Chapter 103

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 103Chapter 103

Drugs for the EyeDrugs for the Eye

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 2

GlaucomaGlaucoma

Glaucoma Glaucoma – – visual field loss secondary to visual field loss secondary to optic nerve damageoptic nerve damage

Leading cause of preventable blindness in Leading cause of preventable blindness in the U.S.the U.S.

Of the 4 million Americans with glaucoma, Of the 4 million Americans with glaucoma, only 50% are diagnosedonly 50% are diagnosed

FormsForms Primary open-angle glaucoma (POAG)Primary open-angle glaucoma (POAG) Acute angle-closure glaucomaAcute angle-closure glaucoma


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.


Aqueous HumorAqueous Humor

Produced in ciliary bodyProduced in ciliary body Secreted into the posterior chamber of the Secreted into the posterior chamber of the

eyeeye Circulates around the iris into the anterior Circulates around the iris into the anterior

chamberchamber Exits the anterior chamber via the trabecular Exits the anterior chamber via the trabecular

meshwork and canal of Schlemmmeshwork and canal of Schlemm


Primary Open-Angle GlaucomaPrimary Open-Angle Glaucoma

CharacteristicsCharacteristics Most common form of glaucoma in U.S.Most common form of glaucoma in U.S. Progressive optic nerve damage with eventual Progressive optic nerve damage with eventual

impairment of visionimpairment of vision Devoid of symptoms until significant and Devoid of symptoms until significant and

irreversible optic nerve injury has occurredirreversible optic nerve injury has occurred


Primary Open-Angle GlaucomaPrimary Open-Angle Glaucoma

Risk factorsRisk factors Elevation of intraocular pressure (IOP)Elevation of intraocular pressure (IOP) African-American (3x more than whites)African-American (3x more than whites) Family history of POAGFamily history of POAG Advancing age Advancing age

Goals of treatmentGoals of treatment Directed at reducing elevated IOP (the only Directed at reducing elevated IOP (the only

modifiable risk factor)modifiable risk factor) Principal method Principal method –– chronic therapy with drugs chronic therapy with drugs


Drug Therapy for GlaucomaDrug Therapy for Glaucoma

Drugs lower IOP by either: Drugs lower IOP by either: Facilitating aqueous humor outflowFacilitating aqueous humor outflow Reducing aqueous humor productionReducing aqueous humor production

Preferred route Preferred route –– topical topical Systemic effects relatively uncommonSystemic effects relatively uncommon

Combined therapy more effective than Combined therapy more effective than monotherapymonotherapy

If drugs ineffective, surgical intervention to If drugs ineffective, surgical intervention to promote outflow of aqueous humorpromote outflow of aqueous humor Laser trabeculoplastyLaser trabeculoplasty Trabeculectomy Trabeculectomy


Drug Therapy for GlaucomaDrug Therapy for Glaucoma

First lineFirst line Beta-adrenergic blocking agentsBeta-adrenergic blocking agents

• TimololTimolol AlphaAlpha22-adrenergic agonists-adrenergic agonists

• Brimonidine (Alphagan)Brimonidine (Alphagan) Prostaglandin analogsProstaglandin analogs

• Latanoprost (Xalatan)Latanoprost (Xalatan) Second lineSecond line

Cholinergic agonistsCholinergic agonists Carbonic anhydrase inhibitorsCarbonic anhydrase inhibitors Nonselective adrenergic agonistsNonselective adrenergic agonists


Angle-Closure GlaucomaAngle-Closure Glaucoma

Also known as narrow-angle glaucomaAlso known as narrow-angle glaucoma Precipitated by displacement of the iris that Precipitated by displacement of the iris that

prevents the exit of aqueous humorprevents the exit of aqueous humor Develops suddenly and is extremely painfulDevelops suddenly and is extremely painful No treatment; irreversible loss of vision in 1-2 No treatment; irreversible loss of vision in 1-2

daysdays Much less common than open-angle Much less common than open-angle

glaucomaglaucoma


Angle-Closure GlaucomaAngle-Closure Glaucoma

TreatmentTreatment Drug therapyDrug therapy Corrective surgeryCorrective surgery

• Laser iridotomyLaser iridotomy• IridectomyIridectomy


Beta-Adrenergic Blocking AgentsBeta-Adrenergic Blocking Agents

Betaxolol, levobetaxolol, carteolol, Betaxolol, levobetaxolol, carteolol, levobunolol, metipranolol, and timolol levobunolol, metipranolol, and timolol –– approved for use in glaucomaapproved for use in glaucoma

Lower IOP by decreasing production of Lower IOP by decreasing production of aqueous humoraqueous humor

Used primarily for open-angle glaucomaUsed primarily for open-angle glaucoma Initial therapy and maintenance therapyInitial therapy and maintenance therapy


Beta-Adrenergic Blocking AgentsBeta-Adrenergic Blocking Agents

Adverse effectsAdverse effects Local – usually minimalLocal – usually minimal Systemic – heart and lungs if absorbed in Systemic – heart and lungs if absorbed in

sufficient amounts (bradycardia, bronchospasm)sufficient amounts (bradycardia, bronchospasm) Asthma patients recommended to use Asthma patients recommended to use

cardioselective (betaxolol and levobetaxolol)cardioselective (betaxolol and levobetaxolol)


Prostaglandin AnalogsProstaglandin Analogs

LatanoprostLatanoprost Lowers IOP by facilitating aqueous humor outflowLowers IOP by facilitating aqueous humor outflow As effective as beta-blockers with fewer side As effective as beta-blockers with fewer side

effectseffects Can cause harmless brown pigmentation of the irisCan cause harmless brown pigmentation of the iris


AlphaAlpha22-Adrenergic Agonists-Adrenergic Agonists

Two agents approved for useTwo agents approved for use Apraclonidine – only for short-term therapyApraclonidine – only for short-term therapy Brimonidine (Alphagan) – first-line drug for long-Brimonidine (Alphagan) – first-line drug for long-

term therapyterm therapy Common side effects Common side effects – – dry mouth, local dry mouth, local

burning and stinging, headache, blurred burning and stinging, headache, blurred vision, foreign body sensation, and ocular vision, foreign body sensation, and ocular itchingitching


PilocarpinePilocarpine

Direct-acting cholinergic agonist that causes:Direct-acting cholinergic agonist that causes: MiosisMiosis Contraction of the ciliary muscle Contraction of the ciliary muscle

Now considered a second-line drugNow considered a second-line drug


Cholinesterase Inhibitor Cholinesterase Inhibitor

Echothiophate (Phospholine Iodide)Echothiophate (Phospholine Iodide) Long duration of actionLong duration of action Inhibits the breakdown of ACh, promotes Inhibits the breakdown of ACh, promotes

accumulation of ACh at muscarinic receptorsaccumulation of ACh at muscarinic receptors No longer a first-line drugNo longer a first-line drug Adverse effectsAdverse effects

• Myopia; absorption into the system can cause Myopia; absorption into the system can cause parasympathomimetic responsesparasympathomimetic responses


Carbonic Anhydrase InhibitorCarbonic Anhydrase Inhibitor

Dorzolamide (Trusopt) topicalDorzolamide (Trusopt) topical Decreases IOP by decreasing production of Decreases IOP by decreasing production of

aqueous humoraqueous humor Generally well tolerated (ocular stinging, bitter Generally well tolerated (ocular stinging, bitter

taste, 10%-15% allergic reaction)taste, 10%-15% allergic reaction) Acetazolamide and methazolamide Acetazolamide and methazolamide –– two two

systemic CAIssystemic CAIs Adverse effectsAdverse effects

Nervous system, teratogenic, acid-base Nervous system, teratogenic, acid-base disturbances, electrolyte imbalancesdisturbances, electrolyte imbalances


Cycloplegics and MydriaticsCycloplegics and Mydriatics

Cycloplegics Cycloplegics – – paralyze ciliary musclesparalyze ciliary muscles Mydriatics Mydriatics – – dilate the pupildilate the pupil UsesUses

Adjunct to measurement of refractionAdjunct to measurement of refraction Intraocular examinationIntraocular examination Intraocular surgeryIntraocular surgery Treatment of anterior uveitisTreatment of anterior uveitis


Cycloplegics and MydriaticsCycloplegics and Mydriatics

Adverse effectsAdverse effects Blurred vision and photophobiaBlurred vision and photophobia Precipitation of angle-closure glaucomaPrecipitation of angle-closure glaucoma Anticholinergic effectsAnticholinergic effects

Phenylephrine, an adrenergic agonistPhenylephrine, an adrenergic agonist Mydriatic agent (pupil dilation)Mydriatic agent (pupil dilation)


Allergic ConjunctivitisAllergic Conjunctivitis

Inflammation of the conjunctiva in response Inflammation of the conjunctiva in response to an allergento an allergen

Seasonal or perennialSeasonal or perennial Itching, burning, thin watery dischargeItching, burning, thin watery discharge Results from biphasic immune responseResults from biphasic immune response Symptoms peak 20 minutes after allergen Symptoms peak 20 minutes after allergen

exposure, abate 20 minutes later, reappear exposure, abate 20 minutes later, reappear after 6 hoursafter 6 hours



Allergic ConjunctivitisAllergic Conjunctivitis

Mast cell stabilizersMast cell stabilizers HH11 receptor antagonists receptor antagonists NSAIDsNSAIDs Glucocorticoids (short-term)Glucocorticoids (short-term)


Age-Related Macular Degeneration Age-Related Macular Degeneration (ARMD)(ARMD)

Painless, progressive disease that blurs Painless, progressive disease that blurs central vision and limits perception of fine central vision and limits perception of fine detaildetail

Leading cause of blindness in older Leading cause of blindness in older Americans: about 15 million have the diseaseAmericans: about 15 million have the disease

Dry ARMDDry ARMD Wet (neovascular) ARMDWet (neovascular) ARMD


Age-Related Macular Degeneration Age-Related Macular Degeneration (ARMD)(ARMD)

StagesStages EarlyEarly IntermediateIntermediate AdvancedAdvanced

Management of dry ARMDManagement of dry ARMD Antioxidants and zinc, multiple vitaminsAntioxidants and zinc, multiple vitamins

Management and treatment of wet ARMDManagement and treatment of wet ARMD Laser therapyLaser therapy Photodynamic therapyPhotodynamic therapy Angiogenesis InhibitorsAngiogenesis Inhibitors


Additional Ophthalmic DrugsAdditional Ophthalmic Drugs

Demulcents (artificial tears)Demulcents (artificial tears) Ocular decongestantsOcular decongestants GlucocorticoidsGlucocorticoids DyesDyes Antiviral agentsAntiviral agents

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