LABORATORY SCIENCES

Accommodation Amplitude AfterLens Refilling With Injectable
Silicone by Sealing the CapsuleWith a Plug in Primates
Okihiro Nishi, MD; Kayo Nishi, MD

Objective: To restore accommodation in primateeyes by refilling the lens capsule with injectable silicone compounds.
Materials and Methods: Eight eyes of 8 monkeys(Macaca fascicularis) were treated by the lens refilling
procedure. To prevent leakage of the injected liquidsilicone before it polymerized in the capsule in vivo, asilicone plug for sealing the capsular opening wasdeveloped. After endocapsular phacoemulsification
following an upper minicircular capsulorhexis, theplug was introduced into the capsulorhexis opening. A
silicone mixture was injected into the capsular bag
through the delivery tube of the plug. Automated refractometry was performed 1 week and 3 months after surgery. Accommodation amplitude was determined as thedifference between the refractions before and 1 hour after
topical application of 4% pilocarpine chloride.
Results: Five of 8 eyes could be refilled. In 4 of 5 eyes,R

From the Nishi Eye Hospital,Osaka, Japan.

refraction could be measured. Accommodation amplitude ranged from 1.0 to 4.5 diopters, with a mean of
2.3 ± 1.3 diopters (8.0 ± 2.0 preoperative values). At
3-month examination, thick posterior capsule opacification precluded refractometry in all eyes.
Conclusions: The lens refilling procedure with theuse of a silicone plug for sealing the capsular opening
was feasible in primate eyes. The accommodation
amplitude attained was a small fraction of the value
before surgery. This may result from the loss of
so-called intracapsular accommodation, ie, active participation of lens fiber cells in accommodation. However, since the obtained accommodation may be sufficient for near vision after cataract surgery, this lens
refilling procedure warrants further study. Elucidationof the mechanism of intracapsular accommodation
may also be necessary.

Arch Ophthalmol. 1998;116:1358-1361

EFILLING the lens capsule af-

ter endocapsular phacoemulsification aspiration
through a minicircular capsulorhexis while preserving capsular integrity offers the potential
to restore ocular accommodation.1-8 There
are a few reports confirming this possibility. Haefliger et al4 observed shallowing of
the anterior chamber after lens refilling after 4% pilocarpine chloride was injected
into the anterior chamber, suggesting restoration of accommodation. We could confirm a mean accommodation amplitude of
4.6 ± 0.5 diopters (D) in young cynomolgus monkey eyes after they were refilledby means of an inflatable endocapsular balloon.7 Sakka et al8 also confirmed some accommodation in 2 monkey eyes with theuse of our procedure.
Because of the technical complexityof the procedure with an inflatable balloon, we developed a new direct lens refilling procedure9: a silicone plug for seal-ing the capsular opening proved to beeffective for preventing leakage of the injected liquid silicone before it polymerized within the capsular bag of a pig cadaver or rabbit eye. In this study, werefilled primate lenses by the same procedure, and the results are reported here.
RESULTS

Five of 8 lenses could be refilled. Failure in 3 lenses was the result of capsular
rupture. In 2 lenses, rupture occurred
during insertion of the capsular plug
because of a large discrepancy in size
between the CCC and capsular plug. In
the remaining lens, rupture occurred
during injection of the silicone mixture.

ARCH OPHTHALMOL / VOL 116, OCT 1998
1358

©1998 American Medical Association. All rights reserved.

Downloaded From: by Okihiro Nishi on 06/27/2018

This article is alsoavailable on our Web site:www.ama-assn.org/ophth.

MATERIALS AND METHODSPREPARATION BEFORE LENS REFILLING
Eight lenses of 8 young crab-eating monkeys (Macaca fascicularis) were used for the study. Two to 3 months before
the lens capsule was refilled, sector iridectomies at the 6- and12-o’clock positions were performed to facilitate the lens refilling procedure and automated refractometry after surgery.
Refraction and accommodation amplitude (see below) weredetermined at least 1 month after iridectomy. The animals werehoused at the Yaotsu Breeding Laboratory (Japan EDM Inc,Gifu, Japan), where the experiments were performed. The monkeys were treated humanely according to the principles of thePrimate Society of Japan.10
CAPSULAR PLUG FOR SEALINGTHE CAPSULAR OPENING
A capsular plug9 for sealing the capsular opening to prevent leakage of the injected silicone was made from silicone. The plug consisted of a thin delivery tube (outer diameter, 0.365 mm; inner diameter, 0.305 mm) with a diskshaped silicone double plate, 0.38 mm thick, fixed to theend of the delivery tube. Between the 2 plates, there was asoft silicone gel that attached the 2 plates. The inner lumen of the delivery tube was filled with a soft, cured silicone gel to prevent reflux of the injected filling material.

blocked the capsular opening. After the anterior chamber was filled with a viscoelastic substance, a small
amount was injected into the capsular bag to inflate only
the CCC region to facilitate plug insertion. The top of
the capsular plug was entirely inserted into the capsularbag, while the CCC opening was widened by hooking its
edge with a blunt Bonn iris hook from the side port,
similar to putting a tire on the wheel. The viscoelastic
was removed from the capsular bag by aspiration with a
Simcoe cannula. The cannula was introduced throughthe capsular opening, within which the thin delivery tubeof the capsular plug and the cannula were now contained.
After the viscoelastic substance was removed from the capsular bag, the upper plate of the plug was brought outside
the capsular opening by pulling with the tire-wheel maneuver described above, so that the soft silicone gel between the2 plates blocked the CCC opening.
Thereafter, 0.2 mL of a mixture of 2 liquid silicone compounds, polymethyldisiloxane as the main component andhydrogen polysiloxane as a cross-linking agent, was injected with an odontology syringe (Citoject, Bayer Dental
Nippon, Osaka, Japan) through the delivery tube. After thecapsular bag was filled with the silicone mixture, the delivery tube was cut at its root. Then, tight corneal sutures
were used for closure.
One percent atropine sulfate ointment was applied in
the conjunctival sack at the end of the surgery to maintainzonular relaxation.
POSTOPERATIVE EXAMINATIONSLENS REFILLING PROCEDURE
After the monkey was anesthetized with ketamine hydrochloride (5 mg/kg) and xylazine hydrochloride (2 mg/kg), the pupil was maximally dilated. Then, a 3-mm incision was made at the limbus by means of a disposable 3-mm
keratome. After the anterior chamber was filled with a viscoelastic substance, a prick was made in the capsule at theupper region near the corneal incision with a disposable
27-gauge needle. From the capsular incision, a small continuous circular capsulorhexis (CCC) 1.5 to 1.8 mm in diameter then was completed with the use of a capsulorhexis forceps.
After endocapsular phacoemulsification was performed with a 0.8-mm thin tip (Alcon Co, Fort Worth, Tex),lens epithelial cells were removed as thoroughly as possible by aspiration. The capsular plug then was inserted insuch a manner that the soft silicone gel between the 2 plates

However, the CCC opening appeared to have alreadybeen damaged during insertion of the capsular bag.
SLITLAMP FINDINGS
At 1-week examination, the whole lens capsule was clear
in 3 eyes, and migrating cells and flare in the anteriorchamber were few and slight. Refraction could be measured by the automated refractometer. Two of 5 eyes
showed fibrinous exudation on the anterior lens capsule (Figure 1). Fibrinous exudation in 1 of these 2 eyesin which refraction could be measured despite the condition had disappeared at 3-month examination. The othereye eventually progressed to phthisis bulbi because of en-After lens refilling, all monkeys underwent slitlamp examination and automated refractometry while they wereanesthetized, as described above, 1 week and 3 months postoperatively.
Refraction was measured in the anesthesized animals
by means of an automated refractometer (Auto-KeratoRefractometer KR-3000, Topcon Co, Tokyo, Japan) before and 1 hour after topical application of 4% pilocarpine
to alter the lens shape. Refraction was determined as anequivalant value. Accommodation amplitude was determined as the difference between these 2 refraction values.
Each measurement was performed 5 times by 1 of 3 masked
persons, and the median value for each animal was used
to calculate the overall mean value.
One monkey was killed 6 months postoperatively by
injection of succinylcholine chloride after anesthesia. The
refilled lens was then examined histopathologically.

dophthalmitis. These monkeys were the first to undergo surgery. Thereafter, we disinfected the eye morestrictly before surgery, as in surgery on humans. As a result, changes in refraction could be measured in 4 eyes
1 week after surgery (Table). However, at 3 months postoperatively, anterior and posterior capsule opacification precluded refractometry in all 4 eyes. The anterior
capsule was relatively clear, sporadically showing a fine
fibrotic type of opacification (Figure 1).
AMPLITUDE OF ACCOMMODATION
The preoperative refraction before pilocarpine application ranged from 0 to −2.0 D, and those 1 hour after such

ARCH OPHTHALMOL / VOL 116, OCT 1998
1359

©1998 American Medical Association. All rights reserved.

Downloaded From: by Okihiro Nishi on 06/27/2018

Preoperative and Postoperative Refractions and Accommodation Amplitude in Lenses Refilled With Injectable Silicone:
Change in Refraction Before and 1 Hour After Topical Application of 4% Pilocarpine
Postoperative Refractions, D

Preoperative Refractions, Diopters (D)MonkeyNo./Age, yBeforeAfter

ChangeBeforeAfter

Change

1/13
2/5
3/5
4/6
Mean ± SD

−2.00
−1.00
0
−1.75
−1.2 ± 0.8−13.25
−6.75
−7.50
−9.25
−9.2 ± 2.5

11.25
5.75
7.50
7.50
8.0 ± 2.0

+5.00
+7.25
+5.00
+8.50
+6.4 ± 1.5+0.50
+6.25
+3.00
+7.00
+4.2 ± 0.6

4.50
1.00
2.00
1.50
2.3 ± 1.3

Figure 2. Histopathological section of a refilled lens capsule from themonkey eye shown in Figure 1, 6 months after surgery. The section was cut
horizontally from the middle of the resected specimen. Note the lensepithelial cells that migrated onto the posterior capsule (toluidine blue,original magnification 39).

Figure 1. Slitlamp finding of the refilled lens of a primate eye 3 months aftersurgery. Fibrotic anterior capsule opacification developed and precludedrefractometry. The posterior capsule is relatively clear. Note the optically empty
silicone within the capsular bag. The arrows indicate the capsular plug.

application ranged from −6.75 to −13.25 D. Postoperative refractions before pilocarpine application ranged from+5.0 to +8.5 D, and those 1 hour after application ranged
from +0.5 to +7.0 D. Accordingly, the preoperative accommodation amplitude ranged from 5.75 to 11.25 D witha mean (±SD) of 8.0 ± 2.0 D, while the postoperative accommodation amplitude ranged from 1 to 4.5 D with amean of 2.3 ± 1.3 D (Table).
HISTOPATHOLOGICAL EXAMINATION
The lens capsule was well stretched and showed that its
integrity was obviously preserved. Thick posterior capsule opacification could be observed (Figure 2).
COMMENT

We performed refractometry 1 week after surgery, because our previous study7,9 showed that posterior capsule opacification occurred rapidly in the refilled lens capsule, precluding refractometry. As a result, changes inrefraction in the refilled lenses could be measured in 4
lenses, excluding 1 that developed fibrinous reaction. At3-month examination, refraction could not be mea-

sured in any of the eyes because of increasing posterior
capsule opacification, obviously showing that prevention of this opacification is an essential issue to be solvedin lens refilling. In this regard, ultrasonographic biometry may provide useful additional data regarding posterior capsule opacification in future studies.
Postoperative refraction will be primarily determined by refractive index of the injected silicone with afixed certain value and anterior capsule curvature that
depends on the degree of filling. The more tautly the capsule is filled, the steeper the anterior capsule curvature,thus the greater the refraction. Filling degree, however,also influences accommodation amplitude. The optimal
accommodation amplitude will be obtained by filling thecapsule with 60% to 70% of bag volume with silicone compounds, according to our previous study.9 Thus, postoperative refraction and accommodation amplitude both
depend on filling degree, yet they comprise 2 reciprocally counterbalancing variables in lens refilling on thepremise that filling material with only 1 specific refractive index is available. In other words, obtaining the optimal accommodation amplitude in lens refilling can beachieved at the price of achieving emmetropia. In thisstudy, we attemped to obtain optimal accommodation byfilling the lens capsule to 60% to 70% of bag volume. As
a result, a mean accommodation amplitude of 2.3 ± 1.3
D could be obtained at the price of hyperopic shift in postoperative refraction with a mean value of +6.4 D (Table).
Postoperative emmetropia may be achieved by intraoperative and postoperative refractive corneal surgery or phakic intraocular lens. Therefore, refractive surgery may havegreat implications in lens refilling.

ARCH OPHTHALMOL / VOL 116, OCT 1998
1360

©1998 American Medical Association. All rights reserved.

Downloaded From: by Okihiro Nishi on 06/27/2018

Although we refilled the lens capsule to obtain apparently optimal accommodation amplitude, we obtained only a small fraction of the amplitude before surgery. Similar results were also obtained in our previous
study7 involving lenses refilled with inflatable endocapsular balloon. We think this may be caused by the lossof intracapsular accommodation, ie, the active participation of lens fiber cells in accommodation.11 On the basis of his mathematical calculations, Gullstrand postulated that the change in the shape of the lens duringaccommodation could be realized only by the shifting oflens fiber cells against each other.
As circumstantial evidence, some findings indicate
the existence of intracapsular accommodation.11,12 The
fiber itself does not shift, but rather the contents of thefibers shift during accommodation. Metabolism in lens
fiber cells is similar to that in muscle contraction. Contractile and cytoskeletal filaments such as actin, vimentin, and tubulin have been detected in the intracellularmatrix of lens fiber cells. The adenosine triphosphate–adenosine diphosphate ratio falls after fiber shifting, but
it is restored rapidly, similar to that in muscle. If there issuch intracapsular accommodation, the full accommodation amplitude cannot be restored simply by refilling
the lens capsule with an artificial material, although 3 Dof accommodation might be clinically sufficient for nearvision after surgery.
The rapidly developing posterior capsule opacification is another problem to be solved. The use of YAG laser capsulotomy may annull the accommodation attained. Furthermore, the question of whether a usefuldegree of accommodation can be obtained in a presbyopic eye by lens refilling remains unanswered. Using highresolution ultrasonographic biometry, Bacskulin et al13
recently showed that ciliary muscles contracted duringaccommodation even in presbyopic eyes. However, theextent to which loss of capsular elasticity affects restoration of accommodation remains unknown. The procedure should be tested in an aged primate eye.
In conclusion, refilling the lens capsule with injectable silicone in monkey eyes was feasible. The obtained
accommodation amplitude was a small fraction of thevalue before surgery. This may have resulted from theloss of so-called intracapsular accommodation. Nevertheless, this lens refilling procedure warrants further investigation, since 3 D of accommodation might be sufficient for near vision after surgery. Posterior capsule
opacification must to be prevented, because capsulotomy might annull the accommodation attained.
Accepted for publication June 26, 1998.
Reprints: Okihiro Nishi, MD, Nishi Eye Hospital, 414-26, Nakamichi, Higashinari-ku, Osaka 537, Japan (email: okihiro@nishi.ganka.or.jp).
REFERENCES

1. Kessler J. Experiments in refilling the lens. Arch Ophthalmol. 1964;71:412-417.
2. Agarwal LP, Narsimhan EC, Mohan M. Experimental lens refilling. Orient Arch
Ophthalmol. 1967;5:205-212.
3. Parel J-M, Gelender H, Treffers WF, Norton EWD. Phaco-ersatz. Graefes Arch
Clin Exp Ophthalmol. 1986;224:165-173.
4. Haefliger E, Parel J-M, Fantes F, et al. Accommodation of an endocapsular silicone lens (phaco-ersatz) in the nonhuman primate. Ophthalmology. 1987;94:471-477.
5. Gindi JJ, Wan WL, Schanzlin DJ. Endocapsular cataract surgery. Cataract. 1985;
2:6-10.
6. Nishi O. Refilling the lens of the rabbit eye after endocapsular cataract surgery.
Folia Ophthalmol. 1987;38:1615-1618.
7. Nishi O, Nakai Y, Yamada Y, Mizumoto Y. Amplitudes of accommodation of primate lenses refilled with two types of inflatable endocapsular balloons. Arch Ophthalmol. 1993;111:1677-1684.
8. Sakka Y, Hara T, Yamada Y, Hara T, Hayashi F. Accommodation in primate eyes
after implantaion of refilled endocapsular balloon. Am J Ophthalmol. 1996;121:
210-212.
9. Nishi O, Nishi K, Mano C, Ichihara M, Honda T. Controlling the capsular shape inlens refilling. Arch Ophthalmol. 1997;115:507-510.
10. Primate Society of Japan. Guiding principles for primates. Primate Res. 1986;
2:111-113.
11. Kleifeld O. Beiträge zum intrakapsulären Akkommodations mechanismus. DocOphthalmol Adv Ophthalmol. 1956;10:132-168.
12. Hockwin O. Biochemie der Linse: ein Rückblick auf thematische und methodische Entwicklungen, ein Ausblick auf zukünftige Forschungen. Klin Monatsbl
Augenheilkd. 1993;202:544-551.
13. Bacskulin A, Gast R, Bergmann U, Guthaff R. Ultrasehallbiomikroskopische Darstellung der akkommodativen Konfigurationsänderungen des presbyopen Ziliarkörpers. Ophthalmologe. 1996;93:199-203.

IN OTHER AMA JOURNALS
JAMATelomerase and the Aging Cell: Implications for Human HealthMichael Fossel, MD, PhD
Recent research has shown that inserting a gene for the protein component of telomerase into senescent human cells reextends their telomeres to lengths typical of young cells, and the cells then display all the other identifiable characteristics ofyoung, healthy cells. This advance not only suggests that telomeres are the central timing mechanism for cellular aging, butalso demonstrates that such a mechanism can be reset, extending the replicative life span of such cells and resulting inmarkers of gene expression typical of “younger” (ie, early passage) cells without the hallmarks of malignant transformation.
It is now possible to explore the fundamental cellular mechanisms underlying human aging, clarifying the role played byreplicative senescence. By implication, we may soon be able to determine the extent to which the major causes of death anddisability in aging populations in developed countries—cancer, atherosclerosis, osteoarthritis, macular degeneration, andAlzheimer dementia—are attributable to such fundamental mechanisms. If they are amenable to prevention or treatment byalteration of cellular senescence, the clinical implications have few historic precedents. (1998;279:1732-1735)
Reprints: Michael Fossel, MD, PhD, 9464 Conservation Ave, Ada, MI 49301 (e-mail: Mfossel@aol.com).

ARCH OPHTHALMOL / VOL 116, OCT 1998
1361

©1998 American Medical Association. All rights reserved.

Downloaded From: by Okihiro Nishi on 06/27/2018