Tonometry and Ocular Blood Flow

Dr Simon B D Si Barnard d
With acknowledgements to g Dr Robert Harper Manchester Royal Eye Hospital

Background: Changing perspectives on IOP
Glaucoma is characterized by raised IOP, optic neuropathy ne ropath and RNFL damage causing visual field ca sing is al loss – traditional view ‘…progressive optic neuropathy, with a typically ‘ i i h ih i ll cupped, pale optic disc and a characteristic loss of sensitivity to light’ – S ii i li h ’ Sponsel in 1980’s l 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 by apoptosis y 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 .

USA Roscommon. USA Beaver Dam.Background: IOP at presentation: epidemiology Study N POAG o % with ‘normal’ IOP 68 35 52 59 32 37 75 Des Moines. Ireland Blue Mountains. Wales Framingham. Aus 189 20 40 194 104 41 108 . USA Ferndale. USA Baltimore.

Background: IOP as a risk factor IOP <15mmHg IOP 16-21mmHg IOP 22-29mmHg IOP >30mmHg 1.0x 1 0x ~ 2.5x ~ 13x ~ 39x Baltimore Eye Study 1991 .

Background: Di ib i of IOP B k d Distribution f Av=15.7 mmHg g SD=2.7 mmHg Range 10-22 mmHg 10 22 Distribution k Di t ib ti skewed d .

CIGTS. EMGT. 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 variation in IOP inter individual reduction/progression relationship . CNTGS.Background: IOP and clinical trials k d d li i l i l Key randomised glaucoma trials OHTS. AGIS.

OHTS summary Multi-centre study. comparing conversion (24 32 H ) 40-80 i i rate to glaucoma in Rx versus No Rx Conversion 4. 1636 patients with OHT (24-32mmHg) 40 80 yrs. predictors for conversion to POAG ↓ CCT was a risk factor for POAG conversion i kf f i . Age CD ratio PSD and IOP were good ratio.e. no Rx) >90% of OHT pts did not convert after 5 years Age.4% in Rx group and ~9% in g p( ) control group (i.

EMGT study summary d First treatment 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 tonometry referral criteria i l f l i i Contact applanation tonometry – IOP >26mmHg and above – IOP >22mmHg with disc changes – IOP >35mmHg (urgent) .

The li Th earliest tonometer Palpation P l ti .

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Indentation tonometers I d i If a 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) .

Mueller) From Henson (1983) . Schiötz) or to electronic recording system (e.g.Plunger may be connected to lever arm and scale (e.g.

Schiotz S hi The footplate 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) .

Additional weights are 7. 10. 15 g .5.5grams giving total of 16.5 grams to be supported by cornea.Normal weight (knurled knob above footplate) = 5.

Indentation I d i

Shiotz

Wolff W lff

Disadvantages Di d
Heavy & potentially dangerous (total weight 50g) Corneal abrasions more likely Difficult to disinfect – note also CJD risk ? Displacement of aqueous Effect of corneal rigidity on reading g y g

Advantages Ad
Cheap Portable Can be done on supine px Can measure ocular tension of eye with scarred cornea ith d

variable force .Applanation tonometry A l i Imbert-Fick law IOP = tonometer weight (g) / area (mm2) Assumptions Method of choice for tonometry (currently) Constant area.

Gambs Cone just touching cornea 3.06 mm diameter .06 mm black square Cone applanating 3.

Difficulty with Gambs – Eye movements .

06 mm – very little fl id displaced (0.SD of differences <1mmHg Inter-observer variability is poorer .SD of differences is ~ 1.6mmHg 1 6mmHg .5μl) er fluid (0 5 l) – bending force = surface tension – 1 gm equiv to 10 mmHg Intra observer Intra-observer variability is good .Goldmann tonometer G ld Applanation diameter 3.

06 mm .Goldmann G ld Doubling prism to separate images by 3.

comparing calibrate new instruments. Gnerally method of choice Used for choice.Gnerally. .

From: Fingeret et al 1990 .

Advantages easy to use cheap comfortable (apart from anaesthetic) quick .

Disadvantages Di d need for anaesthetic cannot be delegated contact with cornea ( li ht chance of t t ith (slight h f abrasion) .

Errors Errors Lids touching the probe (↑ IOP) Surface t i force altered (minimal) S f tension f lt d ( i i l) Prolonged contact (↓ IOP) g ( ) Corneal astigmatism (>3DC) Incorrect vertical alignment (↑ IOP) I i l li C Calibration (systematic or random ↑ or ↓ ) (y Observer errors (↑ or ↓ IOP) Meniscus width (usually ↑ IOP) .

1mm) ~0.3mm*) – excessive (2mm) higher IOP estimates by ~2mmHg – narrow (<0 1mm) lower IOP estimates by (<0.35 mmHg .Meniscus width M i id h Thickness of flourescein ring Ideal ~ 1/10th diameter cone (0.

Perkins P ki .

Hand held Adjustable head rest Portable Can be done on supine patients .

NonNon-contact applanation tonometry l i First NCT designed by Grolman and introduced by American Optical in 1972 Principle P i i l was considered as early as 1951 by Erich id d l b 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 .

time taken from the onset of puff to applanation is recorded electronically (time relates to the IOP) Later generations measure air-pulse p g p pressure at applanation Keeler Pulsair is hand-held and can be used in any position .NCT principle i i l Original O i i l NCT directs an air-puff towards the cornea di i ff d h point of applanation detected by optical system.creates ramped air pulse which automatically iti t d i l hi h t ti ll applanates cornea at alignment. Current fourth generation instrument is Pulsair ‘EasyEye’ Modern NCTs use lower pulse pressure than the p p original Reichert instrument . Optical system detects applanation and samples pulse pressure.

NCT advantages d No need for an anaesthetic Risk f d Ri k of damage to cornea considerably reduced id bl d d Less sensitive effects of operator technique Repeat measures unlikely to change the IOP R lik l h h Much smaller risk of infection/cross contamination IOP can be recorded rapidly b d d 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 i i limitations Some NCT ‘advantages’ could become limitations if the user is unaware of the errors that can be introduced in estimating IOP i d di i i – 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 Goldmann i G ld instrument NCT has not replaced GAT as the technique of choice in the hospital setting h i i h h i l i .

Repeat tonometry and phasing .Factors affecting IOP – short term F ff i h Time of Day (diurnal range) – – – – – Normal ~3-6 mmHg Glaucoma average ~13 mmHg g g Diurnal variation in plasma cortisol (?) Higher in mornings (mid late pm ↓ esp males) (mid-late ↓.

25 20 IOP P 15 10 5 0 0 2 4 6 8 10 12 14 16 18 20 22 0 2 4 6 8 10 12 Time of Day (Hours) . showing nocturnal dip.Diurnal Variation Typical IOP Diurnal Variation in Normals.

Factors affecting IOP – short term F ff i h Arterial pulse – ‘ocular pulse – variation with heartbeat (3 4 mmHg) ocular pulse’ (3-4 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 .

exertion.Factors affecting IOP – short term F ff i h Blood pressure. posture – – – – – – – Body position sitting to supine 1-6 mmHg increase inversion increases++ (to 30-35 mmHg) i i i ++ (t 30 35 H ) aerobic exercise can lower IOP straining can increase IOP tight collar or neck tie (4mmHg) holding breath .

IOP ↑ in African/Asian Inheritance Myopia Systemic/ocular disease Corneal characteristics .IOP ↑ with ↑ age Sex .Factors affecting IOP – ‘longer term’ ff i l Age .IOP ↑ in older females Race .

Systemic and ocular disease S i d l di Systemic disease i di – association between raised IOP/Glaucoma and systemic hypertension and DM Ocular disease – the secondary glaucomas! – anterior uveitis and retinal detachments .

elasticity and l hi k l i i d hydration properties will affect IOP – – – – IOP ↑ (i. higher than true IOP) if CCT ↑ IOP ↓ if CCT ↓ IOP ↑ if steeper K’s (↑ resistance to flattening) IOP ↓ if flatter K’s (~1mmHg/3D) . curvature.e.Corneal characteristics C l h i i Corneal thickness.

The corneal thickness and intraocular pressure story: where are we now? Clin ExpOphthalmol 2002.Corneal thickness and IOP Lee at al. 30: 334-337 .

Corneal thickness and IOP C l hi k d Post PRK 7 IOP reduc ction (mm mHg) 6 5 4 3 2 1 0 0 25 50 75 100 125 150 175 Depth of cut (uM) .

8 -4.4 +4 4 +2.9 15mm Hg +4.8 -3.2 Additive correction (in mmHg) to be added to IOP readings at different CCTs for 5 levels of IOP (after le els Ehlers et al. 1975).56 0.8 +4 8 +3. .7 +1 7 +0.46 0 46 0.3 -2.5 -2.4 +1 4 +0.2 +0.7 -4.Early E l correction factor i f CCT (mm) 0.48 0.3 +5 3 +3.4 -2.0 +4 0 +2.2 -2.1 -1.1 30mm Hg +5.2 -1.58 10mm Hg +3.50 0 50 0.9 +1 9 +0.3 +1.9 +0 9 -0.4 -1.0 20mm Hg +4.3 -1.2 +1 2 -0.9 +1.52 0.0 -1.8 -4.6 -2.1 25mm Hg +4.5 +3 5 +2.6 +1.54 0.6 +1.8 -4.

7mmHg per 10 micron 0 2 0 7mmHg difference from an average CCT is suggested – European Glaucoma Society (2003) .Corneal thickness C l hi k Knowledge of CCT provides information on an i di id l’ risk and allows correction of individual’s i k d ll ti f IOP (OHTS.2-0. Brandt 2004) No single correction factor is agreed upon Error range of 0.

Ultrasound Pachymeters Choose based on – Validity/Precision issues – Ease of use – Portability – Value for money –A Appearance .

Developments in tonometry D l i Ocular Response Analyser p y Tonopen Pneumatonometry P t t Pascal Dynamic Contour tonometer y Integrated tonometer/pachymeter unit .

Ocular Response A l O l R Analyser Reichert ORA – NCT – Bi-directional dynamic applanation process – Corneal ‘hysteresis’: Aggregate effect of corneal rigidity. thickness and hydration – Clinical trials awaited .

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Archives of Ophthalmology 2004 .Pascal Dynamic Contour Tonometry l i Based on principle of contour matching Contour tip concave. with minute pressure sensor flush with contact surface IOP values claimed to be closer l l i d b l to true manometric levels compared to GAT1 1Kniestedt et al.

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g y p Tonopen against cornea. gently tap p . Final averaged reading (of usually 4 – 6) displayed .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 patient has anaesthetic.Tonopen Tonopen Applanation device with small “footprint” on cornea .

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) – pulse a p tude pu se amplitude (mmHg) – pulse volume (μl) p (μ ) – pulse rate (/min) – ocular blood flow (μl/min) OBF tonometer .

IOP continuous recording i di 14 I IOP mm mHg 13 12 11 10 1 2 3 4 5 6 Time (sec) .

Ocular Blood Fl T O l Bl d Flow Tonometer Early studies suggested y gg helpful in vascular gy aetiology of POAG/NTG Benefit of OBF now questioned Still affected by cornel thickness (more than thi k ( th GAT?) .

IOP and POBF in glaucoma .example Distribution of IOP Normal and Glaucoma 20 18 16 14 12 10 8 6 4 2 0 8 12 16 20 24 28 32 36 40 Distribution of POBF Normal and Glaucoma 25 20 15 10 5 0 100 400 700 1000 1300 1600 More IOP POBF .

Anatomy & Ph i l A Physiology of OBF f The eye receives its blood supply from 2 sources of the ophthalmic artery: – Ciliary arteries – Central retinal artery Ciliary supply 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) .

Optic O i nerve bl d supply blood l .

21:359-93. Prog Ret Eye Res 2002.Methods of assessing OBF M h d f i Pulsatile ocular blood flow Angiography Laser Doppler techniques – Laser doppler velocimetry – Laser doppler flowmetry – Heidelberg Retina Flowmetry (HRF) Laser speckle phenomenon Blue fi ld t ti Bl field entoptics Retinal vessel analyser Corneal temperature C lt t Colour Doppler imaging Peripheral bl d fl P i h l blood flow See Flammer et al. .

including the optic nerve head. g p . the retrobulbar and peripheral blood flow – The reduced OBF appears more pronounced in patients with NTG ih – The effect of reduced OBF is more pronounced under conditions of provocation (e.OBF i glaucoma in l Different techniques measure different aspects of Diff tt h i diff t t f ocular blood circulation and numerous studies have been conducted on many different glaucoma subsub groups (see Flammer et al review. – There is reduced OBF in glaucoma that involves different p parts of the eye. retinal y . cold provocation) (e g . 2002) In general terms terms…. circulation.g.

Possible P ibl causes of OBF reduction f d i Increased resistance to OBF – Anatomical variations – Vasculitis or arteriosclerosis – Vascular dysregulation Decreased perfusion pressure D d f i – Due to increased IOP – Due to decreased BP .

IOP and perfusion pressure d f i Ocular perfusion pressure (OPP) cannot be measured directly Estimate: – OPP=2/3 mean arterial BP minus IOP Medical therapy directed towards ed ca e apy d ec ed owa ds increasing OPP Equivalent E i l t IOP reductions may not give the d ti t i th same increase in OPP .

Perfusion pressure and POAG p Tielsch et al (1995) Arch Ophthalmol 113:216-221 .