Review article journal club presentation

1. M
BIRATNAGAR EYE HOSPITAL, BIRATNAGAR 20– 09 - 2014
By
Dr. Diwa lamichhane, Anterior segment fellow.

2. Outline
• IOL adjusted using secondary surgical procedures
• IOL adjusted non invasively in post operative setting
• IOL adjusted using femtosecond laser or 2-photon
chemistry
• LAL

3. PO refraction
Brandser et al 45% of 298
emmetropic
within 0.5 D
Murphy et al 72.3% of 1676
eyes
Within 1D 6.4% beyond2D
Mamalis et al. 20% to 40% Incorrect IOL 1& 3-piece
IOLs

4. • Technological inadequacies --incorrect IOL power, AL, corneal
power, A constant
• Mechanical issues (eg, placement of optic in a position
different from expected pre Operative or axis deviation caused
by unwanted rotation of toric IOL
• Unpredictable effects of wound healing on effective lens
position in capsular bag, capsule shrinkage, untreated
astigmatism (preexisting or iatrogenic), procedural or process
mistakes (eg, insertion of wrong IOL or IOL mislabeling by
manufacturer) or any combination of these
• Incorrect corneal measurements

5. Must Demonstrate
• Biocompatibility with intraocular tissues
• Refractive error correction range of approximately 2.0 D
• Precise correction of hyperopic, myopic, & astigmatic
refractive errors to within 0.25 D of target
• Stability of refraction, safe, noninvasive

6. A: Base IOL showing attachment bridge on the
surface of the lens.
B: Front IOL showing haptic that
are designed to fit within the
attachment bridges on the base
IOL surface in piggyback fashion.
C: Assembled multi component IOL.
Adjusted using secondary surgical procedures
Werblin --- 1996

7. Artist's rendition of the multi
component IOL within the capsular bag
Adjusted using secondary surgical procedures
Infinite Vision Optics, A hydrophilic acrylic foldable dual- IOl system

8. Slit lamp photographs 2 years after
• Portaliou et al report a small 2-
year study including 6 adult
patients. Although VA was not a
primary objective UCVA & BCVA
decimal visual acuity improved
from
– 0.11 ± 0.06 (SD) to 0.68 ± 0.11
– 0.28 ± 0.13 to 0.83 ± 0.16

9. The Clarvista Harmoni modular IOL
system Adjusted using secondary surgical
procedures
Hydrophobic, monofocal, or toric, implanted using conventional
phacoemulsification

10. The mechanically adjustable IOL
Acri.Tec AR-1 PC IOL
Adjusted using secondary surgical procedures
an optic PMMA, that is 5.5 mm in diameter & contains two 1.0 mm high cylinder

11. Implantation of the Acri.Tec AR-1 PC
IOL
Adjusted using secondary surgical procedures

12. The AR-1 IOL --tested in human subjects
Adjusted using secondary surgical procedures
• Jahn & Strotmann --- 35 human eyes.
• Adjustment procedure 2 weeks after initial surgery -- 2 eyes
• No difference was seen between a control PMMA IOL & AR-1 IOL in VA,
stabilization of refractive error, signs of inflammatory reaction, & IOP over a mean
follow-up of 9 ± 6 mths.
• Initial adjustment surgery successfully changed mydriatic refraction from 1.0 ± 0.75
D to 0 ± 0.5 D, resulting in a decimal VA of 1.0.
Immediately after implantation 4 weeks after implantation

13. In a longer study of the same cohort
(median followup time of 18months)
Adjusted using secondary surgical procedures
• None of eyes developed signs of inflammation, corneal
decompensation, iris atrophy, pupil distortion,
decentration, spontaneous capsule tearing, or Amsler grid
abnormalities.
• No difference in VA, refractive stability, or IOP was seen between
control IOL & AcriTec IOL.
• PCO -- (18 of 35 eyes), -- Nd:YAG laser posterior capsulotomy,
restored VA in all patients.
• 2 eyes -- adjusted initially continued to show stable refraction with no
complications noted 15 &18 mths postoperatively.

14. Mechanism of adjustment of the
repeatedly adjustable IOL
Adjusted using secondary surgical procedures
The optic can be adjusted anteriorly & posteriorly in a screw-
like fashion within the outer ring
Perspex CQ PMMA matrix

15. Mechanism of adjustment of the
repeatedly adjustable IOL
Adjusted using secondary surgical procedures
Repeatedly adjustable IOL before polishing & sterilization
• Proof-of-concept study involving 27 prototype IOLs
(each with a 14.0 mm haptic outer diameter, 8.46 mm
outer ring diameter & 5.64 mm optic diameter, inner
optic thickness depended on power of IOL & ranged
from 2.0 to 2.5 mm

16. The first magnetically adjustable
IOL
Adjusted noninvasively in postoperative
setting
• Matthews et al Incorporated magnets into repeatedly adjustable IOL.
• 2 separate magnetic components (IOL & external device) forming a
magnetic coupling external device transfers force & torque to IOL
during adjustment procedure.
• The optic is a Perspex CQ PMMA matrix with an embedded magnetic
spindle consisting of samarium cobalt.
• Spindle ring maximum inner diameter - 4.0 mm, 6.0 mm outer
diameter, 2.0 mm thickness so it could be easily embedded in optic
of repeatedly adjustable IOL.
• The external source consists of neodymium-iron- boride permanent
magnets in 2-pole & 4-pole configurations.

17. Magnetic…
Adjusted noninvasively in postoperative setting
• They embedded magnetic spindles into optic of IOL, created
external magnetic source, & showed magnetic source can
turn IOL optic in forward & reverse directions with magnetic
spindles focus to within 0.04 D for a 26.0 D IOL or to within
0.01 D for a 16.0 D IOL.
• Leaching studies were also performed to demonstrate
whether metallic species would leak out of optic over time.
• Over a 1-mth period, concentrations of cobalt & samarium in
balanced salt solution were comparable to that of dissolving
a bare magnet in solution.

18. Wirelessly controlled liquid crystal IOL
Adjusted noninvasively in postoperative setting
A: A cross-section of the liquid crystal
IOL depicting glass substrates (1); low-
ohmic layer (2); liquid crystal (3);
contact (4); and high-ohmic layer (5).
B: Photograph of the liquid crystal IOL
with rectifying diode (R) and antenna
(A) along the outer surface of the lens

19. Wirelessly controlled liquid crystal IOL
Adjusted noninvasively in postoperative setting
The basic design of wireless radiofrequency control unit
consists of
• A computer attached to a setup
• A function generator
• A radiofrequency oscillator
• A modulator
• A radiofrequency amplifier & a transmitting antenna

20. Wirelessly controlled liquid crystal IOL
Adjusted noninvasively in postoperative setting
• The signal (approx 6 MHz) from radiofrequency oscillator
is amplitude modulated by function generator (F = 0 to 50
kHz), amplified & transmitted to liquid crystal modal IOL
via transmitting antenna.
• Once loop-receiving antenna in IOL receives signal, it is
demodulated by rectifier circuit to produce a low
frequency voltage that is then applied to liquid crystal
modal corrector. This allows adjustment of liquid crystal
IOL

21. Wirelessly controlled liquid crystal IOL
Adjusted noninvasively in postoperative setting
• In vitro measurements of a 5.0 mm clear aperture prototype with an
initial focusing power of + 12.5 D remotely driven by a radiofrequency
control unit at approx 6 MHz were carried out using a Hartmann-
Shack wave front sensor.
• The IOL based on a 40 mm thick liquid crystal layer allows an
adjustable defocus of 4 waves, ie, an accommodation of
approximately 2.51 D at a wavelength of 534 nm, & correction of
spherical aberration coefficient ranging from 0.8 to 0.67 waves.
• Frequency switching technique was used to increase response speed.
Full-scale settling time of adaptive modal corrector was measured to
be approximately 4 seconds.

22. Tentative design of an optic that is amenable
to postoperative power adjustment
Iols that can be adjusted using the femtosecond
laser
Intraocular lens (A) consists of concentric rings (B and C) that have connecting
members (E) Localized regions of pockets of heat absorbing material (D) are
placed on the connecting members

23. Application of a photon produced by
a femtosecond laser onto the heat-
absorbable material, resulting in
tension between the concentric rings
of the IOL
Application of a photon produced by a
femtosecond laser onto the connecting
members, resulting in tension relief
between the concentric rings of the IOL.
Iols that can be adjusted using the
femtosecond laser

24. Iols that can be adjusted using the
femtosecond laser
• F Briefly, the femtosecond laser selectively bombards electrons of a
thin 50 mm layer of material embedded within IOL & alters 3-
dimensional shape of material layer, precisely changing its RI &
inducing dioptric power adjustments.
• Using a commercial 2-photon 500 mw femtosecond laser with an
acousto-optic modulator, perfect Lens treated a 1.0 mm diameter
lens (initial power of 1.6 D) that was incorporated into a hydrophobic
acrylic button. Various phase wrapping techniques were used to
accomplish several diopters of refractive change within material.

25. Iols that can be adjusted using the
femtosecond laser
• Phase wrapping is a process in which surface of IOL is divided into
concentric diffractive zones & total IOL power is a summation of
power of each diffractive zone.
• For eg. a single 50 mm layer in a 6.0 mm optic provides up to 5.0 D of
correction, so 4 layers should theoretically provide 20.0 D.
• Tightening diffractive zones along a single axis & changing relative
heights & profiles of refractive zones can provide astigmatic &
aspheric corrections, respectively. Using an acousto-optic modulator,
total in vivo treatment time is estimated to be 20 to 60 sec with this
potentially revolutionary technology.

26. • Change in RI up to 0.03, enables 2.5 D of IOL adjustment
• Rx of astigmatism
• Bombarding coumarin- based polymers with photons of a wavelength
results in dimerization & production of material with higher RI.
• Conversely, application of photons with different wave length results in
reverse reaction & produces material with lower RI.
• Both reactions occur instantaneously & allow immediate postoperative
refraction of patient.
• Sunlight does not carry enough photon
density to disrupt chemical properties of IOL.
Application of 2-photon chemistry on
coumarin-based polymers

27. Micrograting patterns applied by the
femtosecond laser to an IOL optic. A: Pattern as
seen from the anterior view. B: Pattern applied
to a thin layer of material embedded within the
IOL optic; side view

28. Scanning electron photomicrograph of a
light-adjustable IOL after adjustment &
lock-in.

29. LAL

30. LAL
• Developed by Calhoun Vision
• Studies reported in 2003, it has corrected residual refractive errors of
up to 2.0 D of hyperopia, myopia, & astigmatism in patients with
normal, shortened, & elongated & to provide results close to
emmetropia in patients with history of previous laser refractive
surgery.
• It is a foldable 3-piece silicone PC IOL. It is composed of a medical-
grade UV light–filtering silicone optic containing light activated
photointiator & mobile silicone macromers.
2 Weeks Postoperative Of LAL

31. LAL
• The IOL has an overall diameter of 13.0 mm, optic is 6.0 mm in diameter.
The IOL has squared posterior optic edges, round anterior edges, & blue
PMMA modified-C haptics with a posterior optic– haptic 10-degree
angulation.
• These features prevent PCO & rotation of IOL within capsular bag, which
makes IOL suitable for toric correction.
• The IOL has enhanced UV light–filtering material concentrated along
posterior aspect of optic in a layer that measures up to 100 mm.
protection of retina, preventing during overexposure to UV radiation in
300 to 400 nm range during adjustments & lock-in treatments.

32. LAL
• Healing period of 2 -4 weeks
• Patient's refraction & acuity
• 1 or 2 UV-light adjustment procedures, each 2 min, can be adjusted
multiple times
• Lock-in once optimized.
• Material design of LAL is based on principles of photochemistry &
diffusion where by photoreactive components incorporated in
crosslinked silicone lens matrix are photopolymerized on exposure to
UV light (365 nm) of a select spatial irradiance profile.
• Each adjustment provide up to 2.0 D of power correction based on in
vitro studies.
• 1 case report of a 57-year-old woman whose VA declined secondary
to noncompliance highlights need for adequate UV light protection &
appropriate patient compliance.
2 Years After Implantation

33. A Hyperopic Correction

34. A Myopia Correction

35. The LDD
• Slitlamp & a UV-light source in a computer-controlled system. The
light source mercury arc lamp with a narrowband pass interference
filter producing a 365 nm wavelength.

36. The LDD..
• After dilating & anesthetizing patient's eye, surgeon couples a 0.835
contact lens on eye, fixate on a target, aligns a reticle target on edge of
optic, & then applies treatment for specified time.
• Adjustment procedure 40 to150 sec & may vary
• The lock-in lasts for 100 sec, & whole IOL is irradiated with a light beam
of a higher intensity during this procedure.
• Evaluation of LD System using a rabbit model has demonstrated myopic,
hyperopic, & astigmatic adjustments of LAL are possible without any
evidence of corneal or retinal toxicity apparent on slitlamp &
histopathological examinations.

37. DLDD
• Calhoun Vision, Inc. in collaboration with Carl Zeiss Meditec AG,
developed digital light delivery device that allows correction of
spherical error, astigmatism, & HOAs.
• A study of 13 human patients showed the device can reliably deliver
hyperopic & myopic corrections to within 0.25D of intended
outcome.
• The light-adjustable IOL is currently on market in Europe & Mexico &
is in final phase of FDA clinical trials in U.S.
• It is truly a revolutionary technology that creates possibility of
emmetropia for all pseudophakic patients.
by
g

38. Discussion
Mamalis et al Adjustments of LAL
hyperopic, myopic,
astigmatic, & HOA
No postOp clinical changes on
slitlamp examination & no
evidence of toxicity to cornea,
iris, retina, & choroid on
histopathological examination
Calhoun Vision,
Inc
LAL is stable after Nd:YAG
Werner et al corneal endothelial &
retinal safety
Authors applied therapeutic
irradiation dose of lock-in
procedure to 12 cat corneas &
compared

39. Retinal safety study
• In the LAL (which contains a UV-light filter) was placed in 1 eye & a
control silicone IOL without a UV-light filter in the contra lateral eye
of 16 pigmented rabbits.
• 5 times the expected maximum UV-irradiation dosage applied to
study eye & up to 2 times that dosage to control eye.
• Histopathological evaluation revealed no evidence of corneal,
anterior segment, or retinal toxicity in eyes implanted with LAL.
However, 3 of 16 eyes with control IOL demonstrated focal areas of
retinal damage consistent with laser burn.

40. Safety of the UV-irradiation treatment
dosage in humans
Lichtinger et
al
Mean
endothelial
cell loss
10
eyes
12.6% at 1 wk
post op
9.1% , at 6 mths
Hengerer et
al
mean
endothelial
cell loss
122
eyes
6.91% at 2wk
post op
6.57%, at 12 mths
corneal
thickness
6.18% at 2wks
post op
0.64%, at 1 yr
• These values are in line with values for endothelial cell loss due to
phacoemulsification

41. Safety of myopic & hypermetropic
correction
Chayet et al 14 eyes myopic
adjustment of
LAL with LDD
Purposly
implanted IOL
with myopic
error of 1.5 D
1day after locking 13 0.25D
9mths 14 0.50D
Chayet et al 14 eyes Hyperopic
corrections
of LAL
+0.25 D to
+2.00D
1day after locking 13 +0.25D
6mth 14 +0.5D

42. Effective at treating postoperative toric errors
Hengerer et al. mean
sphere
mean
cylinder
within
0.50 D
Within
0.25 D
40 eyes
4 mths
post op
from 0.58 ±
2.29 D to 0.04
± 0.37 D
improved
from 1.02 ±
2.19 D to
0.24 ± 0.40
D
0.88 ± 0.66
D to 0.41 ±
0.25 D
35 of 40
(88%)
24 of 40
(60%)
Chayet et al. 5
patients
with post op cylindrical
refractive errors of 1.25
to 1.75 D
spherical
equivalent
within 0.25 D
20/25 at
9mths

43. 9 of 10
eyes
mean
pre op
refraction
improved
to
1 mth
after lock-
in mean
astigmatis
m
improved
2 eyes
residual
astigmatis
m
3 eyes
residual
astigmatis
m
10
toric
adjustmen
t
+0.78 ±
4.16 D
0.07 ±
0.21 D
0.88 ±
0.77 D
to 0.15 ±
0.20 D,
0.50 D 0.25 D gained at
least 2
lines of
corrected
VA.
Winkler Von Mohrenfels et al

44. Lichtinger et al. performed 1-year follow-up study in 10 eyes (corneal
astigmatism 1.00 D & 2.00 D) adjustment with lock-in was done
Ten of
10
(100%)
-0.50 D of
targeted
cylindrical
adjustment &
cylinder axis
was same in
60%
At 12 mth
stable
within 10◦
of rotation
LAL rotated 3◦
within 10◦
margin of
error for toric
correction
7of 10,
70% eyes
UDVA
≥20/25
10 (100%)
were
>20/32
after 1 yr
Hengerer et al. report a study of 122 eyes that were followed for 18 mths.
Mean
refraction
in SE
improved
from 0.36 ±
2.78 D
preop to
0.03±0.17
At 18 mths post
mean sphere
improved from
0.82 ± 2.74 D to
0.10 ± 0.22 p
Mean cylinder
improved from
0.92 ± 0.66 D to
0.25 ± 0.22 D
All eyes
≥ 20/25
88%
≥ 20/20 of
UDVA
uncorrected distance visual acuity(UDVA)

45. LAL can correct up to 2.25 D in sphere &
2.75 D in cylinder in axial hyperopia &
myopia.
In a 1-year follow-up study by Hengerer et al, 15 eyes with an AL < 22.20
mm (axial hyperopia) received LAL
• 14 of 15 (93%) -- 0.5 D of the targeted refractive adjustment
• 10 of 15 (67%) -- 0.25 D
• 1 of 15 changed > 0.25 D in MRSE
In another 1-year study by Hengerer et al, 21 eyes with an AL longer than
24.5 mm (axialmyopia) received LAL
• 20 of 21 eyes (96%) -- 0.50D of targeted refractive adjustment
• 17 of 21 (81%) were within 0.25 D
• 1 of 21 changed > 0.25 D in MRSE (this eye suffered from tear film
instability) at completion of study
manifest refraction spherical equivalent (MRSE)

46. • One case report LAL was used to treat a traumatic cataract in a 36-yr-old
man with prior LASIK surgery. Following adjustments & lock-ins, patient
achieved an end refraction of + 0.50 D & an UDVA of 20/20.
• Retrospective case series by Brierley shows LAL implantation & post-
implantation adjustment provide precise refractive outcomes in patients
who have had LASIK or PRK.
• In this study, 34 eyes with a history of refractive surgery received LAL.
One wk after lock-in,
• 25 of 34 eyes were within 0.25 D of targeted refraction
• 33 of 34 eyes were within 0.50 D
• 34 of 34 eyes were within 1.00 D
• 19 of 20 (95%) had a UDVA of 20/25
• 20 of 20 eyes had a UDVA of 20/30.

47. • Calhoun Vision's LAL is adjustable IOL is undergoing third & final phase
of FDA clinical trials In USA.
• Compatibility of certain IOLs with imaging techniques such as MRIs
needs to be assessed.
• Femtosecond laser increasing in popularity & its applications to
cataract surgery being extensively researched, this modality may lend
itself well to adjustable IOL technologies.
• Adjustable IOLs, especially those adjusted noninvasively in
postoperative setting, will become a mainstay of IOL implantation
surgery within next few decades.