Intraocular Pressure (IOP)Intraocular Pressure (IOP) Fluctuations and Compliance in

GlGlaucoma

Don Minckler, MD, MSUC Irvine

National Eye Institute (NEI) Gl T i l SGlaucoma Trials Summary

• Lowering IOP lessens visual damage:– Lowering IOP reduces the risk of progression from

ocular hypertension to open-angle glaucoma1

E l t t t f l d d d l– Early treatment of glaucoma reduces and delays glaucoma progression2–4

– Maintaining a relatively steady level of IOP over time a a g a e a e y s eady e e o O o e eis probably important5

– Early Manifest Glaucoma Trial (EMGT) and C ll b ti I iti l Gl T t t St dCollaborative Initial Glaucoma Treatment Study (CIGTS) suggest a direct correlation between reduced IOP and visual field (VF) progression4,5( ) p g

1. Kass MA et al. Arch Ophthalmol. 2002;120:701–713.2. CNTGS. Am J Ophthalmol. 1998;126:487–497.3. Lichter PR et al. Ophthalmology. 2001;108:1943–1953.4. Heijl A et al. Arch Ophthalmol. 2002;120:1268–1279.5. Nouri-Mahdavi K et al. Ophthalmology. 2004;111:1627–1635.

Predictive Factors for Progression of Glaucomatous VF Loss in the Advanced

Glaucoma Intervention Study (AGIS)

I b t f AGIS i l fi ld d t i hi h 1 IOPIn a subset of AGIS visual field data in which 1 IOP measurement was obtained per visit and intervisit IOP fluctuation was assessed:– IOP fluctuation was consistently associated with

progressive VF loss as was increasing ageand

– IOP fluctuation was an independent and strongerpredictor than mean IOP for VF progressionpredictor than mean IOP for VF progression

Nouri-Mahdavi K et al. Ophthalmology. 2004;111:1627–1635.

Progression of VF Loss in 509 Eyes With IOP Fl i 3 H ≥3 HFluctuation <3 mm Hg vs ≥3 mm Hg

• Significant progression was observed in eyes with higherSignificant progression was observed in eyes with higher IOP fluctuation

3 0

3.5

3.0

2.5

2.0

GIS

Sco

re

Standard Deviationof IOP (mm Hg)

1.5

1.0

0 5ange

in A

G <3.0

≥3.0

P=0.0006

0 20 40 60 80 100–0.5

0.5

0.0Cha

P 0.0006

Reprinted from Ophthalmology, Volume 111, Nouri-Mahdavi K et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study, 2004;1627–1635, with permission from the American Academy of Ophthalmology.

0 20 40 60 80 100Time (mo)

Predictive Factors for Progression ofPredictive Factors for Progression of Glaucomatous VF Loss in AGIS Subgroup Study

• Risk factors that correlated with progressive VF lossloss– Older age at first intervention—risk was increased by

30% for each 5-year increment in age– Number of interventions– Longer follow-up period– Greater intervisit IOP fluctuations—the risk of

progression was increased by 30% for each 1 mm Hg increase in IOP fluctuation

Nouri-Mahdavi K et al. Ophthalmology. 2004;111:1627–1635.

Diurnal IOP Range and P i VF LProgressive VF Loss

6

Risk of disease progression within 5 years

4

5 5.76

Rat

io

2

3

Ris

k R

0

11.00

Diurnal IOP range3.1 mm Hg

Diurnal IOP range5.4 mm Hg3.1 mm Hg 5.4 mm Hg

Asrani S et al. J Glaucoma. 2000;9:134–142.

Diurnal IOP Fluctuations: P ti t With Gl N l S bj tPatients With Glaucoma vs Normal Subjects

12.0 11

8.0

10.0

mm

Hg

4 0

6.0

3.7tuat

ion,

m

2.0

4.0

IOP

Fluc

t

0.0POAG Without

Treatmentn = 138

Normal Eyes

n = 404

Drance SM. Arch Ophthalmol. 1960;64:494–501.

n 138 n 404

POAG = primary open-angle glaucoma.

IOP: 24-Hour vs In-ClinicIOP: 24 Hour vs In Clinic25

Clinic

20

15g

*24-Hour

†

N = 2915

10mm

Hg

0

5

Retrospective comparison between average values for mean and maximum IOP values obtained with 24-hour monitoring vs in-clinic (mean ±95% CI)

Mean IOP Maximum IOP0

Reprinted from J Glaucoma, Volume 12, Hughes E et al. 24-hour monitoring of intraocular pressure in glaucomamanagement: a retrospective review. 2003;12:232–236, with permission from Lippincott, Williams and Wilkins.

*P < 0.0001. †Difference between maximum IOP obtained over a 24-hour period

vs maximum recorded in the clinic is 4.9 mm Hg.

Range of IOP Fluctuation During Office Hours and 24 Hour Period in Patients With Glaucomaand 24-Hour Period in Patients With Glaucoma

11

Mean 24-hour IOP fluctuation Mean office IOP fluctuation

* * *

91011

678

mm

Hg

345

IOP,

012

*P < 0.001.Barkana Y et al. Arch Ophthalmol. 2006;124:793–797.

All Eyes Right Eyes Left Eyes

24-Hour Supine IOP Fluctuations24 Hour Supine IOP Fluctuations

SupineDIURNAL/WAKE NOCTURNAL/SLEEP DIURNAL/WAKE

Supine

24

22

26

m H

g

Older glaucoma (n = 35)

Older22

20

18ne IO

P, m

m Older healthy (n = 35)

Youngerhealthy (n = 33)

14

16

18

Supi

y ( )

Reprinted from Am J Ophthalmol, Volume 139, Mosaed S et al. Correlation between office and peak nocturnal intraocular pressures in healthy subjects and glaucoma patients, 2005;320–324, with permission from Elsevier.

Blindness and Glaucoma: A 30+ Y St dYear Study

• Patients progressing to blindness in at least 1 eye were compared with th i t i i i i 30+ i t ti t lthose maintaining vision over 30+ years in a retrospective, case-control (N=295), cohort study in Olmstead County, Minnesota.

• Mean IOP was similar in both groups.

• Variability of each patient’s IOP over the years was significantly higher in the blind group compared with the nonblind group (mean IOP range, 9.9 ±8.8 mm Hg vs 6.8 ± 6.8 mm Hg; P<0.001).

• Patients at greatest risk for blindness had VF loss at time of diagnosis of glaucoma. Different susceptibilities to IOP were apparent—some patients became blind at pressures that caused no decline in others.

• Different sensitivities of patients to IOP indicate that ongoing monitoring of VF remains essential with the establishment of target IOP and adjustments of the target range as the patient’s condition changes.

Oliver JE et al. Am J Ophthalmol. 2002;133:764–772.

Potential Implications for PracticePotential Implications for Practice

• Perform mini-diurnal curves (checking pressures at 8:00, 10:00, 12:00, 2:00 and 4:00 on the same day)

oror• Have the patient return for multiple “IOP check only”

visitsor

• Schedule return visits at different times of the day to check IOP over multiple days y

or• Consider supine IOP measurements during office hours

using the pneumatonometer1using the pneumatonometer1. Mosead S et al. Am J Ophthalmol. 2005;139:320–324.

The Challenge of Motivating Patients t C t l IOPto Control IOP

• Glaucoma management poses challenges similar to g p gthose of many chronic ailments in which:– Symptoms in their early stages are absent or few when

interventions may be most effectiveinterventions may be most effective – Visual damage is slowly progressive and camouflaged from the

patient by automatic adjustments in visual perception Delay of treatment or nontreatment leads eventually to disabling– Delay of treatment or nontreatment leads eventually to disabling consequences

– To be maximally effective, medical therapy for the majority of patients must be self delivered consistently by elderly often frailpatients must be self delivered consistently by elderly, often frail individuals with waning mental functioning and other important co-morbidities, including depression1

1. Pappa C et al. J Psychosom Res. 2006;61:609–617.

Educating Patients With Glaucoma as an Aid t I C liAid to Improve Compliance

Especially early in the course of disease,Especially early in the course of disease, patients need convincing that they have visual damage1—because the disease is often minimally symptomatic or camouflaged by slow progression and central nervous

t / i l t tisystem/visual system compensation.

1. Shaw ME. Insight. 2005;30:7–9.

Compliance: Tools for Educating Patients

• Standard white-on-white (W/W) perimetry• Confocal scanning laser ophthalmoscope• Confocal scanning laser ophthalmoscope

(CSLO)• GDx and optical coherence tomography (OCT)GDx and optical coherence tomography (OCT)

sequential studies

GDx is a registered trademark of Laser Diagnostic Technologies.

Standard W/W PerimetryStandard W/W Perimetry

Confocal Scanning Laser Ophthalmoscope (HRT)

Early Damage

Advanced Damage

HRT = Heidelberg Retina Tomograph

GDx and OCT sequential studiesq

RNFL = retinal nerve fiber layerGDx is a registered trademark of Laser Diagnostic Technologies.

Compliance: Medication-Related Factors

• Multiple agents for glaucoma1

• Medications for comorbid conditions2• Medications for comorbid conditions2

• Dosing >2x daily1,2

• Drug related adverse reactions3• Drug-related adverse reactions3

• Cost3• Complexity of regimen3Complexity of regimen• Change in regimen3

1. Patel SC et al. Ophthalmic Surg. 1995;26:233–236.2. Gurwitz JH et al. Am J Public Health. 1993;83:711–716.3. Tsai JC et al. J Glaucoma. 2003;12:393–398.

Compliance Among Patients Prescribed Eyedrops for Glaucoma

1 Medication every day/twice a day (n=41)**† day/twice a day (n=41)1 Medication more than twice a day (n=28)*

†

Multiple medications (n=31)(n 31)

*Significantly greater vs 1 medication >2x daily, P<0.05†Significantly greater vs multiple medications, P<0.05g y g p

Patel SC et al. Ophthalmic Surg. 1995;26:233–236.

Summaryy• Studies support the need for early intervention and therapy in

patients with glaucomatous optic neuropathy to prevent further optic nerve damage after diagnosis of POAG1–3

– Resource utilization increases as disease severity increases,4reinforcing the need for early intervention

• Large fluctuations in IOP range may be predictive of higher risk for optic nerve damage5

– Interpatient and intrapatient coefficient of variation in the IOP curve can be greater than 20%6

• Compliance with therapy should help to minimize IOP fluctuation and help minimize the risk of optic nerve damage

1. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthamol. 1998;126:487–497.

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2. Lichter PR et al. Ophthamology. 2001;108:1943–1953.3. Heijl A et al. Arch Ophthamol. 2002;120:1268–1279.4. Schmier JK et al. Pharmacoeconomics. 2007;25:287–308.5. Asrani S et al. J Glaucoma. 2000;9:134–142.6. Brubaker RF. Invest Ophthalmol Vis Sci. 1991;32:3145–3166.