1. Chapter 103
Drugs for the Eye 1

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 2

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. 4

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 5

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 6

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 7

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 8

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 9

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 10

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

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 12

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) 13

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 14

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 15

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

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 17

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 18

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 19

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) 20

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 21

22. 22

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

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 24

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 25

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