Content Consultants

George A. Cioffi, MD Jeffrey M. Liebmann, MD

Chief of Ophthalmology Clinical Professor of Ophthalmology
Legacy Health System Director, Glaucoma Services
Director, Glaucoma Services Manhattan Eye, Ear & Throat Hospital
Director, Discoveries in Sight New York University Medical Center
Devers Eye Institute New York, New York
Portland, Oregon
Robert N. Weinreb, MD
Anne L. Coleman, MD, PhD Director, Hamilton Glaucoma Center
Professor of Ophthalmology Professor of Ophthalmology
Jules Stein Eye Institute University of California San Diego
David Geffen School of Medicine La Jolla, California
Los Angeles, California

Ronald L. Gross, MD
Professor of Ophthalmology and
Clifton R. McMichael Chair in Ophthalmology
Cullen Eye Institute
Baylor College of Medicine
Houston, Texas
Reframing Disease Severity
in Glaucoma
Incidence of open-angle glaucoma
Consequences of poorly managed glaucoma
Paradigm shift away from IOP for glaucoma diagnosis and
evaluation
Evaluation of ON/RNFL
Controlling IOP in glaucoma treatment
Diagnosis & management of glaucoma in clinical practice

IOP=intraocular pressure; ON=optic nerve; RNFL=retinal nerve fiber layer

Glaucoma
Optic neuropathy
Characterized by progressive
injury to retinal ganglion cells
and their axons
Specific pattern of optic
atrophy (cupping)
Associated visual function
deficit
Glaucoma Diagnosis:
An Historical Perspective
Pre -1980s
Elevated intraocular pressure (IOP) glaucoma

1980s - Mid 1990s

Elevated IOP + visual field (VF) defect glaucoma

Mid 1990s - present

Glaucomatous optic disc + retinal nerve fiber layer (RNFL)
changes glaucoma
Incidence of Open-Angle Glaucoma
Affects >2 million over the age of 40 in the
US (1.9%); expected to exceed 3 million by
20201
Average age of onset 54 years of age2
Most patients (63%) have had glaucoma >10
years2
2nd leading cause of blindness3

1. Friedman DS et al. Arch Ophthalmol. 2004;122:532-538.

2. Gallup Eye Health Survey. 2002.
3. Glaucoma Facts. Available at: www.glaucoma.org/learn/facts.html.
Underdiagnosis of
Open-Angle Glaucoma
Population studies suggest over half of all
glaucoma cases in the US have not been
diagnosed
Percentage of patients with undiagnosed glaucoma
- Baltimore Eye Survey: 56%1
- Beaver Dam Eye Study: 94%2
- Proyecto VER: 62%3
Many suffer severe VF loss before diagnosis4

1. Sommer A et al. Arch Ophthalmol. 1991;109:1090-1095.

2. Sponsel WE et al. Clin Experiment Ophthalmol. 2001;29:352-358.
3. Quigley HA et al. Arch Ophthalmol. 2001;119:1819-1826.
4. Gillespie BW et al. Invest Ophthalmol Vis Sci. 2003;44:2613-2620.
How Often Do People With
Untreated Glaucoma Go Blind?
For some patients, failure to diagnose glaucoma and
treat effectively leads to rapid loss of vision1,2
Study of natural history of glaucoma in West Indies2
205 glaucoma patients or suspects in St. Lucia diagnosed
1986-1987
- 16% progressed to blindness in at least 1 eye over 10
years (AGIS criteria)
- 9% progressed to bilateral blindness
- >50% of eyes that progressed to end-stage glaucoma had
no or minimal VF loss at baseline

1. Hattenhauer MG et al. Ophthalmology. 1998;105:2099-2104.

2. Wilson MR. Trans Am Ophthalmol Soc. 2002;100:365-410.
Lack of Effective Treatment
Can Result in Blindness
Retrospective study of 295 patients with newly
diagnosed open-angle glaucoma in Olmsted
County, MN
Probability of blindness after 20 years
- 27% in one eye; 9% in both eyes
Of 114 patients initially treated for OHT
- Probability of blindness after 20 years
14% in one eye and 4% in both eyes

OHT=ocular hypertension.
Hattenhauer MG et al. Ophthalmology. 1998;105:2099-104.
Risk Factors for
Development of Glaucoma
Ocular Factors1,2
IOP
CCT
ON structure (C/D ratio)
Disc hemorrhage
Other ocular disorders

Non-ocular Factors
Age
Race
Family history/genetic predisposition
Vascular disease (HTN, vasospasm)

CCT=central corneal thickness; HTN=hypertension; ON=optic nerve.

1. Wilson MR. In: Clinical Guide to Glaucoma Management. Butterworth Heinemann: 2004.
2. Medeiros FA et al. Am J Ophthalmol. 2003;136:805-813.
Structural Damage Precedes
Functional Change
NFL injury can be observed up to 6 years before
VF defects1
Mean number of axons2 in normal ON ~800,0001,200,000
25-40% of ON fibers can be lost from an eye that retains
a normal visual field2,3

1. Sommer A et al. Arch Ophthalmol. 1991;109:77-83.

2. Quigley HA et al. Arch Ophthalmol. 1982;100:135-46.
3. Kerrigan-Baumrind LA et al. Invest Ophthalmol Vis Sci. 2000;41:741-748.
Structural Damage Precedes
Functional Change (contd.)
VF loss by SAP does NOT mean early disease
By the time VF loss is detected by SAP, substantial
structural damage may exist1,2
Functional loss may be detected earlier using selective tests
(eg, FDT, SWAP)2

FDT=frequency doubing technology; SAP=standard automated perimetry; SWAP=short

wavelength automated perimetry.
1. Sommer A et al. Arch Ophthalmol. 1991;109:77-83.
2. Bowd C et al. Invest Ophthalmol Vis Sci. 2001;42:1993-2003.
Visual Defects Are Associated
With ON Damage
Quadrants with fewer axons correlate with regions of
greatest VF loss1
Clinical measurements of disc rim and nerve fiber layer
depth correlate quantitatively with visual function in
glaucoma2,3

1. Quigley HA et al. Arch Ophthalmol. 1982;100:135-146.

2. Airaksinen PJ et al. Am J Ophthalmol. 1985;99:107-110.
3. Caprioli J et al. Ophthalmology. 1988;95:723-727.
Structure and Function
in Glaucoma
VF

Disc

RNFL

Time
First OHTS POAG Endpoint
per Participant
Medication Observation

n % n %

Visual field 15 41.7 29 32.6

Optic disc 18 50.0 51 57.3

Concurrent visual field and

3 8.3 9 10.1
optic disc

Total 36 100.0 89 100.0

Kass MA et al. Arch Ophthalmol. 2002;120:701-713.

46-year-old man referred for
evaluation of possible glaucoma

GHL
Achromatic visual fields OU
(minimal loss OD, normal OS)

GHL
HRT: cup-to-disc asymmetry

GHL
GDx: inferior RNFL injury OD,
confirming glaucoma injury OD

GHL
Optic Nerve Abnormality Without
Visual Field Loss on SAP
Visual Field Loss on Selective
Functional Test: SWAP
Abnormal SWAP
Visual Field Loss on Selective
Functional Test: FDT
Abnormal FDT
Is This Early Glaucoma?
Yes!
SWAP can detect visual field loss 3 to 5 years
before SAP1
FDT can detect visual field loss 4 years before
SAP2

1. Racette L et al. Ophthalmol Clin North Am. 2003;16:227-236.

2. Johnson CA et al. J Vision. 2002;2:100a.
Pathological Change in ON:
Early Changes
Generalized loss of neuroretinal rim (cup enlargement)
Focal loss of neuroretinal rim (cup enlargement)
Superficial splinter hemorrhage
Loss of nerve fibers
Thinning and translucency of neuroretinal rim
Baring of vessels
Cup/disc ratio asymmetry
Reframing Glaucoma
Disease Severity
Redefine early disease
Include eyes with structural damage early functional loss
Pre-achromatic glaucoma
- Glaucomatous optic neuropathy (GON) without SAP
field loss1
Moderate/severe disease
Reproducible defects in white-on-white perimetry
Enlargement of blind spot
Nasal scotomas (nasal step)
Arcuate defects
Further constriction of visual field and threat to fixation

1. Medeiros FA et al. Am J Ophthalmol. 2003;136:805-813.

Periodic ON Exam Advocated in
Glaucoma Management Guidelines
Evidence-based guidelines for glaucoma
agree1-3
Identification and follow-up of glaucoma requires
careful evaluation of ON and RNFL as well as VF
Optic disc photographs or detailed drawings to be
obtained at initial visit and at regular intervals
during follow-up

1. EGS. Terminology and guidelines for glaucoma. 1998.

2. Damji KF, Behki R, Wang L. Can J Ophthalmol. 2003;38:189-197.
3. Primary open-angle glaucoma. AAO. 2003.
Optic Disc Evaluation
AAO PPP
Detailed drawing
Disc photography

Best technique to detect early changes

Examination of ONH by high magnification, high
intensity light stereo view
Lack of Compliance With
AAO Guidelines
Chart review studies suggest lack of compliance with
ON examination guidelines
193 POAG patients followed for 2 years in 8 private
practices in LA
- Almost all patients had photograph or drawing of optic
disc at initial examination
- At final follow-up visit
33.2% had not had ON drawing or photograph within 2 years
Another 37.8% had not had ON drawing or photograph since
initial examination

Hertzog et al. Ophthalmology. 1996;103:1009-1013.

Lack of Compliance With
AAO Guidelines (contd.)
More recent chart review study
395 POAG patients in 6 managed care plans
- Only 53% of patients had optic nerve photograph or
drawing at initial evaluation

Fremont AM et al. Arch Ophthalmol. 2003;121:777-783.

Is the Issue Examination or
Documentation of the Nerve?
Are there obstacles to ON examination in
clinical practice?
Costs of Examining the
Optic Nerve
Dilation of pupils
Patient and technician time
Patient movement

Increased examination time

3 to 5 minutes

Increased documentation
Patient discomfort
Others
Benefits of Examining the
Optic Nerve
At baseline examination
Diagnosis
- Detect disc hemorrhages
- Detect nerve fiber layer defect
- Diagnose early glaucomatous ON damage

At follow-up examinations
Diagnosis or Progression
- Detect changes in ON appearance
- Detect disc hemorrhages
- Identify patients at risk of disease progression
Benefits of ON Examination
Outweigh Costs
Compliance with AAO Preferred Practice
Patterns will
Improve diagnosis of glaucoma
Detect more cases, miss fewer cases
Help more patients with glaucoma
Reduce disease progression
Integrating ON Examination
Into Clinical Practice
Evaluate and document ON
Use ON evaluation to assess disease severity
Set and achieve lower targets based on risks and
appearance of ON
Reevaluate structure & function critically as patient is
followed
Reset and achieve lower IOP targets
Optic Disc/RNFL Examination
The 5Rs
This section was developed by
Robert N. Weinreb, MD
Felipe Medeiros, MD
Hamilton Glaucoma Center
University of California, San Diego

Remo Susanna Jr., MD

University of San Paulo, Brazil
Five Rules for Assessment of the
Optic Disc in Glaucoma
1 Observe the scleral Ring
to identify the limits of
the optic disc and its size
Five Rules for Assessment of the
Optic Disc in Glaucoma
1 Observe the scleral Ring
to identify the limits of
the optic disc and its size

2 Identify the size of the

Rim
Five Rules for Assessment of the
Optic Disc in Glaucoma
1 Observe the scleral Ring
to identify the limits of
the optic disc and its size

2 Identify the size of the

Rim

3 Examine the Retinal

nerve fiber layer
Five Rules for Assessment of the
Optic Disc in Glaucoma
1 Observe the scleral Ring
to identify the limits of
the optic disc and its size

2 Identify the size of the

Rim

3 Examine the Retinal

nerve fiber layer

4 Examine the Region of

parapapillary atrophy
Five Rules for Assessment of the
Optic Disc in Glaucoma
1 Observe the scleral Ring
to identify the limits of
the optic disc and its size

2 Identify the size of the

Rim

3 Examine the Retinal

nerve fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and

optic disc hemorrhages
Rule #1

Observe the scleral Ring to

identify the limits and the size
of the optic disc
Optic Disc Size
Scleral
ring

Vertical
disc
diameter

Horizontal
disc diameter
Optic Disc Size
Measurement of optic disc size with
direct ophthalmoscope
Small aperture (5 degree) of
Welch-Allen direct
ophthalmoscope

Size of light spot ~ size of average optic disc

Optic Disc Size
Measurement of optic disc size with
biomicroscopy
Volk lens
Measure length of slit beam

Correction factors
Volk 60D x 1.0
Volk 78D x 1.1
Volk 90D x 1.3 Avg vertical diameter: 1.8 mm
Avg horizontal diameter: 1.7 mm
Optic Disc Size
Size of cup varies with size of disc
Large discs have large cups in healthy eyes

1.4 1.9 2.4

Small Average Large

Identify small and large optic discs

Small discs: avg vertical diameter <1.5 mm
Large discs: avg vertical diameter >2.2 mm
Optic Disc Size
Small discs with glaucoma may have small cups

Rim
thinning
Optic Disc Size
Be cautious with myopic discs
Rule #2
Identify the size of the
neuroretinal Rim
ISNT RULE
Rim width S
Distance
between
border of disc
and position of N
blood vessel T
bending

ISNT rule
Inferior > I
Superior >
Nasal >
Temporal
Localized Rim Thinning/Notching

Notching
Notch
Observe the color of the rim
to identify pallor
A pale rim increases the likelihood for
a non-glaucomatous optic neuropathy
Pallor

Diffuse pallor

Pallor > cup

Cup
Non-glaucomatous
neuropathy
Rule # 3

Examine the Retinal nerve

fiber layer (RNFL)
RNFL Examination
Best performed using red-free light
(red-free photographs or green light)

Striations
Look at Brightness
Visibility of parapapillary retinal vessels

Look for diffuse and localized RNFL loss

RNFL Red-Free Photographs

Bright
striations
Diffuse RNFL Loss

Bright Diffuse loss

striations of striations

Diffuse RNFL loss

Diffuse loss of striate pattern +
increased visibility of retinal vessel borders
Diffuse RNFL Loss
Diffuse RNFL loss
Normal RNFL (advanced glaucoma)
Localized RNFL Loss

Localized RNFL defect

Wedge-shaped dark area
Rule # 4

Examine the Region of

parapapillary atrophy (PPA)
Parapapillary Atrophy
Alpha zone
Hypo- and hyper-
pigmented areas
Present in normal as well
as in glaucomatous eyes

Beta zone
Atrophy of the retinal
pigment epithelium (RPE)
and choriocapillaris
Large choroidal vessels
become visible
More common in
glaucomatous eyes
Parapapillary Atrophy
Beta zone
Width of beta zone
inversely correlates with
rim width at same area
Larger beta zone Thin rim
thinner rim
Progression of beta zone
associated with
progressive glaucoma

Larger zone
Rule # 5

Look for Retinal and

optic disc hemorrhages
Optic Disc Hemorrhage
Indicative of glaucoma progression

Flame-
shaped
hemorrhage
Optic Disc Hemorrhage
Normally disappears after 2-6 months
Optic Disc Hemorrhage
Detection of disc hemorrhages requires
careful optic disc examination
EXAMPLES
Example 1
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 1

1 Small disc size

2 Rim thinning (inferiorly)

ISNT rule:
Example 1

1 Small disc size

2 Rim thinning (inferiorly)

ISNT rule:

3 Localized RNFL defect

(inferiorly)

4 No significant PPA

5 Hemorrhage

GLAUCOMA
Example 2
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 2

1 Average disc size

2 Normal rim
ISNT rule: +

3 Normal RNFL

4 No significant PPA

5 No hemorrhage

NORMAL
Example 3
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 3

1 Average disc size

2 Notching (inferiorly
and superiorly)
ISNT rule:
3 RNFL loss

4 Small PPA

5 No hemorrhage

GLAUCOMA
Example 4
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 4

1 Disc size: Average

2 ISNT rule:
Rim thinning (inferiorly)
3 RNFL loss: Diffuse

4 PPA: zone

5 Hemorrhage: No

GLAUCOMA
Example 5
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 5

1 Disc size: Large

2 ISNT rule: Normal +

3 RNFL: Normal

4 PPA: Not significant

5 Hemorrhage: No

NORMAL
Example 6
Glaucoma or Normal?
Use the 5 Rules

1 Observe the scleral Ring

to identify the limits of the
optic disc and its size

2 Identify the size of the Rim

3 Examine the Retinal nerve

fiber layer

4 Examine the Region of

parapapillary atrophy

5 Look for Retinal and optic

disc hemorrhages
Example 6

1 Disc size: Average

2 ISNT rule:
Rim thinning (inferiorly)
3 RNFL loss: Diffuse (inferiorly)

4 PPA: zone

5 Hemorrhage: Reabsorbing

GLAUCOMA
Clinical Practice Today:
Diagnosis & Follow-Up of Glaucoma
Need to evaluate ON, VF, and IOP
Focus on ON damage in early disease
Disc or RNFL changes usually observed prior to
functional damage
Examination of IOP alone, or IOP plus VF, not sufficient

VF testing
Reproducible VF defects in early disease can confirm
glaucoma or progression in cases with an unremarkable
or suspicious disc
Critical in more advanced disease
IOP Control in
Glaucoma Management
Population studies indicate1-3
Incidence, severity, & progression of glaucoma
consistently correlate with elevated IOP

IOP reduction is currently the only treatment

available for decreasing risk of disease
progression4
Accurate understanding of individual patient
IOP affects treatment decisions and guides
treatment plan

1. Quigley HA et al. Am J Ophthalmol. 1996;122:355-363.

2. Leske MC et al. Arch Ophthalmol. 2001;119:89-95.
3. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
4. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
Glaucoma Clinical Trials

OHTS1
Ocular Hypertension Treatment Study
(NEI)
EMGT2
Early Manifest Glaucoma Trial
(NEI)
CNTGS3
Collaborative Normal Tension Glaucoma Study
(GRF)
CIGTS4
Collaborative Initial Glaucoma Treatment Study
(NEI)
AGIS5
Advanced Glaucoma Intervention Study
(NEI)

1. Kass MA et al. Arch Ophthalmol. 2002;120:701-713.

2. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
3. CNTG. Am J Ophthalmol. 1998;126:487-497.
4. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
5. AGIS: 7. Am J Ophthalmol. 2000;130:429-440.
Glaucoma Clinical Trials:
Study Design
Trial N Dx Randomization Follow-Up

OHTS1
1636 pts OHT Medical Tx vs observation 5 years
(NEI)
EMGT2 Tx (ALT + betaxolol)
255 pts OAG 4-9 years
(NEI) vs observation
CNTGS3 Medical Tx and/or surgery
140 eyes NTG 7 years
(GRF) vs observation
CIGTS4
607 pts OAG Medical Tx vs surgery 5 years
(NEI)
AGIS5
738 eyes OAG ALT vs surgery 8 years
(NEI)

ALT=argon laser trabeculoplasty; NTG=normal-tension glaucoma.

1. Kass MA et al. Arch Ophthalmol. 2002;120:701-713.
2. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
3. CNTG. Am J Ophthalmol. 1998;126:487-497.
4. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
5. AGIS: 7. Am J Ophthalmol. 2000;130:429-440.
Glaucoma Clinical Trials:
IOP-Lowering and Progression
% Progression
Study IOP Reduction (Tx/No Tx)
OHTS1 20% target 4.4%/9.5% (over 5 years)
EMGT2* 25% (average) 45%/62% (over 6 years)
CNTGS3 30% target 12%/35% (over 7 years)
CIGTS4 (med) ~38% (average) No progression (average)
CIGTS4 (surg) ~46% (average) No progression (average)
AGIS5 <18 mm Hg target No progression (average)

*10% reduction in risk with every 1 mm Hg of additional IOP lowering6

1. Kass MA et al. Arch Ophthalmol. 2002;120:701-713.
2. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
3. CNTG. Am J Ophthalmol. 1998;126:487-497.
4. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
5. AGIS: 7. Am J Ophthalmol. 2000;130:429-440.
6. Leske MC et al. Arch Ophthalmol. 2003;121:48-56.
OHTS: Treatment Reduces Incidence
of Glaucoma in OHT Patients
1636 patients with OHT

Proportion of participants developing POAG

Medical tx vs observation 0.15
Target IOP
20% reduction to 24
Avg IOP drop: 22.5% vs Observation group
4.0% in untreated controls
Results 0.10
Cumulative probability of
POAG
- 4.4% in treated group
vs 9.5% in observation
group (P<0.001) 0.05
Conclusion
Medical therapy effective in
delaying/preventing onset
of POAG in subjects with Medical treatment group
elevated IOP
0.00 6 12 18 24 30 36 42 48 54 60 66 72 78 84
Follow-up month

Kass MA et al. Arch Ophthalmol. 2002;120:701-713.

Lowering IOP 20% Reduces
Incidence of POAG: OHTS
12%

9.5%
Incidence of POAG

8%

4.4%

4%

0%
Untreated Treated to achieve
20% IOP reduction and
target IOP 24 mm Hg

End point: optic disc alone in >50% of cases

Kass MA et al. Arch Ophthalmol. 2002;120:701-713.
Early Treatment Reduces & Delays
Glaucoma Progression: EMGT
255 patients with newly 80
detected glaucoma
70 62%

Incidence of Progression (%)

(ALT + medical tx) vs
observation 60
Target IOP 45%
No target set 50
Avg IOP drop 25% (range 40
0-29%)
Results 30
Disease progression 45%
in treated vs 62% in
20
untreated (P=0.007) 10
Conclusion
Treatment significantly 0
delays disease Untreated Treated
progression
Each 1-mm Hg reduction
in IOP reduced risk of
progression by 10%

Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.

Early Treatment Reduces & Delays
Glaucoma Progression: EMGT
100

80
Progression (%)

60

40
Untreated
20
Treated

0
12 24 36 48 60 72 84 96 108
Follow-up Month
Median time to progression was 66 months in treated patients
compared with 48 months in controls
Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
Lowering IOP Reduces Vision Loss
in NTG Patients: CNTGS
1.0
145 eyes with NTG

Proportion surviving
(Medical tx surgery) vs 0.8
observation
0.6
Target IOP
30% IOP reduction Treated
0.4
Untreated
Results
0.2
80% survival (no
progression) in treated 0
group vs 60% in control 0 1 2 3 4 5 6 7 8

Eyes that progressed (%)

arm at 3 years (P=0.0018) 45 Time (years)
VF progression 18% in 27%
treated vs 30% in
30
untreated
Conclusion
15 12%
Lowering IOP reduces risk
of vision loss in NTG
0
Untreated eyes Treated eyes

CNTGS. Am J Ophthalmol. 1998;126:498-505.

Lowering IOP Minimizes VF
Loss: CIGTS
30
Medicine
Surgery

Mean IOP (mm Hg)

607 patients with newly 25
diagnosed OAG
Medical tx vs surgery 20
Target IOP
Low target pressure set 15
by formula
Results 10
8 0 6 12 18 24 30 36 42 48 54 60
Both medical tx and
7

Mean visual field

surgery lower IOP &
prevent VF loss 6
Conclusion 5
With aggressive therapy score 4
aimed at IOP-lowering, 3
VF loss in general is 2
minimal 1
0 0 6 12 1 2 30 36 42 4 54 60
8 4 8
Time (months)

Lichter PR et al. Ophthalmology. 2001;108:1943-1953.

IOP Needs to Be Consistently
Low: AGIS
738 eyes with All visits <18 75 to 100% of visits <18
uncontrolled
glaucoma 50 to 75% of visits <18 0 to 50% of visits <18
ALT vs surgery
3.5 Mean IOP
Target IOP

Mean change in visual field

3 20.2 mm Hg
<18 mm Hg
2.5
Results 16.9 mm Hg
2
100% of visits <18 14.7 mm Hg
mm Hg: no change 1.5
in visual field 1
<50% visits <18 mm 0.5
Hg: worsening of VF
0 12.3 mm Hg
by 0.63 units
Conclusion -0.5

Consistently low Follow-up month

IOP associated with
reduced progression
of VF defect

The AGIS Investigators. Am J Ophthalmol. 2000;130:429-440.

Glaucoma Clinical Trials:
Summary of Implications
Treat newly diagnosed glaucoma1,2
Patients with early glaucoma should be treated to reach low
pressures that reduce the risk of progression
Both medical treatment and surgery effectively reduce IOP
and risk of progression

IOP needs to be consistently low3

IOP fluctuation over long time periods increases risk of VF
loss in glaucoma
Results show that to be effective, patients need lower IOP
- Not just most of the time
- Need it lower consistently, all the time

When pressures are low enough, patients on average

have much lower risk of progression2

1. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.

2. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
3. AGIS: 7. Am J Ophthalmol. 2000;130:429-440.
IOP Often Not Lowered to
Recommended Target Pressures
Review of 395 POAG patient charts in 6 managed
care plans
IOP often inadequately controlled
- Mild glaucoma
52.4% of visits IOP >20 mm Hg
21.1% of visits IOP >24 mm Hg
- Moderate to severe glaucoma
65.3% of visits IOP >17 mm Hg
30.4% of visits IOP >21 mm Hg

Fremont AM et al. Arch Ophthalmol. 2003;121:777-783.

Target IOP Should be Established
as a Goal of Therapy
General rule: initial target IOP based on degree of
glaucoma damage
No VF damage, intact neuroretinal rim high teens/low twenties
VF loss on one side of the horizontal meridian mid-teens
VF loss on both sides of the horizontal meridian <12 mmHg

Target IOP range should be

Dynamic
Reviewed and adjusted over course of treatment
Target IOP:
How Low Is Low Enough?
Individualize
Factors
Damaging IOP
Severity of Damage
Other
Age
Family History
Target IOP:
Recommendations
Larger IOP reductions associated with decreased
risk of glaucoma & progression (OHTS, EMGT,
CIGTS)1-3
For some patients, IOP should be reduced to levels
lower than were considered acceptable in past
Guidelines for setting target pressures in glaucoma
developed by the AAO, EGS, and others
Based on evidence from clinical trials and clinical
experience

1. Kass MA et al. Arch Ophthalmol. 2002;120:701-713.

2. Heijl A et al. Arch Ophthalmol. 2002;120:1268-1279.
3. Lichter PR et al. Ophthalmology. 2001;108:1943-1953.
Target IOP in Clinical Practice
Set an individualized target IOP range for each
glaucoma eye
Do not need to record target

Target often more aggressive than in past

Get IOP down to target
Keep IOP down to target
May need to adjust target over time
Target IOP in Clinical Practice
(contd.)
Target IOP ranges
Low teens (10-12 mm Hg)
Mid teens (14-16 mm Hg)
High teens (17-19 mm Hg)

Determine range of % IOP reduction

Damaging IOP plus 0-20% for severity, other factors
Target IOP Examples
Ocular hypertensive, IOP=30, +FH
30% + 5% = 35% reduction = 19 mm Hg
High teens

31 yo, severe POAG, IOP=22

22% + 20% + 5% = 47% = 11 mm Hg
Low teens

Moderate PXF, IOP=45

45% + 10% = 55% = 20 mm Hg
Start at high teens
IOP Measurement in
Glaucoma Assessment
IOP may be higher than measured in clinic
due to
Lack of patient compliance with treatment
Normal variations in IOP

Consider
Fluctuation over time1,2
- Maximum IOP
- Diurnal IOP
- Nocturnal IOP
Central corneal thickness (CCT)3

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

2. Hughes E et al. J Glaucoma. 2003;12:232-236.
3. Gordon MO et al. Arch Ophthalmol. 2002;120:714-720.
When Should Treatment for
Glaucoma Be Initiated?
By the time a VF abnormality is detected, many ON
axons are lost1
Weigh all evidence from examination and testing; ask
Are they glaucomatous?
Optic disc
RNFL
VF

Progressive damage to optic disc and RNFL alone or in

correlation with VF change is sufficient for the
diagnosis of glaucoma and initiation of treatment

1. Kerrigan-Baumrind LA et al. Invest Ophthalmol Vis Sci. 2000;41:741-748.

To Treat or to Advance Treatment?
Ocular hypertension
Treatment is individualized and is most appropriate for
- Suspects at high risk of developing glaucoma
- Patients with pre-achromatic glaucoma

Glaucoma
All patients need to be treated
Treatment needs to be advanced if progression is present or
highly likely
Prevent Progression
Prescribe therapy most likely to achieve and
maintain target IOP or lower
Monitor patients for progression with serial ON
examination as well as VF testing
Patients at risk of disease progression
Need to get IOP even lower
Readjust for lower target IOP and treat more effectively

Primary open-angle glaucoma. AAO. 2003.

Treatment Options to Lower IOP
Medications
Commonly used drug classes include
- Once daily prostaglandins/prostamides
New gold standard for IOP lowering
- Beta-blockers
- Alpha-adrenergic agonists
- Topical CAIs
- Fixed combination product (timolol/dorzolamide)
Surgical Intervention
Laser trabeculoplasty (ALT - SLT)
Filtration surgery

CAI = carbonic anhydrase inhibitor.

Primary open-angle glaucoma. AAO. 2003.
Glaucoma Therapeutic
Option Timeline
Lumigan
Travatan
Alphagan P
Propine
Betagan
Betoptic
Pilocarpine Epinephrine Phospholine Timoptic

1870s 80s 90s 1900s 10s 20s 30s 40s 50s 60s 70s 80s 90s 2000s

Alphagan Ocupress
Diamox
Azopt OptiPranolol
Neptazane
Betimol Rescula
Betoptic-S Timoptic XE
Cosopt Trusopt
Iopidine Xalatan
Once Daily Prostaglandins/
Prostamides
Now dominant class
Not all the same
Important to
Understand differences in efficacy and tolerability
Evaluate weight of evidence & gain experience with each
product
Individualize use to reach treatment goals
- Target pressures
- Structural and functional stability
What Patients Need to Know for
Treatment Adherence
Patient Education
Gallup 2002 survey results1
- 95% of glaucoma patients consider their ophthalmologist
to be most important source for information about
glaucoma
- Other sources
Books/magazines, internet, private foundations, nurses,
pharmacists

1. Gallup Eye Health Survey. 2002.

What Patients Need to Know for
Treatment Adherence (contd.)
Patients need motivation to adhere to vision-
preserving treatment; educate them about
Insidious nature of glaucoma
Need to lower IOP
Available treatment options
- Should consider both efficacy & potential adverse effects
of treatment
Reframing Disease Severity Means
Reframing Disease Treatment
Glaucoma suspect
Treatment based on risk of developing glaucoma

Glaucoma
Abnormal ON, normal SAP, abnormal selective VF test (eg,
SWAP, FDT) treat
Early VF defect moderate or even advanced glaucoma

Based on large population clinical trials

Treat aggressively with most effective therapy
Go lower
- Every 1 mm Hg of IOP lowering matters
- Reduce IOP and keep it low consistently
Conclusions
Evaluate and document ON to
Diagnose glaucoma
Determine disease severity
Evaluate progression

Set target pressure based on risk factors and optic nerve

appearance
Aim for lower targets: every mm Hg counts

Prescribe therapy with best ability to achieve and maintain target

IOP (or lower)
Re-evaluate structure/function critically as patient is followed
Readjust target IOP and treat more effectively when subtle
progression is noted
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