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An Overview of New Developments American Academy of Ophthalmology

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An Overview of New Developments American Academy of Ophthalmology Powered By Docstoc
					Glaucoma: News and Views


   Andrew G. Iwach, M.D.
        Associate Clinical Professor
    University of California, San Francisco
          San Francisco, California
                                              Disclosure
                      Financial relationships to disclose:
• I have the following financial interests or

• Consultant
   –   Carl Zeiss Meditec
   –   Clarity Medical Systems
   –   IRIDEX
   –   Lumenis, Inc.
• Lecture Fees
   –   Alcon Laboratories, Inc.
   –   Carl Zeiss Meditec
   –   IRIDEX
   –   ISTA Pharmacuticals
   –   Lumenis, Inc.
   –   Laserex Systems, Inc.
   –   Merck U.S. Human Health
   –   Optonol
   –   Pfizer Ophthalmics
                      The Glaucoma Graph
                                                 Age at Presentation & Target IOP
          DDLS            Stage       0a
                                     0b
                                      1
          At Risk
                                      2
                                      3
                                      4
          Glaucoma
          Damage                      5
                                      6

          Glaucomatous                7a
          Disease                    7b
                                    Birth                                       Death

The glaucoma graph coordinates a patient’s age with the three main stages of glaucoma.
As presented by George Spaeth, M.D.
           Glaucoma Therapeutic Option Timeline

                                                                                         Betagan
 Pilocarpine           Epinephrine                            Dipivefrin                 Betopic
                                                                                         Timoptic



1870s ‘80s ‘90s 1900s        ‘10s    ‘20s   ‘30s   ‘40s     ‘50s   ‘60s    ‘70s   ‘80s    ‘90s 2000s

                                            Acetazolamide                    Alphagan       Lumigan
                                                                            Alphagan P      Ocupress
                                                                               Azopt         Rescula
                                                                              Betimol     Timoptic XE
                                                                            Betoptic-S      Travatan
                                                                            Combigan       Travatan Z
                                                                              Cosopt        Trusopt
                                                                              Istalol       Xalatan


               IOP REDUCTION            SAFETY                 OPTIC NERVE HEALTH
                           IOP Lowering Medications
                            NRx Shares 2001 - 2008
                                             NRx EQUN Share
  50%



  40%
                                                                                   PGs



  30%


                                                                                   Total BBs
  20%

                                                                                   Alpha Agonists
  10%                                                                              Tim/Dorz
                                                                                   CAIs

   0%
     2001         2002         2003         2004   2005   2006   2007   YTD 2008

Source: WK Health NRx Share 2001-YTD 2008
                                 The Concept of Persistency
                                             Impacting Factors
                          100
                           90
Persistent Patients (%)




                           80
                           70
                           60
                           50
                           40
                           30
                           20
                           10
                            0
                                  3 mo                    6 mo       9 mo                  12 mo
                                Ideal                            With added side effects
                                After human complacency/denial   With economic issues
                                With complicated dosing
   Patients on More Than
One IOP-Lowering Medication
                 2 Medications
                    24.4%            3 Medications
                                    5.6%
                                      0.2%
                                           4 Medications




         69.8%
    1 Medication


                                 Source: Verispan’s PDDA, MAT Nov 2006.
                                Compliance Challenges
                                                               “…in the long run, single drugs that do the work of
                                                               more than one drug…likely would enhance
                                                               compliance.”
                                                                               - George L. Spaeth, M.D.



50%
40%
                             49%
30%                       Compliant                                                32%
20%                                                                              Compliant
10%
0%
                 One Medication                                     Multiple Medications
                        (N = 41)                                               (N = 31)

      Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26(3):234-236
                      The Washout Effect
            45
            40
            35
            30
            25
            20                                                                 % Loss of First Drug
            15                                                                 Effect
            10
             5
             0
                  30 Second        2 Minute         5 Minute
                   Interval        Interval         Interval

Chrai SS, Makoid MC, Eriksen SP, Robinson JR. Drop size and initial dosing frequency problems of
topically applied ophthalmic drugs. J Pharm Sci. 1974; 63(3): 333-338.
    Advantages of Fixed Combinations

•   Dosing-one drop vs. two drops
•   Convenience may help patient compliance
•   No risk of washout from second drug1
•   Possible cost savings (only 1 co-pay)




                                    Choudhri et al. Am J Ophthalmol. 2000.
Review of Fixed Combinations Studies




                             Cox JL, et al: BJO 2008;92:729-734
Short and Long-Term Efficacy
of Cosopt
     Figure 1: Mean Peak (Comparative Study) IOP
                         28

                         27                           TIMOPTIC 0.5% b.i.d. (n=110)
                                                      TRUSOPT t.i.d. (n=109)
                         26
                                                      COSOPT b.i.d. (n=112)
                         25

                         24

                         23                                                                     6.3 mmHg
           Mean IOP
         (mmHg) Hour 2
                         22

                         21

                         20

                         19
                                                                                                2.7 mmHg
                         18
                                                                                p=(to come)
                         17                                                         P<0.001
                              Baseline   Week 2   Month 1             Month 2         Month 3
                                                        Examination


         Figure 1 graphically depicts the peak data. At peak, COSOPT twice daily reduced IOP
         about 33% ( 9.0 mm Hg) from untreated baseline values, compared with about 20% with
         dorzolamide three times daily (5.4 mm Hg) and 23% (6.3 mm Hg) with timolol twice daily.
                  18
                            Baseline Week 2 Month 1          Month 2         Month 3


Short and Long-Term Efficacy of Cosopt          Examination



    Comparison of COSOPT to Concomitant Therapy

           Figure 4: Mean Trough IOP - Equivalence Study

                       27
                                             Timolol baseline
                       26
                                                                       TIMOPTIC 0.5% b.i.d. +
                       25                                              TRUSOPT 2.0% t.i.d. (n=120)

                       24                                              COSOPT b.i.d. (n=119)
         Mean IOP
       (mmHg) Hour 0
                       23

                       22

                       21

                       20

                       19

                       18
                              Baseline Week 2 Month 1           Month 2        Month 3

                                                      Examination
                                                                 Results
                         25
                                     Successfully switched
                                     Unsuccessfully switched
                         20
         # of Patients




                         15


                         10


                          5


                          0
                              -15 -8         -7      -6     -5      -4     -3      -2      -1      0      1       2      5       6      10
                                                          Change in Pressure
Bacharach J., Delgado MF, Iwach AG: Comparison of the Efficacy of the Fixed-Combination Timolol/Dorzolamide Versus Concomitant Administration of Timolol and
Dorzolamide. Journal of Ocular Pharmacology and Therapeutics 2003; 19(2):93-6.
                                               ™
                          COMBIGAN

• Fixed combination of…
   – Alpha-agonist brimonidine 0.2%
   – Beta-blocker timolol 0.5%
• Preserved with 0.005% benzalkonium
  chloride (BAK)
   – Generic timolol is preserved with 0.01%
                       Mean IOP – 10 AM
• Brimonidine/timolol fixed combination at peak

      24

      20

      16
               *   *      *                 *                     *                    *
      12
                                 Brimonidine TID (n = 382)
                                 Timolol BID (n = 392)
       8
                                 Brimonidine/timolol BID (n=385)

       4
                                           *P < .001 vs brimonidine or timolol
       0
           0               3                 6                     9                  12
                                    Months of treatment
   Statistical significance does not necessarily correlate to clinical significance.
                                    1Sherwood    et al. Arch Ophthalmol. 2006; 2Data on file, Allergan, Inc.
                     Diurnal Mean IOP at Month 12
                                       Dose all treatments
                                                                                       Dose brimonidine

                       20

                                   *
Mean IOP (mm Hg)




                       16         **                                               *             *
                                                   *                              **
                                                  **
                       12
                                          Brimonidine (n = 382)
                                          Timolol (n = 392)
                        8
                                          Fixed brimonidine/timolol (n = 385)

                        4                                                  *P < .001 vs timolol
                                                                          **P < .001 vs brimonidine
                        0
                                8 AM          10 AM                              3 PM          5 PM
                   Statistical significance does not necessarily correlate to clinical significance.
                                                                              Sherwood et al. Arch Ophthalmol. 2006.
                               Treatment-Related Adverse Events

                          40
                                      Fixed brimonidine/timolol BID (n = 385)
                          35          Brimonidine 0.2% TID (n = 382)
 Percentage of patients




                                      Timolol 0.5% BID (n = 392)                           *P ≤ .03 vs brimonidine 0.2% TID
                          30                                                              **P ≤ .02 vs timolol 0.5% BID
                          25

                          20      *
                          15
                                 **                                      5.2%
                          10
                                                                             *                *
                                               *              *             **               **
                          5                                                                                  *
                          0
                               Conjunctival    Ocular         Eye          Allergic        Conjunctival        Oral
                                hyperemia     stinging      pruritus     conjunctivitis      follicles       dryness


• Oral dryness and adverse events related to conjunctival allergy/inflammation significantly less
  common with fixed brimonidine/timolol than with brimonidine
                                                                                            Sherwood et al. Arch Ophthalmol. 2006.
Laser Trabecular Therapy History

  1979   Argon Laser [488 nm blue-green, 514 nm green ]
  1984   Krypton Laser [red 647.1 nm, yellow 568.2 nm]
  1988   Nd:YAG Laser [1064 nm]
  1990   Diode Laser [810 nm]
  1996   Solid State “ALT” [532 nm]
  2001   Frequency Doubled Nd:YAG laser: SLT [532 nm]
  2006   Diode MicroPulse Laser: MLT [810 nm]
  2008   Titanium:Sapphire Laser [790 nm]
                          Laser Differences

             1064 nm
                       Q-switched
                       Nd:YAG

                                    MicroPulse    Diode - LTP or
             810 nm
Wavelength




                                                  cyclophoto




             532 nm                               532-green LT
                         SLT
                                                  Argon LT
             514 nm

                        3 nsec                         CW (0.1 sec)

                                 Pulse Duration
           Human Trabecular Meshwork




    ALT                          SLT                           MLT

• MLT and SLT Cause Less Damage than ALT
• MLT and SLT Create Similar Morphologic Effects
                                                   Fudemberg SJ, Katz J et al ARVO Poster 2008
Laser Trabeculoplasty Technique
          Surgical Trends: 1994-2006
200000
180000
160000
140000                                                Trabec
120000                                                Tube
100000                                                CPC
 80000                                                LTP
 60000                                                LPI
 40000
 20000
     0
         94
         95
         96
         97
         98
         99
         00
         01
         02
         03
         04
         05
         06
      19
      19
      19
      19
      19
      19
      20
      20
      20
      20
      20
      20
      20
 Medicare data, courtesy of Dr. William L. Rich III
Glaucoma Center of San Francisco




  www.GlaucomaSF.com

				
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