Glaucoma

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Glaucoma

• Viviany Taqueti and Scott Vafai
• HST 150

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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

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From www.ahaf.org
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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.
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Open Angle Glaucoma

• 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 gt 21 mmHg,
  asymptomatic

From http//www.merckfrosst.ca/e/health/glaucoma/g
laucoma/classify/home.html
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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.
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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

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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 pupil? iris flattens, ? flow via
pupil, iris forward ?iris-cornea angle 3.
Swelling of Ciliary Body
Modified from Wood et al. NEJM 3391298 (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/te
xtbook/Autonomic/Autonomic.html
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TREATMENT RATIONALE

• LOWER IOP BY
• Decreasing Production of Aqueous Humor
• Increasing Outflow of Aqueous Humor

Focus on Pharmacologic Rx First-line
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DRUGS THAT DECREASE AQUEOUS PRODUCTION

• 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 b1-selective betaxolol), depression
• 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
• 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

• 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
• 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 isnt Ach
  used?
• 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
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.
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Rx GLAUCOMA ADDITIONAL CONSIDERATIONS

• No single medication can be used in all patients
• Compliance
• Critical Rx often requires several agents,
• multiple times a day, everyday
• - Role of slow-release drug delivery devices
  (Langer)
• 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
• 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 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