Presentation Glaucoma Endurance

Role of diurnal fluctuation and 24 hr Control in Glaucoma Management

Role of diurnal fluctuation and 24 hr Control in Glaucoma Management

Questions About IOP ControlQuestions About IOP Control

• Intraocular pressure control involves two major factors:

– Level of IOP

• How low should we set target IOP for treatment?

• What is the role of medicine, laser therapy and incisional surgery

to lower IOP?

– Fluctuations in IOP

• Minute-to-minute, daily (24 hours), inter-visit, long-term - how do

we define “fluctuations?

• How do we measure fluctuations in IOP?

• Are fluctuations important for progression of disease?

• Can therapies minimize fluctuations in IOP?

• Intraocular pressure control involves two major factors:

– Level of IOP

• How low should we set target IOP for treatment?

• What is the role of medicine, laser therapy and incisional surgery

to lower IOP?

– Fluctuations in IOP

• Minute-to-minute, daily (24 hours), inter-visit, long-term - how do

we define “fluctuations?

• How do we measure fluctuations in IOP?

• Are fluctuations important for progression of disease?

• Can therapies minimize fluctuations in IOP?

Fluctuations in IOP - Terminology

• Diurnal – Daytime• Nocturnal – Nighttime• Circadian – 24-hour• Short-term IOP fluctuation

– Occurs over hours or days

• Long-term fluctuation– Occurs over months or years

• Ultra short-term fluctuation– Occur over minutes

Measuring fluctuation in IOP

• Interval for measurement of IOP variation– Diurnal, nocturnal, circadian, short, long, ultra-short

– How many measurements over what period of time?• Which measurement?

– Peak, range, standard deviation or some other summary parameter

• Confounding variables– Treatment effects, frequency of measurements, inter and intra

technician variability, corneal thickness and other biomechanical issues, definitions of progression

• No clinically useful technology for continuous measurement of IOP in humans at present

There is strong evidence that IOP is a risk factor for glaucoma development

There is strong evidence that IOP is a risk factor for glaucoma development

• OHTS (2002) – Medical treatment to lower IOP < 24 mmHg

and at least 20% reduction may prevent (or just delay?) disk

and field damage.

– 60 months, probability of developing glaucoma was 4.4%

in treatment group vs. 9.5% in observation group

• OHTS (2002) – Medical treatment to lower IOP < 24 mmHg

and at least 20% reduction may prevent (or just delay?) disk

and field damage.

– 60 months, probability of developing glaucoma was 4.4%

in treatment group vs. 9.5% in observation group

Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open angle glaucoma.  Arch Ophthalmol. 2002;120(6):701-713.

Glaucoma Fluctuation in IOP a higher risk factor for progression

Patients progressing to blindness compared to those maintaining vision over 30 years

• Mean IOP was similar in both group• Variability of each patients IOP over years was significantly

higher in the eyes that went blind

Blindness and Glaucoma: A Comparison of Patients Progressing to Blindness FromGlaucoma With Patients Maintaining Vision Am J Ophthalmol 2002;133:764–772

Compliance on medication is an issue

• Adherence is less than perfect• Lowering eye pressure is essential to slow

glaucoma progression• Interventions can improve adherence• You can help your patients

• 20 - 30% IOP reduction

• ONCE 3 times daily dosing (selective frequency > nonselective frequency)

• 19.0% of US Glaucoma prescriptions

• Poor night time absorption

• Tachyphylaxis

• Inexpensive

Side Effects

• Ocular burning,stinging, irritation, conjunctivitis, blepharitis,keratitis, VA

changes

Systemic

• bradycardia,cardiac arrythmias, hypotension, CHF, COPD, CNS

(depression, confusion, hallucinations), impotence

BetaBlockers

Topical Carbonic Anhydrase Inhibitors

• 16- 26% IOP reduction

• BID – TID dosing

Side Effects

• Ocular

– Stinging (Dorzolamide >> Brinzolamide)

– Blurred vision (Brinzolamide >> Dorzolamide)

• Systemic

– Bitter taste (decreased with punctal occlusion

– Sulfa allergy cross reactivity (? anaphylaxis ?)

Alpha Agonists

• BID or TID do20 - 25% IOP reduction (30 - 40% transiently with Apraclonidine)

• sing

• Brimonidine 99.5% vs Apraclonidine 0.5%

• Tachyphylaxis (Apraclonidine > Brimonidine)

• Use Brimonidine with caution in pediatric patients

Side Effects (worse with Apraclonidine)

• Ocular allergy, burning, stinging, irritation, conjunctivitis, blepharitis, keratitis, VA

changes

• Systemic bradycardia,cardiac arrythmias, hypotension, CHF, COPD, CNS

(depression, confusion, hallucinations), impotence

• Selective vs. Nonselective Blood Flow/Oxygen delivery

Timolol not effective in the night

Need of 24 hour IOP control

Considerations in the choice of a PGA

• Efficacy

• Personal experience

• Patient tolerance

• Samples

• Availability

• Storage Conditions

What is the Relationship Between IOP Fluctuation and Stability of

Glaucoma?

• There have been four studies that suggest that increased diurnal variability in intraocular pressure is positively correlated with progression of visual field defects1-4

1Bergea-1999, 2Asrani-2000, 3Caprioli-2003, 4Collaer-2005

Diurnal IOP Fluctuation and Visual Field LossDiurnal IOP Fluctuation and Visual Field Loss

• ASRANI et al. 2000, Large Diurnal Fluctuations in Intraocular Pressure Are an Independent Risk Factor in Patients With Glaucoma.– Large diurnal IOP fluctuation positively correlated with

visual field loss– Patients used multiple home tonometry assessments,

compared to office visit readings

• ASRANI et al. 2000, Large Diurnal Fluctuations in Intraocular Pressure Are an Independent Risk Factor in Patients With Glaucoma.– Large diurnal IOP fluctuation positively correlated with

visual field loss– Patients used multiple home tonometry assessments,

compared to office visit readings

Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.

Large IOP Fluctuations Are a Risk Factor for VF Loss

Large IOP Fluctuations Are a Risk Factor for VF Loss

• Diurnal IOP measurements– 5x/day for 5 days– Used home tonometry

• Mean follow-up: 5 years• Risk factors for progression

of glaucoma and VF loss– Wide range in daily IOP– Large variation in weekly IOP

• Diurnal IOP measurements– 5x/day for 5 days– Used home tonometry

• Mean follow-up: 5 years• Risk factors for progression

of glaucoma and VF loss– Wide range in daily IOP– Large variation in weekly IOP

Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.

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Patients with IOPPatients with IOP

range > 11.8range > 11.8

mm Hg over daysmm Hg over days

Patients with IOPPatients with IOP

range < 7.7 mm Hgrange < 7.7 mm Hg

over daysover days

Pa

tien

ts (

%)

Pa

tien

ts (

%)

StableStable

Vision LossVision Loss

0

2

4

6

8

10

12

POAG OffTreatment

POAGControlled

Normal Eyes Latanoprost Travoprost

Drance SM

Diurnal IOP Fluctuation in Glaucoma Patients

Diurnal IOP Fluctuation in Glaucoma Patients

IOP

Flu

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mm

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IOP

Flu

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3.73.7 3.93.93.23.2

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1 1 3 3 2 2

1. Drance SM et al. The significance of the diurnal tension variations in normal and glaucomatous eyes. Arch Ophthalmol. 1960;64:494-501.2. Drance SM et al. Diurnal Variation of intraocular pressure in treated glaucoma. Arch Ophthalmol. 1963;70:62-71.3. Konstas AG, et al. 24-hour intraocular pressures with brimonidine purite versus dorzolamide added to latanoprost in primary open-angle glaucoma subjects. Ophthalmol. April 2005; 112: 603-608.4. Konstas AGP, Mikropoulos D, Kaltsos K, et al. 24-hour intraocular pressure control obtained with evening – versus morning-dosed travoprost in primary open-angle glaucoma. Ophthalmology. 2006;113:446-450.

1. Drance SM et al. The significance of the diurnal tension variations in normal and glaucomatous eyes. Arch Ophthalmol. 1960;64:494-501.2. Drance SM et al. Diurnal Variation of intraocular pressure in treated glaucoma. Arch Ophthalmol. 1963;70:62-71.3. Konstas AG, et al. 24-hour intraocular pressures with brimonidine purite versus dorzolamide added to latanoprost in primary open-angle glaucoma subjects. Ophthalmol. April 2005; 112: 603-608.4. Konstas AGP, Mikropoulos D, Kaltsos K, et al. 24-hour intraocular pressure control obtained with evening – versus morning-dosed travoprost in primary open-angle glaucoma. Ophthalmology. 2006;113:446-450.

44

Travoprost Therapy Results in a Narrow Range of Diurnal IOP Fluctuation

Travoprost Therapy Results in a Narrow Range of Diurnal IOP Fluctuation

1. Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.2. Konstas AG, et al. 24-hour intraocular pressures with brimonidine purite versus dorzolamide added to latanoprost in primary open-angle glaucoma subjects. Ophthalmol. April 2005; 112: 603-608.3. Konstas AGP, Mikropoulos D, Kaltsos K, et al. 24-hour intraocular pressure control obtained with evening – versus morning-dosed travoprost in primary open-angle glaucoma. Ophthalmology. 2006;113:446-450.

1. Asrani S et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.2. Konstas AG, et al. 24-hour intraocular pressures with brimonidine purite versus dorzolamide added to latanoprost in primary open-angle glaucoma subjects. Ophthalmol. April 2005; 112: 603-608.3. Konstas AGP, Mikropoulos D, Kaltsos K, et al. 24-hour intraocular pressure control obtained with evening – versus morning-dosed travoprost in primary open-angle glaucoma. Ophthalmology. 2006;113:446-450.

0

2

4

6

8

10

12

14

12% Stable VF 43% Stable VF Latanoprost Travoprost

Asrani et al.

Mea

n I

OP

Ran

ge

(mm

H

g)

Mea

n I

OP

Ran

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(mm

H

g)

1212

88

3.93.9 3.23.2

Quartile with Highest IOP

Range1

Quartile with Highest IOP

Range1

Quartile with Lowest IOP

Range1

Quartile with Lowest IOP

Range1

22 33

Travatan is effective in day and night unlike Beta blockers

Travatan provides consistent IOP control from peak to trough

Ref1 :Orzalesi N , Rossetti L , Bottoli A, et al. Comparison of the Effects of Latanoprost, Travoprost, and Bimatoprost on Circadian Intraocular Pressure in Patients with Glaucoma or Ocular Hypertension. Ophthalmology 2006 ;113:239-246. Ref2:Konstas A, Mikropoulos D, et al. 24-Hour Intraocular Pressure ControlObtained with Evening - versus Morning - Dosed Travoprost in PrimaryOpen-Angle Glaucoma Ophthalmology 2006; 113:446–450

Why is Endurance beyond 24 hours important?Why is Endurance beyond 24 hours important?

COMPLIANCE• Compliance is the extent to which a patients behavior

complies with the providers’ therapy– Deliberate non-compliance can be due to adverse

effects and complexity of treatment regimen– Involuntary non-compliance can be due to poor

instillation of drops, forgetfulness, being away from home, etc.

COMPLIANCE• Compliance is the extent to which a patients behavior

complies with the providers’ therapy– Deliberate non-compliance can be due to adverse

effects and complexity of treatment regimen– Involuntary non-compliance can be due to poor

instillation of drops, forgetfulness, being away from home, etc.

Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598-606.Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598-606.

Travoprost EfficacyTravoprost Efficacy

20 Hours Travoprost showed significantly lower IOP than Latanoprost at 4 PM.Netland PA, Landry T, Sullivan EK, et al. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132:472-484.

20 Hours Travoprost was superior in IOP lowering to Latanoprost at 5 PM.Maul E, Carrasco FG, Costa VP, et al. A six-week double-masked study comparing travoprost 0.004% to latanoprost 0.005% followed by a six-week open-label treatment on travoprost 0.004%. Clin Ther. 2007;29:1915-1923.

21 Hours Significantly lower IOP levels for Travoprost vs. Latanoprost at 6 pm.Konstas AG, Kozobolis VP, Katsimpris IE et al. Efficacy and safety of latanoprost 0.005% versus travoprost 0.004% in exfoliative glaucoma. Ophthalmology. 2007;114:653-657.

24 Hours Travoprost had significantly lower IOP levels than Latanoprost at 8 PM.Dubiner HB, Sircy MD, Landry T, et al. Comparison of the diurnal ocular hypotensive efficacy of travaprost and latanoprost over a 44-hour period in patients with elevated intraocular pressure. Clin Ther. 2004;26:84-91.

24 Hours Travoprost had significantly lower IOP levels than Latanoprost at 8AM.Yan DB, Battista RA, Haidich A-B, Konstas AGP. Comparison of morning versus evening dosing and 24-h post-dose efficacy of travoprost compared with latanoprost in patients with open-angle glaucoma. Cur Med Res Opin. 2008;24:3023–3027.

Up to 48 hours Statistically lower mean IOP with Travoprost compared to Latanoprost 2 days post dose.Garcia-Feijoo J, Martinez-de-la-Casa JM, Castillo A, et al. Circadian IOP- lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%. Curr Med Res Opin. 2006;22:1689-1697.

Until 63 hours With Travoprost significant IOP lowering persisted for up to 63 hours.Sit AJ, Weinreb RN, Crowston JG, et al. Sustained effect of travoprost on diurnal and nocturnal intraocular pressure. Am J Ophthalmol. 2006;141:1131-1133.

All the way to 84 hours Significant IOP reduction (6.6 mm Hg) at 3.5 days with Travoprost.Dubiner HB, Sircy MD, Landry T, et al. Comparison of the diurnal ocular hypotensive efficacy of travaprost and latanoprost over a 44-hour period in patients with elevated intraocular pressure. Clin Ther. 2004;26:84-91.

Hours Post DoseHours Post Dose

Percentage of Patients Complaining of Hyperemia by TelephonePercentage of Patients Complaining of Hyperemia by Telephone

• Trademarks are property of their respective owners.

Stewart WC, Rhodes JS, Jessica NL, et al. Survey assesses red eye and prostaglandin use. Rev Ophthalmol. 2002;72-73.

• Trademarks are property of their respective owners.

Stewart WC, Rhodes JS, Jessica NL, et al. Survey assesses red eye and prostaglandin use. Rev Ophthalmol. 2002;72-73.

SolutionSolution

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P=0.001P=0.001

Medical Problems of Non-complianceMedical Problems of Non-compliance

• Poorer outcomes1

– Higher mean IOP and range of diurnal IOP– Progressing disease and declining visual field

• Mistaken medical treatment failure1

• Unnecessary changes to treatment regimen2

• Unnecessary surgery2

• Increased health costs3

• Poorer outcomes1

– Higher mean IOP and range of diurnal IOP– Progressing disease and declining visual field

• Mistaken medical treatment failure1

• Unnecessary changes to treatment regimen2

• Unnecessary surgery2

• Increased health costs3

1. Kontas AGP, Maskaleris G, Gratsonidis S, et al. Compliance and viewpoint of glaucoma patients in Greece. Eye. 2000;14:752-6.2. Neelakantan A, Vaishnav HD, Iyer SA, et al. Is the addition of a third or fourth antiglaucoma medication effective? J Glaucoma. 2004;13:130-6.3. Lee PL, Walt JG, Doyle JJ, et al. A multi-center, retrospective pilot study of resource utilization and costs associated with severity of disease in glaucoma. Arch Ophthalmol. 2006;124:122-9.