Chapter 103 Drugs for the Eye 1

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 2

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

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. 4

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 5

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 6

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 7

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 8

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 9

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 10

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

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 12

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) 13

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 14

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 15

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

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 17

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 18

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 19

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

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 21

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

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 24

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 25

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