
intraocular pressure (IOP) but the disease can occur inthe conte!t of normal IOP
Our understanding and treatment of the disease is very
focused on IOP
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From www.ahaf.org
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Case 1
Mr" # presents to you with diminished peripheral vision" $e
complains that he feels li%e the world is closing in on him" $e also
notes that he has trouble loo%ing at lights as they all appear to be
surrounded by halos" &ou perform fundoscopic and gonioscopic
e!am with tonometry and diagnose glaucoma"
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Open Angle Glaucoma
From http://www.merckfrosst.ca/e/health/glaucoma/glaucoma/classify/home.html
Obstruction at the level of the
trabecular meshwor%
Progressive loss of visual field
over time from periphery to
center
Presence of hollowed out optic
disc ('cupping) due to retinal
ganglion cell death
Open anterior chamber angle
Majority of patients have IOP
*+ mm$g asymptomatic
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Case 2
Mrs" P is a ,- yr" old female who has become acutely ill in the
waiting room" .n ophthalmologic assistant had dilated her eyes in
preparation for e!amination" #he is now complaining of nausea
diaphoresis and pain in her right eye which is now red and swollen"
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Closed Angle Glaucoma
.pposition of iris andtrabecular meshwor%
Parasympatholytics
(pupillary dilation) can
precipitate attac% Increase ris% with age
increase in volume of lens
.cute onset patient
complains of nausea
headache (rather than eye
ache) malaise general
distress
/e0uires immediate
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BOTTOM LINE: IOP from Aqueous Flow, 3 Sites
1. Obstructed Trabecular Mesh Open Angle: Age-related, genetic
Closed Angle: Anatomic,
exacerbated by:
2. Pupillary Block Dilation of pupiliris flattens,
flow via pupil, iris forwardiris-cornea angle
3. Swelling of Ciliary Body
1
2
3
SIDENOTE:
WHYWOULD YOU WANT TO DILATEMRS. Ps PUPILS
WITHPHENYLEPHRINE VS. ANANTICHOLINERGIC?
Modified from: Wood et al. NEJM 339:1298 (1998)
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REVIEW: Autonomic NS Effect on the Eye
RECEPTOR ACTIVATION WILL: TO LOWER IOP, AIM FOR:
IRIS, Circular Fibers mAchR : Constrict Pupil Activity
IRIS, Radial Fibers 1 R : Dilate Pupil Activity
CILIARY MUSCLES mAchR : Contract for Accomodation
2 R : Relax for Far Vision
Activity
Activity
Modified from: http://pharma1.med.osaka-u.ac.jp/textbook/Autonomic/Autonomic.html
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TREATMENT RATIONALE
LOWER IOP BY:
(1) Decreasing Production of Aqueous Humor
(2) Increasing Outflow of Aqueous Humor
Focus onPharmacologi
c Rx: First-line
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DRUGS THAT DECREASE AQUEOUS PRODUCTION
I. Beta-Blockers[levobunolol, timolol, carteolol, betaxolol]
-Mechanism: Act on ciliary body to production of aqueous humor -Administration: Topical drops to avoid systemic effects
-Side Effects: Cardiovascular (bradycardia, asystole, syncope),bronchoconstriction (avoid with 1-selective betaxolol), depression
II. Alpha-2 Adrenergic Agonists[apraclonidine, brimonidine]
-Mechanism: production of aqueous humor-Administration: Topical drops
-Side Effects: Lethargy, fatigue, dry mouth [apraclonidine is a derivative ofclonidine (antihypertensive) which cannot cross BBB to causesystemic hypotension]
III. Carbonic Anhydrase Inhibitors[acetazolamide, dorzolamide] -Mechanism: Blocks CAII enzyme production of bicarbonate ions
(transported to posterior chamber, carrying osmotic water flow),thus production of aqueous humor
-Administration: Oral, topical
-Side Effects: malaise, kidney stones, possible (rare) aplastic anemia
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DRUGS THAT INCREASE AQUEOUS OUTFLOW
I. Nonspecific Adrenergic Agonists [epinephrine, dipivefrin]
-Mechanism: uveoscleral outflow of aqueous humor
-Administration: Topical drops
-Side Effects: Can precipitate acute attack in patients with narrow iris-corneal angle, headaches, cardiovascular arrhythmia, tachycardia
II. Parasympathomimetics[pilocarpine, carbachol, echothiophate]
-Mechanism: contractile force of ciliary body muscle, outflow via TM
-Administration: Topical drops or gel, (slow-release plastic insert)
-Side Effects: Headache, induced miopia. Few systemic SE for direct-actingagonists vs. AchE inhibitors (diarrhea, cramps, prolonged paralysis insetting of succinylcholine). Why isnt Ach used?
III. Prostaglandins[latanoprost] -Mechanism: May uveoscleral outflow by relaxing ciliary body muscle
-Administration: Topical drops
-Side Effects: Iris color change
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LOWERING IOP SLOWS PROGRESSION OF VISUAL LOSS
IN OPEN ANGLE GLAUCOMA
1arly Manifest Glaucoma 2rial3
4+st (ade0uately powered) randomi5ed trial
with untreated control arm to evaluate effects of IOP reduction in
patients with open4angle glaucoma"
42reatment significantly delayed progression"
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Rx GLAUCOMA: ADDITIONAL CONSIDERATIONS
1. No single medication can be used in all patients
2. Compliance- Critical: Rx often requires several agents,
multiple times a day, everyday
- Role of slow-release drug delivery devices (Langer)
3. Non-pharmacologic ways to lower IOP:- Laser (argon laser trabeculoplasty)
- aqueous outflow, loses effectiveness over time- Surgical (trabeculectomy)
- Creates alternative path for aqueous outflow- Only definitive therapy for closed angle
4. Effectiveness of Rx measured by ability to lower IOP, but
other factors may be (more) important:
- Neuroprotection/increased blood flow to optic nerve
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GLAUCOMA: Key Points
Glaucoma: -Visual loss from optic neuropathy
-Open angle chronic, Closed angle acute
-Final common pathway: IOP (usually)
Drug Rx: -All directed towardsIOP either via: - aqueous production: Beta blockers
Alpha-2 agonists Carbonic anhydrase inhibitors
- aqueous outflow: (Adrenergic agonists, nonspecific) Parasympathomimetics
Prostaglandins Treatment slows progression
Understanding ANS effect on the eye is critical for reasoning throughdrug mechanisms of action
Understanding ANS effect on the whole body is critical for predictingand avoiding dangerous side effects