INNOVATIONS IN THE MEDICAL MANAGEMENT OF GLAUCOMA

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INNOVATIONS IN THE MEDICAL MANAGEMENT OF GLAUCOMA
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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

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TREATMENT ALGORITHM

• IOP gt21mm Hg
• If no cardiac or pulmonary problem
• ? Blockers

Failure
IOP controlled
IOP controlled
Continue treatment, Review every 3-6 months
Alternate monotherapy. ?2- agonist, PG, CAI
Failure
Failure
Surgery
Combination
European Glaucoma Society, 1998.
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Glaucoma Treatment Goal
LOWER IOP
VASOPROTECTION/ NEUROOPROTECTION
PERSISTENCY/COMPLIANCE
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• THE FIRST TARGET ACHIEVING A LOW TARGET IOP
  WHICH IS UNIFORM DAY AND NIGHT

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Target IOP Definition

• Target IOP may be defined as a pressure, rather a
  range of intraocular pressure levels within which
  the progression of glaucoma and visual field loss
  will be delayed or halted
• Ref Surveys of Ophthalmology 2003 48 (suppl 1)
  53-57

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AAO Guidelines Target IOP
reduction from baseline
Ref Surveys of Ophthalmology 2003 48 (suppl 1)
53-57
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FLUCTUATIONS IN IOP
REQUIREMENT OF AN AGENT FOR PROVEN 24-HOUR
CONTROL

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

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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

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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
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• 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

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• THE SECOND TARGET VASOPROTECTION/
• NEUROPROTECTION

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GLAUCOMA OPTIC NERVE DAMAGE
Rise in IOP gt 21 mm Hg Mechanical back
pressure On the junction of optic
nerve/retina Reduce the blood supply to the optic
nerve (prolonged AVP time) Loss of blood supply
(lt in pOBF) Ischaemia RGC cell loss
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Dorzolamide Vasoprotection

• Vasoprotection
• May be effective in preventing damage resulting
  from vascular dysfunction of eye
• Can lead to improved visual function

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Dorzolamide Vasoprotection
Baseline 2.53 secs

Retinal AVP times were significantly shortened
after dorzolamide application compared to
baseline examination (p 0.009) indicating
improved blood flow. Neither timolol nor
latanoprost resulted in any significant retinal
AVP time changes
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Dorzolamide Vasoprotection

• Dorzolamide accelerates blood velocity in the
  optic nerve head
• Dorzolamide treatment may benefit optic nerve
  head preservation
• Significantly shortens AVP times as compared to
  timolol and latanoprost
• Significant effect on visual fields and ocular
  blood flow in POAG patients
• Significantly improves contrast sensitivity in
  NTG patients.
• Dorzolamide treatment may significantly improve
  visual function
• Benefit patients with retinal or optic nerve head
  vascular insufficiency

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BRIMONIDINE THE NEUROPROTECTIVE a2 AGONIST

• IOP lowering is the main aim of any anti-glaucoma
  agent.
• But, there is something beyond this IOP
  reduction. Neuroprotection.

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NEUROPROTECTION COMPARISON WITH VEHICLE
A
B

• More labeled cells in the brimonidine treated (A)
  retina than in the vehicle treated one (B).

IOVS, No. 2001, 42 (12), 2849-2855.
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BRIMONIDINE VISUAL FIELD

• Aim To evaluate the efficacy of topical
  brimonidine in visual field preservation and / or
  improvement in eyes undergoing controlled
  glaucoma
• No. of Patients 70 eyes of patients were checked
  for improvements in visual field following 2-4
  months of brimonidine treatment
• Conclusion Brimonidine may prevent visual field
  loss in patients with glaucoma. It is possible
  that the neuroprotective qualities of brimonidine
  may contribute to visual field preservation in
  glaucomatous eyes.

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• THE THIRD TARGET
• PERSISTENCY/ COMPLIANCE
• WITH DRUG THERAPY IN GLAUCOMA MANAGEMENT

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Glaucoma Therapy Persistency

• Pharmacologic therapy for glaucoma can be
  effective only if patients fill their
  prescriptions (persistency) and take their
  medications as directed (compliance)
• Ref Am. J. Ophthalmol 2004 137 S3-S12

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Persistency Glaucoma Therapy

• Persistency with glaucoma medications reflects
• Patients satisfaction with medication
  tolerability
• Physician satisfaction with IOP control
• Medication costs
• Patient understanding of the importance of taking
  their medication over the long term
• Ref Am. J. Ophthalmology 2004 137 S3-S12

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Lack of Persistency Glaucoma Therapy

• Lack of persistency can lead to undesirable
• clinical outcomes
• Uncontrolled IOP
• Progression of glaucoma ultimately blindness
• Increased costs by requiring more intensive
  medical interventions (e.g. extra physician
  visits, tests, combination therapy and ultimately
  surgery)
• Ref P and T Society A class Review of
  Prostaglandin Analogs, Sept 2003

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Persistency Prostaglandin Analogues

• Patients treated with bimatoprost were 31 more
  likely to discontinue/change therapy compared
  with Latanoprost
• Patients treated with travoprost were 29 more
  likely to discontinue/change therapy compared
  with Latanoprost
• Ref Clinical therapeutics 2003 25 1172-1185

Latanoprost treated patients demonstrated
significantly greater persistency than did those
treated with other ocular hypotensive therapies.
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• COMPLIANCE THE HIDDEN CHALLENGE OF GLAUCOMA
  MANAGEMENT

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• Compliance is defined as the process of patient
  adherence to a therapeutic regimen prescribed by
  a physician.
• Ref Am. J. Ophthalmol 2000 130 S1-S11

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Patient Compliance Glaucoma

• Patient compliance is a particularly important
  issue
• In glaucoma because
• Asymptomatic, preventive in nature
• Chronic disease requiring long term therapy
• Benefit of treatment not apparent
• Several medications
• Expense of treatment
• Inconvenience of treatment
• Local side effects of treatment
• Systemic side effects of treatment
• Ref 1) J of Glaucoma 1992 1 134-136

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Patient Non-compliance Glaucoma

• Available literature suggests that between 28
  and 58 of glaucoma patients do not use their
  medications as prescribed
• Non compliance is probably 30-40
• Ref http//www.escrs.org/April 2003 assessed on
  27/03/04

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• PATIENTS AND PHYSICIANS PREFER ONCE DAILY
  DOSING
• Ref Pan-European Survey on Glaucoma done in UK,
  France, Germany, Italy and Spain included 250
  ophthalmologists and 243 glaucoma patients who
  were asked questions about use of multiple
  medication regimens.

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Latanoprost Enhances Patient Compliance

• The advantage of a once daily dosing regimen in
  the context of the underlying pharmacological
  basis that a drug which is enough once a day has
  a minimal duration of 24 hours.
• Latanoprost has the advantage of once daily
  usage.
• Thus even a mild non-compliance, the occasional
  Forgotten drop will not change the level of IOP
  very much.
• Ref http//www.escrs.org/april2003

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Getting to the Targets of Glaucoma Management

• Newer drugs
• fulfill all the
• 3 targets for
• glaucoma
• management