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Medical Treatment of Glaucoma

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By Dr. Fritz Allen

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Medical Treatment of Glaucoma

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

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