Chapter 103

1. Chapter 103 Drugs for the Eye

2. Glaucoma • Glaucoma – visual field loss secondary to optic nerve damage • Leading cause of preventable blindness in the U.S. • Of the 4 million Americans with glaucoma, only 50% are diagnosed • Forms • Primary open-angle glaucoma (POAG) • Acute angle-closure glaucoma

3. Fig. 103-1. Anatomy of the normal eye.

4. Fig.103-2. Comparative anatomy of the eye in open-angle and angle-closure glaucoma. A, Note that the angle between the iris and cornea is open in open-angle glaucoma, permitting unimpeded outflow of aqueous humor through the canal of Schlemm and trabecular meshwork. B, Note that the angle between the iris and cornea is constricted in angle-closure glaucoma, thereby blocking outflow of aqueous humor through the canal of Schlemm and trabecular meshwork.

5. Aqueous Humor • Produced in ciliary body • Secreted into the posterior chamber of the eye • Circulates around the iris into the anterior chamber • Exits the anterior chamber via the trabecular meshwork and canal of Schlemm

6. Primary Open-Angle Glaucoma • Characteristics • Most common form of glaucoma in U.S. • Progressive optic nerve damage with eventual impairment of vision • Devoid of symptoms until significant and irreversible optic nerve injury has occurred

7. Primary Open-Angle Glaucoma • Risk factors • Elevation of intraocular pressure (IOP) • African-American (3x more than whites) • Family history of POAG • Advancing age • Goals of treatment • Directed at reducing elevated IOP (the only modifiable risk factor) • Principal method – chronic therapy with drugs

8. Drug Therapy for Glaucoma • Drugs lower IOP by either: • Facilitating aqueous humor outflow • Reducing aqueous humor production • Preferred route – topical • Systemic effects relatively uncommon • Combined therapy more effective than monotherapy • If drugs ineffective, surgical intervention to promote outflow of aqueous humor • Laser trabeculoplasty • Trabeculectomy

9. Drug Therapy for Glaucoma • First line • Beta-adrenergic blocking agents • Timolol • Alpha2-adrenergic agonists • Brimonidine (Alphagan) • Prostaglandin analogs • Latanoprost (Xalatan) • Second line • Cholinergic agonists • Carbonic anhydrase inhibitors • Nonselective adrenergic agonists

10. Angle-Closure Glaucoma • Also known as narrow-angle glaucoma • Precipitated by displacement of the iris that prevents the exit of aqueous humor • Develops suddenly and is extremely painful • No treatment; irreversible loss of vision in 1-2 days • Much less common than open-angle glaucoma

11. Angle-Closure Glaucoma • Treatment • Drug therapy • Corrective surgery • Laser iridotomy • Iridectomy

12. Beta-Adrenergic Blocking Agents • Betaxolol, levobetaxolol, carteolol, levobunolol, metipranolol, and timolol – approved for use in glaucoma • Lower IOP by decreasing production of aqueous humor • Used primarily for open-angle glaucoma • Initial therapy and maintenance therapy

13. Beta-Adrenergic Blocking Agents • Adverse effects • Local – usually minimal • Systemic – heart and lungs if absorbed in sufficient amounts (bradycardia, bronchospasm) • Asthma patients recommended to use cardioselective (betaxolol and levobetaxolol)

14. Prostaglandin Analogs • Latanoprost • Lowers IOP by facilitating aqueous humor outflow • As effective as beta-blockers with fewer side effects • Can cause harmless brown pigmentation of the iris

15. Alpha2-Adrenergic Agonists • Two agents approved for use • Apraclonidine – only for short-term therapy • Brimonidine (Alphagan) – first-line drug for long-term therapy • Common side effects – dry mouth, local burning and stinging, headache, blurred vision, foreign body sensation, and ocular itching

16. Pilocarpine • Direct-acting cholinergic agonist that causes: • Miosis • Contraction of the ciliary muscle • Now considered a second-line drug

17. Cholinesterase Inhibitor • Echothiophate (Phospholine Iodide) • Long duration of action • Inhibits the breakdown of ACh, promotes accumulation of ACh at muscarinic receptors • No longer a first-line drug • Adverse effects • Myopia; absorption into the system can cause parasympathomimetic responses

18. Carbonic Anhydrase Inhibitor • Dorzolamide (Trusopt) topical • Decreases IOP by decreasing production of aqueous humor • Generally well tolerated (ocular stinging, bitter taste, 10%-15% allergic reaction) • Acetazolamide and methazolamide – two systemic CAIs • Adverse effects • Nervous system, teratogenic, acid-base disturbances, electrolyte imbalances

19. Cycloplegics and Mydriatics • Cycloplegics – paralyze ciliary muscles • Mydriatics – dilate the pupil • Uses • Adjunct to measurement of refraction • Intraocular examination • Intraocular surgery • Treatment of anterior uveitis

20. Cycloplegics and Mydriatics • Adverse effects • Blurred vision and photophobia • Precipitation of angle-closure glaucoma • Anticholinergic effects • Phenylephrine, an adrenergic agonist • Mydriatic agent (pupil dilation)

21. Allergic Conjunctivitis • Inflammation of the conjunctiva in response to an allergen • Seasonal or perennial • Itching, burning, thin watery discharge • Results from biphasic immune response • Symptoms peak 20 minutes after allergen exposure, abate 20 minutes later, reappear after 6 hours

23. Allergic Conjunctivitis • Mast cell stabilizers • H1 receptor antagonists • NSAIDs • Glucocorticoids (short-term)

24. Age-Related Macular Degeneration (ARMD) • Painless, progressive disease that blurs central vision and limits perception of fine detail • Leading cause of blindness in older Americans: about 15 million have the disease • Dry ARMD • Wet (neovascular) ARMD

25. Age-Related Macular Degeneration (ARMD) • Stages • Early • Intermediate • Advanced • Management of dry ARMD • Antioxidants and zinc, multiple vitamins • Management and treatment of wet ARMD • Laser therapy • Photodynamic therapy • Angiogenesis Inhibitors

26. Additional Ophthalmic Drugs • Demulcents (artificial tears) • Ocular decongestants • Glucocorticoids • Dyes • Antiviral agents