Tonometry and Ocular

Blood Flow
D Si
Dr Simon B
Barnard
d
With acknowledgements
g to
Dr Robert Harper
Manchester Royal Eye Hospital
Background: Changing perspectives on IOP

‹ Glaucoma is characterized by raised IOP, optic

ne ropath and RNFL damage causing
neuropathy ca sing visual
is al field
loss – traditional view
‹ ‘…progressive
‘ i optic i neuropathy,
h with
i h a typically
i ll
cupped, pale optic disc and a characteristic loss of
sensitivity
i i i to light’
li h ’ – Sponsel
S l in 1980’s
1980’
‹ ‘…a variable combination of raised IOP, optic disc
changes and visual field loss’ – Quigley in 1990’s
‹ Randomised controlled trial evidence – 2000+
Background: Pathophysiology of glaucoma

‹ Elevated IOP caused by impaired outflow

‹ Theories of optic nerve damage
– Vascular (von Jaeger theory)
Reduced blood flow/vascular dysregulation
– Mechanical (Muller theory) Compression of axons by
laminar plates
‹ Current view: RGC death is causes byy apoptosis
p p
and remodelling of the optic nerve head, mediated
by mechanical forces, ischaemia and reperfusion
injury (IOP and OBF implicated in these issues)
Background: Risk factors for POAG
‹ Age
‹ IOP
‹ Race
‹ Family History
‹ Diabetes Mellitus
‹ Hypertension
‹ Myopia
y p
‹ Corneal thickness
‹ Others including vascular factors
Background: IOP at presentation:
epidemiology
o
Study N POAG % with
‘normal’ IOP

Des Moines, USA 189 68

Ferndale, Wales 20 35
Framingham, USA 40 52
Baltimore, USA 194 59
Beaver Dam, USA 104 32
Roscommon, Ireland 41 37
Blue Mountains, Aus 108 75
Background: IOP as a risk factor

‹ IOP <15mmHg 11.0x

0x
‹ IOP 16-21mmHg ~ 2.5x
‹ IOP 22-29mmHg ~ 13x
‹ IOP >30mmHg ~ 39x

Baltimore Eye Study 1991

B k
Background:
d Di
Distribution
ib i off IOP

Av=15.7 mmHgg
SD=2.7 mmHg
Range 10-22
10 22 mmHg

Di t ib ti skewed
Distribution k d
Background:
k d IOP andd clinical
li i l trials
i l

‹ Key randomised glaucoma trials

OHTS, EMGT, CNTGS, CIGTS, AGIS, EGPS
‹ Lowering IOP exerts a favourable influence on the
development and progression of glaucoma
‹ Lower IOP means better protection
p
‹ Lowering IOP does not always stop progression
‹ Large inter-individual
inter individual variation in IOP
reduction/progression relationship
OHTS summary

‹ Multi-centre study, 1636 patients with OHT

(24 32
(24-32mmHg) H ) 4040-80
80 yrs, comparing
i conversion
i
rate to glaucoma in Rx versus No Rx
‹ Conversion 4.4% in Rx group and ~9% in
control ggroupp (i.e.
( no Rx))
‹ >90% of OHT pts did not convert after 5 years
‹ Age,
Age CD ratio
ratio, PSD and IOP were good
predictors for conversion to POAG
‹ ↓ CCT was a risk i k factor
f for
f POAG conversion
i
EMGT study
d summary
‹ Firsttreatment versus no treatment RCT in
early glaucoma
‹ Population screening 44K – 255 pts recruited
‹ Randomised to IOP ↓ or no Rx
‹ Limited treatment (laser + Betaxolol) of ~25%
25%
IOP reduction reduced progression risk by
~50%
‹ Lower risk patients and no treatment option
Typical
i l tonometry referral
f l criteria
i i
‹ Contact applanation tonometry
– IOP >26mmHg and above
– IOP >22mmHg with disc changes
– IOP >35mmHg (urgent)
Th earliest
The li tonometer

P l ti
Palpation
I d
Indentation
i tonometers
‹ Ifa plunger of known weight is rested
on the cornea, the depth of plunger
indentation should (?) be proportional to
IOP
‹ Note: ocular rigidity/facility of aqueous
outflow (see separate lecture on
tonometry)
o o e y)
‹ Plunger may be connected to lever arm and
scale (e.g. Schiötz) or to electronic recording
system (e.g. Mueller)

From Henson (1983)

S hi
Schiotz
‹ Thefootplate is rested on the cornea and the
plunger is free to indent the cornea. A variety
of weights may be used to minimise errors
due to corneal rigidity (use with tables)
‹ Normal weight (knurled knob above
footplate) = 5.5grams giving total of 16.5
grams to be supported by cornea. Additional
weights are 7.5, 10, 15 g
I d
Indentation
i

Shiotz W lff
Wolff
Di d
Disadvantages

‹ Heavy & potentially dangerous (total weight

50g)
‹ Corneal abrasions more likely
‹ Difficult to disinfect – note also CJD risk ?
‹ Displacement of aqueous
‹ Effect of corneal rigidity
g y on reading g
Advantages
Ad

‹ Cheap
‹ Portable
‹ Can be done on supine px
‹ Can measure ocular tension of eye
with
ith scarred
d cornea
A l
Applanation
i tonometry

‹ Imbert-Fick law
‹ IOP = tonometer weight (g) / area (mm2)
‹ Assumptions
‹ Method of choice for tonometry (currently)
‹ Constant area, variable force
‹ Gambs Cone just touching cornea

3.06 mm black square

Cone applanating
3.06 mm diameter
‹ Difficulty
with Gambs
– Eye movements
G ld
Goldmann tonometer
‹ Applanation diameter 3.06 mm
– very
er little fl
fluid
id displaced (0.5μl)
(0 5 l)
– bending force = surface tension
– 1 gm equiv to 10 mmHg
‹ Intra
Intra-observer
observer variability is good
- SD of differences <1mmHg
‹ Inter-observer variability is poorer
- SD of differences is ~ 1.6mmHg
1 6mmHg
G ld
Goldmann
‹ Doubling prism to separate images by 3.06
mm
Gnerally, method of choice
Gnerally choice. Used for
comparing calibrate new
instruments.
From: Fingeret et al 1990
Advantages

‹ easy to use
‹ cheap
‹ comfortable (apart from anaesthetic)
‹ quick
Di d
Disadvantages

‹ need for anaesthetic

‹ cannot be delegated
‹ contact
t t with
ith cornea ((slight
li ht chance
h off
abrasion)
Errors
Errors
‹ Lids touching the probe (↑ IOP)
‹ Surface
S f ttension
i force
f altered
lt d (minimal)
( i i l)
‹ Prolonged
g contact (↓ ( IOP))
‹ Corneal astigmatism (>3DC)
‹ Incorrect
I vertical
i l alignment
li (↑ IOP)
‹CCalibration (systematic
(y or random ↑ or ↓ )
‹ Observer errors (↑ or ↓ IOP)
‹ Meniscus width (usually ↑ IOP)
M i
Meniscus width
id h

‹ Thickness of flourescein ring

‹ Ideal ~ 1/10th diameter cone (0.3mm*)
– excessive (2mm) higher IOP estimates by
~2mmHg
– narrow (<0
(<0.1mm)
1mm) lower IOP estimates by
~0.35 mmHg
P ki
Perkins
‹ Hand held
‹ Adjustable head rest
‹ Portable
‹ Can be done on supine patients
Non--contact applanation
Non l i tonometry
‹ FirstNCT designed by Grolman and introduced by
American Optical in 1972
‹ Principle
P i i l was considered
id d as early
l as 1951 by
b Erich
Ei h
Zeiss
‹ Currently >8 different NCTs commercially available:
– Reichert (formerly American Optical) NCT II and
auto NCT AT550 and portable PT100 instruments
– Keeler Pulsair EasyEye
– Topcon CT80/80A
– Nidek NT-2000/4000
– Kowa KT-500
KT 500
– Canon TX-10
NCT principle
i i l
‹ Original
Oi i l NCT directs
di an air-puff
i ff towards
d the
h cornea -
point of applanation detected by optical system, time
taken from the onset of puff to applanation is recorded
electronically (time relates to the IOP)
‹ Later ggenerations measure air-pulse
p ppressure at
applanation
‹ Keeler Pulsair is hand-held and can be used in any
position
iti - creates
t rampedd air i pulse
l which
hi h automatically
t ti ll
applanates cornea at alignment. Optical system detects
applanation and samples pulse pressure. Current fourth
generation instrument is Pulsair ‘EasyEye’
‹ Modern NCTs use lower p pulse pressure
p than the
original Reichert instrument
NCT advantages
d

‹ No need for an anaesthetic

‹ Ri k off damage
Risk d to cornea considerably
id bl reduced
d d
‹ Less sensitive effects of operator technique
‹ R
Repeat measures unlikely
lik l to change
h the
h IOP
‹ Much smaller risk of infection/cross contamination
‹ IOP can beb recorded
d d rapidly
idl
‹ Acceptable for use in children or in others where
tolerance to contact presents difficulties
‹ Can be used by non-clinically qualified staff
NCT li
limitations
i i
‹ Some NCT ‘advantages’ could become limitations
if the user is unaware of the errors that can be
i
introduced
d d in i estimating
i i IOP
– See variations in IOP in slides below
‹ Essential to take at least 3-4 readings per eye in
order to balance out the effect of the ocular pulse
‹ NCTs can provide clinically meaningful measures
of IOP which equate to those obtained by the
G ld
Goldmann i
instrument
‹ NCT has not replaced GAT as the technique of
choice
h i ini the
h hospital
h i l settingi
F
Factors affecting
ff i IOP – short
h term

‹ Time of Day (diurnal range)

– Normal ~3-6 mmHg
– Glaucoma averageg ~13 mmHg g
– Diurnal variation in plasma cortisol (?)
– Higher in mornings (mid late pm ↓,
(mid-late ↓ esp males)
– Repeat tonometry and phasing
Diurnal Variation
Typical IOP Diurnal Variation in Normals,
showing nocturnal dip.

25

20

15
IOP
P

10

0
0 2 4 6 8 10 12 14 16 18 20 22 0 2 4 6 8 10 12
Time of Day (Hours)
F
Factors affecting
ff i IOP – short
h term
‹ Arterial pulse
– ‘ocular
ocular pulse
pulse’ – variation with heartbeat (3
(3-44 mmHg)
‹ Drinking/Fluid intake
– Water and coffee +3 mmHg in 20 min
– alcohol -3mmHg in 5 min
‹ Contraction of extra/intraocular muscle ↑IOP
– Gaze away from primary position
– Accommodation
– Blinking and lid squeezing
F
Factors affecting
ff i IOP – short
h term
‹ Blood pressure, exertion, posture
– Body position
– sitting to supine 1-6 mmHg increase
– i
inversion
i increases++
i ++ (to
(t 30-35
30 35 mmHg)
H )
– aerobic exercise can lower IOP
– straining can increase IOP
– tight collar or neck tie (4mmHg)
– holding breath
Factors affecting
ff i IOP – ‘longer
l term’
‹ Age - IOP ↑ with ↑ age
‹ Sex - IOP ↑ in older females
‹ Race - IOP ↑ in African/Asian
‹ Inheritance
‹ Myopia
‹ Systemic/ocular disease
‹ Corneal characteristics
S
Systemic
i and
d ocular
l disease
di
‹ Systemic
i disease
di
– association between raised IOP/Glaucoma and
systemic hypertension and DM
‹ Ocular disease
– the secondary glaucomas!
– anterior uveitis and retinal detachments
C
Corneal
l characteristics
h i i
‹ Corneallthickness,
hi k curvature, elasticity
l i i andd
hydration properties will affect IOP
– IOP ↑ (i.e. higher than true IOP) if CCT ↑
– IOP ↓ if CCT ↓
– IOP ↑ if steeper K’s (↑ resistance to flattening)
– IOP ↓ if flatter K’s (~1mmHg/3D)
Corneal thickness and IOP

Lee at al. The corneal thickness and intraocular pressure story: where are we
now? Clin ExpOphthalmol 2002; 30: 334-337
Corneal
C l thickness
hi k andd IOP
‹ Post PRK
7
6
mHg)

5
ction (mm

4
3
IOP reduc

2
1
0
0 25 50 75 100 125 150 175
Depth of cut (uM)
E l correction
Early i factor
f
CCT 10mm 15mm 20mm 25mm 30mm
(mm) Hg Hg Hg Hg Hg
0 46
0.46 +3 5
+3.5 +4 0
+4.0 +4 4
+4.4 +4 8
+4.8 +5 3
+5.3
0.48 +2.2 +2.6 +2.9 +3.3 +3.6
0 50
0.50 +0 9
+0.9 +1 2
+1.2 +1 4
+1.4 +1 7
+1.7 +1 9
+1.9
0.52 -0.4 -0.2 +0.0 +0.1 +0.3
0.54 -1.6 -1.5 -1.4 -1.3 -1.2
0.56 -2.8 -2.8 -2.8 -2.8 -2.7
0.58 -3.9 -4.0 -4.1 -4.1 -4.2

Additive correction (in mmHg) to be added to IOP

readings at different CCTs for 5 levels
le els of IOP (after
Ehlers et al, 1975).
C
Corneal
l thickness
hi k
‹ Knowledge of CCT provides information on
an individual’s
i di id l’ riski k andd allows
ll correction
ti off
IOP (OHTS, Brandt 2004)
‹ No single correction factor is agreed upon
‹ Error range of 0.2-0.7mmHg
0 2 0 7mmHg per 10 micron
difference from an average CCT is suggested
– European Glaucoma Society (2003)
Ultrasound Pachymeters

‹ Choose based on
– Validity/Precision
issues
– Ease of use
– Portability
– Value for money
– Appearance
A
D l
Developments in
i tonometry

‹ Ocular Response
p Analyser
y
‹ Tonopen
‹ Pneumatonometry
P t t
‹ Pascal Dynamic
y Contour tonometer
‹ Integrated tonometer/pachymeter unit
O l R
Ocular Response A
Analyser
l
‹ Reichert ORA
– NCT
– Bi-directional dynamic
applanation process
– Corneal ‘hysteresis’:
Aggregate effect of
corneal rigidity,
thickness and hydration
– Clinical trials awaited
 Pascall Dynamic
i Contour Tonometry
‹ Based on principle of contour
matching
‹ Contour tip concave, with
minute pressure sensor flush
with contact surface
‹ IOP values
l claimed
l i d to beb closer
l
to true manometric levels
compared to GAT1

1Kniestedt et al, Archives of Ophthalmology 2004

Tonopen
Tonopen

‹ Applanation device with small “footprint”

on cornea - easier to use with corneal
abnormalities
‹ Patient can be lying or sitting
‹ A sterile cover must be over the tip
‹ Must be calibrated by pressing activation
button until “CAL” appears in the window
‹ Ensure ppatient has anaesthetic,, gently
g y tapp
Tonopen against cornea. Final averaged
reading (of usually 4 – 6) displayed
Pneumatonometer
Pneumatonometer
Resistance to air flow
varies with IOP

3mm diameter area

of applanation

Back pressure in air

supply varies with
resistance to air flow

Force applied adjusts to maintain

constant area of applanation
OBF Ocular blood flow tonometer

‹ Overcomes some of the problems

encountered in earlier Langham tonometer
‹ Measures
– IOP (mmHg)
– pu
pulse
se aamplitude
p tude
(mmHg)
– ppulse volume (μ
(μl))
– pulse rate (/min)
– ocular blood flow
(μl/min) OBF tonometer
 IOP continuous
i recording
di

14
mHg

13
IIOP mm

12

11

10

1 2 3 4 5 6
Time (sec)
O l Bl
Ocular Bloodd Flow
Fl Tonometer
T

‹ Early
y studies suggested
gg
helpful in vascular
gy of POAG/NTG
aetiology
‹ Benefit of OBF now
questioned
‹ Still affected by cornel
thi k
thickness (more
( than
th
GAT?)
IOP and POBF in glaucoma - example

Distribution of IOP Distribution of POBF

Normal and Glaucoma Normal and Glaucoma

20 25
18
16 20
14
12 15
10
8 10
6
4 5
2
0 0
8 12 16 20 24 28 32 36 40 100 400 700 1000 1300 1600 More
IOP
POBF
A
Anatomy & Ph
Physiology
i l off OBF
‹ The eye receives its blood supply from 2 sources of
the ophthalmic artery:
– Ciliary arteries
– Central retinal artery
‹ Ciliarysupply accounts for 95% of total OBF
‹ Blood supply to optic nerve
– Intraorbital (pial arteries and CRA)
– Laminar (short posterior ciliary arteries)
– Pre-laminar (posterior ciliary arteries)
– Surface RNFL (arterioles from CRA)
O i nerve bl
Optic bloodd supply
l
Methods
M h d off assessing
i OBF
‹ Pulsatile
ocular blood flow
‹ Angiography
‹ Laser Doppler techniques
– Laser doppler velocimetry
– Laser doppler flowmetry
– Heidelberg Retina Flowmetry (HRF)
‹ Laser speckle phenomenon
‹ Blue
Bl field
fi ld entoptics
t ti
‹ Retinal vessel analyser
‹ Corneal
C l temperature
t t
‹ Colour Doppler imaging
‹ Peripheral
P i h l blood
bl d flow
fl
See Flammer et al, Prog Ret Eye Res 2002, 21:359-93.
OBF iin glaucoma
l
‹ Different
Diff t techniques
t h i measure different
diff t aspects
t off
ocular blood circulation and numerous studies have
been conducted on many different glaucoma sub-
sub
groups (see Flammer et al review, 2002)
‹ In general terms
terms….
– There is reduced OBF in glaucoma that involves different
pparts of the eye,
y , including
g the optic
p nerve head,, retinal
circulation, the retrobulbar and peripheral blood flow
– The reduced OBF appears more pronounced in patients
with
i h NTG
– The effect of reduced OBF is more pronounced under
conditions of provocation (e.g.
(e g cold provocation)
P ibl causes off OBF reduction
Possible d i

‹ Increased resistance to OBF

– Anatomical variations
– Vasculitis or arteriosclerosis
– Vascular dysregulation
‹ Decreased
D d perfusion
f i pressure
– Due to increased IOP
– Due to decreased BP
IOP and
d perfusion
f i pressure
‹ Ocular perfusion pressure (OPP) cannot be
measured directly
‹ Estimate:
– OPP=2/3 mean arterial BP minus IOP
‹ Medical
ed ca therapy
e apy directed
d ec ed towards
owa ds
increasing OPP
‹ Equivalent
E i l t IOP reductions
d ti may nott give
i the
th
same increase in OPP
Perfusion ppressure and POAG

Tielsch et al (1995) Arch Ophthalmol 113:216-221