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Ophthalmology in FocusOphthalmology in Focus
Empowering Pharmacists to Improve Glaucoma Outcomes and
Ocular Health
PresentersRandall Seifert, PharmDS i A i DSenior Associate DeanProfessorPharmacy Practice and Pharmaceutical SciencesUniversity of MinnesotaUniversity of MinnesotaCollege of PharmacyDuluth, Minnesota
Tim Cernohous, PharmD, RPhPhD Candidate, Social and Administrative PharmacyUniversity of MinnesotayCollege of PharmacySPC Therapeutics, LLCEssentia HealthDuluth, Minnesota
Disclosures
Dr. Cernohous and Dr. Seifert disclosed no relevant financial relationships with any p y
commercial interests.
Learning Objectives
After completing this activity, participants will be able to:
g j
• Outline the safety and efficacy of available glaucoma medications, including associated adverse events of treatment
• Describe the factors involved in ocular inflammation and dry eye disease, including comorbid conditions, modifiable risk factors, and appropriate pp ppharmacotherapy
• Take a more active role in screening, treating, and counseling patients with glaucoma and other ocular g p gdiseases
• Adhere to guideline-directed and evidence-based pharmacotherapy in the treatment of glaucomap py g
Audience Response Question
How often do you screen for or discuss ocular
p
How often do you screen for or discuss ocular conditions with your patients?
1. Always2. Often3. Rarely4. Never
Audience Response Question
How confident are you in your ability to consult and
p
How confident are you in your ability to consult and medically manage patients with glaucoma?
1. Very confident2. Confident3. Somewhat confident4. Not confident
US Prescription Ophthalmic Drug MarketDrug Market
$2,500 –
$3,000 –2007
2010
2015-2020
Mill
ions
$1,500 –
$2,000 –
$ in
M
$1,000 –
$500 –
$0 –Dry Eye, Allergy,
Inflammation
Infection Glaucoma Retinal and Vitreous
Disorders
Insight Pharma Reports/H.M. Pharma Consultancy.
Definition of Glaucoma
• Family of ocular diseases ycharacterized by progressive optic neuropathy and VF loss
Gradual optic disk cupping a structural– Gradual optic disk cupping—a structural change characteristic of glaucoma
– Associated VF deficitsP i ti l li ll l– Progressive retinal ganglion cell loss
• No longer defined alone by elevated IOP
VF = visual field; IOP = intraocular pressure.Quigley HA. Prog Retin Eye Res. 1999;18(1):39-57. David R. Expert Opin Investig Drugs. 1998;7(7):1063-1086.
Glaucoma
• Estimated 2.5 million people in the United States have POAG as of 2000
• 130,000 will be blind as a result of the disease• Half of those with POAG may not be aware they have the disease
S d l di f bli d ld id l di i• Second leading cause of blindness worldwide; leading cause in African Americans and Hispanics
• 10 million people have above normal IOP that may lead to glaucoma• 120 000 are presently blind from glaucoma• 120,000 are presently blind from glaucoma• 5500 become blind each year from the disease• Direct annual medical cost related to glaucoma was estimated to be
$2 9 billion$2.9 billion
POAG = primary open-angle glaucoma.Fleming C, et al. Ann Fam Med. 2005;3(2):167-170. Congdon N, et al. Arch Ophthalmol. 2004;122(4):477-485. Rein DB, et al. Arch Ophthalmol. 2006;124(12):1754-1760. Glaucoma Research Foundation. http://www.glaucoma.org/learn/glaucoma_facts.php. Accessed February 20, 2012. Quigley HA, et al. Br J Ophthalmol. 2006;90(3):262-267. Prevent Blindness America®. Vision problems in the U.S.: prevalence of adult vision impairment and age-related eye disease in America. http://www.preventblindness.org/vision-problems-us. Accessed February 10, 2012.
Major Types of Glaucoma
Primary glaucomas
j yp
Primary glaucomas• POAG• NTG• NTG• OH
ACG• ACGSecondary glaucomas
NTG = normal- (low) tension glaucoma; OH = ocular hypertension; ACG = angle-closure glaucoma.
Progression of ON Damageg g
ON = optic nerve.
Aqueous Humor Dynamicsq y
In glaucoma,outflow isimpaired
Angle-Closure Glaucoma
• Characterized by sudden:
g
y– Onset of visual loss – Excruciating pain
Halos– Halos– Nausea and vomiting
• Patients are occasionally thought to have acute gastrointestinal disease
• Requires immediate• Requires immediate transfer from ED to ophthalmology for treatment
ED = emergency department.Salmon JF. Glaucoma. In: Riordan-Eva, P, et al. Vaughan & Asbury's General Ophthalmology. 18th ed. New York, NY: McGraw Hill; 2011.
Normal-Tension Glaucoma
– 25% to 50% of individuals with primary glaucomatous optic disc changes and visual field deficits have normal IOP measurements
– Glaucomatous optic disk or VF changes have an IOP consistently below 21 mm Hg
• May be caused by an abnormality in the optineurin gene on chromosome 10• May be caused by vascular or mechanical abnormalities at the optic nerve head• May be a purely vascular disease
– Before a diagnosis of normal tension glaucoma is made a differential diagnosis for many other factors must be ruled out
– Bottom line, approximately 60% have progressive VF loss– Increased IOP is no longer considered to be part of the definition of
POAG
Quigley HA. New Engl J Med. 1993;328(15):1097-1106. Salmon JF. Glaucoma. In: Riordan-Eva, P, et al. Vaughan & Asbury's General Ophthalmology. 18th ed. New York, NY: McGraw Hill; 2011.
Ocular Hypertension
• Elevated IOP without disk or field
yp
Elevated IOP without disk or field abnormalities and is more common than POAGthan POAG– Rate at which such individuals develop
glaucoma is approximately 1% to 2% per yearglaucoma is approximately 1% to 2% per year• Should undergo regular monitoring (once
or twice a year) of IOPs optic disks andor twice a year) of IOPs, optic disks, and VFs
Salmon JF. Glaucoma. In: Riordan-Eva, P, et al. Vaughan & Asbury's General Ophthalmology. 18th ed. New York, NY: McGraw Hill; 2011.
Primary Open-Angle Glaucoma
• Glaucomatous optic
y p g
Glaucomatous optic disk or field changes – Associated with
elevated IOPs– Normal-appearing open
anterior chamber angleanterior chamber angle– No other reason for IOP
elevation
Salmon JF. Glaucoma. In: Riordan-Eva, P, et al. Vaughan & Asbury's General Ophthalmology. 18th ed. New York, NY: McGraw Hill; 2011.
Risk Factors for POAG• Elevated IOP
– IOP >21 mm Hg• Diurnal fluctuation in IOP—higher in early morning• Patient susceptibility
– Cup/disc > 50– Cup/disc >.50– Advanced age ( >50 years)– Central corneal thickness <555 microns– Race (African descent 6 to 8 times more common than non-African descent)
A 40– Age >40 years• Family history of glaucoma• Concomitant conditions (eg, diabetes, hypertension)• Myopia• Myopia• Compromised ocular and systemic hemodynamics• History of migraine, Raynaud’s phenomenon, cardiogenic factors
American Academy of Ophthalmology. Preferred Practice Pattern® guidelines. http://one.aao.org/CE/PracticeGuidelines/PPP.aspx. Accessed February 20, 2012. Wolfs RC, et al. Arch Ophthalmol.1998;116(12):1640-1645.
Screening for POAG
• Either direct ophthalmoscopy of the dilated
g
Either direct ophthalmoscopy of the dilated eye or slit lamp examination
• Direct ophthalmoscopyDirect ophthalmoscopy – Sensitivity of 59% and a specificity of 73% in
detecting and classifying optic disc changes• VF analyzers
– Sensitivity of 95% and a specificity of 93% for y p ydetecting moderate to severe glaucoma (n=137)
Quigley HA, et al. Ophthalmology. 1992;99(1):19-28. Coleman AL, et al. J Glaucoma. 1996;5(6):384-389. Patel SC, et al. Am J Ophthalmol. 2000;129(3):323-327.
VF Examination
http://webeye.ophth.uiowa.edu/eyeforum/images/glaucoma/fig-6-12.gif. Accessed February 17, 2012.
Relationship Between IOP and VF Deterioration POAG
12
Deterioration—POAG
8
10
ents
Visual Field LossStable Visual Field
4
6
mbe
r of P
atie
2
4
Num
012 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Mean IOP (mm Hg)
Mao LK, et al. Am J Ophthalmol. 1991;111(1):51-55. AGIS Investigators. Am J Ophthalmol. 2000;130(4):429-440. Shirakashi M, et al. Ophthalmologica. 1993;207(1):1-5. Stewart WC, et al. Am J Ophthalmol. 1993;116(2):176-181. Bojić L, et al. Acta Med Croatica. 1998;52(4-5):219-220.
Measuring IOPg
Treatment of POAG
• Most recent treatment is based on theMost recent treatment is based on the results of the OHTS
• Patient characteristics with greatest risk:• Patient characteristics with greatest risk:– IOP >25 mm Hg
V ti l t di k ti f th 0 5– Vertical cup-to-disk ratio of more than 0.5 – Central corneal thickness of less than 555 μm
• Patients may have glaucomatous changes without elevated IOP
OHTS = Ocular Hypertension Treatment Study.Kass MA, et al. Arch Ophthalmol. 2002;120(6):701-713.
Goals of Therapy
• Dependent on clinical findings and extent of IOP
py
p g• Individualized to patient• Reduction in mean IOP to <18 mm Hg or
20% to 30% lowering• Those with normal IOP may be reduced to 10 to
12 mm Hg12 mm Hg• Control of diurnal IOP fluctuation throughout the
dayy• IOP lowering to <18 mm Hg with monotherapy if
possible
Kass MA, et al. Arch Ophthalmol. 2002;120(6):701-713.
Nonpharmacologic Therapies
Lifestyle factors potentially contributing to POAG
p g p
y p y g• Smoking • Alcohol• Physical activities
Nonpharmacologic treatment approaches• Exercise (isokinetic)
Mi i i ff i i t k• Minimize caffeine intake• Limited evidence for diet and supplementation
Klein BE, et al. Am J Ophthalmol. 2007;144(6):961-969. Rhee DJ, et al. Survey Ophthalmol. 2001;46(1):43-55.
Treatment Considerations
• Although high IOP is certainly not the only factor g g y ycontributing to ON damage, it is the only risk factor that can be clinically modified
• Medically lowering IOP in patients with OH may reduce• Medically lowering IOP in patients with OH may reduce the incidence of glaucoma
• In at least two-thirds of patients with high-tension f Oglaucoma, marked lowering of the IOP stops progression
of the disease• Even in NTG patients, the IOP level is a risk factor p ,
related to the degree of glaucomatous damageCartwright MJ, et al. Arch Ophthalmol. 1988;1067):898-900. Crichton A, et al. Ophthalmology. 1989;96(9):1312-1314. Kass MA, et al. Arch Ophthalmol. 1989;107(11):1590-1598. Kidd MN, et al. Br J Ophthalmol. 1985;69(11):827-1314. Kass MA, et al. Arch Ophthalmol. 1989;107(11):1590 1598. Kidd MN, et al. Br J Ophthalmol. 1985;69(11):827831. Odberg T. Acta Ophthalmol. 1987;65(suppl 182):27-29. Roth SM, et al. Ophthalmic Surg. 1991;22(12):724-729. Kolker AE. Trans Am Ophthalmol Soc. 1977;75:539-555. Leydhecker W, et al. Int Ophthalmol. 1989;13(1-2):113-117. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126(4):487-497. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126(4):498-505.
Audience Response Question
Which one of the following therapeutic categories
p
Which one of the following therapeutic categories is the most effective in lowering IOP?
1. Beta-blockers2. Carbonic anhydrase inhibitors3. Prostaglandins4. Cholinergics
Topical Medications for Glaucoma p
Drug Class IOP Lowering mm HG
Prostaglandin analogues 6 – 8
Combination—dorzolamide and timolol ophthalmic 4 – 6
Miotics 3 – 5
Beta-blockers 3 – 5
Carbonic anhydrase inhibitors 2 – 4
Alpha agonists 2 – 6
Single-Bottle Treatments
• Prostaglandin
g
g– Bimatoprost, latanoprost,* travoprost
• Beta-adrenergic antagonist– Timolol,* levobunolol,* betaxolol,* metipranolol*
• Selective alpha-adrenergic agonistApraclonidine * brimonidine*– Apraclonidine, brimonidine
• Topical CAI– Brinzolamide, dorzolamide*o a de, do o a de
• Fixed combinations– Timolol/dorzolamide, timolol/brimonidine
*Denotes generic available (generic availability varies by strength and dosage form). CAI = carbonic anhydrase inhibitor.Gheith ME, et al. Clin Ophthalmol. 2008;2(1):15-20.
High Responder Ratesto Desired Target IOPto Desired Target IOP
PGAs have higher responder rates than beta-blockers12-month US study; all patients; mean IOP at 4 PM; phase 3 clinical trial
9187
100(%)
54
8073
87
62
82
60708090
ing
at 4
AM
4536
20304050
s R
espo
ndi
010
<22 mm Hg <20 mm Hg <18 mm HgPatie
nts
PGAs = prostaglandin analogues.Netland PA, et al. Am J Ophthalmol. 2001;132(4):472-484.
Travoprost 0.004% (n=197) Latanoprost 0.005% (n=193) Timolol 0.5% (n=195)
Two-Bottle Treatment
Prostaglandin • Topical beta-blockerProstaglandin Topical beta blocker• Topical CAI• Selective alpha agonist
Timolol/dor olamide
++• Timolol/dorzolamide• Timolol/brimonidine
Topical beta-blocker• Prostaglandin• Topical CAI++ Topical CAI• Selective alpha agonist
Drug Treatments for Glaucomag
Drug Pharmacology Mechanism of Action Dosage FormUsual Dose
(drops)Drug Pharmacology Mechanism of Action Dosage Form (drops)
Prostaglandin analogues
Increases aqueous uveoscleral outflow and to a lesser extent
trabecular outflow
T t S l ti 1 Q HSTravoprost Solution 1 Q HS
Latanoprost Prostaglandin F2α Solution 1 Q HS
Bimatoprost Prostaminde analog Solution 1 Q HS
β-adrenergic Decreases aqueous production blocking agents of ciliary body
Betaxolol Relative β1 selective Solution 1 BID
Relative β1 selective Suspension 1 BID
Cartelol Nonselective Solution 1 BIDCartelol Nonselective Solution 1 BID
Levobunolol Nonselective Solution 1 BID
Metipranolol Nonselective Solution 1 BID
Timolol Nonselective Solution/gelling solution 1 QD to 1-2 QDsolution
HS = bedtime; BID = twice daily; QD = once daily.
Drug Treatments for GlaucomaDrug Pharmacology Mechanism of Action Dosage Form Usual Dose (drops)
Nonspecific agonists Increases aqueous humor outflow
Dipivefrin Prodrug Solution 1 BID
α2 adrenergic agonists
Both decrease aqueous production; brimonidine increases uveoscleral
outflow
Apraclonidine α2 agonist Solution 1 BID to TID
Brimonidine α2 agonist Solution 1 BID to TID
Carbonic anhydrase inhibitors
Decreases aqueous production of ciliary body
TopicalTopical
Brinzolamide Carbonic anhydrase II inhibition Suspension 1 BID to TID
Dorzolamide Carbonic anhydrase II inhibition Solution 1 BID to TID
Systemic
Acetazolamide Carbonic anhydrase II inhibition Capsuleceta o a de Ca bo c a yd ase b t o Capsu e
Methazolamide Carbonic anhydrase II inhibition Tablet
Combinations
Timolol-dorzolamide Solution 1 BID
Timolol-brimonidine Solution 1 BID
TID = three times daily.
Summary of Class-Specific ADRsy p
D Cl Sid Eff tDrug Class Side Effects
Prostaglandin agonistsHyperemia (25% to 45%), pigmentation of the iris, eye lids, and lashes (2% to 6%) and hypertrichosis (15% to 45%
ith bi t t) d (2% t 6%)with bimatoprost), dry eye (2% to 6%)
Beta-adrenergic blockers Localized stinging (5% to 15%), hyperemia, somnolence, decreases in HR and BP, bronchospasm
Alpha-adrenergic agonistsHyperemia (10% to 20%), itching (pruritus 10% to 20%), foreign object sensation (5% to 9%), decrease BP and/or HR, dizziness, allergic reactions
CAIs Burning and stinging, blurred vision, punctate keratitis
Nonspecific (dipivefrin) Headache, tearing, burning, stinging, hyperemia (1% to 10%) photophobia10%), photophobia
ADRs = adverse drug reactions; HR = heart rate; BP = blood pressure. American Hospital Formulary Service (AHFS) Drug Information 2012. Bethesda, MD: American Society of Health System Pharmacists; 2011.
Hyperemiay
Hyperpigmentationyp p g
Generic Ophthalmic Medications
• Testing of innovator and generic ophthalmic
p
g g pproducts– Prior to 1992, the FDA used to permit changes in
inactive ingredients for ophthalmic genericinactive ingredients for ophthalmic generic products without testing
– After 1992, generic ophthalmic solutions must have the same active and inactive ingredientshave the same active and inactive ingredients
– For products other than a solution, the generic has to demonstrate bioequivalence
• Stability, concentration, color coding
FDA = US Food and Drug Administration.American Glaucoma Society. Generic ophthalmic medications position statement. http://one.aao.org/ce/practiceguidelines/clinicalstatements_content.aspx?cid=e90121fe-1a9d-4030-a991-782f54cf23f5. Accessed February 20, 2012.
Adherence to Topical Ophthalmic MedicationsMedications
100 100
90
80
70inin
g on
90
80
70
60
50
40
Patie
nts
Rem
aM
edic
atio
n 60
50
40
Prostaglandins
Alpha-agonists
40
30
20Perc
enta
ge o
f M 40
30
20
Prostaglandins
CAIsCAIs
Beta-blockers10
0 |
0|
6|
12|
18|
24|
30|
36Months After Treatment Initiation
10
0 |
0|
6|
12|
18|
24|
30|
36
Alpha-agonistsBeta-blockers
Months After Treatment Initiation
Nordstrom BL, et al. Am J Ophthalmol. 2005;140(4):598-606.
Diagnosed Glaucoma Glaucoma Suspect
Strategies to Improve Adherence
• Actively address at-risk patients • Review drug administration with h fill
g p
• Simplify and optimize treatment regimen when possible
• Reduce drug costs when ibl
each refill• Suggest that patients keep a
medication diaryU t l h il i dpossible
• Understand the patient’s health beliefs about glaucoma
• Provide patient disease
• Use telephone or mail reminders when possible
• Suggest the patient incorporate drops into daily activities• Provide patient-disease
education– Reinforce regularly– Use verbal and written delivery
drops into daily activities• Involve a helpful
caregiver/family member• Use open communicationUse verbal and written delivery
– Adapt information to those with poor vision or low literacy
Use open communication– Ask-tell-ask dialogue– Motivational interviewing– Stages of readiness for change
Budenz DL. Ophthalmology. 2009;116(11 suppl):S43-S47.
Glaucoma SurgeryLaser Trabeculoplasty
g y
Laser trabeculoplasty can be considered as initial therapy in selected patients [A:I]* or an alternative for patients who cannot or will not use medications reliably due to cost, memory problems, difficulty with instillation, or intolerance to the medication.
Incisional Glaucoma SurgeryTrabeculectomyFiltering surgery is effective in lowering IOP It is generally indicated whenFiltering surgery is effective in lowering IOP. It is generally indicated when medicine or laser therapy is insufficient to control disease and can be considered in selected cases as initial therapy.
Aqueous ShuntsAqueous ShuntsAqueous shunts have traditionally been used to manage medically uncontrolled glaucoma when trabeculectomy has failed to control IOP or is deemed unlikely to succeed.
*Level of importance A. Level of evidence I.National Guideline Clearinghouse. Primary open-angle glaucoma. http://www.guideline.gov/content.aspx?id=24810. Accessed March 14, 2012.
Figure 1: Incisional Glaucoma Surgery: Trabeculectomy
Figure 2: Laser Trabeculoplasty
http://ohioeyecareconsultants.com/eyeinfo/glaucomasurgery2.jpg. Accessed April 28, 2011. http://www.uwhealth.org/images/ewebeditpro2/upload/4588_Figure_1.jpg. Accessed April 28, 2011.
g p y
Audience Response Question
Dry eye incidence and severity of symptoms
p
Dry eye incidence and severity of symptoms is correlated with the number of ocular medications in usemedications in use.
1. True2 False2. False
Ocular Surface Anatomyy
Meibomian glands
Dry Eye Syndrome, Dry Eye Disease, or Dysfunctional Tear Syndrome
A multifactorial disease of the tears and
or Dysfunctional Tear Syndrome
A multifactorial disease of the tears and ocular surface that is characterized by:
Increased osmolarity of the tear film– Increased osmolarity of the tear film– Tear film instability
Inflammation of the ocular surface– Inflammation of the ocular surface
Ocul Surf. 2007;5(2):75-92. Perry HD, et al. Curr Opin Ophthalmol. 2004;15(4):299-304.
Symptoms of Dry Eye Syndrome
Patients usually present with the following
y p y y y
y p gcomplaints:
• Painful or sore eyesB i / ti i d (h i )• Burning/stinging, redness (hyperemia)
• Foreign body sensation• Blurred or poor visionBlurred or poor vision• Photophobia• Tired eyes• Paradoxical tearing• Dryness worse later in the day• Contact lens intolerance• Contact lens intolerance
Pictures of Dry Eye Syndromey y y
Prevalence and Risk Factors for Dry Eye
• Dry eye is a significant public health problem
for Dry Eyey y g p p
• US statistics– 7 million Americans over 40 years of age
5 7% of women over 50 years of age– 5.7% of women over 50 years of age– 9.8% of women over 75 years of age– 3.9% of men 50 to 54 years of age– 97.6% men over 80 years of age
• Prevalence increases with:– AgeAge– Menopause– Glaucoma
Schaumberg DA, et al. Am J Ophthalmol. 2003;136(2):318-326. Moss SE. Arch Ophthalmol. 2000;118(9): 1264-1268. Schaumberg DA, et al. Arch Ophthalmol. 2009;127(6):763-768.
OSD Prevalence Study: Conclusions
• OSD is a significant problem for many glaucoma
ConclusionsOSD is a significant problem for many glaucoma patients (48.4%)
• Prevalence is much higher than previously g p yreported in a population-based study of elderly patients (approximately 15%)
• OSD severity increases with the number of medications used
OSD = ocular surface disease.Fechtner R, et al. Presented at: Annual Meeting of the American Glaucoma Society; March 8, 2008; Washington, DC. Schein OD, et al. Am J Ophthalmol. 1997;124(6):723-728.
Major Categories of Dry Eye Syndromej g y y y
Both categories are characterized by increased tear filmBoth categories are characterized by increased tear film osmolarity and ocular surface inflammation
Aqueous Deficient-State Lack of tear production
Evaporative State Rapid tear evaporationEvaporative State p p(Intrinsic or Extrinsic)
Dry Eye Cascade: Causes and Contributing Factors of Abnormal Tear FilmContributing Factors of Abnormal Tear Film
Healthy Ocular SurfaceSurface
Abnormal or
Tears
Abnormal or Insufficient
Tears
ObservablePathophysiologies
A i
Increased Ocular
Reduced Tear Clearance
Aqueous Deficiency
TBUT LessTBUT Less
• Aging• Smoking• Dry environment• Hormonal changes• Contact lens• Blepharitis Osmolarity Irritation
Increased
Rate
TBUT Less Than Blink
Rate
Mucin
Blepharitis• LASIK• Auto-immune disease• Alcohol use• Pollution• Computer use
Cytokines
I fl ti
Mucin Abnormalities • Antidepressants
• Specific preservatives in topical medications
TBUT = tear film breakup time; LASIK = laser-assisted in situ keratomileusis. Gayton JL. Clin Ophthalmol. 2009;3:405-412.
Inflammation
Healthy Tear Film With Lipid, Aqueous, and Mucin Layers and Healthy Ocular Surface With Intact MicrovilliLayers and Healthy Ocular Surface With Intact Microvilli
Gayton JL. Clin Ophthalmol. 2009;3:405-412.
Progressive Damage of Corneal Surface Cells (Lost Microvilli) Due to Unhealthy Tear Film(Lost Microvilli) Due to Unhealthy Tear Film
Gayton JL. Clin Ophthalmol. 2009;3:405-412.
Commonly Used Drugs Associated With Dry EyeCommonly Used Drugs Associated With Dry Eye
Antihistamines
Antidepressants especially tricyclic antidepressants
Anticholinergics
Diuretics
Angiotensin-converting enzyme inhibitors
Oral contraceptives
Opioid narcotics
Antiparkinsonism agents
B t bl kBeta-blockers
Antipsychotics
Anxiolytics—benzodiazepinesAnxiolytics benzodiazepines
Mild/Moderate Patient
• 63-year-old female with POAG63 year old female with POAG• Postmenopausal • Controlled IOP• Mild field loss• Seasonal allergies• Contact lenses• Latanoprost• Red and gritty eyes• Comes to pharmacy asking for artificial tears
When May BAK Use Be Most Problematic?
• High BAK concentration: cell death is dose-dependent
Problematic?High BAK concentration: cell death is dose dependent– High concentration in a single drop or due to the accumulation of
dose with multiple drops
Growth arrest NecrosisApoptosis0.0001% BAK 0.05% – 0.1% BAK0.01% BAK
• Treatment of chronic ophthalmic diseases, such as glaucoma, with BAK-containing medications– Longer duration of BAK exposure increased corneal
epithelial cell lysis
BAK = benzalkonium chloride. De Saint Jean M, et al. Eye Res. 2000;20(2):85-94. Cha SH, et al. Clin Experiment Ophthalmol.2004;32(2):180-184.
Therapeutic Approaches
Remember that dry eye is a chronic condition and
p pp
Remember that dry eye is a chronic condition and our treatment is targeted to reducing symptoms and improving quality of life.
• Remove/avoid offending agent• Tear replacement• Increase tear production• Decrease inflammation
Tear conservation• Tear conservation
Nonpharmacologic Options• Remove/avoid offending agent or condition
p g p
• First identify environmental changes– Wear glasses—decrease evaporation of tears– Adjust vents
Adj t ili f id i t– Adjust ceiling fans—avoid air currents– Control humidity and a humidifier– Take frequent breaks from looking at a computer screen or other
visually demanding tasksvisually demanding tasks• Discontinue or avoid smoking• Pharmacists should review potential offending prescription
and non-prescription medicationsa d o p esc p o ed ca o s• Dietary changes
– Reduce alcohol– Add omega-3, fish oils, and/or flaxseedg , ,
Therapeutic Options
Artificial Tears Goal is to improve symptoms (but these t d t h l i th lagents do not heal or repair the ocular
surface)
Lipid-containing artificial tears Useful in patients with meibomian gland dysfunction as they tend to stabilize tear film by increasing the existing tear film layer
Preservative-free artificial tears Useful in moderate to severe dry eye patients who require artificial tears more than 4 timeswho require artificial tears more than 4 times a day. They avoid ocular surface damage from preservatives
Artificial tears with solutes Beneficial for patients with excessive tear film evaporationevaporation
Hypotonic artificial tears Decrease the osmolarity of the tear film
Ophthalmic gels and ointments Useful in severe cases and in patients with incomplete eyelid closureincomplete eyelid closure
Korb DR, et al. Optom Vis Sci. 2005;82(7):594-601. Noecker R. Adv Ther. 2001;18(5):205-215. Garrett Q, et al. Invest Ophthalmol Vis Sci. 2007;48(4):1559-1567. Troiano P, et al. Cornea. 2008;27(10):1126-1130.
Commercial Artificial Tear Products
Product Ingredients Brand NameCMCCMC 0.5%, glycerin, erythritol, levocarnitine, Purite preservative
Optive
CMC 0.5%, Purite preservative Refresh TearsCMC 1%, Purite preservative Refresh LiquigelCMC 0.25%, hypotonic, preservative free Thera TearsPEGPEG 400 0.4%, propylene glycol 0.3%, hyproxypropyl guar gelforming matrix and polyquaternium preservative
Systane
PEG 400 0.4%, propylene glycol 0.3%, hyproxypropyl guar gelforming matrix with sorbitol* and polyquaternium preservative
Systane Ultra
PEG 400 0.25%, hyaluronic acid, sodium chlorite preservative Blink Tears
*Addition of sorbitol is promoted to produce less blurred vision.CMC = carboxyl methylcellulose; PEG = polyethylene glycol.
Commercial Artificial Tear Products
Product Ingredients Brand NameHPMCHPMC 0.3%, Dextran 70 0.1%, bicarbonate, zinc Bion Tears
HPMC 0 3% Dextran 70 0 1% glycerin 0 2% polyquad Tears Naturale ForteHPMC 0.3%, Dextran 70 0.1%, glycerin 0.2%, polyquad 0.001% preservative
Tears Naturale Forte
HPMC 0.3%, Dextran 70 0.1%, polyquad 0.001% preservative
Tears Natural II
HPMC 0.3%, Dextran 70 0.1%, preservative free Tears Natural Free
HPMC 0.3%, sodium perborate preservative Genteal*
HPMC 0 2% di b t ti G t l MildHPMC 0.2%, sodium perborate preservative Genteal Mild
HPMC 0.2%, glycerin 0.2%, PEG 1%, BAK 0.01% as preservative
Visine Tears†
*Also available as a single-use, preservative-free vial. †Contains BAK.HPMC = hydroxypropyl methylcellulose.
Anti-inflammatory Agentsy g
Anti-inflammatory Medications Reserved for patients with moreAnti-inflammatory Medications Reserved for patients with more severe dry eye syndrome who have failed treatment with artificial tears
Topical steroids Used in pulse dosing to decrease p p gocular surface inflammation and symptoms
Oral tetracyclines Used for patients with ocular rosaceaand blepharitis
Topical cyclosporine 0.05% Used in aqueous-deficient states
O l 3 f tt id l t M ib i l d d f ti dOral omega-3 fatty acid supplements Meibomian gland dysfunction and evaporative states
Marsh P, et al. Ophthalmology. 1999;106(14);811-816. Frucht-Pery J, et al. Am J Ophthalmol. 1993;116(1): 88-92. Sall K, et al. Ophthalmology. 2000;107(4):631-639. Macsai MS. Trans Am Ophthalmol Soc. 2008;106:336-356.
Role of Topical Corticosteroids in Dry Eye
• All patients with dry eye have ocular inflammation
in Dry Eyep y y
• Not indicated for patients with mild dry eye responsive to artificial tears
• If patients do not respond to artificial tears with continued• If patients do not respond to artificial tears with continued signs of conjunctival redness, a course of topical steroids should be addedAd t t t i l ti t id i id t• Advantage to topical corticosteroids is rapid onset of action
• Short-term therapy is most appropriate because of the yrisk of elevating IOP and cataracts
• May be used in combination with cyclosporine– Why?Why?
Cyclosporine
• Therapeutic issues for the pharmacist
y p
p p– Comes as an emulsion. So remind patients to NOT SHAKE but
to GENTLY ROLL the container in their hands prior to administration
– Long onset of action—patience required so use of topical corticosteroids in combination is reasonable
– Used BID and should be used with artificial tears but wait 15 minutes between instillation of artificial tears and cyclosporineminutes between instillation of artificial tears and cyclosporine
– Side effects• Burning and stinging are the most common and can be troublesome• Blurred vision; clear or yellow fluid from eye; difficulty reading; eye pain;Blurred vision; clear or yellow fluid from eye; difficulty reading; eye pain;
feeling of having something in the eye; halos around lights; itching skin; redness of the white part of eye or inside of eyelid; sticky or matted eyelashes; watery eye
Dry Eye Treatment Guidelines
Severity Level* Signs and Symptoms Recommended Treatment
y y
1 Mild to moderate symptoms and no signsMild to moderate conjunctival signs
Patient counseling, preserved tears, environmental management, allergy eye drops, water intake, hypoallergenic productsIf i t t 2If no improvement go to 2
2 Moderate to severe symptomsTear film signsMild corneal punctate stainingConjunctival staining
Unpreserved tears, gels, ointments, topical steroids, topical cyclosporine, nutritional supportIf no improvement go to 3Conjunctival staining
Visual signsIf no improvement go to 3
3 Severe symptomsMarked corneal stainingCentral corneal staining
Tetracycline, punctal plugsIf no improvement go to 4
Central corneal stainingFilamentary keratitis
4 Severe symptomsSevere corneal staining, erosionsConjunctival scarring
Systemic anti-inflammatory therapy, oral cyclosporine, moisture goggles, punctal cautery surgertConjunctival scarring cautery, surgert
*At least one sign and one symptom of each category should be present to qualify for the corresponding level assignment.Ocul Surf. 2007;5(2):163-178.
Nutritional Supplements in Dry Eye
• Essential fatty acids—flaxseed oil and omega-3
pp y y
Essential fatty acids flaxseed oil and omega 3 fatty acids– May reduce inflammation in meibomian gland
dysfunction, rheumatoid arthritis, and tear gland inflammationMay improve the oily layer of tear film– May improve the oily layer of tear film
• In a pilot-prospective, randomized, double-masked, placebo-controlled trial of omega-3 fatty acid p g ysupplementation:– 70% of patients became asymptomatic and 30% experienced
improvement in symptoms from moderate to mildimprovement in symptoms from moderate to mild
Wojtowicz JC, et al. Cornea. 2011;30(3):308-314.
Dry Eye Treatment Pipeliney y p
Product Name Active Principle Clinical Trial Phase
Rebamipide 2(1H)quinolone derivative 3 (ongoing)
Ecabet sodium 12-sulfodehdroabietic acid(natural phenantrene-type
d)
2b (concluded)
compound)Idestrin (NP50301) 17beta-estradiol ester 2b (concluded)
Prolacria Diquafosol (P2Y2 receptor agonist)
3 (concluded in US; ongoing inJapan)agonist) Japan)
Vekacia Cyclosporin A 3 (ongoing)
Civamide Cis-capsaicin (zucapsaicin) TRPV-1 receptor modulator neuronal
3 (nasal formulation in cluster headache)1 receptor modulator, neuronal
calcium channel blockerheadache)
ST-603 Cyclosporin 3 (commenced April 2007)
ALTY-0501 Doxycycline 3 (concluded)ALTY 0501 Doxycycline 3 (concluded)
AL-2178 (FID 109980)
Rimexolone 3 (ongoing since July 2006)
Pharmacist Counseling Pearls About Lifestyle and Ocular Disease
POAG
Lifestyle and Ocular Disease
• Smoking cessation, alcohol avoidance, antioxidants and vitamins do not seem to be risk modifiers
• MarijuanaBilb d i k bil b d t h i ifi t i t• Bilberry and ginko biloba do not have significant impact on IOP
Dry EyeSmoking cessation is a risk modifier and ma help impro e• Smoking cessation is a risk modifier and may help improve symptoms
• Coffee drinking and moderate alcohol may be beneficial but data are mixeddata are mixed
• Essential fatty-acids: omega-3• Vitamins and antioxidants are not helpful
Kang JH, et al. Am J Epidemiol. 2003;158(4):337-346.
Pharmacist Counseling Pearls About Lifestyle and Ocular Disease (cont)
ARMD
Lifestyle and Ocular Disease (cont)
• Smoking cessation• Sunglasses—UV protection• Vitamins C E zinc and beta carotene*• Vitamins C, E, zinc, and beta-carotene*
– Some reduced progression in AREDS – Used AREDS formulation in late-stage ARMD in one eye and moderate to severe
disease in the other eyey
• Yellowish color of macula – dietary xanthophylls – lutein and zeaxanthin – absorb blue light and minimize oxidative damage
• AREDS-2 lutein, zeaxanthin, and omega-3 fatty acids—ongoingAREDS 2 lutein, zeaxanthin, and omega 3 fatty acids ongoing enrollment ended 2008 and patients followed for 5 and 6 years
*Vitamin C 500 mg, vitamin E 400 IU, beta carotene 15 mg, zinc oxide 80 mg, and copper 2 mg to preventcopper deficiency anemia from high-dose zinc.ARMD = age-related macular degeneration; AREDS = Age-related Eye Disease Study.
Color Code for Topical Ocular Medications
• Tan: Indicates anti-infectives or antimicrobials
MedicationsTan: Indicates anti infectives or antimicrobials
• Pink: Indicates anti-inflammatories or steroids• Gray: Indicates non-steroidal anti-inflammatories• Red: Indicates mydriatics and cycloplegics • Dark Green: Indicates miotics• Yellow: Indicates beta blockers• Yellow: Indicates beta-blockers• Dark Blue: Indicates beta-blocker combinations• Purple: Indicates adrenergic agonists• Orange: Indicates carbonic anhydrase inhibitors • Turquoise: Indicates prostaglandin analogues
American Academy of Ophthalmology. Policy statement color code for topical ocular medications. http://www.aao.org/about/policy/upload/Color-Codes-for-Topical-Ocular-Medications-2010.pdf. Accessed March 15, 2012.
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