Empowering Pharmacists to Improve Glaucoma Outcomes and Ocular Health

Transcription

1 Ophthalmology in Focus Empowering Pharmacists to Improve Glaucoma Outcomes and Ocular Health

2 Presenters Randall Seifert, PharmD Senior Associate Dean Professor Pharmacy Practice and Pharmaceutical Sciences University of Minnesota College of Pharmacy Duluth, Minnesota Tim Cernohous, PharmD, RPh PhD Candidate, Social and Administrative Pharmacy University of Minnesota College of Pharmacy SPC Therapeutics, LLC Essentia Health Duluth, Minnesota

3 Disclosures Dr. Cernohous and Dr. Seifert disclosed no relevant financial relationships with any commercial interests.

4 Learning Objectives After completing this activity, participants will be able to: 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 p pharmacotherapy Take a more active role in screening, treating, and counseling gpatients with glaucoma and other ocular diseases Adhere to guideline-directed and evidence-based pharmacotherapy py in the treatment of glaucoma

5 Audience Response Question How often do you screen for or discuss ocular conditions with your patients? 1. Always 2. Often 3. Rarely 4. Never

6 Audience Response Question How confident are you in your ability to consult and medically manage patients with glaucoma? 1. Very confident 2. Confident 3. Somewhat confident 4. Not confident

7 US Prescription Ophthalmic Drug Market $3,000 $2, $ in Millions $2,000 $1,500 $1,000 $500 $0 Dry Eye, Allergy, Inflammation Infection Glaucoma Retinal and Vitreous Disorders Insight Pharma Reports/H.M. Pharma Consultancy.

8 Definition of Glaucoma Family of ocular diseases characterized by progressive optic neuropathy and VF loss Gradual optic disk cupping a structural change characteristic of glaucoma Associated VF deficits 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): David R. Expert Opin Investig Drugs. 1998;7(7):

9 Glaucoma Estimated 2.5 million people in the United States have POAG as of ,000 will be blind as a result of the disease Half of those with POAG may not be aware they have the disease 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, 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 9billion POAG = primary open-angle glaucoma. Fleming C, et al. Ann Fam Med. 2005;3(2): Congdon N, et al. Arch Ophthalmol. 2004;122(4): Rein DB, et al. Arch Ophthalmol. 2006;124(12): Glaucoma Research Foundation. Accessed February 20, Quigley HA, et al. Br J Ophthalmol. 2006;90(3): Prevent Blindness America. Vision problems in the U.S.: prevalence of adult vision impairment and age-related eye disease in America. Accessed February 10, 2012.

10 Major Types of Glaucoma Primary glaucomas POAG NTG OH ACG Secondary glaucomas NTG = normal- (low) tension glaucoma; OH = ocular hypertension; ACG = angle-closure glaucoma.

11 ON = optic nerve. Progression of ON Damage

12 Aqueous Humor Dynamics In glaucoma, outflow is impaired

13 Angle-Closure Glaucoma Characterized by sudden: Onset of visual loss Excruciating pain Halos Nausea and vomiting Patients are occasionally thought to have acute gastrointestinal disease 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.

14 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): Salmon JF. Glaucoma. In: Riordan-Eva, P, et al. Vaughan & Asbury's General Ophthalmology. 18th ed. New York, NY: McGraw Hill; 2011.

15 Ocular Hypertension Elevated IOP without disk or field abnormalities and is more common than POAG Rate at which such individuals develop glaucoma is approximately 1% to 2% per year Should undergo regular monitoring (once or 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.

16 Primary Open-Angle Glaucoma Glaucomatous optic disk or field changes Associated with elevated IOPs Normal-appearing open anterior 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.

17 Risk Factors for POAG Elevated IOP IOP >21 mm Hg Diurnal fluctuation in IOP higher in early morning Patient susceptibility 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) Age >40 years Family history of glaucoma Concomitant conditions (eg, diabetes, hypertension) Myopia Compromised ocular and systemic hemodynamics History of migraine, Raynaud s phenomenon, cardiogenic factors American Academy of Ophthalmology. Preferred Practice Pattern guidelines. /PracticeGuidelines/PPP.aspx. Accessed February 20, Wolfs RC, et al. Arch Ophthalmol. 1998;116(12):

18 Screening for POAG Either direct ophthalmoscopy of the dilated eye or slit lamp examination Direct 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 detecting moderate to severe glaucoma (n=137) Quigley HA, et al. Ophthalmology. 1992;99(1): Coleman AL, et al. J Glaucoma. 1996;5(6): Patel SC, et al. Am J Ophthalmol. 2000;129(3):

19 VF Examination Accessed February 17, 2012.

20 Relationship Between IOP and VF Deterioration POAG 12 Num mber of Patie ents Visual Field Loss Stable Visual Field Mean IOP (mm Hg) Mao LK, et al. Am J Ophthalmol. 1991;111(1): AGIS Investigators. Am J Ophthalmol. 2000;130(4): Shirakashi M, et al. Ophthalmologica. 1993;207(1):1-5. Stewart WC, et al. Am J Ophthalmol. 1993;116(2): Bojić L, et al. Acta Med Croatica. 1998;52(4-5):

21 Measuring IOP

22 Treatment of POAG Most recent treatment is based on the results of the OHTS Patient characteristics with greatest risk: IOP >25 mm Hg 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):

23 Goals of Therapy Dependent on clinical findings and extent of IOP 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 Hg Control of diurnal IOP fluctuation throughout the day IOP lowering to <18 mm Hg with monotherapy if possible Kass MA, et al. Arch Ophthalmol. 2002;120(6):

24 Nonpharmacologic Therapies Lifestyle factors potentially contributing to POAG Smoking Alcohol Physical activities Nonpharmacologic treatment approaches Exercise (isokinetic) Minimize i i caffeine intake Limited evidence for diet and supplementation Klein BE, et al. Am J Ophthalmol. 2007;144(6): Rhee DJ, et al. Survey Ophthalmol. 2001; 46(1):43-55.

25 Treatment Considerations Although high IOP is certainly not the only factor contributing to ON damage, it is the only risk factor that can be clinically modified Medically lowering IOP in patients with OH may reduce the incidence of glaucoma In at least two-thirds of patients with high-tension glaucoma, marked lowering of the IOP stops progression of the disease Even in NTG patients, the IOP level is a risk factor related to the degree of glaucomatous damage Cartwright MJ, et al. Arch Ophthalmol. 1988;1067): Crichton A, et al. Ophthalmology. 1989;96(9): Kass MA, et al. Arch Ophthalmol. 1989;107(11): Kidd MN, et al. Br J Ophthalmol. 1985;69(11): Odberg T. Acta Ophthalmol. 1987;65(suppl 182): Roth SM, et al. Ophthalmic Surg. 1991;22(12): Kolker AE. Trans Am Ophthalmol Soc. 1977;75: Leydhecker W, et al. Int Ophthalmol. 1989;13(1-2): Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126(4): Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126(4):

26 Audience Response Question Which one of the following therapeutic categories is the most effective in lowering IOP? 1. Beta-blockers 2. Carbonic anhydrase inhibitors 3. Prostaglandins 4. Cholinergics

27 Topical Medications for Glaucoma 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

28 Single-Bottle Treatments Prostaglandin Bimatoprost, latanoprost,* travoprost Beta-adrenergic antagonist Timolol,* levobunolol,* betaxolol,* metipranolol* Selective alpha-adrenergic agonist Apraclonidine, * brimonidine* Topical CAI Brinzolamide, dorzolamide* o 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.

29 High Responder Rates to Desired Target IOP PGAs have higher responder rates than beta-blockers 12-month US study; all patients; mean IOP at 4 PM; phase 3 clinical trial Patients Respondi ing at 4 AM (%) <22 mm Hg <20 mm Hg <18 mm Hg Travoprost 0.004% (n=197) Latanoprost 0.005% (n=193) Timolol 0.5% (n=195) PGAs = prostaglandin analogues. Netland PA, et al. Am J Ophthalmol. 2001;132(4):

30 Two-Bottle Treatment Prostaglandin + Topical beta-blocker blocker Topical CAI Selective alpha agonist Timolol/dorzolamideolamide Timolol/brimonidine Topical beta-blocker Prostaglandin + Topical CAI Selective alpha agonist

31 Drug Treatments for Glaucoma Usual Dose Drug Pharmacology Mechanism of Action Dosage Form (drops) Prostaglandin analogues Increases aqueous uveoscleral outflow and to a lesser extent trabecular outflow Travoprost Solution 1QHS Latanoprost Prostaglandin F2α Solution 1 Q HS Bimatoprost Prostaminde analog Solution 1 Q HS β-adrenergic blocking agents Decreases aqueous production of ciliary body Betaxolol Relative β1 selective Solution 1 BID Relative β1 selective Suspension 1 BID Cartelol Nonselective Solution 1BID Levobunolol Nonselective Solution 1 BID Metipranolol Nonselective Solution 1 BID Timolol Nonselective Solution/gelling solution 1 QD to 1-2 QD HS = bedtime; BID = twice daily; QD = once daily.

32 Drug Treatments for Glaucoma Drug 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 Topical Decreases aqueous production of ciliary body Brinzolamide Carbonic anhydrase II inhibition Suspension 1 BID to TID Dorzolamide Carbonic anhydrase II inhibition Solution 1 BID to TID Systemic Acetazolamide a Carbonic anhydrase ase II inhibition Capsule Methazolamide Carbonic anhydrase II inhibition Tablet Combinations Timolol-dorzolamide Solution 1 BID Timolol-brimonidine Solution 1 BID TID = three times daily.

33 Summary of Class-Specific ADRs Drug Class Side Effects Prostaglandin agonists Beta-adrenergic blockers Alpha-adrenergic agonists CAIs Nonspecific (dipivefrin) Hyperemia (25% to 45%), pigmentation of the iris, eye lids, and lashes (2% to 6%) and hypertrichosis (15% to 45% with bimatoprost), t) dry eye (2% to 6%) Localized stinging (5% to 15%), hyperemia, somnolence, decreases in HR and BP, bronchospasm Hyperemia (10% to 20%), itching (pruritus 10% to 20%), foreign object sensation (5% to 9%), decrease BP and/or HR, dizziness, allergic reactions Burning and stinging, blurred vision, punctate keratitis Headache, tearing, burning, stinging, hyperemia (1% to 10%), photophobia ADRs = adverse drug reactions; HR = heart rate; BP = blood pressure. American Hospital Formulary Service (AHFS) Drug Information Bethesda, MD: American Society of Health System Pharmacists; 2011.

34 Hyperemia

35 Hyperpigmentation p

36 Generic Ophthalmic Medications Testing of innovator and generic ophthalmic products Prior to 1992, the FDA used to permit changes in inactive ingredients for ophthalmic generic products without testing After 1992, generic ophthalmic solutions must have 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. /practiceguidelines/clinicalstatements_content.aspx?cid=e90121fe-1a9d-4030-a f54cf23f5. Accessed February 20, 2012.

37 Adherence to Topical Ophthalmic Medications Percentage of Patients Rema ining on Medication Beta-blockers Alpha-agonists Prostaglandins CAIs Months After Treatment Initiation Diagnosed Glaucoma Alpha-agonists 6 Prostaglandins CAIs Months After Treatment Initiation Glaucoma Suspect Beta-blockers 36 Nordstrom BL, et al. Am J Ophthalmol. 2005;140(4):

38 Strategies to Improve Adherence Actively address at-risk patients Review drug administration with Simplify and optimize treatment each refill regimen when possible Suggest that patients keep a Reduce drug costs when medication diary possible Use telephone or mail reminders Understand the patient s health when possible beliefs about glaucoma Suggest the patient incorporate Provide patient-disease drops into daily activities education Involve a helpful Reinforce regularly caregiver/family member Use verbal and written delivery Use open communication Adapt information to those with poor vision or low literacy Ask-tell-ask dialogue Motivational interviewing Stages of readiness for change Budenz DL. Ophthalmology. 2009;116(11 suppl):s43-s47.

39 Glaucoma Surgery Laser Trabeculoplasty 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 Surgery Trabeculectomy Filtering 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 Shunts Aqueous 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. /content.aspx?id= Accessed March 14, 2012.

40 Figure 1: Incisional Glaucoma Surgery: Trabeculectomy Figure 2: Laser Trabeculoplasty Accessed April 28, Accessed April 28, 2011.

41 Audience Response Question Dry eye incidence and severity of symptoms is correlated with the number of ocular medications in use. 1. True 2. False

42 Ocular Surface Anatomy Meibomian glands

43 Dry Eye Syndrome, Dry Eye Disease, or Dysfunctional Tear Syndrome A multifactorial disease of the tears and ocular surface that is characterized by: Increased osmolarity of the tear film Tear film instability Inflammation of the ocular surface Ocul Surf. 2007;5(2): Perry HD, et al. Curr Opin Ophthalmol. 2004;15(4):

44 Symptoms of Dry Eye Syndrome Patients usually ypresent with the following complaints: Painful or sore eyes Burning/stinging, redness (hyperemia) Foreign body sensation Blurred or poor vision Photophobia Tired eyes Paradoxical tearing Dryness worse later in the day Contact lens intolerance

45 Pictures of Dry Eye Syndrome

46 Prevalence and Risk Factors for Dry Eye Dry eye is a significant public health problem US statistics 7 million Americans over 40 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: Age Menopause Glaucoma Schaumberg DA, et al. Am J Ophthalmol. 2003;136(2): Moss SE. Arch Ophthalmol. 2000;118(9): Schaumberg DA, et al. Arch Ophthalmol. 2009;127(6):

47 OSD Prevalence Study: Conclusions OSD is a significant problem for many glaucoma patients (48.4%) Prevalence is much higher than previously reported 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):

48 Major Categories of Dry Eye Syndrome Both categories are characterized by increased tear film osmolarity and ocular surface inflammation Aqueous Deficient-State Lack of tear production Evaporative State Rapid tear evaporation (Intrinsic or Extrinsic)

49 Dry Eye Cascade: Causes and Contributing Factors of Abnormal Tear Film Healthy Ocular Surface Observable Pathophysiologies Aqueous Deficiency TBUT Less Than Blink Rate Mucin Abnormalities Aging Smoking Dry environment Hormonal changes Contact lens Blepharitis LASIK Auto-immune disease Alcohol use Pollution Computer use Antidepressants Specific preservatives in topical medications Abnormal or Insufficient Tears Reduced Tear Clearance Increased Ocular Osmolarity Irritation Increased Cytokines Inflammation TBUT = tear film breakup time; LASIK = laser-assisted in situ keratomileusis. Gayton JL. Clin Ophthalmol. 2009;3:

50 Healthy Tear Film With Lipid, Aqueous, and Mucin Layers and Healthy Ocular Surface With Intact Microvilli Gayton JL. Clin Ophthalmol. 2009;3:

51 Progressive Damage of Corneal Surface Cells (Lost Microvilli) Due to Unhealthy Tear Film Gayton JL. Clin Ophthalmol. 2009;3:

52 Commonly Used Drugs Associated With Dry Eye Antihistamines Antidepressants especially tricyclic antidepressants Anticholinergics Diuretics Angiotensin-converting enzyme inhibitors Oral contraceptives Opioid narcotics Antiparkinsonism agents Beta-blockers Antipsychotics Anxiolytics benzodiazepines

53 Mild/Moderate Patient 63-year-old female with POAG 63 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

54 When May BAK Use Be Most Problematic? High BAK concentration: cell death is dose-dependent dependent High concentration in a single drop or due to the accumulation of dose with multiple drops % BAK 0.01% BAK 0.05% 0.1% BAK Growth arrest Apoptosis Necrosis 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): Cha SH, et al. Clin Experiment Ophthalmol. 2004;32(2):

55 Therapeutic Approaches 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

56 Nonpharmacologic Options Remove/avoid offending agent or condition First identify environmental changes Wear glasses decrease evaporation of tears Adjust vents Adjust ceiling fans avoid air currents Control humidity and a humidifier Take frequent breaks from looking at a computer screen or other visually demanding tasks Discontinue or avoid smoking Pharmacists should review potential offending prescription and non-prescription p o medications Dietary changes Reduce alcohol Add omega-3, fish oils, and/or flaxseed

57 Therapeutic Options Artificial Tears Lipid-containing artificial tears Preservative-free artificial tears Artificial tears with solutes Hypotonic artificial tears Ophthalmic gels and ointments Goal is to improve symptoms (but these agents do not heal or repair the ocular surface) Useful in patients with meibomian gland dysfunction as they tend to stabilize tear film by increasing the existing tear film layer Useful in moderate to severe dry eye patients who require artificial tears more than 4 times a day. They avoid ocular surface damage from preservatives Beneficial for patients with excessive tear film evaporation Decrease the osmolarity of the tear film Useful in severe cases and in patients with incomplete eyelid closure Korb DR, et al. Optom Vis Sci. 2005;82(7): Noecker R. Adv Ther. 2001;18(5): Garrett Q, et al. Invest Ophthalmol Vis Sci. 2007;48(4): Troiano P, et al. Cornea. 2008;27(10):

58 Commercial Artificial Tear Products Product Ingredients CMC CMC 0.5%, glycerin, erythritol, levocarnitine, Purite preservative CMC 0.5%, Purite preservative CMC 1%, Purite preservative CMC 0.25%, hypotonic, preservative free PEG PEG %, propylene glycol 0.3%, hyproxypropyl guar gel forming matrix and polyquaternium preservative PEG %, propylene glycol 0.3%, hyproxypropyl guar gel forming matrix with sorbitol* and polyquaternium preservative PEG %, hyaluronic acid, sodium chlorite preservative Brand Name Optive Refresh Tears Refresh Liquigel Thera Tears Systane Systane Ultra Blink Tears *Addition of sorbitol is promoted to produce less blurred vision. CMC = carboxyl methylcellulose; PEG = polyethylene glycol.

59 Commercial Artificial Tear Products Product Ingredients HPMC HPMC 0.3%, Dextran %, bicarbonate, zinc HPMC 0.3%, Dextran %, glycerin 0.2%, polyquad 0.001% preservative HPMC 0.3%, Dextran %, polyquad 0.001% preservative HPMC 0.3%, Dextran %, preservative free HPMC 0.3%, sodium perborate preservative Brand Name Bion Tears Tears Naturale Forte Tears Natural II Tears Natural Free Genteal* HPMC 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.

60 Anti-inflammatory Agents Anti-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 ocular surface inflammation and symptoms Oral tetracyclines Used for patients with ocular rosacea and blepharitis Topical cyclosporine 0.05% Used in aqueous-deficient states Oral omega-3 fatty acid supplements Meibomian i gland dysfunction and evaporative states Marsh P, et al. Ophthalmology. 1999;106(14); Frucht-Pery J, et al. Am J Ophthalmol. 1993;116(1): Sall K, et al. Ophthalmology. 2000;107(4): Macsai MS. Trans Am Ophthalmol Soc. 2008;106:

61 Role of Topical Corticosteroids in Dry Eye All patients with dry eye have ocular inflammation Not indicated for patients with mild dry eye responsive to artificial tears If patients do not respond to artificial tears with continued signs of conjunctival redness, a course of topical steroids should be added Advantage to topical corticosteroids t id is rapid onset of action Short-term therapy is most appropriate because of the risk of elevating IOP and cataracts May be used in combination with cyclosporine Why?

62 Cyclosporine Therapeutic issues for the pharmacist 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 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; 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

63 Dry Eye Treatment Guidelines Severity Level* Signs and Symptoms Recommended Treatment 1 Mild to moderate symptoms and no signs Mild to moderate conjunctival signs 2 Moderate to severe symptoms Tear film signs Mild corneal punctate staining Conjunctival staining Visual signs 3 Severe symptoms Marked corneal staining Central corneal staining Filamentary keratitis 4 Severe symptoms Severe corneal staining, erosions Conjunctival scarring Patient counseling, preserved tears, environmental management, allergy eye drops, water intake, hypoallergenic products If no improvement go to 2 Unpreserved tears, gels, ointments, topical steroids, topical cyclosporine, nutritional support If no improvement go to 3 Tetracycline, punctal plugs If no improvement go to 4 Systemic anti-inflammatory therapy, oral cyclosporine, moisture goggles, punctal 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):

64 Nutritional Supplements in Dry Eye Essential fatty acids flaxseed oil and omega-3 fatty acids May reduce inflammation in meibomian gland dysfunction, rheumatoid arthritis, and tear gland inflammation May improve the oily layer of tear film In a pilot-prospective, randomized, double-masked, placebo-controlled trial of omega-3 fatty acid supplementation: 70% of patients became asymptomatic and 30% experienced improvement in symptoms from moderate to mild Wojtowicz JC, et al. Cornea. 2011;30(3):

65 Dry Eye Treatment Pipeline Product Name Active Principle Clinical Trial Phase Rebamipide 2(1H)quinolone derivative 3 (ongoing) Ecabet sodium 12-sulfodehdroabietic acid (natural phenantrene-type compound) 2b (concluded) Idestrin (NP50301) 17beta-estradiol ester 2b (concluded) Prolacria Diquafosol (P2Y2 receptor 3 (concluded in US; ongoing in agonist) Japan) Vekacia Cyclosporin A 3 (ongoing) Civamide Cis-capsaicin (zucapsaicin) TRPV- 1 receptor modulator, neuronal calcium channel blocker 3 (nasal formulation in cluster headache) ST-603 Cyclosporin 3 (commenced April 2007) ALTY-0501 Doxycycline 3 (concluded) AL-2178 (FID ) Rimexolone 3 (ongoing since July 2006)

66 Pharmacist Counseling Pearls About Lifestyle and Ocular Disease POAG Smoking cessation, alcohol avoidance, antioxidants and vitamins do not seem to be risk modifiers Marijuana Bilberry and ginko biloba b do not have significant ifi impact on IOP Dry Eye Smoking cessation is a risk modifier and may help improve symptoms Coffee drinking and moderate alcohol may be beneficial but data are mixed Essential fatty-acids: omega-3 Vitamins and antioxidants are not helpful Kang JH, et al. Am J Epidemiol. 2003;158(4):

67 ARMD Pharmacist Counseling Pearls About Lifestyle and Ocular Disease (cont) Smoking cessation Sunglasses UV protection 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 eye 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 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 prevent copper deficiency anemia from high-dose zinc. ARMD = age-related macular degeneration; AREDS = Age-related Eye Disease Study.

68 Color Code for Topical Ocular Medications Tan: Indicates anti-infectives 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-blockersblockers 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. Accessed March 15, 2012.