Glaucoma: Treatment Goal

1
Glaucoma Treatment Goal

• The goal of glaucoma treatment is to preserve
  the visual field of patients and prevent the loss
  of visual function that is associated with the
  disease.
• Ref Survey of Ophthalmology 2003 Vol. 48(1)
  S1-S3

2
Getting to the Targets of Glaucoma Management

• You need a drug that
• fulfills all the
• 3 targets for
• glaucoma
• management

3

• INTRODUCING LATANOPROST
• THE GOLD STANDARD PROSTAGLANDIN ANALOGUE

4
Latanoprost Pharmacology

• Latanoprost is a prodrug of latanoprost acid
• Latanoprost is hydrolysed to its active form in
  cornea or in plasma
• Ref Drugs and Ageing 1999 14(5) 387-398

5
Latanoprost Pharmacodynamic Properties

• Ocular effects
• Reduction in IOP occurs within 3-4 hours, peaks
  within 8-12 hours and persists for upto 24 hours
  or longer after topical application
• Similar efficacy during day-time and night-time
  hours
• Maximum effect achieved with a concentration of
  50 mcg/ml given once daily in the evening
• Once daily administration is superior to twice
  daily (related to the loss of some of the effect
  due to development of receptor subsensitivity)
• Ref 1. Drugs and Aging 1999 14(5) 387-398 2.
  Drugs and Aging 2003 20(8) 597-630 3. AHFS
  2000 2596-2600 4. Can. J. Ophthalmol 33(5)
  1998 255-266

6
Why Latanoprost to be administered at 9 pm

• 9 pm Prime time for instillation of Latanoprost

7
Why Latanoprost Instillation at 9 p.m.

• In patients with POAG or OHT, IOP is
  characterized by a peak in the morning (between 8
  and 10 a.m.)

Ref 1) Hospital Medicine Sept 2002 63(9)
540-544
8
Why Latanoprost Instillation at9 p.m.

• Maximum IOP lowering effect of Latanoprost
  achieved at 12 hours
• Ref Surv. Ophthalmol 2002 47 (suppl 1) S90-S96

9
Why Latanoprost Instillation at9 p.m.
Latanoprost instilled at 9 pm
10
Why Latanoprost Instillation at9 p.m.

• When a glaucoma patient instills latanoprost at 9
  pm, the maximum IOP lowering effect is after 12
  hours i.e. at 9 am (and thats also the time when
  IOP is at its peak)
• Therefore 2 peaks meet i.e. the IOP at its peak
  Latanoprost at its peak

11
Latanoprost Instillation at 9 pm

• Purpose
• To compare the IOP reduction induced by timolol
  0.5, latanoprost 0.005 and dorzolamide in
  patients with POAG or OHT
• Methods
• In this crossover trial 20 patients with POAG
  over OHT were treated with timolol (8 am and 8
  pm), latanoprost (9 pm) and dorzolamide(8 am, 2
  pm, 8 pm) for 1 month. IOP measurements were
  taken at 3,6 and 9 am and noon and at 3,6 and 9
  pm at midnight
• Ref. IOVS 2000412566-2573

12
Latanoprost Instillation at 9 pm
Latanoprost when instilled at 9 pm effective
controlled IOP at 9 am
Baseline
Latanoprost
0
13
FLUCTUATIONS IN IOP

• Not only controlling peak IOP is important but
  the drug should also control fluctuations in IOP

14
Latanoprost Proven for 24 hour IOP Control

• Purpose
• To compare the around the clock IOP reduction
  induced by timolol 0.5, latanoprost 0.0005 and
  dorzolamide in patients with POAG or OHT
• Methods
• In this crossover trial 20 patients with POAG
  over OHT were treated with timolol (8 am and 8
  pm), latanoprost (9 pm) and dorzolamide(8 am, 2
  pm, 8 pm) for 1 month. IOP measurements were
  taken at 3,6 and 9 am and noon and at 3,6 and 9
  pm at midnight

15
Latanoprost Proven for 24 hour IOP Control

• Latanoprost when instilled at 9 p.m. effectively
  lowered IOP at 3, 6 and 9 a.m. at noon at 9 p.m.
  and at midnight
• Latanoprost compared to other agents lead to a
  fairly uniform circadian reduction in IOP
• Ref Invest ophthalmol Vis Sci 2000 41
  2566-2573

• Ref Invest Ophthalmol Vis Sci 2000 41 2566-2573

16
Latanoprost Monotherapy

• In well-controlled clinical trial including
  patients with open-angle glaucoma or ocular
  hypertension (IOP gt 21 mmHg), monotherapy with
  latanoprost reduced IOP levels by

22-39 over 1 to 12 months treatment
Ref Drugs and Aging 2003 20(8) 597-630
17
Latanoprost Superior IOP Reduction
Latanoprost (once daily)(n187)Baseline IOP
25.0 mm Hg
Brimonidine(twice daily)(n192)Baseline IOP
25.0 mm Hg
Latanoprost (once daily)(n109)Baseline IOP
27.2 mm Hg
Dorzolamide(twice daily)(n104)Baseline IOP
27.2 mm Hg
Superior IOP reduction compared to Topical
a2-agonist and CAIs
21 Reduction
21 Reduction
28 Reduction
31 Reduction
Plt0.001
Plt0.001
In a 6 month, randomised, observer-masked study,
patients were treated with Latanoprost or with
brimonidine
In a 3 month, open-label, randomised, study,
patients were treated with Latanoprost or with
Dorzolamide
18
Latanoprost Comparison with other PG Analogues

• XLT Trial
• The only trial comparing the efficacy and
  tolerability of Latanoprost, Bimatoprost and
  Travoprost.
• Ref Am. J. of Ophthalmology 2003 135 688-173

19
No Difference in Mean Diurnal IOP Reduction
Across 12-Weeks Study
Mean Diurnal IOP (mm Hg)
Time (Weeks)
20

• For more than 20 years we have used timolol
  first then added other medications.
• Is it now time to use latanoprost first and add
  other medications if necessary? I think it is
  now time to change this 20 year paradigm.
• Professor or T. Zimmerman,
• University of Louisville, Kentucky, USA
• at the From the Glaucoma in the 21st century
  Conference
• Hong Kong, China, 14-17 Dec. 1999

21
Latanoprost Approved for first line Treatment of
ElevatedIntraocular Pressure

• Latanoprost is approved by U.S. Food and Drug
  Administration (FDA), as a first line treatment
  for elevated (IOP) associated with open angle
  glaucoma or ocular hypertension
• http//www. medscape.com assessed on 18/11/03

22
Latanoprost Adjunctive Therapy

• The range of reported additional reductions in
  IOP with Latanoprost as adjunctive therapy
• Ref 1) Surv. Ophthalmol 47 (suppl 1) S133-140,
  2002

Latanoprost-timolol ? 13-37 Latanoprost-pilocarpi
ne ? 7-14 Latanoprost -CAIs ?
15-24.1 Latanoprost dipivefrin ? 15-28
23
Latanoprost Adjunctive Therapy
-4.2mmHg
-6.3mmHg
Reduction in IOP mmHg

• Ref Surveys of Ophthalmology 2002 47 (suppl
  1) S133-S140

24

• Latanoprost reduces the need for surgery in
  glaucoma patients
• Ref 1) J of Glaucoma 2000 9 183-186
• 2) Drugs of future 1998 23(8) 908-911

25
Latanoprost Ocular Hyperemia

• Ocular hyperemia is defined as an excessive
  reddening of the conjunctiva as a consequence of
  vasodilation.
• Compromises the outcome of filtration surgery
• Represent a cosmetic problem to the patient
  thereby leading to noncompliance.
• Conjunctival hyperemia typically is worse the
  second day after beginning dosing.
• Hyperemia abates by day 5 and to be steady from
  week 2 upto month 6.
• Ref 1. J of Ocular Therapeutic 2003 vol. 19
  (1) 23 35
• 2. Am J of Ophthalmology 2003 135 314 320

Latanoprost - 5 - 15 Bimatoprost - 15 -
45 Travoprost - 35 - 50
26
Latanoprost Allied Indications

• Control of Post-operative IOP spikes
• Reducing Intraocular Pressure in
• Primary angle closure glaucoma
• Steroid induced glaucoma
• Pigmentary glaucoma
• Paediatric glaucoma

27
Latanoprost Indications

• Latanoprost sterile ophthalmic solution is
  indicated for the reduction of IOP in patients
  with open angle glaucoma or ocular hypertension.

28
Latanoprost Dosage and Administration

• One drop (1.5 ?g) in the affected eye(s). Once
  daily in the evening
• Solution should not exceed once daily since it
  has been shown that more frequent administration
  may decrease the IOP lowering effect
• Reduction of IOP starts approximately 3-4 hours
  after administration and the maximum effect is
  reached after 8-12 hours
• If more than one topical ophthalmic drug is being
  used, the drugs should be administered at least
  (5) minutes apart

29
Latanoprost Special Population

• Pregnancy Category C used on a risk-benefit
  ratio
• Lactation Caution to be exercised
• Paediatrics Safety not established

30
Latanoprost Storage

• Protect from light. Store unopened bottle(s)
  under refrigeration and 2o to 8o C (36o to 46o
  F). Once a bottle is opened for use, it may be
  stored at room temperature up to 25o C (77o F)
  for 6 weeks.