Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Saturday, March 24 - Eyeing What’s New in Ophthalmic Pharmacotherapy

47 views

Published on

Eyeing What’s New in Ophthalmic Pharmacotherapy
0006-0000-18-012-L01-P | .1 CEU |
Linda J. Margulies, MD

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

Saturday, March 24 - Eyeing What’s New in Ophthalmic Pharmacotherapy

  1. 1. EYEING WHAT’S NEW IN OPHTHALMIC PHARMACOTHERAPY Linda J. Margulies, M.D. University of California, Davis Veterans Affairs Northern California Health Care System
  2. 2. Disclosure  Own stock, Merck, Pfizer Pharmaceuticals  The content of this presentation represents the opinion of the presenter and does not necessarily represent those of the VA Salvador Dali’s Spellbound (1945)
  3. 3. Topics  Anatomy  Glaucoma Medications  Dry Eye Disease Medications (Rx and OTC)  Anti Vascular Endothelial Growth Factor Medications (Anti-VEGF)  Miscellaneous Medications
  4. 4. Objectives  Enumerate the various classes of drugs that are available for the treatment of glaucoma and understand the pathophysiology of the disease.  Discuss the various medications available for the treatment of dry eye, including prescription and over the counter medications.  Identify the new developments in the pharmacologic treatment of wet and dry age-related macular degeneration, diabetic retinopathy and retinal vein occlusion.  Discuss the role of angiogenesis in the development of neovascular (wet) macular degeneration, and compare the use of the anti VEGF drugs in the treatment  List the newest drugs available to treat specific ocular diseases
  5. 5. Normal Aqueous Flow
  6. 6. Year 1982  Began my residency in 1982  Gas 91 cents a gallon  The first commercial use of genetic engineering- human insulin produced by bacteria  Michael Jackson released popular Thriller album  Glaucoma Drops - pilocarpine, epinephrine, timolol
  7. 7. MANY GLAUCOMA AGENTS
  8. 8. Glaucoma  Second leading cause of blindness in the US  Prevalence 3% in over 65 yrs  Primary Open Angle Glaucoma  Most common type of glaucoma  Disease causes optic nerve damage  Progressive cupping and nerve atrophy  Visual field loss
  9. 9. Optic Nerve Cupping Normal Optic Nerve Glaucomatous Optic Nerve
  10. 10. Normal Visual Field Visual Field Loss Glaucomatous Visual Field Loss
  11. 11. Primary Open-Angle Glaucoma  Visual Field Test Results Over Time: Progressive Scotoma
  12. 12. Glaucoma Treatment  Therapeutic goal is to reduce the intraocular pressure (IOP)  The higher the IOP the greater likelihood of optic nerve and visual field damage  Drugs mechanism of action  Decrease aqueous production  Increase aqueous outflow/drainage
  13. 13. Glaucoma Medications  Prostaglandins  β-Blockers  α-2 Adrenergic Agonists  Carbonic Anhydrase Inhibitors  Combination Medications  Miotics (rarely used)  Sympathomimetics (rarely used)
  14. 14. Prostaglandins (PGA) (teaching tool) Generic Name Brand Name Advantage Disadvantage Comments/ Cap Color QHS Effective Well tolerated No systemic effect Gold Standard Conjunctivitis Iris pigmentation Lash growth Small bottle Teal cap Increase outflow Similar efficacy 1st line therapy Bedtime Latanoprost Bimatoprost Travoprost Travoprost Z Tafluprost PF Xalatan Lumigan Travatan Travatan Z Zioptan Drug PF Generic TravZ no BAK Preservative PF single use 0.3 mm vials
  15. 15. EYELASH ENHACER  Bimatoprost ophthalmic solution 0.03% (Latisse, Allergan)  Cosmetic product  Enhance eyelash length, thickness, darkness  Initial effect at eight weeks
  16. 16. Latanoprostene Bunod (Vyzulta) New Glaucoma Drug  Vyzulta ( Bausch & Lomb)  Prostaglandin analog  latanoprostene bunod solution, 0.024%  Q HS, 5ml, IOP decrease 7-9 mm, teal  Dual mechanism action  Metabolizes: latanoprost, nitrous oxide  Increased outflow  Uveal scleral and TM  Side effects similar to prostaglandins
  17. 17. β-Blockers (teaching tool) Generic Name Brand Name Advantage Disadvantage Comments/ Cap Color QD or BID Rapid onset Effective Systemic Side Effects β 1 and β 2 Advise punctal Occlusion Yellow/Blue Cap Decrease Aqueous 1st line therapy Similar efficacy Generics Timolol Carteolol Levobunolol Metipranolol Betaxolol Timoptic Betimol, Istalol Timoptic XE Ocupress Betagan Optipranolol Betopic S PF timolol unit dose XE gel forming Compliance cap β 1 selectivity
  18. 18. Alpha 2- Adrenergic Agonist (teaching tool) Generic Name Brand Name Advantage Disadvantage Comments/ Cap Color BID Effective BID or TID Conjunctivitis Tachyphylaxis Dry mouth , Fatigue Purple/White Cap Decrease Aqueous Additive therapy Generic neuroprotective ? Brimonidine 0.2% Apraclonidine 1% Alphagan P 0.15% and 0.1% Iopidine 1% Use only for Pre/Post Laser, control IOP spikes High allergy rate with chronic use P- neutral PH and purite preservative less allergy Two single unit vials- foil wrapped
  19. 19. Carbonic Anhydrase Inhibitors (CAI) (teaching tool) Generic Name Brand Name Advantage Disadvantage Comments/ Cap Color PO med effective Topical – minimal systemic effects PO- Systemic Side Effects Topical Less effective TID Decrease Aqueous White/Orange Additive Therapy Generic Acetazolamide Methazolamide Dorzolamide Brinzolamide Diamox Neptazine Trusopt Azopt Both po meds Poorly tolerated Ocumeter bottle Less Stinging
  20. 20. Fixed Combination Medications (teaching tool) Generic Brand Comments Dorzolamide /Timolol BID Brimonidine/Timolol BID Brinzolamide/Brimonidine Prostaglandin/Timolol Cosopt Cosopt PF Combigan Simbrinza Not in USA BID dosing- may be less effective than non combination Improved compliance with combination therapies May reduce exposure to preservatives PF-unit dose
  21. 21. Medication Costs Medication Size (30 day supply) AWP Cost Latanoprost Generic 2.5 ml $24 - $95 Latanoprost Brand (Xalatan) 2.5 ml $244 Bimatoprost Brand (Lumigan) 2.5 ml $215 Travoprost Z ( Travatan Z) 2.5 ml $204 Tafluprost PF (Zioptan) 30 single dose units $220 Timolol Generic 0.5% 5 ml $ 6 - $17 Timoptic XE Brand 5 ml $125 - $198 Brimonidine 0.2% Generic 5 ml $18 - $32 Alphagan P brand 5 ml $175 Dorzolamide 2% Generic 10 ml $12 - $67 Dorzolamide/Timolol Generic 10 ml $12 - $122 Brinzo/Brimonidine (Simbrinza) 8 ml $180 Vyzulta 5 ml (60 day) $432
  22. 22. Netarsudil (Rhopressa)0.02% New Glaucoma Drug  New class of drug  Release Spring 2018, Aerie Pharmaceuticals,  ROCK Inhibitor (Rho Kinase) that targets the trabecular meshwork and increases outflow by inhibiting actin myosin contraction  Q HS  BAK preservatives  Conj hyperemia rate 53%  Cost ?
  23. 23. Flowchart for Glaucoma Drops Pharmacologic Treatment PGA HS Brimonidine AM/AFT(EVE) CAI topical AM/AFT (EVE) Combo bid B-Blocker AM or Combo
  24. 24. Marijuana  Tetrahydrocannabinol (THC)  Stimulate the CB1 receptor in uveal tissue  Reduce aqueous production  Increase uveal scleral outflow  IOP decrease 25-30%  Limited duration 3-4 hours  Need to smoke 6-8 x per day  For round the clock IOP reduction.
  25. 25. Summary  Glaucoma complex disease  Major public health problem  Options for medication therapy  Patient compliance very important  Requires detection, long term follow up and treatment to prevent vision loss and blindness
  26. 26. Class Color Examples (Generic Name) Dilation Agents Mydriatics Cycloplegics Red Phenylephrine Tropicamide, Cyclopentolate, Atropine Anti-Inflammatory Steroids Pink Prednisolone acetate, Fluromethalone, Difluprednate Non Steroidal Anti-Inflammatory Drugs (NSAIDs) Grey Ketorolac, Diclofenac Glaucoma Prostaglandin Analogs (PGAs) Teal Latnoprost, travoprost, Bimatoprost, Latanoprostene bunod Beta-Blockers (0.25%) Light Blue Timolol, Betaxolol, Levobunolol, Metipranolol Beta-Blockers (0.5% Yellow Timolol, Betaxolol, Levobunolol, Metipranolol Alpha Agonists Purple Brimonidine, Apraclonidine Carbonic Anhydrase Inhibitors Orange Dorzolamide, Brinzolamide Miotics Green Pilocarpine Beta-Blocker Combinations Dark Blue Brinzolamide/Timolol Dorzolamide/Timolol Alpha Agonist Combinations Mint Green Brinzolamide/Brimonidine Anti-Bacterials Tan Moxifloxacin, Gatifloxacin, Ofloxacin, Besifloxacin, Ciprofloxacin, Levofloxacin Cap Color By Drug Class
  27. 27. Dry Eye Disease (DED) Dysfunctional Tear Film
  28. 28. Dry Eye Disease (DED) Dysfunctional Tear Film  Increased complexity management options  New algorithms to help clinicians 2017  TFOS DEWS II Report 2017 (400 pages) ( Tear Film and Ocular Surface Society Dry Eyes Workshop II Report)  150 experts, from 23 countries, reviewed thousands of publications, evidence based  Aqueous and Evaporative deficient dry eye
  29. 29. What is Dry Eye New Definition DEWS ll “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” TFOS DEWS ll Report. The Ocular Surface 2017; 15(3) 269-650
  30. 30. Tear Film Composition  Mucin - tear adherence-goblet cells  Aqueous - 90% tear film, moisture/nutrition – lacrimal gland  Lipid - stability, prevent evaporation- meibomian glands
  31. 31. Pathophysiology DED Aqueous Deficient and Evaporative Dry Eye Ocular Surface (2017) 441-515 Bron, Aj et al, TFOS DEWS ll, p. 460 pathophysiology report
  32. 32. Dry Eye Disease  Variety of etiologies cause or aggravate DED  Topical medications glaucoma or other drops with preservatives (BKA benzalkonium chloride)  Oral medications- i.e. antihistamines, bp meds  Contact lens wear  Lasix  Environmental – i.e. computer use, dry environment  Systemic Diseases- i.e. rheumatoid arthritis, rosacea  Hormonal- i.e. menopause
  33. 33. DES- Signs and Symptoms  Burning, dryness, foreign body sensation, blurred vision, photophobia, crusted lids, corneal punctate erosions
  34. 34. DEWS ll - Step 1  Educate patient about condition and treatment  Modification of local environment  Education potential dietary modifications, essential fatty acids supplementation  Identification of systemic or topical medications  Lid hygiene and warm compresses  Ocular lubricants of various types  Tears, ointments
  35. 35. DEWS ll - Step 2  Non preserved ocular lubricants to minimize preservative toxicity  Tear conservation-  punctal occlusion  moisture chambers goggles  In office expression heating and expression of meibomian glands (Lipiflow)  Prescription drugs- in context of individual patient presentation and disease state
  36. 36. DED- Non Prescription OTC  Artificial Tears and Ointments  Electrolytes, preservatives, polymers for buffers, ph, prevent contamination, increase viscosity, contact time  Lipids and vitamins  Tears  Preservative - bottles  No Preservative - unit dose packaging  Disappearing presevative-Genteal (oxidizes water and oxygen)  Ointments  Emollients - petrolatum, lanolin, mineral oil  Retained longer in the eye, blur vision , best at bedtime  Preservative and preservative free
  37. 37. DEWS ll - Step 2 Prescription Drugs for DES  Topical antibiotic or antibiotic/steroid combinations to lid margins for anterior blepharitis  Topical corticosteroids (limited pulse duration)  Topical immunomodulatory agents (cyclosporin)  Topical LFA-1 antagonists drugs (lifitigrast)  Oral tetracycline or macrolide antibiotics
  38. 38. Cyclosporin Emulsion (Restasis) 0.05%  Increase tear production in patients whose tear production is suppressed due to ocular inflammation  Single unit PF vials (30 or 60)  Multidose PF bottle 5.5 /10 ml unidirectional valve  BID  AWP $611, Allergan  Protect patent, transfer to Mohawk Indian Tribe New York
  39. 39. Lifitigrast (Xiidra) 5%  Inflammation plays key role in DED  LFA-1 (lymphocyte function associated antigen)  Triggers T cell migration, activation  Release of pro-inflammatory cytokines  Blocks LFA-1 and interrupts the inflammatory cycle of DED  BID  Preservative Free, Single unit, Foil pouch  AWP $608, Shire pharmaceuticals
  40. 40. AntiVascular Endothelial (anti-VEGF)  Age Related Macular Degeneration  Diabetes  Vein Occlusions Central Retinal Vein Occlusion
  41. 41. AMD Prevalence  Incidence of AMD increases with age  18% among 70-74 years old  47% among 85 years old and older  Early AMD in 7.3 million individuals in USA  Advanced AMD 1.75 million in USA
  42. 42. Pathogenesis of AMD  ]Non Modifiable Risk Factors  Age  Race-More common in Caucasian population  Light eye color  Family History/Genetics  Mutation in Complement Factor H gene (20-50% risk)  Perhaps increased risk for inflammatory damage to retina
  43. 43. Pathogenesis of AMD  Modifiable Risk Factors  Diet  Low intake of antioxidants  High dietary fat intake  High Body Mass Index (BMI)  Hypertension  Smoking
  44. 44. Age Related Macular Degeneration  Two Forms of AMD  Non-Neovascular - “Dry AMD”  More common- 90% of all AMD  10% of severe vision loss  Neovascular AMD – “Wet AMD”  Less common  But accounts for most cases (90%) of severe vision loss
  45. 45. Age Related Macular Degeneration  Dry- Medium and large drusen (may or may not have symptoms)  Drusen -High risk (18% over 5 years) for wet AMD  Wet-Fluid, hemorrhage, lipid, distortion, vision loss  Bilateral disease
  46. 46. AMD Prevention  AREDS 2 vitamins – if high risk drusen  Healthy diets - fruits and vegetables  Dark green leafy vegetables kale, spinach, broccoli  Avoid smoking  Omega 3 fatty acids in diet  Look for and report changes in vision
  47. 47. Age Related Eye Disease Study (AREDS 2) Supplements  Antioxidants: daily dose  Vitamin C 500 mg  Vitamin E 400 mg  Lutein 10 mg,  Zeaxanthin 2 mg  Zinc oxide 80 mg  Cupric oxide 2 mg  PreservVision AREDS2  NIH 2013 trial  OK to take Multivitamin
  48. 48. Angiogenesis Plays Multiple Roles in Vascular Development  Angiogenesis is the growth of new blood vessels important in normal development and maintenance of vasculature  Angiogenesis is activated in a variety of diseases:  Proliferative eye retinopathies  Hypoxia, oxidative, inflammatory stresses  Diabetic retinopathy, Vein occlusions, Neovascular AMD
  49. 49. VEGF-A Plays a Key Role in Angiogenesis  Vascular endothelial growth factor (VEGF-A) is a powerful stimulator of angiogenesis  Angiogenesis can lead to the overgrowth of blood and leakage of permeable blood vessels in retinal diseases  VEGF-A is a pharmacologic target
  50. 50. Intravitreal Anti-VEGF For Wet AMD  Ranibizumab (Lucentis)  FDA approved 2006  Bevacizumab (Avastin)  Not FDA approved for eye  Aflibercept (Eylea)  FDA approved 2012  Intravitreal injections monthly
  51. 51. Ranibizumab (Lucentis) MARINA and ANCHOR AMD Trials  Ranibizumab (Lucentis) maintained or improved VA  ~1/3 of eyes improved at least 15 letters (3 lines)  ~70% of eyes improved or remained stable (<0 letter loss) Rosenfield et al, NEJM 2006; 355: 1419-1431 Brown et al, NEJM 2006; 355: 1432-1444
  52. 52. Potential Risks Intravitreal Injections  Infection  The most common adverse reactions are conjunctiva hemorrhage, eye pain, floaters, increased IOP, inflammation  Arteriothrombotic and cardiovascular events
  53. 53. Bevacizumab (Avastin)  Bevacizumab (Avastin)-Anti-VEGF monoclonal antibody binds all forms of VEGF-A  FDA approved for metastatic colon cancer  Not approved to use inside the eye  Lucentis and Avastin molecularly similar  Used off label
  54. 54. Bevacizumab (Avastin)  Most commonly used anti-VEGF drug  1.25 mg intravitreal monthly injection  Much less expensive-Compounded  Genentech  NIH- multicenter trial comparing  Ranibizumab to Bevacizumab (CATT Trial)  Both drugs have similar effects on visual acuity with same dosing regimen at 2 years  60% of patients in all groups had 20/40 or better vision CATT Research Group, NEJM 2011; 364: 1897-1908
  55. 55. Aflibercept (Eylea)  Released 2012 by Regeneron  Advantage is less frequent dosing for AMD  Intravitreal 2 mg dose  AMD q 4 wks x 3 months, then q 8 wks  Vein occlusions, q 4 wks  Similar side effect profile as other antivegfs  Arterial thromboembolic events 1.8% first year
  56. 56. Indications (teaching tool) Indications Ranibizumab (Lucentis) Aflibercept (Eylea) 2 mg Bevacizumab (Avastin) 1.25 mg AMD Yes (0.5mg) Yes Yes- off label Retinal Vein Occlusion Yes (0.5mg) Yes Yes- off label Diabetic Macular Edema (DME) Yes (0.3mg) Yes- First Choice if VA 20/50 or worse Yes- off label Diabetic retinopathy (PDR) Yes (0.3mg) Yes with DME Yes- off label
  57. 57. Anti VEGF Treatments  Treat monthly injections until flat on OCT  Then may extend treatment interval  Retreat based on OCT fluid and VA  If unresponsive to treatment with one drug - switch medications  Possible life long treatment
  58. 58. Anti VEGF Drug Costs Per Treatment (AWP) Generic Name Brand name Cost per injection AWP Ranibizumab 0.5 mg Lucentis $2,340 Ranibizumab 0.3 mg Lucentis $1,404 Bevacizumab 1.25 mg Avastin $ 65 (repackaged) Aflibercept 2 mg Eylea $2,220
  59. 59. Compounding / Repackaging Bevacizumab  Several isolated endophthalmitis outbreaks after intravitreal bevacizumab injection  Present 1-6 days post injection  Patients received drug compounded at same pharmacy from the same group of bevacizumab syringes  Serious complication - vision loss  VA does not compound avastin
  60. 60. Summary  Many New Advances for Treatment of Retinal Diseases  AREDS 2 Vitamins for High Risk Dry AMD  Importance of Healthy Diet, Not smoking  Anti VEGF intravitreal monthly injections is now the primary treatment of wet AMD  Anti VEGF can prevent vision loss and improve vision  Wet AMD is a chronic disease, life long treatment  Three medications available with similar efficacy
  61. 61. Summary  Ranibizumab (Lucentis) –Prevents vision loss and improves vision, expensive  Bevacizumab (Avastin) – Off label use  Most commonly used anti VEGF  Inexpensive, CATT trial proved efficacy  Aflibercept (Eylea)-Less frequent, expensive  All used for AMD, vein occlusions, diabetic retinopathy (macular edema and proliferative)
  62. 62. Intravitreal Steroids  Use for DME and Vein Occlusions  Second line agents  Triamcinolone (Triescence) 4-6 weeks  Dexamethasone (Ozurdex) 3-6 months  AWP Dexa- $1,599 Triam- $180  Side effects Steroids  Elevated IOP  Cataracts
  63. 63. Voretigene Neparvovec-Rzyl- Luxturna (Spark Therapeutics)  2018, First true gene therapy approved in USA inherited genetic disease  Mutations in a gene called RPE65.  Leber’s congenital amaurosis and Retinitis pigmentosa  Vision loss, field loss, blindness  Rare: 1000-2000 patients in USA
  64. 64. Luxturna - Gene Therapy  AAV2 adneno viral vector to replace mutated copies of RPE65 gene- delivers a normal copy of RPE65  One time surgical subretinal injection OU  Increased light perception ability to navigate obstacle course, stable up to 3 yrs  Cost $850,000 for two eyes
  65. 65. Thank you
  66. 66. Questions? All images are found on Google images unless stated otherwise

×