LABORATORY SCIENCE

Accommodation amplitudes after anaccommodating intraocular lens refilling
procedure: In vivo update
Okihiro Nishi, MD, PhD, Yutaro Nishi, MD, Shiao Chang, PhD, Kayo Nishi, MD

PURPOSE: To evaluate whether a new capsular bag–refilling procedure provides some accommodation in monkey eyes and to assess the difference in accommodation with different volumes ofcapsular bag refilling.
SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan.
DESIGN: Experimental study.
METHODS: A central 3.0 to 4.0 mm continuous curvilinear capsulorhexis was created, after which
phacoemulsification was performed in the usual manner. A new accommodating-membrane
intraocular lens (IOL) for sealing the capsular opening was implanted in the capsular bag.
Silicone polymers were injected beneath the IOL into the capsular bag through the delivery hole.
In 3 study groups, each with 6 monkey eyes, the lens capsule was refilled with 0.080 mL ofsilicone polymers, corresponding to a 65% bag volume; 0.100 mL, corresponding to an 80%
bag volume; or 0.125 mL, corresponding to a 100% bag volume. To calculate theaccommodation amplitudes achieved, automated refractometry was performed before and 1
hour after topical pilocarpine 4.0% application preoperatively and 4 weeks postoperatively.
RESULTS: The refilling technique was successful without polymer leakage in all monkeys. Fourweeks after surgery, the mean accommodation amplitudes were 2.56 diopters (D) G 0.74 (SD),
2.42 G 1.00 D, and 2.71 G 0.63 D, respectively, in the 3 study groups.
CONCLUSIONS: The technique provided some accommodation in young monkey eyes. Leakage ofthe injectable silicone polymers and anterior capsule opacification in the visual axis were avoided.
The results suggest that the capsular bag–refilling procedure warrants further study for possible
clinical application.
Financial Disclosure: All authors have a proprietary interest in the accommodating membrane IOL
mentioned in the article.
J Cataract Refract Surg 2014; 40:295–305 Q 2014 ASCRS and ESCRS

Refilling the lens capsule with an injectable malleable
material that would restore ocular accommodation
has long been the goal of cataract surgeons. However,
2 persistent problems with capsular bag–refilling
methods have hampered the clinical application of
the procedure.1–11 The first is leakage of the injectedmaterial, usually a mix of 2 silicone compounds,
from the capsular bag before the material's transformation into a gel-formed polymerized consistency.
The second is capsule opacification. Despite these
problems, previous studies2,4,5,8,11 have achieved
from 2.0 to 8.0 diopters (D) of accommodation in monkey eyes, although for a relatively short postoperative

Q 2014 ASCRS and ESCRS
Published by Elsevier Inc.

period, and have attempted to prevent leakage of theinjected material. These methods include use of precured silicone gel,1–3 an endocapsular balloon,4,5 endocapsular polymerization by applying ultraviolet
light,6 a capsule-sealing plug,7–10 or an expansible
full-size intraocular lens (IOL).11 Capsule opacification
has proven to be extensive,12 although in some instances it was minimized by treating residual lensepithelial cells (LECs).10 None of these techniques
has been proved to be clinically useful.
To address the problems of silicone leakage andcapsule opacification, we recently developed a newaccommodating IOL that serves as an optic as well

0886-3350/$ - see front matter
http://dx.doi.org/10.1016/j.jcrs.2013.06.028

295

296

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

as a plug that seals the capsular opening. In our previous studies using rabbit eyes and pig cadaver eyes,13
the accommodating IOL sealed the large central 3.0
to 4.0 mm continuous curvilinear capsulorhexis(CCC) opening and successfully prevented silicone
leakage. Posterior capsule opacification in the visual
axis was prevented by the creation of a posterior
CCC, which was sealed by an inversely implanted
posterior accommodating IOL. Silicone polymers
were injected between the 2 IOLs to fill the capsularbag. Thus, capsule opacification, at least in the visual
axis, was prevented in the rabbit eyes by creating anterior and posterior CCCs, which were sealed using
2 accommodating IOLs.13
In the current study, we applied this technique inyoung monkey eyes to determine whether it can
provide some accommodation. We also evaluatedthe difference in accommodation with different volumes of capsular bag refilling. The study design was
based on our previous experimental in vitro study,7in which the accommodation amplitudes varied withdifferent volumes of bag filling and a capsular bagwith approximately 70% volume provided the optimum accommodation amplitude. In this study, a posterior CCC was not performed. The goal was to attaina high degree of surgical reproducibility because of thehigh cost of monkey experiments and because theprimary purpose was to confirm whether the capsularbag–refilling procedure provides some accommodation in young monkey eyes.
MATERIALS AND METHODSThis study was performed at the Japan Life Science Center
in Gifu prefecture. It adhered to the Association for
Research in Vision and Ophthalmology statement for the
Use of Animals in Ophthalmic and Vision Research andthe rules of the Primate Society of Japan. Eighteen young

Submitted: January 30, 2013.
Final revision submitted: May 23, 2013.
Accepted: June 7, 2013.
From the Jinshikai Medical Foundation (O. Nishi, Y. Nishi, K. Nishi),
Nishi Eye Hospital, Osaka, Japan; Calhoun Vision Institute (Chang),
Pasadena, California, USA.
Supported in part by Small Business Innovative Research National
Institutes of Health grant (EY015321-02) and Calhoun Vision
Institute.
Presented in part at the XXIX Congress of the European Societyof Cataract and Refractive Surgeons, Vienna, Austria,
September 2011.
Corresponding author: Okihiro Nishi, MD, PhD, Nishi Eye Hospital,
4-14-26 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
E-mail: okihiro@nishi-ganka.or.jp.

Figure 1. Foldable silicone accommodating-membrane IOL. The
central part is between the 2 arrows.

Macaca fascicularis monkeys aged 3 to 5 years weighing
5.5 to 6.3 kg were used.

Anesthesia
Animals were anesthetized with intramuscular ketamine
chloride 0.5 mg/kg (Ketalar) and xylazine chloride
2.0 mg/kg (Selactar). Additional corneal anesthesia wasprovided with lidocaine hydrochloride 1.0% eyedrops (Xylocaine) before and during surgery.

Accommodating-Membrane Intraocular Lens
and Injectable Silicone Polymers
The foldable silicone accommodating-membrane IOL
used in previous rabbit eye and pig cadaver eye experiments13 was modified for the monkey experiment. The
modified IOL serves as an optic as well as a plug for sealing
the capsule opening to prevent leakage of the injectedsilicone polymers until their polymerization. The IOL is silicone and has a thin, plate, disk–shaped haptic with a 9.0 mm
overall diameter (Figure 1). At the margin, there is a 0.8 mm
delivery hole for insertion of a 22-gauge needle. More central
to the optic is a 0.2 mm positioning pocket (not perforating
the plug) through which the IOL can be positioned using a
Sinskey hook. The IOL, which is thick at its margins, tapers
to a 100 mm center. The most significant modification of theoriginal IOL13 is the absence of a transition zone between
the optic and the haptic. This region is now a disk-shaped
IOL. The anterior curvature is 15.5 mm and the posterior curvature, 9.0 mm. The refractive index of the silicone is 1.410.
Accordingly, the refractive power of the membrane in the
air calculated using ray tracing is C19.5 D.
Using a dynamic mechanical analyzer, the injectablesilicone was formulated with an optimized mix ratio of silicone polymer part A to part B to achieve a modulus of
100 Pa, mimicking the natural lens of young humans. The
refractive index in air after polymerization is 1.397.

Primary Treatment: Total Iris Removal
The entire iris of each monkey eye was removed 2
weeks before the capsular bag–refilling procedure to

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

297

Preoperative and Postoperative Examinations

Figure 2. Capsular bag–refilling technique. The cross-section of theaccommodating IOL is different than in Figure 1 because Figure 1
shows the modified IOL (reprinted with permission of the Journalof Cataract & Refractive Surgery).

facilitate postoperative observation of the refilled lens
capsule and permit accurate measurement of the refraction. A 2.0 mm corneal limbal incision was created.
A fine forceps was used to grasp the iris root and slowly
and carefully pull the iris tissue away from the iris root
insertion, resulting in an iridodialysis at the iris periphery.
When the iridodialysis reached approximately one fourthof the iris circumference, the iris root at the corneal incision was regrasped. This procedure was repeated until total iridodialysis was obtained. This technique10 resulted in
an anterior chamber hemorrhage that ceased spontaneously when the intraocular pressure was raised for 1 to
2 minutes.

Surgical Technique
The refilling technique has been described13 (Figure 2). In
brief, phacoemulsification was performed and a 3.0 to
4.0 mm CCC created in the middle of the anterior capsule.
Sodium hyaluronate 2.3% (Healon5) was injected into thecapsular bag, and the foldable accommodating-membrane
IOL was implanted. After the ophthalmic viscosurgicaldevice (OVD) was removed from the capsular bag, in particular from underneath the IOL, a small amount of OVD wasinjected above the IOL. The injectable silicone polymer
mixture was then injected beneath the IOL into the capsularbag using a purpose-designed dispenser13 that delivers anarbitrary preset amount of the silicone material. The blunt
needle of the dispenser containing the silicone polymers
was inserted through the delivery hole, while the CCC
edge was pulled slightly aside. The silicone mixture polymerized within 2 hours in vitro. After a certain amount of
the silicone material was injected, the needle was withdrawn. The CCC edge returned, covering the delivery
hole. The IOL was centered using a Sinskey hook.
Next, 0.2 mL of atropine sulfate 0.5% was applied to thelower subconjunctiva at the beginning of surgery in an
attempt to make the injected silicone material conform to
the disaccommodated capsular bag shape after polymerization of the material. This was done because according to aprevious study,4 the disaccommodated form may yield
more accommodation. Gentamicin 4.0 mg and dexamethasone 0.33 mg were applied subconjunctivally at the end of
surgery. Topical levofloxacin 0.5% (Clavid), diclofenac
sodium 0.1 % (Diclod), and fluorometholone 0.1%, wereapplied 3 times a day for 3 days after surgery.

A slitlamp examination and anterior segment photography were performed before surgery and 2 and 4 weeks after surgery. Scheimpflug photography (EAS 1000, Nidek,
Inc.) and measurement of refraction using an automatedrefractometer (ARK-10000, Nidek, Inc.) were performed
before and 1 hour after application of topical pilocarpine
4.0% before surgery and 4 weeks after surgery. (Longer
follow-up was not possible because the monkey facility
was closed.)In the Scheimpflug photography, 5 microphotographs
were analyzed for the anterior chamber depth (ACD), lens
thickness, and anterior and posterior capsule curvature.
The 5 values of each parameter were averaged.
For the measurement of refraction, 5 to 7 consecutive
dioptric power values were obtained. These were averaged
to obtain the final value. The equivalent value in each eye
was calculated from the spherical and cylindrical powers.
The difference between the refractions, measured in spherical equivalence before and 1 hour after topical pilocarpine
4.0% application, was considered the accommodation
amplitude. The ratio of the accommodation amplitude
before surgery to that after surgery was also calculated.

Measurement of Crystalline Lens Volume
and Refilled Capsular Bag Volume
Using Scheimpflug photography, the crystalline lens volume in each monkey eye was measured before surgery. First,
the curvature of the anterior and posterior lens capsulesdelineated by Scheimpflug photography was represented
as a part of a circle line by manually plotting 3 points on
the capsule contour so that both lines of the anterior and posterior capsule meet at both sides, delineating and extrapolating a simulated crystalline lens. The crystalline lensvolume was calculated by adding the volume of each of
the 2 hemispheric cones, which was determined by drawing
a straight line between the 2 cross points of each curvatureline. The height of the hemispheric cone was mathematicallydetermined from the crystalline lens thickness.
The ACD and crystalline lens thickness were corrected forthe distortion caused by the cornea and aqueous humor using ray tracing. However, the measurement of the crystalline
lens curvature was performed using the dedicated software
for the anterior corneal curvature measurement and was notcorrected for the distortion caused by the cornea andaqueous humor. Postoperatively, the refilled capsular bagvolume was also measured in the same manner.

Research Design
The experiments comprised 18 eyes of 18 monkeys inwhich total iris removal was performed. Two weeks afteriris removal, all eyes had the capsular bag–refilling procedure using the accommodating-membrane IOL. In 3 groupsof 6 Macaca monkeys each, the lens capsule of each eye wasrefilled, respectively, with 0.080 mL of silicone polymers,
corresponding to 65% of the mean capsular bag volume(Group A); 0.100 mL of silicone polymers, corresponding
to 80% of the mean capsular bag volume (Group B); and0.125 mL of silicone polymers, corresponding to 100% of
the mean capsular bag volume (Group C). The mean crystalline lens volume of the monkeys was defined as 0.125 mL(see Results).

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

298

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Table 1. Preoperative measurements of ACD, lens thickness, and capsule curvatures using Scheimpflug photography.
Mean (mm) G SD
ACD (mm)Lens Thickness (mm)Anterior Capsule
Curvature (mm)Posterior Capsule
Curvature (mm)Capsular Bag
Volume (mL)

Before pilo
1 h after pilo

2.67 G 0.17
2.19 G 0.21

3.07 G 0.10
3.81 G 0.12

10.99 G 0.80
7.23 G 0.54

7.52 G 0.68
5.78 G 0.40

0.126 G 0.008d

Before pilo
1 h after pilo

2.83 G 0.07
2.40 G 0.11

2.89 G 0.17
3.47 G 0.09

11.81 G 0.79
8.41 G 0.58

8.53 G 0.58
6.91 G 0.39

0.124 G 0.007
d

Before pilo
1 h after pilo

2.64 G 0.09
2.29 G 0.12

3.01 G 0.16
3.33 G 0.14

11.07 G 0.64
8.31 G 0.76

7.35 G 0.36
6.58 G 0.56

0.124 G 0.073dGroup/TimeABC

ACD Z anterior chamber depth; pilo Z pilocarpine 4.0%

Statistical Analysis
The Kruskal-Wallis test was used for statistical evaluationof the accommodation amplitudes before surgery and after
surgery as well as for the accommodation ratio.

RESULTS
Preoperative Scheimpflug Analysis and Crystalline
Lens Volume
Table 1 shows the mean ACD, lens thickness, anterior and posterior capsule curvatures, and crystalline
lens volume in the 3 groups.

The Scheimpflug photography before surgery
showed 3 characteristic findings after pilocarpine
4.0% eyedrops: shallowing of the anterior chamber,thickening of the crystalline lens, and steepening of
the anterior lens curvature (Figure 3). The calculated
mean crystalline lens volume before surgery in the 3groups was 0.125 G 0.029 mL. From the results, themean crystalline lens volume in the monkey eyes
was determined to be 0.125 mL.

Figure 3. Scheimpflug photography of a Macaca monkey eye inGroup B. Note that the lens capsuleafter surgery is optically empty due
to the silicone polymers.

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

299

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Table 2. Refractions and accommodation amplitudes in Group A (65% bag volume filling).
Mean G SD
Before Refilling
Monkey/Time
A1
Before pilo
1h after pilo
Accommodation
A2
Before pilo
1h after pilo
Accommodation
A3
Before pilo
1h after pilo
Accommodation
A4
Before pilo
1h after pilo
Accommodation
A5
Before pilo
1h after pilo
Accommodation
A6
Before pilo
1h after pilo
Accommodation
Overall
Before pilo
1h after pilo
Accommodation

After RefillingSph (D)

Cyl (D)

Equ (D)

Sph (D)

Cyl (D)

Equ (D)

Ratio (%)

0.35 G 0.12
12.00 G 0.00d0.75 G 0.00
2.86 G 0.13d0.73 G 0.23
13.50 G 0.09
12.75 G 0.32

0.33 G 0.12
1.40 G 0.24
d2.56 G 0.11
3.25 G 0.42d1.48 G 0.25
3.93 G 0.45
2.48 G 0.42dd19.6 G 1.3

C0.10 G 0.00
12.80 G 0.77d0.70 G 0.19
3.50 G 0.27
d0.19 G 0.12
14.63 G 0.73
14.51 G 0.77

C1.10 G 0.12
1.05 G 0.10d1.90 G 0.12
1.70 G 0.10
d0.15 G 0.09
1.90 G 0.05
2.09 G 0.05

dd14.6 G 1.4

C1.00 G 0.16
13.50 G 0.27
d0.95 G 0.56
2.00 G 0.16
d1.54 G 0.17
14.50 G 0.35
12.97 G 0.22

C2.13 G 0.38
C0.75 G 0.00
d6.63 G 0.13
4.25 G 0.70d1.13 G 0.50
2.36 G 0.47
1.73 G 0.47dd13.4 G 1.1

C0.40 G 0.12
11.95 G 0.10d1.70 G 0.73
1.30 G 0.33d0.45 G 0.23
12.60 G 0.12
12.15 G 0.32

C2.58 G 0.12
C1.63 G 0.11d2.75 G 0.20
2.19 G 0.45
dC1.25 G 0.10
2.66 G 0.29
3.92 G 0.50

32.1 G 1.3

0.25 G 0.16
10.25 G 0.27d1.45 G 0.10
1.86 G 0.38
d0.73 G 0.05
11.30 G 0.26
11.92 G 1.70

NA
NA
d

NA
NA
d

NA
NA
d

d
d

1.25 G 0.12
15.25 G 0.00
d0.25 G 0.00
0.40 G 0.12d1.50 G 0.00
15.50 G 0.06
13.85 G 0.06

1.60 G 0.12
4.95 G 0.10
d2.05 G 0.10
0.45 G 0.10d2.63 G 0.11
5.20 G 0.10
2.58 G 0.19dd18.6 G 0.6

0.06 G 0.69
12.63 G 1.54
d0.97 G 0.48
1.99 G 1.00
d0.86 G 0.50
13.67 G 1.40
13.02 G 0.91

C0.78 G 1.55
1.00 G 2.27
d2.31 G 2.37
5.71 G 3.44d0.83 G 1.31
3.21 G 1.20
2.56 G 0.74dd19.7 G 6.6

Equ Z equivalant power; NA Z not applicable; pilo Z pilocarpine 4.0%; Ratio Z accommodation amplitude after refilling:accommodation amplitude before
refilling; Sph Z sphere

Preoperative Refractions and Accommodation
Amplitudes
Table 2, Table 3, and Table 4 show the preoperative andpostoperative refractions and accommodation amplitudes in Group A, Group B, and Group C, respectively.
Surgical Outcomes
The surgical time required was 20 to 30 minutes foreach monkey. In some cases, when the injection needle
was withdrawn, small silicone spheres were released
outside the capsular bag. This occurred when the
CCC edge was pulled aside and then returned to cover
the delivery hole of the IOL within 1 to 2 seconds.
Because of their cohesiveness, the fine silicone globules
could be distinctly recognized and easily removed byaspiration. During the injection and the course of surgery, no silicone leakage occurred in any eye. Posterior

capsule rupture occurred during phacoemulsificationin 1 monkey (C-1) (Table 4); the postoperative
Scheimpflug analysis and the refraction and accommodation measurements could not be performed inthis case, and the monkey was excluded from the postoperative analysis. Once phacoemulsification wascompleted, there were no cases of capsule rupture
during or after injection of the silicone polymers.
Two weeks and 4 weeks after surgery, all the lens
capsules in all 3 groups remained well filled andshowed no silicone leakage. However, some eyes
had a tiny, very thin silicone particle attached to thedelivery hole at the CCC margin. This did not involvethe central optic of the IOL.
Slight to mild capsule opacification of the remaining
anterior capsule was observed 4 weeks after surgery.
Lens epithelial cells did not reach the central area ofthe posterior capsule in any eye 4 weeks after surgery.

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

300

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Table 3. Refractions and accommodation amplitudes in Group B (80% bag volume filling).
Mean G SD
Before Refilling
Monkey/Time
B1
Before pilo
1h after pilo
Accommodation
B2
Before pilo
1h after pilo
Accommodation
B3
Before pilo
1h after pilo
Accommodation
B4
Before pilo
1h after pilo
Accommodation
B5
Before pilo
1h after pilo
Accommodation
B6
Before pilo
1h after pilo
Accommodation
Overall
Before pilo
1h after pilo
Accommodation

After RefillingSph (D)

Cyl (D)

Equ (D)

Sph (D)

Cyl (D)

Equ (D)

Ratio (%)

10.05 G 0.49
23.20 G 0.48
d2.33 G 0.57
9.65 G 0.12d11.28 G 0.67
27.93 G 0.47
16.65 G 0.81

13.56 G 0.32
16.00 G 0.00
d6.13 G 0.28
6.44 G 0.11
d16.63 G 0.23
19.70 G 0.06
3.08 G 0.27

dd18.5 G 1.5

8.10 G 0.12
20.25 G 1.25
d7.20 G 1.00
10.12 G 0.11d11.70 G 0.30
25.58 G 1.25
13.14 G 1.00

15.75 G 0.00
16.25 G 0.00
d8.25 G 0.00
9.75 G 0.00
d19.88 G 0.00
21.38 G 0.00
1.25 G 0.00dd
9.5 G 1.3

5.50 G 0.00
8.02 G 0.12d0.75 G 0.00
5.85 G 0.12d5.88 G 0.00
11.08 G 0.09
5.64 G 0.09

12.25 G 0.20
15.25 G 0.22
d5.00 G 0.00
1.60 G 0.75
d14.75 G 0.20
16.04 G 0.17
1.85 G 0.49dd32.6 G 1.2

5.50 G 0.16
17.15 G 0.20d0.45 G 0.10
0.56 G 0.11d5.73 G 0.12
17.93 G 0.37
12.33 G 0.44

C3.25 G 0.00
4.95 G 0.10
d8.95 G 0.10
0.75 G 0.00
d1.23 G 0.05
5.20 G 0.10
4.04 G 0.10

32.8 G 1.1

3.17 G 0.31
9.75 G 0.11d0.40 G 0.12
2.63 G 0.13
d3.38 G 0.29
11.06 G 0.09
7.68 G 0.250

4.50 G 0.00
6.25 G 0.00
d3.13 G 0.13
3.20 G 0.10
d6.05 G 0.06
7.95 G 0.05
1.88 G 0.10dd24.5 G 1.0

5.65 G 0.20
11.23 G 0.20d2.70 G 0.10
5.44 G 0.21d7.00 G 0.19
13.60 G 0.46
6.54 G 0.55

NA
NA
d

NA
NA
d

NA
NA
d

d
d

6.33 G 2.19
14.93 G 5.63
d2.31 G 2.37
5.71 G 3.44d7.50 G 3.03
17.86 G 6.73
10.33 G 3.98

8.56 G 7.02
11.74 G 5.04
d6.92 G 2.13
4.35 G 3.33
d11.71 G 6.96
14.05 G 6.41
2.42 G 1.00

dd
23.6 G 8.9

Equ Z equivalant power; NA Z not applicable; pilo Z pilocarpine 4.0%; Ratio Z accommodation amplitude after refilling:accommodation amplitude before
refilling; Sph Z sphere

In some eyes, fibrin deposits were observed 2 weeks
after surgery but absorbed after 4 weeks (Figure 4).
Postoperative Scheimpflug Photography Analysis
After surgery, changes in the ACD, lens thickness, and anterior and posterior capsule curvatures
were present but were much less marked than
before surgery. The results are shown in Table 5
and Figure 3.
Postoperatively, the ACD became shallower withincreasing bag volume in all 3 groups. The mean lens
thickness became thinner in Group A but was thicker
in Groups B and C. The mean anterior curvature wassignificantly steeper with increasing bag volume inall 3 groups. The mean posterior curvature was significantly flatter in Group A after surgery. The mean posterior curvature in Group B was similar to thepreoperative value. In Group C, the entire posterior
capsule could not be photographed on Scheimpflug
imaging because it was pushed too posteriorly.
The mean refilled capsular bag volume in Group A
ranged from 0.075 to 0.081 mL. The mean refilled lensvolume in Group B could be measured in 3 eyes andranged from 0.100 to 0.117 mL.

Postoperative Refractions and Accommodation
Amplitudes
In Group A (Table 2), the spherical power ranged
from 1.60 to C2.58 D. The equivalent dioptric power
ranged from 2.63 to C1.25 D.
In Group B (Table 3), the spherical power ranged
from 15.75 to C3.25 D. The equivalent dioptric
power ranged from 19.88 G 0.00 to 1.23 G 0.05 D.

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

301

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Table 4. Refractions and accommodation amplitudes in Group C (100% bag volume filling).
Mean G SD
Before Refilling
Monkey/Time
C1
Before pilo
1h after pilo
Accommodation
C2
Before pilo
1h after pilo
Accommodation
C3
Before pilo
1h after pilo
Accommodation
C4
Before pilo
1h after pilo
Accommodation
C5
Before pilo
1h after pilo
Accommodation
C6
Before pilo
1h after pilo
Accommodation
Overall
Before pilo
1h after pilo
Accommodation

After RefillingSph (D)

Cyl (D)

Equ (D)

Sph (D)

Cyl (D)

Equ (D)

Ratio (%)

C2.25 G 0.40
9.92 G 0.68d2.50 G 0.00
9.25 G 0.81d1.00 G 0.40
14.63 G 0.61
15.46 G 0.49

NA
NA
d

NA
NA
d

NA
NA
d

d
d
d

C1.81 G 0.48
4.23 G 0.11d2.65 G 0.20
8.06 G 1.62
dC0.35 G 0.41
8.47 G 070
9.10 G 0.46

1.44 G 0.11
3.25 G 0.18
d4.19 G 0.21
7.56 G 0.54
d3.53 G 0.05
7.05 G 0.14
3.48 G 0.17dd38.1 G 1.0

7.05 G 0.10
18.60 G 0.19
d1.05 G 0.10
1.40 G 0.20
d7.58 G 0.10
19.10 G 0.49
11.54 G 0.52

12.50 G 0.18
14.13 G 0.22
d5.10 G 0.57
8.56 G 0.21
d15.13 G 0.38
18.56 G 0.26
3.43 G 0.27dd29.8 G 1.3

1.40 G 0.22
10.35 G 0.20
d2.20 G 0.37
1.05 G 0.10
d2.03 G 0.56
10.85 G 0.19
8.85 G 0.34

4.75 G 0.00
6.41 G 0.20d3.75 G 0.00
4.05 G 0.37
d6.63 G 0.00
8.57 G 0.56
1.94 G 0.56

21.9 G 1.3

6.60 G 0.12
13.94 G 0.11
d2.05 G 0.48
2.50 G 0.00
d7.63 G 0.21
15.19 G 0.11
7.64 G 0.10

15.85 G 0.20
18.90 G 0.38
d8.60 G 0.12
6.90 G 0.56
d20.15 G 0.24
22.50 G 0.58
2.35 G 0.50dd30.7 G 1.2

C1.70 G 0.48
10.50 G 0.27d2.65 G 0.20
1.31 G 0.11
dC0.35 G 0.41
11.15 G 0.23
11.65 G 0.27

6.35 G 0.12
8.36 G 0.42d4.65 G 0.41
6.70 G 1.74
d8.72 G 0.35
11.75 G 1.02
2.35 G 1.18

dd20.2 G 1.9

1.55 G 3.92
11.26 G 4.35
d2.18 G 0.55
3.93 G 3.39
d2.92 G 3.41
13.23 G 3.49
10.71 G 2.57

8.18 G 5.25
10.21 G 5.61
d5.26 G 1.73
6.75 G 1.50
d10.83 G 6.01
13.69 G 5.92
2.71 G 0.63dd28.1 G 6.5

Equ Z equivalant power; NA Z not applicable; pilo Z pilocarpine 4.0%; Ratio Z accommodation amplitude after refilling:accommodation amplitude before
refilling; Sph Z sphere

In Group C (Table 4), the spherical power ranged
from 15.85 to 1.44 D. The equivalent dioptric
power ranged from 20.15 to 3.53 D.
The refractions of monkeys A-5 and B-6 (Table 2 andTable 3) could not be measured due to cell deposits withposterior synechia on the anterior surface of the IOLs.
Table 2, Table 3, and Table 4 show the mean
postoperative accommodation amplitudes and theaccommodation ratios in Group A, Group B, andGroup C, respectively. There was no statistically significant difference in the accommodation amplitude
before or after surgery and in the accommodation
ratios after surgery between the 3 groups.
DISCUSSION
This study confirmed that despite the creation of alarge central CCC, our capsular bag–refilling

technique prevented intraoperative and postoperative leakage of the injected silicone polymers, similar
to the findings in our previous studies using pig
cadaver eyes and rabbit eyes.13 The injected polymers presses the IOL in the capsular bag against
the CCC and anterior capsule, which is most likely
the result of the buoyancy of the silicone. As a result,unless the IOL is forcibly pushed posteriorly, the injected cohesive silicone polymers with its high molecular weight does not leak through the space between
the anterior capsule and IOL before it polymerizes
in a consistent gel form.13 This simple technique
should be considered in future studies of capsular
bag refilling to prevent silicone leakage from thecapsular bag.
There has been a concern that sufficient accommodation cannot be achieved because a great portion of
the middle of the anterior capsule (w3.0 mm in

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

302

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Figure 4. Slitlamp findings of the
Macaca monkey eye shown in
Figure 3. Top left: Preoperative
view. Top right: Findings 2 weeks
after surgery show a fine fibrinous
membrane deposit in the CCC.
The lens capsule is well filled withno obvious leakage of the injectedsilicone polymers. Bottom left:
Findings 4 weeks after surgery
show a slightly opacified peripheral
posterior capsule due to LEC
migration but a clear visual axis.
Bottom right: On retroillumination,
the CCC edge is clearly seen. The
arrows show the delivery hole in
the anterior membrane IOL, which
is located behind the anterior
capsule. There is no silicone
leakage.

In this study, aged presbyopic monkeys shouldhave been used to simulate the human condition thatwould require a capsular bag–refilling procedure forpresbyopia. However, it was extremely difficult tofind aged monkeys. We chose the monkeys mainly
for facial contours that can make surgery easier toperform, such as a flatter nose, flatter forehead, andthe absence of enophthalmos. Although these characteristics provided a better surgical approach, theyalso contributed to a higher incidence of myopia, as
seen in Group B. Group B monkeys, however, hadpreoperative accommodation amplitudes comparable
to those in the other 2 groups. Thus, the high myopia

diameter), which contributes physiologically to ocular
accommodation by substantial steepening, wasremoved to prevent anterior capsule opacification. In
the current study, despite a large central capsule defectcreated by the CCC, mean accommodation amplitudes
of approximately 2.5 D were obtained independent of
the amount of filling, after a 4-week follow-up. The obtained accommodation amplitudes may be clinicallyuseful for near vision because multifocal IOLs with a
3.0 D addition (add) allow patient's to read, and this
3.0 D add in vivo corresponds to approximately 2.5
D of accommodation if the amplitudes do not declinewith time.

Table 5. Postoperative measurements of ACD, lens thickness, and capsule curvatures using Scheimpflug photography.
Mean G SD
Group/Time

ACD (mm) Lens Thickness (mm)Anterior Capsule
Curvature (mm)Posterior Capsule
Curvature (mm)Capsular Bag Volume (mL)A
Before pilo 2.52 G 0.25
1 h after pilo 2.39 G 0.24

2.50 G 0.17
2.66 G 0.37

7.74 G 1.01
7.38 G 0.92

11.20 G 1.54
10.65 G 1.36

0.079 G 0.002d

Before pilo 2.43 G 0.07
1 h after pilo 2.32 G 0.05

3.17 G 0.34
3.35 G 0.24

7.35 G 0.99
7.07 G 0.84

7.64 G 1.26
6.91 G 1.52

0.106 G 0.008d

Before pilo 2.14 G 0.24
1 h after pilo 2.02 G 0.26

3.60 G 0.15
3.85 G 0.27

6.28 G 0.34
6.09 G 0.40

NA
NA

d
d

B

C

ACD Z anterior chamber depth; NA Z not applicable; pilo Z pilocarpine 4.0%

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

in Group B may not have adversely affected theresults.
We were unable to find references to the crystalline
lens volume in Macaca monkey eyes. We therefore
tried to calculate it using Scheimpflug photography
and a dedicated computer program. This may haveresulted in errors in our calculations. The peripheral
part of the crystalline lens was extrapolated usinggraphs with the curvatures and lens periphery; thecalculated curvatures were not corrected for the distortion caused by the cornea and aqueous humor.
However, 5 refilled capsules injected with 0.080 mLof silicone polymers (Group A) and 3 refilled capsules
injected with 0.100 mL of silicone polymers (Group B)
showed a mean calculated volume of 0.079 mL and
0.108 mL, respectively, values that were very close to
the injected silicone volumes. Therefore, the calculated
crystalline lens volume of 0.125 mL suggests no error
occurred that would have significantly affected theresults.
Because the anterior accommodating IOL used inthis technique does not have a refractive power,
the steepening of the anterior surface of theaccommodating-membrane IOL shown by Scheimpflug analysis may have played the main role inachieving accommodation. The use of an IOL with athinner, softer, and more elastic center that is moresimilar to the anterior capsule might achieve higher accommodation amplitude levels. Furthermore, more
flattening of the anterior curvature might achieve
higher accommodation because the flatter the lensand the smaller the volume of the anterior segment,
the more potential energy is stored in the capsule forrelease by zonular relaxation.14 The mean anterior
curvature of the present accommodating-membrane
IOL after surgery was 7.74 mm, 7.35 mm, and6.28 mm in Group A, Group B, and Group C, respectively, and was significantly steep compared withnot only its own anterior curvature of 15.5 mm but
also with the mean preoperative anterior curvature
values of 10.99 mm, 11.81 mm, and 11.07 mm, respectively. This may explain the high postoperative
myopic shift in Groups B and C. Thus, controlling
and restoring the preoperative original capsular bag
shape is a must for achieving emmetropia and obtaining useful accommodation. This issue should be
resolved in future studies.
The accommodation amplitudes in the 3 study
groups, ranging from approximately 2.0 to 4.0 D
with a mean of approximately 2.5 D, were independent of the volume of capsular bad filling. The
Scheimpflug analysis showed analogous findings,
with shallowing of the ACD, thickening of the refilled
lens, and steepening of the anterior curvature of the

303

IOL, although these changes were not great whencompared with the preoperative values.
Results in previous in vitro studies7,9 suggest that
there is an optimum amount of filling to obtain greateraccommodation. In these in vitro experiments, underfilling the capsular bag with a volume of 60% to 80%
yielded significantly higher accommodation amplitudes. However, in the present study, there were no
statistically significant differences before or after surgery in the accommodation amplitudes and accommodation ratios between the 3 amounts of filling. In otherwords, with this procedure, optimum accommodation
amplitude was not dependent on the extent of
capsular bag filling. The reason may be that in theprevious in vitro experiment, the refilled capsule wasstretched to generate accommodation, implying thatthe mechanism of accommodation was different.
Another
explanation
may
be
that
the
accommodating-membrane IOL was much thicker andstiffer than the anterior capsule and was not sufficiently
thin and resilient; thus, the anterior curvature of themembrane did not change as much as the anterior
capsule, and in fact changed very little, during accommodation. The membrane might have been too stiff toreact sensitively to different amounts of silicone polymers and thus to exactly mimic the accommodation
mechanism. Therefore, as discussed, making the membrane much thinner might result in greater accommodation amplitude but might also result in a different
relationship between the accommodation amplitude
and different amounts of filling. This might be advantageous because both factors do not need to be consideredto achieve optimum accommodation amplitude andemmetropia if clinically useful accommodation can beobtained independent of the degree of capsular bag
filling. If this were the case, the surgeon could concentrate on achieving emmetropia only, facilitating surgery.
The postoperative accommodation amplitudes attained were a small fraction of the preoperative values.
This result is similar to the findings in our monkey experiments.4,8 Koopmans et al.10 report similar results(3.0 to 4.0 D of accommodation [up to 6.0 D]) in theirrhesus monkey experiments using the plug-sealing
technique; these values were far lower than preoperatively. The use of a thick (IOL-like) centrally locatedplug may be a cause. The structure of the polymerized
silicone gel is different from that of the natural crystalline lens. Thus, the IOL may not be able to consistently
follow the change in the shape of the capsular bag after
pilocarpine application, as the normal crystalline lens
capsule does. Another reason may be less adhesion between the lens capsule and polymerized silicone thanis present preoperatively, which may result in lessefficient transmission of the capsule forces.4,10

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

304

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

Regarding postoperative refraction, there was asignificant tendency toward a myopic shift withincreasing ACD, lens thickness, and anterior curvaturethat occurred with increasing bag volume after
surgery. The results suggest that the postoperativerefractive state depends, to a large degree, on theextent of capsular bag filling. Koopmans et al.10 foundthat the postoperative refraction was influenced by
overfilling and underfilling the lens capsule. The
attainment of emmetropia is an important issue thatmust be solved before the potential clinical applicationof this procedure is determined.
Similar to the refractive error, the degree of the astigmatism increased with increased capsular bag filling.
This may be caused by unwanted deformation of theaccommodating-membrane IOL. Future studies mustbe performed to verify this finding and to offer apossible explanation for and to prevent the toricphenomenon.
As reported previously,13 anterior and posterior
CCCs eliminated capsule opacification for several
weeks in the visual axis in rabbit eyes, which have amuch higher propensity for LEC proliferation.
Performing posterior CCCs might decrease the accommodation amplitude. However, we think the decrease
would be limited because the posterior capsule does
not play much of a role in accommodation. In fact,with 65% filling (Group A), the posterior capsulecurvature became much flatter and was almost thesame as with 80% filling (Group B) after surgery andsimilar accommodation amplitudes were attained.
Apart from this series of experiments, we refilled 1monkey lens in which both an anterior CCC and posterior CCC were created; an accommodation amplitude of 3.1 D was attained.
Although capsule opacification in the visual axis canbe prevented by anterior and posterior CCCs, how andto what extent capsule opacification in other areas andresidual LEC proliferation in the form of a Soemmerring ring affect accommodation have to be clarified.
In the present study, we could not determine theanswer to these questions because of the shortfollow-up. This remains a task for future studies.
In conclusion, our new capsular bag–refilling procedure, which required 20 to 30 minutes of surgical time,
was highly reproducible in monkey eyes. There wasno significant leakage of the injectable silicone
polymers in young monkey eyes, as shown innumerous rabbit eye and pig cadaver eye experiments,
and approximately 2.5 D of accommodation was obtained independent of the volume of capsular bag
filling. These results suggest that this capsular bag–refilling technique warrants further studies to determine
whether it has clinical application.

WHAT WAS KNOWN
 The new capsular bag–refilling procedure using anaccommodating-membrane IOL prevented leakage ofsilicone polymers injected into the capsular bag in rabbit
eyes. However, there was a concern that ocular accommodation cannot be obtained because the central partof the anterior capsule (3.0 to 4.0 mm CCC) is removed
to avoid anterior capsule opacification.
WHAT THIS PAPER ADDS Despite creation of a central CCC in young monkey eyes,
approximately 2.5 D of accommodation amplitude was obtained independent of the volume of capsular bag filling.

REFERENCES
1. Parel J-M, Gelender H, Trefers WF, Norton EW. Phaco-ersatz:
cataract surgery designed to preserve accommodation. Graefes
Arch Clin Exp Ophthalmol 1986; 224:165–173
2. Haefliger E, Parel J-M, Fantes F, Norton EW, Anderson DR,
Forster RK, Hernandez E, Feuer WJ. Accommodation of an endocapsular silicone lens (phaco-ersatz) in the nonhumanprimate. Ophthalmology 1987; 94:471–477
3. Gindi JJ, Wan WL, Schanzlin DJ. Endocapsular cataract
surgery- I. Surgical technique. Cataract 1985; 2(5):6–10
4. Nishi O, Nakai Y, Yamada Y, Mizumoto Y. Amplitudes of accommodation of primate lenses refilled with two types of inflatableendocapsular balloons. Arch Ophthalmol 1993; 111:1677–1684
5. Sakka Y, Hara T, Yamada Y, Hara T, Hayashi F. Accommodation in primate eyes after implantation of refilled endocapsularballoon. Am J Ophthalmol 1996; 121:210–212
6. Hettlich H-J, Lucke K, Asiyo-Vogel MN, Schulte M, Vogel A.
Lens refilling and endocapsular polymerization of an injectable
intraocular lens: in vitro and in vivo study of potential risks andbenefits. J Cataract Refract Surg 1994; 20:115–123
7. Nishi O, Nishi K, Mano C, Ichihara M, Honda T. Controlling thecapsular shape in lens refilling. Arch Ophthalmol 1997;
115:507–510
8. Nishi O, Nishi K. Accommodation amplitude after lens refillingwith injectable silicone by sealing the capsule with a plug in primates. Arch Ophthalmol 1998; 116:1358–1361. Available at:
http://archopht.jamanetwork.com/data/Journals/OPHTH/6633/
els8317.pdf. Accessed September 5, 2013
9. Koopmans SA, Terwee T, Barkhof J, Haitjema HJ, Kooijman AC.
Polymer refilling of presbyopic human lenses in vitro restores theability to undergo accommodative changes. Invest Ophthalmol
Vis Sci 2003; 44:250–257. Available at: http://www.iovs.org/
content/44/1/250.full.pdf. Accessed September 5, 2013
10. Koopmans SA, Terwee T, Glasser A, Wendt M, Vilipuru AS, vanKooten TG, Norrby S, Haitjema HJ, Kooijman AC. Accommodative lens refilling in rhesus monkeys. Invest Ophthalmol Vis Sci
2006; 47:2976–2984. Available at: http://www.iovs.org/cgi/
reprint/47/7/2976.pdf. Accessed September 5, 2013
11. Assia EI, Blumenthal M, Apple DJ. Effect of expandable full-size
intraocular lenses on lens centration and capsule opacification in
rabbits. J Cataract Refract Surg 1999; 25:347–356
12. Nishi Y, Mireskandari K, Khaw P, Findl O. Lens refilling to restore
accommodation. J Cataract Refract Surg 2009; 35:374–382

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

LABORATORY SCIENCE: ACCOMMODATING LENS REFILLING

13. Nishi O, Nishi K, Nishi Y, Chang S. Capsular bag refilling using a
new accommodating intraocular lens. J Cataract Refract Surg
2008; 34:302–309
14. Fisher RF. The significance of the shape of the lens and capsularenergy changes in accommodation. J Physiol 1969; 201:21–47.
Available at: http://jp.physoc.org/content/201/1/21.full.pdf.
Accessed September 5, 2013

J CATARACT REFRACT SURG - VOL 40, FEBRUARY 2014

First author:
Okihiro Nishi, MD, PhD
Jinshikai Medical Foundation, Nishi
Eye Hospital, Osaka, Japan305