The document discusses various medical treatments for glaucoma, including different drug classes and their mechanisms of action, indications, contraindications and side effects. It provides detailed information on adrenergic agonists, beta-adrenergic antagonists, carbonic anhydrase inhibitors, and combined medications used to treat glaucoma. Key points covered include how the drugs work to lower intraocular pressure, when they should and should not be used, and common adverse effects.

1. Medical Treatment of Glaucoma
Fritz Allen ,MD
Visionary Ophthalmology
September 7th 2014
Medical Management of Glaucoma
 Beta-adrenergic Antagonists (Beta Blockers)
 Parasympathomimetic Agents
 Carbonic Anhydrase Inhibitors (CAI)
 Adrenergic Agonists
 Prostaglandin Analogues
 Combined Medications
 Hyperosmotic Agents
A 64-year-old male with POAG is taking timolol, dorzolamide, brimonidine, and latanoprost OU. He must begin phenelzine, a systemic monoamine oxidase (MAO) inhibitor. Which one of the following should

2. be discontinued?
• Latanoprost
• Brimonidine
• Dorzolamide
• Timolol
Which of the following glaucoma medications is contraindicated for use in children younger than age 2?
• Timolol
• Levobunolol
• Brimonidine
• Dorzolamide
Adrenergic Agonists
 Indications
 Non-selective agonists (epinephrine, dipivefrin)
 Selective adrenergic agonists (apraclonidine, brimonidine)
 IOP lowering
 OAG / ocular hypertension
 Prophylaxis against post-op pressure spikes

3.  Prior to and immediately after laser treatment (trabeculoplasty, laser PI, Nd:YAG capsulotomy)
 Cataract surgery
 Acute ACG
 Miosis after refractive surgery (off-label use)
Adrenergic Agonists
 Contraindications and precautions
 Non-selective
 Narrow AC angles- may precipitate pupillary block
 Blepharoptosis surgery- stimulates Müller’s muscle, inadequate correction
 Retrobulbar anesthesia
 Local – risk of vasospasm & occlusion of ophthalmic or central retinal artery
 Systemic – tachyarrhythmias, death
 Aphakia- CME risk (13-30%)
Adrenergic Agonists
 Selective
 Proven sensitivity to these agents

4.  Concomitant use of monoamine oxidase inhibitors (MAOI)
 Infants and children < 2 years: brimonidine is an absolute contraindication due to apnea, bradycardia, dyspnea
 Pediatric (ages 2-7) usage reports: convulsions, cyanosis, hypoventilation, lethargy; brimonidine is relatively contraindicated
 Precaution in patients with severe cardiovascular disease
 Precaution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension
 Pregnancy: category B drug- use only if potential benefits justify risk
Adrenergic Agonists
 Method of action
 Non-selective-mixed α and ß adrenergic agonist; effect varies over time, initially raising IOP slightly, followed by reduction lasting 12-24 hours
 Selective-alpha adrenergic receptor agonist; reduction of aqueous humor production is

5. primary mechanism of action
 Fluorophotometric studies suggest that Brimonidine tartrate also increases uveoscleral outflow
 Controversial neuroprotective effect: prevent demise of retinal ganglion cells due to trauma or toxins
Adrenergic Agonists
 Complications of therapy
 Non-selective
 Local - conj injection, follicular conjunctivitis, burning, stinging, mydriasis, blurry vision, headache
 Cardiovascular - tachycardia, arrhythmias, hypertension
 Selective
 Local - hyperemia, follicular conjunctivitis, conjunctival blanching
 Systemic - dry mouth, fatigue, anxiety, respiratory depression in neonates
Adrenergic Agonists
 Contraindications and precautions
 Non-selective
 Narrow AC angles- may precipitate

6. pupillary block
 Blepharoptosis surgery- stimulates Müller’s muscle, inadequate correction
 Retrobulbar anesthesia
 Local – risk of vasospasm & occlusion of ophthalmic or central retinal artery
 Systemic – tachyarrhythmias, death
 Aphakia- CME risk (13-30%)
Adrenergic Agonists
 Selective
 Proven sensitivity to these agents
 Concomitant use of monoamine oxidase inhibitors (MAOI)
 Infants and children < 2 years: brimonidine is an absolute contraindication due to apnea, bradycardia, dyspnea
 Pediatric (ages 2-7) usage reports: convulsions, cyanosis, hypoventilation, lethargy; brimonidine is relatively contraindicated
 Precaution in patients with severe cardiovascular disease
 Precaution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic

7. hypotension
 Pregnancy: category B drug- use only if potential benefits justify risk
Adrenergic Agonists
 Method of action
 Non-selective-mixed α and ß adrenergic agonist; effect varies over time, initially raising IOP slightly, followed by reduction lasting 12-24 hours
 Selective-alpha adrenergic receptor agonist; reduction of aqueous humor production is primary mechanism of action
 Fluorophotometric studies suggest that Brimonidine tartrate also increases uveoscleral outflow
 Controversial neuroprotective effect: prevent demise of retinal ganglion cells due to trauma or toxins
Adrenergic Agonists
 Complications of therapy
 Non-selective
 Local - conj injection, follicular conjunctivitis, burning, stinging, mydriasis, blurry vision, headache

8.  Cardiovascular - tachycardia, arrhythmias, hypertension
 Selective
 Local - hyperemia, follicular conjunctivitis, conjunctival blanching
 Systemic - dry mouth, fatigue, anxiety, respiratory depression in neonates
Adrenergic Agonists - Allergy
Adrenergic Agonists - Allergy
Adrenergic Agonists - Allergy
A 64-year-old male with POAG is taking timolol, dorzolamide, brimonidine, and latanoprost OU. He must begin phenelzine, a systemic monoamine oxidase (MAO) inhibitor. Which one of the following should

9. be discontinued?
• Latanoprost
• Brimonidine
• Dorzolamide
• Timolol
Which of the following glaucoma medications is contraindicated for use in children younger than age 2?
• Timolol
• Levobunolol
• Brimonidine
• Dorzolamide
A 52-year-old woman with ocular hypertension is started on a monocular trial with a glaucoma medication. Which glaucoma medication is most likely to produce a decrease in IOP the contralateral (untreated) eye?
• Dorzolamide
• Latanoprost
• Timolol

10. • Brimonidine
Which class of glaucoma medications should be avoided in myasthenia gravis?
• Miotics
• Prostaglandin analogues
• Beta blockers
• Topical CAIs
Beta-adrenergic Antagonists (Beta Blockers)
 Agents
 Non-selective
 Timolol maleate (Timoptic)
 Timolol hemihydrate (Betimol)
 Levobunolol HCL (Betagan)
 Carteolol HCL (Ocupress)
 Metipranolol HCL (Optipranolol)
 Selective
 Betaxolol (Betoptic-S)

11. Beta-adrenergic Antagonists (Beta Blockers)
 Indications
 First line and adjunctive therapy to lower IOP
 All types of glaucoma
 Before or after laser surgery
 After cataract surgery
 Contraindications
 Proven sensitivity to agents
 Reactive airway disease
 Bronchospasm
 COPD
 Greater than first degree heart block
Beta-adrenergic Antagonists (Beta Blockers)
 Relative contraindications

12.  Congestive heart failure
 Bradycardia
 Method of action
 1- and 2- receptors are on the ciliary processes. Receptor blockade reduces aqueous humor production via direct action
 Direct effect on non-pigmented ciliary epithelium to decrease secretion via inhibition of cyclic adenosine monophosphate
 Decreases local capillary perfusion to reduce ultrafiltration
Beta-adrenergic Antagonists (Beta Blockers)
 Administration
 Good corneal penetration
 Peak aqueous concentration within 1-2 hours of topical dose. IOP effect peaks at 2 hours
and lasts at least 24  Short-term escape
 Dramatic reduction in IOP after

13. initial use followed by small pressure rise that plateaus within few days
 May be due to increase in  receptors during first few days
 Wait approximately 1 month to evaluate response
 Long-term drift / tachyphylaxis
 Approximately 3 months after initiating therapy, some patients have a mild decrease in IOP response
 Some will regain responsiveness after a
drug holiday
Beta-adrenergic Antagonists (Beta Blockers)
 Efficacy
 Non-selective 1- and 2- antagonists: 20-30% IOP reduction
 1- selective antagonist: 14-17% IOP

14. reduction
 Decreased efficacy possible when used concomitantly with oral beta-blockers
 Systemic absorption may result in IOP lowering in contralateral eye
Beta-adrenergic Antagonists (Beta Blockers)
 Complications
 Ocular toxicity
 Burning, hyperemia
 Corneal anesthesia, punctate keratopathy, erosions, toxic keratopathy
 Periocular contact dermatitis
 Dry eye
 Cardiovascular
 1 blockade slows pulse and decreases cardiac contractility
 May cause syncope, bradycardia, arrhythmias, heart failure, decreased exercise tolerance
Beta-adrenergic

15. Antagonists (Beta Blockers)
 Respiratory
 2 blockade produces contraction of bronchial smooth muscle
 May cause bronchospasm and airway obstruction, especially in asthmatics
 May cause dyspnea and apneic spells especially in young children
 Central nervous system
 Depression, anxiety, confusion, hallucinations, lightheadedness, drowsiness, fatigue, weakness, disorientation
Beta-adrenergic Antagonists (Beta Blockers)
 Cholesterol levels
 Alterations in plasma lipid profile have been reported with timolol when administered without punctal occlusion
 Decreases plasma high density lipoprotein

16. and possibly increases risk of coronary artery disease
 Other
 Exacerbation of myasthenia gravis
 May mask awareness of hypoglycemia in diabetics
 GI distress
 Dermatologic disorders
 Sexual impotence
Beta-adrenergic Antagonists (Beta Blockers)
 Prevention of complications
 Avoid use of beta-blockers in high-risk patients
 Nasolacrimal occlusion
 Use topical beta-blockers with special properties
 Betaxolol – 1- selective antagonist
 Decreased incidence of respiratory side effects in patients with bronchospastic disease
 Carteolol – intrinsic sympathomimetic

17. activity
 Adrenergic agonist effect that may partially protect against adverse effects of beta-blockade
 Has less adverse affect on plasma lipid profile
Beta-adrenergic Antagonists (Beta Blockers)
 Management of complications
 Discontinue drug
 Consider switch to beta-blocker with special properties if indicated
A 52-year-old woman with ocular hypertension is started on a monocular trial with a glaucoma medication. Which glaucoma medication is most likely to produce a decrease in IOP the contralateral (untreated) eye?
• Dorzolamide

18. • Latanoprost
• Timolol
• Brimonidine
Which class of glaucoma medications should be avoided in myasthenia gravis?
• Miotics
• Prostaglandin analogues
• Beta blockers
• Topical CAIs
Carbonic Anhydrase Inhibitors
 Agents
 Oral
 Acetazolamide 125 mg, 250 500 mg
 Methazolamide 25 mg, 50 mg
 Topical
 Dorzolamide 2%
 Brinzolamide 1%

19. Carbonic Anhydrase Inhibitors
 Indications
 Reduction of chronically elevated IOP in adults and children
 Monotherapy
 Additive therapy
 Prophylaxis of elevated IOP after a surgical intervention
 Reduction of acutely elevated IOP
Carbonic Anhydrase Inhibitors
 Contraindications
 Sulfa allergy
 Kidney stones
 Aplastic anemia
 Thrombocytopenia
 Sickle cell disease
 History of blood dyscrasia
Carbonic Anhydrase

20. Inhibitors
 Method of action
 Block aqueous production by inhibition of carbonic anhydrase
 > 90% must be blocked to decrease aqueous production
 Possible effects on ocular blood flow
Carbonic Anhydrase Inhibitors
 Complications
 Burning and stinging
 Metallic taste
 Cautious use of topical CAI for history sulfa allergy or kidney stones
 Corneal toxicity
 Paresthesias
 Stevens-Johnson syndrome
 Blood dyscrasias (aplastic anemia and sickle cell disease)
 Hypokalemia (after systemic use)
 Conjunctival injection
 Periocular contact dermatitis

21. Carbonic Anhydrase Inhibitors
Carbonic Anhydrase Inhibitors
Carbonic Anhydrase Inhibitors
Carbonic Anhydrase Inhibitors
 Prevention of complications
 Monitor blood potassium, especially with systemic CAIs
 Consider pre-treatment blood counts, especially with systemic CAIs
 Avoid CAIs for diseased corneas with marginal endothelium
 No CAIs for history of sulfa allergy, blood

22. dyscrasia or kidney stones
Carbonic Anhydrase Inhibitors
 Management of complications
 Stop the medication
 Topical toxicity
 Change topical therapy
 Consider brinzolamide instead of dorzolamide
 Oral CAIs
 Systemic toxicity
 Decrease the dose of oral medication
 Change to topical therapy
 Change from acetazolamide to methazolamide
 Medical consult for serious side effects
 Switch to acetazolamide sequels
Combined Medications
 Agents
 Dorzolamide HCL/Timolol maleate
 Brinzolamide/Brimonidine
 Brimonidine/Timolol
 Latanoprost/Brimonodine/Timolol (outside

23. the US)
 Indications
 Reduction of elevated IOP in patients with OAG or ocular hypertension who are insufficiently responsive to beta-blockers
 Patients who have difficulty taking multiple medications
Combined Medications
 Method of action
 Dorzolamide hydrochloride
 Inhibitor of human carbonic anhydrase II, which decreases aqueous humor secretion
 Timolol maleate
 Nonselective beta-blocker which decreases aqueous humor secretion
Combined Medications
 Complications
 Most frequently reported ocular adverse events
 Taste perversion, ocular burning/stinging, conjunctival hyperemia, blurred vision, superficial punctate keratitis, pruritis
 Most frequently reported systemic adverse

24. events
 Worsening of restrictive airway disease, fatigue, arrhythmia, syncope, heart block, palpitation, insomnia, impotence, memory loss, confusion
 Prevention of complications
 Discussion of potential side effects with patient
 Nasolacrimal occlusion
 Emphasis on correct dosing
Combined Medications
Glycerin is a hyperosmotic agent that should be avoided in patients with which systemic disease?
• Hypertension
• Diabetes mellitus
• Hyperthyroidism
• Anemia
Hyperosmotic Agents
 Dosing technique
 Oral agents

25.  Glycerin (Osmoglyn)
 50% solution
 4-7 oz.
 Give solution cold for improved tolerability
 Isosorbide (Ismotic) currently unavailable (1/2 - full 250 ml over ice)
 Intravenous agents
 Mannitol (Osmitrol)
 5-25% solution
 2 g/kg body weight (intravenously)
Hyperosmotic Agents
 Indications
 Short-term or emergency treatment of elevated IOP
 Useful in acute conditions of elevated IOP (e.g. ACG)
 Effective when elevated IOP renders iris non-reactive to agents which combat pupillary block such as the miotics (e.g., pilocarpine)
 Used to lower IOP and/or reduce vitreous volume prior to initiation of surgical procedures

26. Hyperosmotic Agents
 Contraindications
 Should not be used for long-term therapy (becomes ineffective with repeated dosing)
 Some agents increase blood sugar levels (may be contraindicated in patients with diabetes)
 Long-term use may perturb electrolytes
 Of limited value when blood-ocular barrier is disrupted
 May cause rebound elevation in IOP if agent penetrates eye and reverses osmotic gradient
Hyperosmotic Agents
 Pre-therapy evaluation
 Accurate measurement of IOP
 Slit-lamp biomicroscopic exam: pupil/iris evaluation for ischemic and non-reactive iris sphincter muscle
 Shallowing of AC pre-therapy (e.g., ACG) with subsequent deepening of chamber after therapy (from dehydration of vitreous)

27.  Gonioscopy to evaluate for signs of refractory glaucoma necessitating short-term hyperosmotic therapy prior to surgery (e.g., traumatic glaucoma, neovascular glaucoma)
Hyperosmotic Agents
 Alternatives
 Aqueous suppressants (i.e., beta-blockers, topical and/or oral CAIs, alpha-agonists)
 Outflow enhancers (i.e., prostaglandin analogues, miotic agents, epinephrine-like agents)
 Laser surgery procedures to correct acute glaucoma (e.g., iridotomy and/or iridoplasty for acute ACG)
 Paracentesis
 Glaucoma surgical procedure (e.g., trabeculectomy, tube shunts, etc.)
Hyperosmotic Agents
 Method of action
 When given systemically, lowers IOP by increasing blood osmolality (creates osmotic gradient between blood and

28. vitreous humor)
 The larger the dose and more rapid administration, the greater reduction in IOP (because of increased gradient)
 Limited effectiveness and duration of action when blood-aqueous barrier is disrupted (osmotic agent enters the eye)
Hyperosmotic Agents
 Complications
 Headache
 Backache
 Nausea and vomiting (oral agents)
 Urination frequency and retention
 Cardiac (chest pain, pulmonary edema, congestive heart failure)
 Renal impairment
 Neurologic status (lethargy, seizures, obtundation)
 Subdural hemorrhage
 Hypersensitivity reactions
 Hyperkalemia or ketoacidosis (when glycerin given to patients with diabetes)
Hyperosmotic Agents

29.  Prevention of complications
 Consider alternative therapies
 Use cautiously in patients with known compromised cardiac, hepatic, or renal status
 Avoid use of glycerin in diabetics
 Closely observe for complications
 Management of complications
 Discontinue medication
 Symptomatic relief of side effects until resolution if applicable
 Consider urinary catheter (if intravenous mannitol is given preoperatively)
Hyperosmotic Agents
 Follow-up care
 Closely monitor IOP (to determine efficacy of hyperosmotic agents)
 Discontinue therapy as soon possible
 Closely monitor ocular and systemic symptoms and exam
 Patient instructions
 Alert physician of any complications
 Substitute IOP-lowering agents when hyperosmotic agents no longer needed

30. Glycerin is a hyperosmotic agent that should be avoided in patients with which systemic disease?
• Hypertension
• Diabetes mellitus
• Hyperthyroidism
• Anemia
What is the mechanism of action for pilocarpine in reducing IOP?
• Contraction of the ciliary muscle resulting in increased outflow of aqueous through the trabecular meshwork
• Contraction of the ciliary muscle resulting in a reduced rate of aqueous production
• Inhibition of the enzyme acetylcholinesterase with prolonged and enhanced action of naturally secreted acetylcholine

31. • Inhibition of carbonic anhydrase causing a decreased rate of aqueous production
Echothiophate iodide (Phospholine iodide) is an example of which type of glaucoma medication?
• Direct-acting parasympathomimetic agent
• Indirect-acting parasympathomimetic agent
• Beta blocker
• CAI
Indirect parasympathomimetics initiate their effect by:
• Binding directly to muscarinic receptors
• Suppressing acetylcholine release from nerve terminals
• Suppressing enzymes that inactivate acetylcholine
• Increasing the sensitivity of post-synaptic nerve terminals to acetylcholine
Parasympathomimetic

32. Agents
 Agents
 Carbachol
 Pilocarpine HCL
 Echothiopate iodide
 Indications
 Increased IOP in patients with at least some open filtering angle
 Prophylaxis for ACG prior to iridotomy
Parasympathomimetic Agents
 Contraindications
 Patients with no trabecular outflow
 Patients with peripheral retinal disease that predisposes them to retinal detachment
 Uveitic glaucoma
 Acute infectious conjunctivitis
 Proven sensitivity to these agents
 Significant lens changes with chronic use (relative contraindication)

33. Parasympathomimetic Agents
 Method of action
 Reduces IOP by causing contraction of the ciliary muscle, which pulls the scleral spur to tighten TM, increasing the outflow of aqueous humor
 Direct-acting agents affect the motor end plates in the same way as acetylcholine, which is transmitted at postganglionic parasympathetic junctions, as well at other autonomic, somatic, and central synapses
 Indirect-acting agents inhibit the enzyme acetylcholinesterase, thereby prolonging and enhancing the action of naturally secreted acetylcholine
Parasympathomimetic Agents
 Complications
 Ocular
 More frequent

34.  Induced myopia
 Brow ache
 Conjunctival and intraocular vascular congestion
 Cataracts
 Paradoxical angle closure (by inducing greater lenticular-pupillary block)
 Posterior synechiae
 Corneal toxicity
 Periocular contact dermatitis
Parasympathomimetic Agents
Parasympathomimetic Agents
 Less frequent
 Iris pigment epithelial cysts (cholinesterase inhibitors)
 Lacrimal stenosis
 Pseudopemphigoid
 Fibrinous iritis (especially in post op

35. period)
 Retinal detachment
 Complications may be minimized by titrating initial dosage and starting at lower concentrations in those with blue eyes and higher concentrations in those with darker eyes
 Compliance probably more problematic than with other agents
Parasympathomimetic Agents
What is the mechanism of action for pilocarpine in reducing IOP?
• Contraction of the ciliary muscle resulting in increased outflow of aqueous through the trabecular meshwork
• Contraction of the ciliary muscle resulting in a reduced rate of aqueous

36. production
• Inhibition of the enzyme acetylcholinesterase with prolonged and enhanced action of naturally secreted acetylcholine
• Inhibition of carbonic anhydrase causing a decreased rate of aqueous production
Echothiophate iodide (Phospholine iodide) is an example of which type of glaucoma medication?
• Direct-acting parasympathomimetic agent
• Indirect-acting parasympathomimetic agent
• Beta blocker
• CAI
Indirect parasympathomimetics initiate their effect by:
• Binding directly to muscarinic receptors
• Suppressing acetylcholine release from nerve terminals
• Suppressing enzymes that inactivate

37. acetylcholine
• Increasing the sensitivity of post-synaptic nerve terminals to acetylcholine
Prostaglandin Analogues
 Contraindications
 Uveitis/iritis (controversial)
 Macular edema
 Relative contraindications
 Aphakia or pseudophakia with open posterior capsule, especially after complicated surgery
 Recent intraocular surgery
 History of herpetic keratitis
 Previous CME (multiple previous surgeries/trauma)
Prostaglandin Analogues
 Method of action
 Latanoprost, travoprost, bimatoprost and

38. Rescula increase uveoscleral and TM outflow
 Maximal IOP reduction by 12 hours, but maximal effect may take 3-4 weeks
Prostaglandin Analogues
 Complications
 Darkening of iris and periocular skin
 Secondary to increased numbers of melanosomes within melanocytes
 Risk of iris pigmentation greatest in light brown, blue-green, or two-toned irides; least in blue irides
 CME
 Uveitis suspected
 Exacerbations of underlying herpes keratitis (pseudodendrites)
Prostaglandin Analogues
Prostaglandin

39. Analogues
Exotic Drug
 Canasol (extract from Cannabis Sativa)
Thank you