Download Glaucoma Handout 2016

Glaucoma
Mikael Jones, Pharm.D., BCPS
PHR 946 Spring 2016
Lecture Objectives
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Evaluate a patient for risk factors of glaucoma
Explain the differences between the various type of glaucoma
Recognize the signs and symptoms of glaucoma
Choose the most rationale therapy in a patient with glaucoma
Counsel a patient on the use of eye drops and tools to improve compliance
Counsel a patient on common and serious adverse effects of glaucoma medications
Review of Eye Anatomy and Physiology:
Overview:
 Glaucoma refers to a spectrum of ophthalmic disorders characterized by
o Neuropathy of the Optic Nerve
o Loss of retinal ganglion cells
o Permanent deterioration of vision
 The spectrum can be divided into Primary and Secondary glaucomas and by whether the
angles are open or closed
 Types of Glaucoma
o Ocular Hypertension
 elevated IOP without glaucomatous changes
o Primary Open-Angle Glaucoma Suspects
 normal appearing anterior chamber angles
 eye exam suspicious of early glaucomatous damage
o Primary Open-angle Glaucoma (POAG)
 Normal anterior chamber angles
 Glaucomatous changes of the optic disc
 Peripheral visual field loss
o Primary Angle-Closure Glaucoma (PACG)
 obstruction of the anterior angle by the iris
 moderate to high elevations in IOP
POAG
Vision loss occurs over years
Risk Factors:
 Elevated IOP
 African or Hispanic descent
 Family History of Glaucoma
 Older Age
 Thinner Central Corneal Thickness
Symptoms:
 Slow, insidious vision loss
o Years for noticable
 Peripheral vision most susceptible
 Scotoma
Exam Findings:
 Optic disc changes
o “Cupping” (cup to disk ratio
>0.5)
o Splinter hemorrhages
o Notching
 Elevated IOP (but not always)
o 21-30 mmHg
o Normal Tensions Glaucoma
PACG
Acute PACG is a Medical Emergency: Vision
loss in hours to days
Risk Factors:
 Hyperopia
 Family history
 Age (>30)
 Gender
 Asian/Eskimo ethnicity
Symptoms:
 Blurred vision/ hazy vision
 Ocular pain or discomfort
 N/V
 Abdominal Pain
 Can progress to same visual findings as
POAG
Exam findings:
 Edematous cornea
 Closed angles
 Optic disc changes
 Very Elevated IOP
o 40-50 mmHg and higher
Diagnostic/Monitoring Parameters:
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Diagnostics
o Gonioscopy-Examination of the anterior chamber angle. A gonioprism or
Goldman lens are used to perform gonioscopic evaluation.
o Perimetry-Measurement of the field of vision
o Tonomtery- Tonometry is a method by which the cornea is indented or
flattened by an instrument. The pressure required to achieve corneal
indentation or flattening is a measure of IOP
o Slit lamp biomicroscope- An instrument that allows for the microscopic
examination of the cornea, anterior chamber lens and posterior chamber
Intraocular Pressure
o Balance between aqueous humor production and outflow
o Refractive properties of the eye depend on IOP to maintain the curvature of
the cornea
o 10-21 mmHg
 Use caution with the normal range
 Elevated IOP 21 mmHg.
o Diurnal variation
o Central Corneal Thickness
 <555 m increases risk of glaucoma
Screening:
 Frequency of exams should be determined by severity/number of risk factors
 Exam includes:
o Tonometry
 Measure IOP
 Does not test for glaucomatous changes
o Dilated eye exam
Age
(years)
With Risk Factors for
Glaucoma
No Known Risk
Factors
≥65
6-12 months
1-2 years
55-64
1-2 years
1-3 years
40-54
1-3 years
2-4 years
Under 40
2-4 years
5-10 years
POAG Goals of Therapy:
 Prevent further loss of visual function
 Minimize adverse effects of therapy and its impact on the patient’s vision, general
health, and quality of life
 Maintain IOP at or below a pressure which further optic nerve damage is unlikely to
occur
 Educate and involve the patient in the management of their disease
Treatment Principles:
 Early treatment may slow progression
 The ideal therapeutic regimen
o maximal effectiveness
o maximal safety
o patient tolerance
 Decision of when and how to treat patients is difficult since
o treatment modalities
o expensive
o potential adverse effects or complications
 Treatment Modalities
o Medical
o Surgical
o Laser
o Combination
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Setting Target IOP
o Target IOP is range that slows progression of optic neuropathy
o Initial Target estimate
 20% baseline IOP
 30-50% for
 Severe disease
 Normal Tension Glaucoma
Pharmacotherapy (See Algorithm in textbook)
o Start with well tolerated agents
 Prostaglandin Analogs (can reduce IOP the most)
 Beta-Blockers (some prefer because of lower cost)
 Brimonidine
o If partial/failed response to monotherapy at 8 week
 Consider combination therapy or switching agents
 Increasing the concentration or dose frequency can also be tried (not
possible with many agents)
o If continued inadequate response to combination therapy
 Consider adding cholinergic agents or carbonic anhydrase inhibitors
 Or non-pharmacologic treatment modality
o Therapy must be adjusted when patient
 Fails to reach their target IOP
 At target IOP but have disease progression
 Needs further work-up
 Establish lower goal
 Patient intolerant, non-adherent, develops contraindications to therapy
o Adherence to Therapy
 Non-adherence among patients on topical medical therapy ranges from
5% to 80%
 Suspect non-adherence in patients that have
 visual field and optic nerve progression despite a low IOP
measurement
 Pharmacy refill histories may be useful in assessing adherence but
do not confirm that the patient is actually taking the regimen as
prescribed
 Techniques to improve adherence
 adherence aids
 prescribing the least complex regimen
 educating patients about their glaucoma
 Integrate drops into patient’s life
Instilling Topical Ocular Solutions and Suspensions
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Wash hands
Tilt head backward
Gently pull down the outer portion of
lower eyelid to form a “pocket”
Grasp the dropper bottle between thumb
and fingers. Brace hand against the cheek
Place the dropper over the eye by looking
directly at it
Just before applying drop look upward
Close lids without pressure for 1-3 minutes
Minimize blinking and squeezing of eyelid
Separate additional instillation of drugs by
at least 5 minutes
Suspensions and ointments are instilled
last
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Nasolacrimal Occlusion
o NLO improves ocular
bioavailability
o May reduce side effects
o May allow less frequent dose
intervals
o With closed eyes place fingers
over puncta for 1 to 3 minutes
Evaluation of therapy:
Typical ophthalmologist evaluation
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Patients will have these test performed at
every visit:
 IOP measurement
 Visual acuity assessment
 Slit-lamp biomicroscopy
Visual Fields and Optic Nerve Evaluations are
performed based on
o IOP is controlled
o the length of time IOP has been
controlled
o progression of the disease
 Frequency increase with uncontrolled
IOP or progression of disease
Evaluate every 2-4 week after initiation or
alteration of therapy
 Ocular health
 Systemic Medical hx
 Medication Hx (including presence of
ADRs and adherence)
Pharmacist Evaluation
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Evaluate Patient Adherence at
each refill
Evaluate administration Technique
Evaluate for adverse effects
(systemic and local)
Evaluate for any drug interactions
Counsel on importance of
medications
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Non-pharmacologic Therapies
Laser Surgery
 Trabeculoplasty
o laser energy aimed at the
trabecular meshwork to
improve the outflow of
aqueous humor
o Possible first-line therapy
 Least as effective as
timolol
 unable or unwilling
to adhere to
medical therapy
o Bridge therapy between
medical and surgical
intervention
o Approximately 50% of laser
trabeculoplasty procedures
will fail at 10 years.
Surgery
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Trabeculectomy
o Removal of a portion of the
trabecular meshwork to improve
aqueous humor outflow
o Failure rates of trabeculectomy are
less compared to laser
trabeculoplasty
o Fibrosis occludes surgical channel
 Mitomycin C and
fluorouracil are used as
antifibrotic agents to
decrease scarring
Special Therapeutic Considerations:
 Primary Open-Angle Glaucoma Suspects & Ocular Hypertension
o Consider therapy
o Choose well tolerated agents
o Follow POAG algorithm
o Ocular Hypertension Treatment Study
o Target patients at most risk for Glaucoma
o Consider drug burden and costs
o Consider patient factors
o Risk vs. Benefit
 Normal Tension Glaucoma
o Set Target IOP lower (30-50%)
Acute PACG:
Acute PACG Goals of Therapy:
 Preserve visual function by controlling the elevation in IOP
 Manage an acute attack of angle closure
 Reverse or prevent angle closure using a laser and/or surgical intervention
 Educate and involve the patient in the management of the disease.
Treatment Principles:
 Treatment of choice is laser iridotomy
 Medical Therapy is used to
o Lower IOP
o Reduce Pain
o Reverse corneal edema
 Therapy sequencing
o topical -blockers, topical -agonist, prostaglandin F2 analog, systemic carbonic
anhydrase inhibitors, or hyperosmotic agents can be used to initially lower IOP
o Once IOP controlled, pilocarpine (or other miotic) can be used to break the
pupillary block
o Continue therapy to maintain lower IOP until surgery
 Endpoints of initial treatment
o Reduction of IOP
o Pupillary constriction
o Deepening of the anterior chamber
o All patients should have laser iridotomy or surgical iridectomy
Drug Induced Glaucoma:
Open Angle
Drug
Mechanism
Closed Angle
Drug
Mechanism
Docetaxel/Paclitaxel
Unknown
Adrenergic agents
(epinephrine,
albuterol)
Induce papillary dilation which can cause
angle closure in those at risk
Corticosteroids
 resistance to
aqueous outflow
secondary to steroid
induced structural/
functional changes in
outflow pathway
Anticholinergics
(Atropine,
Ipratropium and
drugs with
anticholinergic
properties)
Sulfa-based Drugs
Induce papillary dilation which can cause
angle closure in those at risk
Ciliary body edema causes relaxation of
the zonules leading to anterior
displacement of the lens and iris. This
shallows the angle
Glaucoma Medications:
Prostaglandin Analogs: Bimatoprost 0.03% (Lumigan); Latanoprost 0.005% (Xalatan); Travaprost 0.004%
(Travatan, Travatan Z) tafluprost 0.0015% (Zioptan)
Mechanism of Action: Latanoprost , travoprost,
tafluprost are agonists of the prostanoid FP receptor.
Bimatoprost is a prostamide analog and appears to
lower IOP by activating prostamide . These agents
increase uveoscleral outflow
IOP Lowering: 25-35%
ADRs: (Frequent) burning, stinging, conjunctival
hyperemia, foreign-body sensation, blurred vision.
Increased pigmentation of the iris in patients with
green-brown, yellow-brown, and blue/gray-brown
eyes that occurs from months to years in about 5-15%
of patients. The darkening is irreversible. Reversible
darkening of the eyelids and increase in eyelashes and
eyelash length after use can occur.
Precautions: Patients with diabetic retinopathy or
complicated ocular surgery have a greater risk of
developing cystoid macular edema, anterior uveitis, or
vitreous hemorrhage.
Administration: One drop daily QHS. For all ocular
prostaglandin analogs once daily administration is
more effective than bid and evening administration is
more effective than morning administration.
Pearls:
 Prostaglandins have the greatest 24-hour IOP
reduction compared to timolol, dorzolamide,
and brimonidine
 An eye drop applicator (Xal-Ease®) is available
to patients through the manufactuer.
 Travoprost is available in two formulations.
Travatan® uses benzalkonium chloride as a
preservative while Travatan Z® uses a
proprietary ionic buffer system (SofZia®).
 Travoprost has a dosing aid with a
programmable reminder is available through
the manufactuer. Dosing aid tracks
medication use and can be downloaded by
practitioner.
Contraindications: Hypersensitivity
ADRs: (Rare) Diplopia occasionally occurs; retinal artery
embolus, retinal detachment, and vitreous hemorrhage
occur rarely.
Special Instructions:
 Latanoprost: Protect from light, Store unopened
bottles in refrigerator. Once opened it may be
store at room temperature for 6 weeks.
 Tafluprost is packaged in single-use containers
β-ADRENERGIC Antagonists: (Betaxolol) Ophth Soln 0.5%; Ophth Susp 0.25%. (Carteolol) Ophth Soln 1%.
(Levobunolol) Ophth Soln 0.25, 0.5%. (Metipranolol) Ophth Soln 0.3%. (Timolol) Ophth Gel-Forming Soln 0.25, 0.5%;
Ophth Soln 0.25, 0.5%.
Mechanism of Action: β-Adrenergic blocking drugs down
Precautions: Diabetes mellitus; cerebrovascular
regulate adenylate cyclase by blocking β2-adrenergic
insufficiency; myasthenia gravis.
receptors in the ciliary body, resulting in a decrease in
aqueous production and intraocular pressure. Although
betaxolol is a β1-selective adrenergic blocker, it is effective
in treating glaucoma.
IOP Lowering: 20-25%
ADRs: Frequent, but mild, ocular adverse effects include
ADRs: Occasional, but serious, granulomatous anterior
burning and stinging at instillation. Betaxolol ophthalmic
uveitis is caused by metipranolol. Occasional, but
suspension and timolol gel-forming solution frequently
serious, systemic reactions include bronchospasm,
cause temporary blurred vision.
bradycardia, CHF, heart block, cerebral vascular
ischemia, mask symptoms of hypoglycemia and
depression.
Administration: 1 drop BID; Timolol gel forming soln 1
Contraindications: Sinus bradycardia; greater than firstdrop/day of 0.25% soln initially; if target IOP is not reached degree AV block; cardiogenic shock; overt cardiac
in 4 weeks, increase to 0.5%.
failure. Nonselective drugs are also contraindicated in
patients with histories of bronchial asthma or severe
COPD.
Pearls: Timolol reduces the mean 24-hour IOP reduction by Special Instructions: Timolol gel forming solution needs
19% and is similar to dorzolamide
to be inverted and shake once before use.
NLO can reduce risk of systemic effects
α2-ADRENERGIC AGONISTS (Apraclonidine) Ophth Soln 0.5, 1%. (Brimonidine) Ophth Soln 0.15, 0.2%.
Mechanism of Action: Apraclonidine and brimonidine act
Precautions: Severe cardiovascular disease,
at α2-adrenergic sites in the ciliary body to inhibit
cerebrovascular disease, chronic renal failure, Raynaud’s
norepinephrine release, causing a decrease in aqueous
diease; children
humor production. Brimonidine also increases uveoscleral
outflow and may have neuroprotective properties.
IOP Lowering: 18-27%
ADRs: Local Conjunctival blanching, Eyelid retraction,
ADRs: Systemic: Brimonidine does not decrease heart
Mydriasis (apraclonidine only),Dry eyes
rate. It can mildly decrease blood pressure in some
patients, although it frequently causes lethargy; dry
mouth, dry nose
Administration: Apraclonidine: 1-2 drop of 0.5% soln tid.
Brimonidine: 1 drop of 0.2% soln tid, about 8 hr apart.
Contraindications: Hypersensitivity; Pt on MAO
inhibitors
Pearls: Brimonidine 0.15% preserved with an oxychloro
complex (Alphagan P) is equivalent to the 0.2% solution
preserved with benzalkonium chloride (Alphagan). Generic
Brimonidine 0.15% is preserved with polyquaternium-1.
Pearls:Brimonidine bid is equivalent to timolol 0.5% in
lowering peak IOP at peakbut much less effective in
lowering trough. Brimonidine bid is less effective in
decreasing IOP over 24 hours compared to
prostaglandin analogs, timolol, and dorzolamide.
CARBONIC ANHYDRASE INHIBITORS: Acetazolamide Tab 125, 250 mg; SR Cap 500 mg; Inj 500 mg. Brinzolamide
Ophth Susp 1%. Dorzolamide Ophth Soln 2%. Methazolamide Tab 25, 50 mg.
Mechanism of Action: CAIs inhibit the carbonic anhydrase
Precautions: Neither topical nor oral CAIs are
II isoenzyme in the ciliary epithelium, thereby blocking the recommended in patients with severe renal impairment.
formation of bicarbonate. This causes a decrease in sodium Caution in patients with hepatic impairment. Acidosis
and water outflow from the ciliary body. More than 99% of can cause sickling of RBC in patients with sickle cell
carbonic anhydrase must be inhibited to be effective.
anemia.
IOP Lowering: 15-25%
Topical Solution ADRs:
Oral/ IV prep ADRs: frequently cause paresthesias, GI
Topical ophthalmic solutions frequently cause ocular
disturbances, anorexia, drowsiness, and confusion.
burning, stinging, foreign body sensation, ocular pain or
Occasionally, metabolic acidosis, hypokalemia, or
allergic ocular reactions. Frequent systemic effects of
urolithiasis occurs. Rare, but possibly fatal, reactions
topical ophthalmic solutions consist of bitter taste,
include aplastic anemia, agranulocytosis, and
occasional headache, nausea, fatigue, and, rarely,
thrombocytopenia.
urolithiasis and iridocyclitis.
Administration: (brinzolamide) 1 drop tid; (dorzolamide) 1
drop tid. When used adjunctively, dorzolamide is
administered bid. (acetazolamide) SR cap 500 mg bid has
been better tolerated than tablets; Tab 125 mg q 4 hr to
250 mg qid. Dosages >1 g/day are not more effective.
(Methazolamide) 50–100 mg bidtid.
Contraindications: (Oral) sulfonamide allergy,
hypokalemia; hyponatremia; hyperchloremic acidosis;
adrenocortical insufficiency; marked renal or hepatic
impairment; severe COPD. Long-term use of oral CAIs is
contraindicated in angle-closure glaucoma. (topical)
Hypersensitivity
Pearls: Because of their severe adverse effects and poor
tolerability, use oral CAIs in primary open-angle glaucoma
only as a last resort
Oral agents can be used for high-altitude sickness
Special Instructions:
Patients on oral agents need to have the following
monitored: Malaise or fatigue, Crs, serum potassium,
serum carbon dioxide. Baseline CBC and platelet count.
CHOLINERGICS AND CHOLINESTERASE INHIBITORS: (Carbachol) Ophth Soln 0.75, 1.5, 2.25, 3%.
(Echothiophate Iodide) Pwdr for reconstitution 0.03, 0.06, 0.125, 0.25%. (Pilocarpine) Ophth Gel 4%;. (Pilocarpine
HCl) Ophth Soln 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10%. (Pilocarpine Nitrate) Ophth Soln 1, 2, 4%.
Mechanism of Action: Carbachol and pilocarpine are direct Precautions: Pregnancy, lactation. Night driving or
cholinergic agonists that act at acetylcholine receptors to
other activities in poor light. Use cholinesterase
stimulate the ciliary muscle. Carbachol is also a weak
inhibitors cautiously in patients with histories of
cholinesterase inhibitor. Echothiophate iodine, and other
retinal detachment, asthma, bradycardia,
cholinesterase inhibitors, act indirectly by inhibiting AChE.
hypotension, epilepsy, parkinsonism, recent MI, or
Ciliary body contraction causes pupilary constriction and
patients using systemic cholinesterase inhibitors for
eases the restriction of outflow of aqueous humor
myasthenia gravis. Cholinesterase inhibitors can
through the trabecular meshwork. Echothiophate is
cause prolonged respiratory paralysis if
irreversible cholinesterase inhibitors with long durations of succinylcholine is utilized during general anesthesia
action
ADRs: Reduced visual acuity in poor lighting occurs
frequently because of papillary constriction and
accommodative spasm. Occasional effects include ciliary
spasm, headache, lacrimation, myopia, blurred vision,
retinal detachment, and iris cysts.
ADRs: Cataracts have been reported with
echothiphate. Cholinergic syndrome consisting of
weakness, nausea, diaphoresis, and dyspnea occurs
rarely. Patients with myopia of –6 diopters or
greater and those with histories of retinal
detachment are at greater risk of developing retinal
detachment.
Administration: (carbachol) initiate at 1 drop tid of the
0.75% solution; (echothiophate) 1 drop daily–bid;
(pilocarpine ophth soln) initiate with 1 drop of 1–2%
solution q 6–8 hr. Most patients eventually require qid
administration. Because pilocarpine is bound to pigments
in the iris and the ciliary body, patients with dark eyes
sometimes require 4% and occasionally 6% solutions;
(pilocarpine gel) apply a thin (1/4 inch strip hs)
Pearls:
Use long-acting cholinesterase inhibitors in patients who
are not controlled with pilocarpine.
Contraindications: Acute iritis, uveal inflammation,
and pupillary block glaucoma
Special Instructions:
Refrigerate echothiophate iodide before
reconstitution. Once reconstituted store at room
temperature for no more than 4 weeks.