LABORATORY SCIENCE

Capsular bag refilling using a newaccommodating intraocular lensOkihiro Nishi, MD, Kayo Nishi, MD, Yutaro Nishi, MD, Shiao Chang, PhD

PURPOSE: To describe a capsular bag refilling procedure using an accommodating intraocular lens(IOL).
SETTING: Jinshikai Medical Foundation Nishi Eye Hospital, Osaka, Japan.
METHODS: A disk-shaped anterior foldable silicone accommodating IOL that serves as an
optical device and as a mechanical device to prevent leakage of the injected silicone polymers
was developed. The IOL optic is 6.0 mm and the overall diameter, 9.0 mm. After a 3.5 to 4.0 mm
continuous curvilinear capsulorhexis (PCCC) is created, phacoemulsification and aspiration
are performed in the usual manner. Then, a posteriorly placed accommodating IOL with sharpedges is implanted in the capsular bag to prevent posterior capsule opacification (PCO) andleakage of the injected silicone polymer. A PCCC is an option at this point. Then, an anterior accommodating IOL is piggybacked over the existing IOL and silicone polymers are injected between the
2 IOLs.
RESULTS: Experiments in numerous pig cadaver eyes and in 10 rabbit eyes showed minimal to no silicone leakage. In cases in which a PCCC was not created, 2 eyes had no PCO and 3 showed slight tomoderate PCO. None of the 5 eyes with a PCCC had no PCO 5 to 8 weeks after surgery within the PCCC.
CONCLUSION: The procedure in rabbit eyes overcame 2 problems of lens-refilling techniques: leakage of the injectable silicone polymer and capsule opacification.
J Cataract Refract Surg 2008; 34:302–309 Q 2008 ASCRS and ESCRS

Refilling the lens capsule with an injectable malleable
material while preserving capsule integrity, including
zonules and ciliary muscles, offers the potential to restore ocular accommodation.1,2 As many experimental
studies over almost 3 decades show, 2 main problems
persist in capsular bag refilling. First is leakage of theinjectable material from the capsular opening andAccepted for publication September 11, 2007.
From Nishi Eye Hospital (O. Nishi, K. Nishi), Osaka, Japan;
Moorfields Eye Hospital (Y. Nishi), London, United Kingdom; andCalhoun Vision, Inc. (Chang), Pasadena, California, USA.
The authors have a proprietary interest in the accomodating intraocular lens and procedure mentioned in the text.
Presented in part at the ASCRS Symposium on Cataract, IOL and
Refractive Surgery, San Diego, California, USA, April 2007.
Corresponding author: Okihiro Nishi, MD, Nishi Eye Hospital,
4-14-26 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan. E-mail:okihiro@nishi-ganka.or.jp.

302

Q 2008 ASCRS and ESCRS
Published by Elsevier Inc.

second, formation of anterior (ACO) and posterior(PCO) capsule opacification.
Numerous methods to prevent leakage have beendeveloped.3–7 We developed an inflatable endocapsular balloon and a silicone plug to seal the capsular
opening.8,9 Using this method, we confirmed the preservation of some accommodation in a series of experiments using young Macaca monkeys. We suggestthat refilling the lens capsule to preserve accommodation is technically feasible.
For such a technique to restore ocular accommodation in humans would, however, require that certain
technical problems be overcome before significant
clinical application can be achieved. These include
refining and simplifying the technique, preventing
ACO and PCO, and reducing the considerable surgically induced astigmatism resulting from even thesmall unilateral continuous curvilinear capsulotomy(CCC) used in the technique (unpublished data).
Recently, we developed a new concept and lensrefilling procedure that may solve these problems.
We describe the technique and report the results in
pig cadaver eyes and rabbit eyes.
0886-3350/08/$dsee front matterdoi:10.1016/j.jcrs.2007.09.042

LABORATORY SCIENCE: CAPSULAR BAG REFILLING WITH AN ACCOMMODATING IOL

303Surgical TechniqueFigure 2 shows an overview of the surgical technique. As
in conventional cataract surgery, a 3.5 to 4.0 mm diameter
CCC is created in the middle of the anterior capsule in theusual manner. After phacoemulsification and aspiration,
ophthalmic viscosurgical devices (OVDs) are injected into
the capsular bag. The foldable accommodating IOL is placed
entirely in the capsular bag. Then, the OVD that was injectedbeneath the accommodating IOL within the capsular bag isthoroughly removed using bimanual irrigation/aspiration.
During irrigation, the 22-gauge aspiration cannula is introduced through the injection hole and the OVD is aspirated.
Then, the OVD is again injected into the anterior chamber infront of the IOL, with care taken not to inject it into the capsular bag. A Sinskey hook is placed in the positioning
pocket, and the IOL is pushed slightly downward so the injection hole in the haptic comes close to the CCC edge. While
the CCC edge is moved aside with the top of the injectionneedle attached to a special syringe containing silicone polymers, the needle is inserted through the injection hole underneath the accommodating IOL in the capsular bag. A
mixture of silicone polymers 0.3 to 0.4 mL in volume isthen injected using the device described below. The silicone
polymers polymerize in 2 hours, as determined by in vitro
studies.

Figure 1. Foldable Silicone anterior accommodating IOL serves as an
optic and a plug. The overall length is 9.0 mm and the optic, 6.0 mm.
An injection hole is seen in the disk-shaped haptic. A 0.2 mm positioning pocket is central to the optic.

MATERIALS AND METHODS
Anterior Accommodating Intraocular Lens
An accommodating intraocular lens (IOL) (Figure 1) was
developed. The IOL serves as an optical device and prevents
leakage of the injected silicone polymers before they polymerize in the capsular bag. The IOL is disk-shaped, with an overall diameter of 9.0 mm and a central optic diameter of 6.0 mm.
In the disk-shaped haptic, there is a small hole for placementof a 22-gauge needle through which the silicone polymers are
injected. More central to the optic is a 0.2 mm positioning
pocket through which the IOL is positioned using a Sinskey
hook. The IOL is foldable and made of silicone.

Posterior Capsule Opacification Prevention
Refilling Without Posterior Continuous Curvilinear Capsulorhexis To prevent PCO, a posterior accommodating IOL
was developed. In the procedure, a posterior accommodating IOL is implanted. The posterior IOL is similar to the anterior IOL in design but has no sharp edges and injection
hole. First, the IOL is inversely inserted and the anterior accommodating IOL is piggybacked in the capsular bag. The
silicone polymers are injected between the 2 IOLs. The posterior accommodating IOL helps prevent PCO by providing
a sharp bend in the posterior capsule (Figure 3).

Refilling with Posterior Continuous Curvilinear Capsulorhexis In a second procedure, a small PCCC is created
and the accommodating IOL is inversely implanted in thecapsular bag against the PCCC. After the anterior accommodating IOL is inserted by piggybacking, the silicone polymers are injected between the 2 IOLs. The PCCC is createdto help prevent PCO (Figure 4).

Figure 2. Schematic of the lens-refilling procedure. After phacoemulsification with a 3.5 to 4.0 mm
incision is performed, a CCC is created in the usual manner. Next, theanterior accommodating IOL isfolded and implanted in the capsular bag. An injectable silicone polymer is then injected beneath the IOL
through the delivery hole while the
CCC edge is pulled aside slightly.

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limbus, and the accommodating IOL was pushed downward with considerable force using a Sinskey hook. Afterthe amount of leakage was noted, the IOL was pushed
farther using increasing force.

Rabbit Eyes
The crystalline lens was consecutively refilled in 5 rabbit
eyes (Table 1). One eye received a posterior accommodating
IOL with sharp edges, and the contralateral eye had PCCC
and implantation of a posterior accommodating IOL. After
5 to 8 weeks, the rabbits were killed by an injection of ketamine chloride (0.5 mg/kg) and succinylcholine chloride(0.15 mg/kg) and the eyes were enucleated. Slitlamp observations were noted, and gross stereomicroscopic and histopathologic examinations were performed.
Figure 3. To prevent PCO, a posterior accommodating IOL similar indesign to the anterior accommodating IOL but with sharp edges is
implanted. Silicone polymers are injected between 2 IOLs. The sharp
optic edge should create a capsular bend (AC IOL Z accommodating intraocular lens).

Injection of Silicone Polymers
Silicone polymers are injected using an injection apparatus (Dispenser 1500XL, EFD Inc.). A 22-gauge blunt needle
is attached to a special syringe (3 mL), and its cylinder ispushed by a gas compressor, which is operated by a footswitch. The speed of the syringe and volume of the injection
can be programmed preoperatively.

Pig Cadaver Eyes
Silicone polymers were injected into pig cadaver eyes.
When the injected silicone polymers polymerized the
day after surgery, the refilled lens was removed fromthe eye.
To test the security of leakage prevention, the pig cadavereyes were refilled with 0.3 to 0.4 mL of silicone polymers. The
cornea was removed by a circumferential incision at the

Figure 4. A PCCC is created to prevent PCO. A posterior accommodating IOL is inversely implanted to seal the PCCC. Silicone polymers are injected between the 2 IOLs (AC IOL Z accommodating
intraocular lens; CCC Z continuous curvilinear capsulorhexis).

RESULTS
Pig Cadaver Eyes
Initial Refilling A small amount of silicone polymers
leaked through the injection hole when the injectionneedle was withdrawn, and the CCC slowly returned
to its original position, covering the injection hole inthe disk haptic. This leakage occurred infrequently
and could be easily removed by aspiration or irrigation. Once the injection hole was covered by the anterior capsule, there was no further leakage. Even with
nonstandard positioning overnight, there was no leakage in any eye the next morning. After the injectedsilicone polymers polymerized the day after surgery,the refilled lens was removed from the eye. There
was a resiliency similar to that of the original crystalline lens.
Leakage Test After the pig cadaver eye was refilledwith silicone polymers and the cornea removed, andthe accommodating IOL was pushed downward totest for leakage. The silicone polymers first appeared
over the peripheral haptic. When the accommodating
IOL was pushed farther with increasing force, the silicone polymers moved farther centrally to the CCC
edge. When the pushing force on the accommodating
IOL was stopped, the silicone polymers returned
slowly to their original position beneath the IOL(Figure 5, A). With continuous pushing force on the
IOL, the silicone polymers extended to the CCC edge
and in some cases parted, segregated, and leaked
into the anterior chamber (Figure 5, B). When the
Sinskey hook was lifted and the IOL no longer pushed,
the IOL returned to its original site, the leaking silicone
polymers returned to beneath the IOL, and there wasno further leakage. The silicone that did leak could
be removed by aspiration or irrigation.
Rabbit Eyes
Figure 6 shows a slitlamp view of a rabbit eye witha refilled crystalline lens, 2 accommodating IOLs, andJ CATARACT REFRACT SURG - VOL 34, FEBRUARY 2008

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305

Stereomicroscopy With stereomicroscopic observation, no significant leakage of silicone polymers wasseen in any eye. The capsular bag was refilled well inall but 1 eye. When the anterior accommodating IOL
was pushed posteriorly and the posterior accommodating IOL was pushed anteriorly with a spatula via
the posterior capsule, a resiliency similar to that of
the original crystalline lens was noted.
Capsule Opacification The remaining anterior capsuleshowed almost no fibrosis and remained relatively
clear. None of the PCO observed was fibrotic in nature.
Refilling Without Posterior Continuous Curvilinear Capsulorhexis Two eyes (R1 and R2) were free of PCO(Table 1). In these eyes, a distinct capsular bend wasseen around the entire circumference (Figure 7). In
2 eyes, slight PCO was observed and the capsularbend was seen only partially throughout circumference. One eye had moderate PCO; no capsular bend
formation was seen.
Refilling with Posterior Continuous Curvilinear Capsulorhexis All eyes were PCO free within the PCCC
(Table 1). The remaining area of the posterior capsule
had slight to moderate PCO in all eyes. The opacification appeared to consist mainly of migrating lensepithelial cells (LECs) (Figures 8 to 10) and was not
fibrotic in nature. Histopathologic examination was
not performed.
Figure 5. Testing for leakage. A: When the IOL was pushed eccentrically, silicone extruded between the IOL and anterior capsulebut then returned when the Sinskey hook was lifted, even though
the silicone reached the CCC edge. B: When the force was continuous, a small amount of silicone leaked. When the force wasstopped, the silicone slowly returned to behind the IOL, segregating the leaked silicone, which could be separately irrigated or
aspirated.

no CCC. All lenses were successfully refilled. There
was a small amount of leakage in some eyes that could
be removed by aspiration or irrigation at the end of
surgery.

DISCUSSION
When capsule integrity was preserved, there was little
to no leakage of the injectable silicone compound in
pig eyes or rabbit eyes. Even in the pig cadaver eyesthat were maintained deliberately perpendicularly
during polymerization, there was no silicone leakage
the following day. There was also no silicone leakage
in the rabbit eyes, although the eyes were always positioned perpendicularly. These findings suggest that
there would be no leakage should a patient stand up
immediately after the procedure. Leakage can occur
when the accommodating IOL is forcibly pressed
Figure 6. A refilled rabbit crystalline lens with 2 accommodating
IOLs without CCC. Five weeks
after surgery, the IOL was firmly
and securely fixed. There wasno leakage of the injected silicone
compound. Left: Anterior CCC andanterior accommodating IOL. Right:
Posterior accommodating IOL
under the slitlamp. The posterior
capsule is clear.

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Table 1. Results in the rabbit eyes refilled with 2 accommodating IOLs and enucleated.
RabbitR1
Without PCCC
With PCCC
R2
Without PCCC
With PCCC
R3
Without PCCC
With PCCC
R4
Without PCCC
With PCCC
R5
Without PCCC
With PCCC

Postop Period (Wk)

Filling

Capsular Bend

8

Well refilled, no leakage
Poorly refilled, no leakage

Circumferential

Well refilled, no leakage
Well refilled, no leakage

Circumferential

5Well refilled, no leakage
Well refilled, no leakage

Partial

C
C

NA

7

Well refilled, no leakage
Well refilled, no leakage

Partial

C
C

NA

7

Well refilled, no leakage
Well refilled, no leakage

No bend

CC
CC

NA

6

PCO Degree*

PCO Within PCCC

NA
C
NA
C

NA Z not applicable; PCCC Z posterior continuous curvilinear capsulorhexis; PCO Z posterior capsule opacification* Z no PCO; C Z slight PCO; CC Z moderate PCO; CCC Z severe.

posteriorly, mimicking what happens when patientsvigorously press or rub the eye.
When leakage did occur as a consequence of thesilicone injection, it was a small amount that could
be easily aspirated or irrigated. Postoperatively, noleakage was noted in any rabbit eye. Thus, this highly
reproducible surgical technique using the accommodating IOL could successfully prevent leakage of injectable silicone polymers.
Our early studies7,8 showed that silicone leakage
can be successfully prevented through an uppermini-CCC (approximately 1.2 mm) when it was sealed
by a single plate silicone plug slightly larger than themini-CCC diameter. The principle of sealing the
CCC should be the same, independent of CCC size.
That the anterior accommodating IOL seals sucha large CCC opening and thus prevents silicone

leakage is consistent with our previous experience. Because the injected polymer presses the IOL from inside
the capsular bag against the CCC and anterior capsule,and possibly as a result of the buoyancy of the silicone,
the injected, very cohesive silicone polymer with its
high molecular weight does not leak through the space
between the anterior capsule and IOL unless the IOL ispushed very far posteriorly (Figure 11).
Similarly, the inversely implanted posterior accommodating IOL also sealed the PCCC, preventing silicone leakage. The operative principle may be thesame as for the anterior CCC. This general principle
should be recognized in future development of capsular bag refilling.
Historically, leakage of the injectable IOL wasthe main problem preventing clinical application of
the lens-refilling procedure. Therefore, preventing

Figure 7. Posterior view of an enucleated rabbit lens refilled with 2
accommodating IOLs without PCCC
5 weeks after surgery. The arrows
show the distinct posterior capsulebend created by the sharp edge ofthe posterior accommodating IOL.
There is no PCO as the letters can
be clearly seen.

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307

Figure 8. Slitlamp findings in a rabbit eye that was refilled with 2 typesof accommodating IOLs and inwhich a PCCC was created. Left:
The anterior capsule and anterior
accommodating IOL. The capsule
is refilled, and there is no leakage.
Right: The posterior capsule andposterior accommodating IOL under the slitlamp. The arrow shows
the apparently fibrotic PCCC edgein the slit.

the leakage is crucial for a lens-refilling procedure to
be clinically useful. We think the present techniquecould be a breakthrough in the lens-refilling procedureand contribute to its future development.
Capsule opacification occurred in all rabbit’s eyeswith a few exceptions in which LECs were removed
drastically.10 Although neodymium:YAG laser posterior capsulotomy will not cause herniation or leakageof the injected silicone,11 posterior capsulotomy may
affect the accommodation attained.
In an attempt to prevent LEC migration, we implanted a posterior accommodating IOL with sharpedges. In the posterior view, there was a distinct capsular bend at the sharp edge of the IOL in some eyes.
In the other eyes, however, the bend was not distinct
and formed only partially throughout the circumference or did not form at all. In these eyes, there was significant migration of LECs. Bend formation may
depend on the amount of silicone injected, which
may in turn depend on the desired postoperativerefraction. Further evaluation of whether this method
can eliminate PCO is warranted.
No PCO, at least within the PCCC area, wasobserved in the eye with a PCCC at least 5 to 8 weeks
after surgery. This was an expected outcome. No silicone leakage was seen in any of these eyes.
Under slitlamp examination and stereomicroscopic
observation of the rabbit eyes, ACO in the form of capsule fibrosis was not seen, even 8 weeks after surgery.
This may be due to characteristics of the IOL material.
Posterior capsule opacification in the form of LEC migration was observed, but there was no fibrosis except
what seemed to be fine fibrotic structures at the marginof the PCCC, although we did not perform a histologic
examination.
The question is whether the opacification observedin the periphery as the cell mass of migrating LECs significantly affects the accommodating response. Thesecell masses can be regarded as lens regenerates, compared to the silicone, which might be expected not to

Figure 9. Posterior view of an enucleated rabbit lens refilled with 2 accommodating IOLs with PCCC 6
weeks after surgery. Left: The visual
axis is PCO free as the letters can beclearly seen. Right: The arrows
show the PCCC edge.

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Figure 10. A refilled rabbit capsule with PCCC. The iris wasremoved. The visual axis is clear. The peripheral opacification was
mainly caused by PCO, which apparently consisted of migrating
LECs.

interfere with the elastic properties of the residual lens
capsule. However, the physical properties of thesemasses, including the elastic property, may significantly differ from those in the physiological condition,
possibly affecting the accommodating response. Thisis one of the numerous questions about lens refilling
future studies may address.
The peripheral PCO may also affect visualization of
the peripheral retina through a small PCCC. The only
solution may be the prevention of PCO by eliminating
the residual LECs, although in the past numerous
methods have been developed, none of which havebeen proved to be easy, simple, safe, and effective asa routine clinical procedure. If an effective means is developed, the posterior accommodating IOL, as well as

PCCC in our procedure, will become unnecessary, rendering the procedure even simpler.
Another advantage of the second IOL in addition to
PCO prevention may be that it could enhance the accommodation-amplitude attained. The IOL can havea concave optic with minus dioptric power, which
may give a greater power to the anterior accommodating optic, resulting in emmetropia. During accommodation, an anterior optic with a greater power when
it moves forward may enhance the accommodationamplitude attained.12
In this series, we observed ACO and PCO in thevisual axis but no silicone leakage. Anterior CCCs
and PCCCs, however, do not provide an optimum
range of accommodation. A change in the anterior capsule curvature, including the fully preserved elasticityof the lens capsule, which may be the main factor foraccommodation, may not occur. Therefore, the proposed mechanism of accommodation in this procedure may be a dual-optic shift of the accommodating
IOLs and possibly steepening of the anterior curvatureof the IOL when a very soft, very thin membranous
accommodating IOL is used.
These problems and questions can be answered onlyin studies of primates. Because the present techniqueeffectively solves the major setback to previous injectable IOL techniques (ie, leakage of the injectable silicone polymers) and is easy to perform and highly
reproducible, we will soon perform a primate experiment and report the results.
In conclusion, restoration of accommodation by refilling the lens capsule is a goal of refractive cataract
surgery. Technical feasibility has been repeatedly
shown in primates by the creation of useful accommodation. Leakage of the injectable materials and formation of capsule opacification have hindered thedevelopment of the procedure in the past. The technique we describe may provide a future breakthroughfor possible clinical application of lens capsule refilling.
REFERENCES

Figure 11. The principle of preventing leakage of injectable silicone.
The injected silicone polymer presses the IOL from the inside of thecapsular bag against the CCC and anterior capsule (arrows). The injected silicone polymer did not leak through the space between theanterior capsule and IOL unless the IOL was pushed very far posteriorly (AC IOL Z accommodating intraocular lens; CCC Z continuous curvilinear capsulorhexis).

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First author:
Okihiro Nishi, MD
Nishi Eye Hospital, Osaka, JapanJ CATARACT REFRACT SURG - VOL 34, FEBRUARY 2008