Sommer et al. Current Opinion in Ophthalmology. 1996. Leske M et al. JAMA Ophthalmology. 2003. Mansouri K et al. JAMA Ophthalmology. 2012 ...
Intraocular Pressure Fluctuation Recording with a Wireless Smart Silicone Contact Lens Sensor: From Bench to Bedside
KC Shih1, J Shum1, GZ Chen2, LK Leung2, L Yuen1, J Lai1, DC Lam2 1Department
of Ophthalmology, The University of Hong Kong 2Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology
Financial Disclosure • The Department of Mechanical and Aerospace Engineering, Hong Kong University of Science and Technology holds a patent for the contact lens sensor device • Members of the Department of Ophthalmology, University of Hong Kong do not hold any financial interests in the contact lens sensor device
Background • Elevated(intraocular(pressure((IOP)(is(a(major(risk(factor(for(glaucoma( • The(most(significant(shortcoming(of(current(available(methods(of( measuring(IOP(is(the(sta?c(nature(of(its(measurements( • A(single(IOP(measurement(performed(in(a(clinic(visit(once(every(4(months( may(fail(to(reflect(the(true(nature(of(an(individual's(IOP(( • The(Sensimed(Triggerfish((Sensimed(AG)(was(the(first(commercially( available(contact(lens(sensor(for(use(in(con?nuous(monitoring(of( intraocular(pressure(fluctua?ons( – Concept(validated(in(vitro( – Repeatability(and(safety(validated(in(Phase(I(trials( Sommer et al. Current Opinion in Ophthalmology. 1996 Leske M et al. JAMA Ophthalmology. 2003 Mansouri K et al. JAMA Ophthalmology. 2012
Detec%on(of(Contact(Lens(Deforma%on ΔL = γ ⋅ Δd avg 1 γ = µ n 2 [ln(2.46 / ρ ) + 0.2 × ρ 2 ] 2 Δf 1 ΔL 1 γ ⋅ a ⋅ Δr ⋅ d 0 =− =− f 2 L 2 L IOP(changes
Δcoil&diameter!Δinductance!Δresonance&
d(
Corneal+curvature+ deforms
d+∆d(
Contact+lens+sensor+ deforms
IOP(signal(was(obtained(by(a( Wireless(Reading(device 4(
Contact(Lens(Sensor((CLS) Items
Spec.
Lens(diameter
14.0mm(
Radius(of(curvature
8.00,8.25,8.50,8.75 mm
Central(thickness
150V180(um
CL(material:(( NuSil(MEDV6015,(Liquid(silicone(elastomer,(NuSil(Technology(LLC,(Carpinteria,(CA,(USA(
Pressure(Sensing(Element Items
Spec.
Total(size((length(x(width(x(height)
3(x(2(x(0.14mm(
Top/Bobom(electrodes(thickness
1.02um
Dielectric(thickness((middle(layer)
12um
!
Materials:(( Electrodes(:(Ti/Au((20nm/1um)( Dielectric(:((Copper(phthalocyanine((CuPc)
Contact(Lens(Treatment(and(Storage •
Biocompatibility - The sensing elements were fully sealed by 3um Parylene C (poly-chloro-p-xylylene)
•
Surface treatment – Treated with oxygen (O2) plasma (Branchy Plasma Cleaner-P100E) for 90 seconds to induce hydrophilic surfaces . • Sterilization – Autoclave Sterilization Machine (105oC, 1 hour) to prevent bacteria contamination on the contact lens sensor’s surface. • Storage – Stored in a multi-purpose contact lens care solution until it is used
Comparison of Contact Lens Sensors Sensimed CLS
HKUST CLS
Acuvue Contact Lens
Diameter
14.2 mm
14.0 mm
14.1 mm
Central thickness
560 um
200 um
50-120 um
Available curvature
8.4, 8.7, 9.0mm
8.0, 8.25, 8.5, 8.75mm
8.4, 8.8, 9.1mm
Material
Medical Grade Silicone (Med6019)
Medical Grade Silicone (Med6015)
Etafilcon A
Every 5 minutes
Every 3 seconds
-
In sterile glass vial
In buffered saline
In buffered saline
Measurements Package
Purpose • Laboratory validation of the contact lens sensor
– Ex vivo validation: Enucleated porcine eyes – In vivo validation: Eyes of live rabbits – In vivo validation: Eyes of fresh cadavers • Testing on healthy individuals in an ambulatory setting
– 24 hour monitoring – Posture-related changes: Sitting vs Supine – Exercise related changes: 60-80% Wmax activity
Ex Vivo Validation: Enucleated Porcine Eye various IOP in three different curvature procine eyes 115
Curvature=9.00mm Curvature=8.93mm curvature=8.89mm
Signal output (MHz)
115.2 115.4 115.6
CLS Base Curve: 9.0mm
115.8 116 116.2
5
10
15
Pressure sensor implanted in the anterior chamber
20 25 Pressure (mmHg)
30
35
In Vivo Validation: Live Rabbit Eye in-vivo testing on rabbit eye
Sensor signal (MHz)
113.9
CLS Base Curve: 8.0mm Eye Base Curve: 7.2mm
Sensor Signal
114
y = 114.44 - 0.02782x R= 0.99716
114 114.1 114.2 114.2 8
10
12
14
Control Pressure (mmHg)
16
Signal = 0.0278IOP + 114.44 Signal − 114.44 IOP = 0.0278 Pressure sensor implanted in the anterior chamber
18
In Vivo Validation: Fresh Cadaver 203.5
Frequency (MHz)
203.4 203.3
Eye open
203.2 203.1
2
y = 203.48 - 0.010664x R = 0.96723 203 5
10
15 20 IOP (mmHg)
25
30
35
200.8 200.75
Frequency (MHz)
200.7
Aim to mimic normal eyelid closure during sleep
200.65
Eye closed with tarsorrhaphy
200.6 200.55 200.5 2
200.45
y = 200.81 - 0.0091929x R = 0.98425
200.4 5
10
15 20 IOP (mmHg)
25
30
35
Study
Patient Recruitment
Method of Ambulatory Testing • • • •
Age 18- 80 years old Healthy subjects VA > 20/80 in study eye Cylinder refraction of ≤ 2D in the study eye YES
Any reason to exclude patient?
No
Excluded
YES
Excluded
No
Study enrollment
Pre-Testing • Signing of consent • Corneal topography • Insertion of device • Assessment of fitting
Testing • Cyclic posturing • Exercise testing (moderate)
Continuous Recording of IOP Fluctuation Patient in seated position 152
Eye open
Eye open
Frequency (MHz)
151.5 151 150.5 150 149.5
Eye closed
149 148.5 0
50
100
Signal spikes correspond with eye blinking
Time (s)
150
200
250
Continuous Recording of IOP Fluctuation Patient in seated position 152
Frequency (MHz)
151.5
151
150.5
150
149.5 0
5
10 time (s)
Signal frequency remains stable between spikes
15
20
Posture Related Fluctuation Subject 1
Base curve: 8.25 mm Thickness: 225 um Central frequency: 150 MHz
150.5
Frequency (MHz)
150
150.2135
149.4944
sitting
149.5
❑ Sitting - 5 minutes ❑ Supine - 5 minutes
149
❑ Repeat 5 cycles 148.5
supine
Posture(Related(Fluctua%on Subject 2
Base curve: 8.25 mm Thickness: 188 um Central frequency: 181 MHz
182
181.56 MHz 181.28 MHz
❑ Sitting - 5 minutes ❑ Supine - 5 minutes
Frequency (MHz)
181.5
181
180.5
180
❑ Repeat 5 cycles 179.5
Sitting
supine
Posture Related Fluctuation Subject 3
Base curve: 8.25 mm Thickness: 195 um Central frequency: 171 MHz
172.5
❑ Sitting - 5 minutes ❑ Supine - 5 minutes
Frequency (MHz)
172
171.6 MHz 171.45 MHz
171.5 Sitting 171
❑ Repeat 5 cycles 170.5
Supine
Exercise on bicycle ergometer Subject 2
❑ On a bicycle ergometer
183
❑ Exercise – 10 minutes Frequency (MHz)
182.5
182
181.5
181 0
100
200
300 Time (s)
400
500
600
Exercise on bicycle ergometer Subject 3
❑ On a bicycle ergometer
172.5
❑ Exercise – 10 minutes
Frequency (MHz)
172
171.5
171
170.5 0
100
200
300
400
Time (s)
500
600
700
Summary • The inverse relationship between signal frequency and intraocular pressure (in mmHg) is validated ex vivo and in vivo • Fluctuation profiles in an ambulatory setting are repeatable and highly individualized • Eye closure changes the relationship between the tear surface, contact lens sensor and the cornea, thereby setting a new baseline reading
Conclusions • As fluctuation profiles are highly individualized, this particular device is currently more useful in comparing pre and post-treatment changes for individuals rather than as a standardized measurement tool of intraocular pressure • Algorithms will be needed to translate these units into clinically relevant measurements. Specific ones for open eyes and closed eyes will be needed. • Further studies on tolerability and validation in glaucoma eyes are needed
