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INNOVATIONS IN THE MEDICAL MANAGEMENT OF GLAUCOMA

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

TREATMENT ALGORITHM
IOP >21mm Hg If no cardiac or pulmonary problem Blockers

IOP controlled Continue treatment, Review every 3-6 months IOP controlled

Failure Alternate monotherapy. 2- agonist, PG, CAI Failure Failure Combination


European Glaucoma Society, 1998.

Surgery

Glaucoma: Treatment Goal

LOWER IOP

VASOPROTECTION/ NEUROOPROTECTION

PERSISTENCY/COMPLIANCE

THE FIRST TARGET: ACHIEVING A LOW TARGET IOP WHICH IS UNIFORM DAY AND NIGHT

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

AAO Guidelines: Target IOP


40

% reduction from baseline

40 35 30 25 20 15 10 5 0

30

30 20

Mild Damage

Advance Damage

NTG

OHT

Ref: Surveys of Ophthalmology 2003; 48 (suppl 1); 53-57

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

Latanoprost: Proven for 24 hour IOP Control


Latanoprost when instilled at 9 p.m. effectively
Dorzolomide three times daily Timolol twice daily Latanoprost 27 25 23 21 19 17 15 Baseline

lowered IOP at 3, 6 and 9 a.m. at noon at 9 p.m. Latanoprost compared to other agents lead to a fairly uniform circadian reduction in IOP
0

IOP (mmHg)

and at midnight

Ref: Invest ophthalmol Vis Sci 2000; 41: 2566-2573


15 18 21 24 03 06 09 12 Time (hours)

Ref: Invest Ophthalmol Vis Sci 2000; 41: 2566-2573

Latanoprost: Monotherapy
In well-controlled clinical trial including patients with open-angle glaucoma or ocular hypertension (IOP > 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

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

THE SECOND TARGET: VASOPROTECTION/ NEUROPROTECTION

GLAUCOMA: OPTIC NERVE DAMAGE


Rise in IOP > 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 (< in pOBF)


Ischaemia RGC cell loss

Dorzolamide: Vasoprotection

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

Dorzolamide: Vasoprotection
2.5 2.35

Baseline= 2.53 secs


1.94 *

2.33

AVP time (sec)

2 1.5 1 0.5 0 Timolol

Dorzolamide

Latanoprost

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

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

BRIMONIDINE : THE NEUROPROTECTIVE 2 AGONIST IOP lowering is the main aim of any anti-glaucoma agent.

But, there is something beyond this IOP


reduction. Neuroprotection.

NEUROPROTECTION COMPARISON WITH VEHICLE


B

More labeled cells in the brimonidine treated (A) retina than in the vehicle treated one (B).
IOVS, No. 2001, 42 (12), 2849-2855.

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.

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

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

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

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

Persistency: Prostaglandin Analogues


Patients treated with bimatoprost were 31% more likely Latanoprost treated therapy compared with patients demonstrated to discontinue/change significantly greater persistency than did Latanoprost Patients treated with travoprost were 29% more likely those treated with other ocular hypotensive to discontinue/change therapy compared with therapies. Latanoprost
Ref: Clinical therapeutics 2003; 25: 1172-1185

COMPLIANCE: THE HIDDEN CHALLENGE OF GLAUCOMA MANAGEMENT

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

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

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

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.

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

Getting to the Targets of Glaucoma Management

LOWER IOP

INCREASE OUTFLOW

NEUROPROTECTION/ VASOPROTECTION

Newer drugs fulfill all the 3 targets for glaucoma management