2. What is glaucoma?
• 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
4. Case 1
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.
5. Open Angle Glaucoma
From http://www.merckfrosst.ca/e/health/glaucoma/glaucoma/classify/home.html
• 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
6. Case 2
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.
7. Closed Angle Glaucoma
• 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
treatment
8. 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 pupil→ iris flattens,
flow via pupil, iris forward
iris-cornea angle
3. Swelling of Ciliary Body
1
2
3
SIDENOTE:
WHY WOULD YOU WANT TO DILATE MRS. P’s PUPILS
WITH PHENYLEPHRINE VS. AN ANTICHOLINERGIC?
Modified from: Wood et al. NEJM 339:1298 (1998)
9. 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
10. TREATMENT RATIONALE
LOWER IOP BY:
(1) Decreasing Production of Aqueous Humor
(2) Increasing Outflow of Aqueous Humor
Focus on Pharmacologic Rx: First-line
11. 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 of
clonidine (antihypertensive) which cannot cross BBB to cause systemic
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
12. 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-acting
agonists vs. AchE inhibitors (diarrhea, cramps, prolonged paralysis in
setting of succinylcholine). Why isn’t Ach used?
III. Prostaglandins [latanoprost]
-Mechanism: May uveoscleral outflow by relaxing ciliary body muscle
-Administration: Topical drops
-Side Effects: Iris color change
13. LOWERING IOP SLOWS PROGRESSION OF VISUAL LOSS IN
OPEN ANGLE GLAUCOMA
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.
14. 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
15. GLAUCOMA: Key Points
• Glaucoma: -Visual loss from optic neuropathy
-Open angle chronic, Closed angle acute
-Final common pathway: IOP (usually)
• Drug Rx: -All directed towards IOP 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 through
drug mechanisms of action
• Understanding ANS effect on the whole body is critical for predicting and
avoiding dangerous side effects
