Medical Management of Glaucoma

Medical Management
- When to Treat
- How to Treat
- Medical Agents
- General Principles

When to Treat
- As soon as the diagnosis is made
  - Primary Angle-Closure
  - Infantile Glaucoma
- Open-Angle Glaucoma
  - Damage to the Optic Nerve has been demonstrated
  - Progressive pathologic cupping
  - Characteristic visual field defects
  - When IOP is elevated to an extent that it is likely to cause damage to the optic nerve
  - Glaucoma Suspect
  - High risk of damage to the optic nerve
- Secondary Glaucoma
  - Treated like the primary glaucoma it most resembles

Goal of Therapy

Preserve visual function by lowering IOP below a level that is likely to produce further damage to the nerve
Treatment regimen with lowest risk, fewest side effects, and least disruption of the patient’s life
Initial reduction of IOP by 20-30%
Progressive normal-tension glaucoma may require >30% reduction
Therapy adjusted according to response
Benefits justify the risks

Medical Agents

Beta-adrenergic antagonists (nonselective and selective)
Parasympathomimetic agents
Carbonic anhydrase inhibitors
Adrenergic agonists (nonselective and selective alpha2 agonists)
Prostaglandin analogues
Combination medications
Hyperosmotic agents

Beta-Adrenergic Antagonists

Inhibit cAMP production in ciliary epithelium
Reduces aqueous humor secretion 20-50%
Corresponding IOP reduction of 20-30%
Effect within 1 hour of instillation
Present up to 4 weeks after discontinuation
Additive in combination with miotics, adrenergic agonists, CAIs, and prostaglandin analogues
10-20% of patients treated with topical beta blockers fail to respond
If patient is on a systemic beta blocker, topical therapy will be less effective
Six approved topical beta-blockers
- Betaxolol
- Carteolol
- Levobunolol
- Metipranolol
- Timolol Maleate
- Timolol Hemihydrate
Betaxolol is the only selective beta1 antagonist
- Useful in patients with broncospastic disorders
- Less IOP lowering effect than other beta-blockers
Carteolol demonstrates intrinsic sympathomimetic activity
- Beta-blocking effects tempered by receptor activation
- Less likely to adversely effect the systemic lipid profile
Side Effects
- Bronchospasm, Bradycardia, Increased heart block, Lowered blood pressure, Reduced exercise tolerance, CNS depression
- Masks hypoglycemic signs and symptoms
- Myasthenia gravis may be aggravated by these drugs

Parasympathomimetic Agents

Direct-Acting Cholinergic Agonists
- Affect motor endplates the same way as acetylcholine
- Pilocarpine
- Carbachol (both direct and indirect, primarily direct)
Indirect-Acting Anticholinesterase Agents
- Inhibit the enzyme acetylcholinesterase
- Echothiophate iodide
- Demecarium bromide
Mechanism of Action
- Cause contraction of the ciliary muscle which pulls the scleral spur to tighten the trabecular meshwork, increasing the outflow of aqueous humor
- Reduce IOP by 10-20%
- Also causes pupillary sphincter contraction, stimulate secretory activity in the lacrimal and salivary glands, and disrupt the blood-aqueous barrier
Indications
- Chronic treatment of increased IOP in patients with at least some filtering angle
- Prophylaxis for angle-closure glaucoma prior to iridectomy
Side Effects
- Associated with retinal detachment (use of stronger agents)
- Induced myopia due to ciliary muscle contraction
- Paradoxical angle closure (pupil block)
- Cataractogenic (indirect > direct)
- Epiphora (direct lacrimal stimulation and punctal stenosis)
- Increased inflammation after surgery
- Indirect agents induce systemic side effects: Diarrhea, abdominal cramps, increased salivation, bronchospasm, enuresis
Sustained-release pilocarpine membranes and gel minimize the pharmacologic side effects
- Polymer “sandwich” containing absorbed pilocarpine (Ocusert) release medication for 1 week
- Ocusert 20 comparable to Pilocarpine 1% (40 = 2%)
- Pilocarpine gel lasts 24 hours

Carbonic Anhydrase Inhibitors
- Decrease aqueous humor formation by direct antagonist activity upon ciliary epithelial carbonic anhydrase
- Over 90% of the ciliary epithelial enzyme activity must be abolished to decrease aqueous production and lower IOP
- Derived from sulfa
- Oral agents (Acetazolamide and Methazolamide) reserved for acute episodes
  - Side effects usually dose related
  - Paresthesias of the fingers or toes, lassitude, loss of energy, anorexia
- Topical agents (Dorzolamide and Brinzolamide)
  - Fewer systemic side effects
  - Reduce IOP by 14-17%
  - Side effects include bitter taste, blurred vision, puntate keratopathy
Adrenergic Agonists
- Increase conventional trabecular and uveoscleral outflow
- Epinephrine
  - Initially increases IOP, decreases over time
  - Less hypotensive effect in eyes with dark irides
  - Onset at 1 hour, maximal at 2-6 hours
  - 15-30% decrease in IOP
  - Tolerance common with long-term use
- Dipivefrin
  - Pro-drug chemically transformed into epinephrine by esterase enzymes in the cornea
  - Greater corneal penetration than epinephrine salts
- Side Effects
  - Headache, increased BP, tachycardia, arrhythmia, nervousness
  - Deposits in conjunctiva, cornea, lacrimal system
  - Stains contact lenses
  - Allergic blepharoconjunctivitis in 20% over time
- Alpha2-Adrenergic Agonists
  - Alpha1 effects include vasoconstriction, pupillary dilation, eyelid retraction
  - Alpha2 effects are primarily IOP reduction and possible neuroprotection
  - Aproclonidine
    - Prevents release of norepinephrine
    - Decreases aqueous production and episcleral venous pressure
    - Improves trabecular outflow
    - Short-term use only (topical sensitivity)
  - Brimonidine (more selective)
    - Less allergenicity
    - 26% IOP reduction 2 hours post-administration
    - 14-15% IOP reduction at trough (12 hours post-dose)
    - Caution when used with MAOIs or tricyclic antidepressents in patients with severe cardiac disease
Prostaglandin Analogues
- Lantanoprost (Xalatan) and Unoprosterone (Rescula)
- Analogues of PGF2alpha
- Lantanoprost
  - Pro-drug penetrates the cornea and is hydrolyzed by corneal esterase
  - Lowers IOP by enhancing uveoscleral outflow
  - Reduces IOP 6-9mmHg (25-35%)
  - Once-daily dosing
  - Side Effects
    - Darkening of the iris and periocular skin (increased numbers of melanosomes)
    - Blue irides experience 10-20% increase in pigmentation during initial 18-24 months
    - Hypertrichosis, CME, uveitis, herpetic keratitis
Combined Medications
- Benefits: improved efficacy, convenience, compliance, reduced cost
- FDA guideline that the combination be more efficacious than either agent given alone
- Epinephrine and Pilocarpine: Weakly additive
- Timolol and Dorzolamide: Similar efficacy
- Convenience, lessened confusion, greater compliance
- Greater exposure to beta-blocker side effects
Hyperosmotic Agents
- Control acute episodes of elevated IOP
- Oral glycerin and isosorbide; IV mannitol
- Usually only given for a few hours
- Headache, mental confusion, backache, acute congestive heart failure, MI
- Glycerin can produce hyperglycemia in diabetics
General Approach
- Open-Angle Glaucoma
  - Establish target IOP
  - Start only one agent unless IOP is very high
  - Start in only one eye to determine efficacy of treatment
  - Eyedrops separated by 5 minutes
  - Must inquire about systemic side effects, as patients rarely associate these with topical medications.
  - Careful monitoring
- Angle-Closure Glaucoma
  - Medical therapy aimed at preparing the eye for laser iridectomy
  - Goals
    - Reduce IOP rapidly to prevent further damage to optic nerve
    - Clear the cornea
    - Reduce intraocular inflammation
    - Allow pupillary constriction
    - Prevent formation of posterior and peripheral anterior synechiae