Abstract
Purpose
To describe a new capsular bag refilling procedure using a novel accommodative intraocular lens (IOL).
Settings
Jinshikai Medical Foundation Nishi Eye Hospital, 4-14-26 Nakamichi, Higashinari-ku, Osaka 537-0025, Osaka, Japan
Methods
A disc-shaped anterior accommodative IOL (AC-IOL) serving both as an optical device and also as a mechanical device to prevent leakage of the injected silicone polymers has been developed. The optic and overall diameters of this foldable silicone IOL are 6 and 9 mm, respectively,. After 3.5 to 4 mm continuous curvilinear capsulorhexis (CCC) is completed, phacoemulsification and aspiration are performed in the usual manner. Then a posteriorly placed AC-IOL with sharp edges, is implanted into the capsular bag that both prevents PCO formation as well as leakage of the injected silicone polymer. A posterior CCC may be considered as an option at this point. Then, an anterior AC-IOL is piggy-backed over the existing IOL and silicone polymers are injected between two IOLs.
Results
Experiments in numerous pig cadaver eyes and as well as 10 rabbit eyes, showed minimal to absent silicone leakage. In the eyes without a posterior CCC, two eyes were PCO free and three eyes showed slight to moderate PCO. All 5 eyes with posterior CCC were PCO free 5 to 8 weeks after surgery.
Conclusions
This procedure which has the potential to overcome the two persisting problems that plague lens-refilling techniques, namely, leakage of the injectable silicone polymer and capsular opacification may represent a breakthrough in lens-refilling technique. The procedure will soon be tested in primate eyes to confirm the accommodation range achieved.
SYNOPSIS
The experimental results of a new lens refilling procedure showed that it may solve the two persisting problems, leakage of the injected silicone polymer and capsular opacification, and thus may demonstrate potential clinical application.
Refilling the lens capsule with an injectable malleable material, while preserving capsular integrity including zonules and ciliary muscles, offers the potential to restore ocular accommodation.1,2 From many experimental studies over almost 3 decades, two main problems in capsular bag refilling persist: Firstly, leakage of the injectable material from the capsular opening and secondly, anterior and posterior capsule opacification.
In order to prevent leakage, numerous methods have been described.3–6 We developed an inflatable endocapsular balloon and a silicone plug to seal the capsular opening.7,8 By this method, we could confirm the preservation of some accommodation in a series of the experiments utilizing young macaca monkyes. We suggested that refilling the lens capsule as a means to preserve accommodation is technically feasable.
For such a technique to restore ocular accommodation in humans would, however, require that certain technical problems be overcome before any significant clinical application could be achieved. These include: Refining and simplifying the technique; prevention of anterior capsule opacification (ACO) and posterior capsule opacification (PCO); reducing the considerable surgically-induced astigmatism resulting from even the tiny unilateral continuous curvilinear capsulotomy (CCC) employed in the technique (unpublished data).
Recently, we have developed a completely new concept and novel lens refilling procedure that may solve these problems which we will describe.
MATERIALS AND METHODS
1. Anterior Accommodative Intraocular Lens (Fig. 1)
Figure 1.
Anterior accommodative intraocular lens. It is made of silicone and foldable. The overall length is 9 mm, the optic 6 mm. An injection hole (22 gauge) is seen in the disc-shaped haptic. A much smaller positioning pocket (0.2 mm) is seen centrally to the optic.
A novel accommodative intraocular lens has been developed. The IOL will serve as an optical device but will also prevent leakage of the injected silicone polymers before they polymerize within the capsular bag. The lens is a disc-shaped IOL with an overall diameter of 9 mm, with a central IOL optic of 6 mm diameter. In the disc-shaped haptic, there is a small hole for placement of a needle (22 gauges) through which the silicone polymers are injected. Further central to the optic, a very small positioning pocket can be seen. It serves to position the IOL using a Sinskey hook. The IOL is made of silicone and is foldable.
2. Surgical Procedure (Fig. 2)
Figure 2.
Schematic illustration of the lens refilling procedure: After phacoemulsification aspiration with a 3.5 to 4.0 mm CCC is performed in the usual manner, the anterior accommodative IOL is folded and implanted into the capsular bag. An injectable silicone polymer is then injected beneath the IOL through the delivery hole, while the CCC edge is slightly pulled aside. The silicone polymer polymerizes 2 hours in vitro.
As in conventional cataract surgery, a CCC of 3.5 to 4 mm in diameter, is created in the middle of the anterior capsule in the usual manner. After phacoemulsification aspiration, viscoelastics are injected into the capsular bag. The folded accommodative IOL is introduced entirely into the capsular bag. Then, viscoelastics beneath the accommodative IOL within the capsular bag are thoroughly removed using bimanual irrigation aspiration. While irrigating, the aspiration cannula (22 gauge) is introduced through the injection hole, and viscoelastics is aspirated. Then, viscoelastics is again injected into the anterior chamber in front of the IOL, taking care to not inject it into the capsular bag. A Sinskey hook is placed into the positioning pocket, and the IOL is slightly pushed downward, so that the injection hole in the haptic comes closely to the CCC edge. While the CCC edge is moved aside with the top of the injection needle attached to a special syringe containing silicone polymers, the needle is inserted through the injection hole underneath the accommodative IOL within the capsular bag. A mixture of silicon polymers 0.3 to 0.4 ml in volume is then injected using a special device (see below). The silicone polymers polymerize in 2 hours as determined by in vitro studies.
Prevention of Posterior Capsule Opacification
Refilling without posterior CCC
To prevent PCO, a posterior accommodative IOL has been developed. The first involves implantation of a posterior accommodative IOL similar to the anterior one in design, but with sharp-edges and without the injection hole. It is first revertedly inserted, and the anterior accommodative IOL is piggybacked in the capsular bag. The silicone polymers are injected between both IOLs. The posterior accommodative IOL has the function to prevent PCO by providing a sharp bend in the posterior capsule (Fig. 3).
Figure 3.
Prevention of PCO with a posterior accommodative IOL with sharp edges: First, a posterior accommodative IOL is implanted that is similar in design to the anterior accommodative IOL, but with sharp edges. Silicone polymers are injected between two IOLs. The sharp optic edge should create a capsular bend.
Refilling with posterior CCC
The second procedure creates a small posterior CCC, and the accommodative IOL is revertedly implanted into the capsular bag against the posterior CCC. After the anterior accommodative IOL is inserted by piggybacking, the silicone polymers are injected between both IOLs. The posterior CCC serves as a preventive method to counteract PCO (Fig. 4).
Figure 4.
Prevention of PCO with a posterior CCC: A posterior CCC is created and a posterior accommodative IOL is inversely implanted to seal the posterior CCC. Silicone polymers are injected between the two IOLs.
Injection of Silicone Polymers
Silicone polymers are injected using an injection apparatus (Dispenser 1500XL, EFD Inc. Dunstable, Bedfordshire LU54SB, UK). A 22-gauge blunt needle is attached to a special syringe (3 ml), and its cylinder is pushed by a gas-compressor which is operated by a foot-switch. The speed of the syringe and the volume of the injection can be programmed pre-operatively.
RESULTS
Pig Cadaver Eyes
A small amount of silicone polymers leaked through the injection hole, when the injection needle was withdrawn, and the CCC slowly returned to its original position covering the injection hole in the disc haptic. This leakage occurred however infrequently, and it 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 non standard positioning overnight, the next morning, there was no leakage found in any eye. After polymerization of the injected silicone polymers on the day following surgery, the refilled lens was taken out from the eye. There was a resiliency similar to the original crystalline lens.
Testing How Securely the Leakage Prevented
After the pig cadaver eye was refilled with 0.3 to 0.4 ml silicone polymers, and the cornea was removed by the circumferential incision at the limbus, the accommodative IOL was pushed down-ward considerably with a Sinskey hook. The silicone polymers first appeared over the peripheral haptic. When the accommodative IOL was further pushed by an increasing force, the silicone polymers moved further centrally to the CCC edge. When the pushing force on the accommodative IOL was abolished, the silicone polymers returned slowly beneath the IOL, reestablishing their original position (Fig. 5A). With continuous pushing force on the IOL once the silicone polymers extended to the CCC edge, and in some cases, parted and segregated and leaked into the anterior chamber (Fig. 5B). But, when the Sinskey hook pushing the IOL ceased, the IOL returned to its original site, the leaking silicone polymers also returned beneath the IOL, and there was no further leakage. The silicone that did leak could be removed by aspiration or irrigation.
Figure 5.
Testing how securely the silicone leakage prevented. A: When the IOL is pushed eccentrically, silicone extrudes between the IOL and anterior capsule, but it returns, though the silicone reached the CCC edge, when the sinsky hook is lifted up. B: When the force is kept up continuously, there is a small amount of silicone leaked. When the force is abolished, the silicone slowly returns behind the IOL, segregating the leaked silicone, which can be separately irrigated or aspirated.
Rabbit Eyes
We consecutively refilled the crystalline lens in 5 rabbits. One eye received a posterior accommodative IOL with sharp edges and the contralateral eye underwent posterior CCC, and implantation of a posterior accommodative IOL. After 5 to 8 weeks, the rabbits were sacrificed by injecting ketamine chloride (0.5 mg/kg) and succinyl choline chloride (0.15 mg/kg), and the eyes were enucleated. Observations by slit lamp, (Fig. 6) grossly under a stereo-microscope and histopathologically were performed. All eyes were successfully refilled. There was a small amount of leakage in some eyes, as described above, which could be removed by aspiration or irrigation at the end of surgery.
Figure 6.
A refilled rabbit crystalline lens with two accommodative IOLs without CCC. Five weeks after surgery. Note that the IOL was firmly and securely fixed. There was no leakage of the injected silicone compound. Left: Anterior CCC and the anterior accommodative IOL. Right: Posterior accommodative IOL in slit. The posterior capsule is clear.
Observation under a Stereo-Microscope
No remarkable leakage of silicone polymers were found in any eye. The capsular bag was well refilled in all but one of the eyes. When pushing the anterior accommodative IOL posteriorly and the posterior accommodative IOL via the posterior capsule anteriorly with a saptula, a resiliency similar to the original crystalline lens was noted.
Capsular Opacification
The remaining anterior capsule showed almost no fibrosis and remained relatively clear. PCO, if any, was not fibrotic in nature.
Refilling without posterior CCC
Two eyes (R1 and R2) were PCO free. In these eyes, a distinct capsular bend was seen around the entire circumference (Fig. 7). Two eyes showed a slight PCO, in which capsular bend was seen only partially in the circumference and one eye showed a moderate PCO, where no capsular bend formation was seen.
Figure 7.
Posterior view of an enucleated rabbit lens refilled with two accommodative IOLs without posterior CCC. 5 weeks after surgery. The arrows show the distinct posterior capsular bend created by the sharp edge of the posterior accommodative IOL. There is no PCO, as the letters can be clearly seen.
Refilling with posterior CCC
All eyes were PCO free within the posterior CCC. But, the remaining area of the posterior capsule except the CCC area showed slight to moderate PCO in all eyes. The opacification in these eyes appeared to be consisted mainly of migrating LECs (Fig. 8–Fig. 10) and not fibrotic in nature. Histopathological examination was not performed.
Figure 8.
Slit lamp findings of a rabbit eye that was refilled by two types of accommodative IOLs with a posterior CCC. Left: The anterior capsule and anterior accommodative IOL. The capsule is well-refilled, and there is no leakage. Right: The posterior capsule and posterior accommodative IOL in a slit. The arrow shows the apparently fibrotic posterior CCC edge in the slit.
Figure 10.
A refilled rabbit capsule with posterior CCC. The iris was removed. The visual axis is clear due to both anterior and posterior CCCs. The peripheral opacification is mainly due to PCO, which is apparently consisted of migrating LECs.
DISCUSSION
When the capsular integrity was preserved, there was insignificant to absence of leakage of the injectable silicone compound in both the pig as well the rabbit eyes. Even in the pig cadaver eyes that were maintained deliberately perpendicularly during polymerization, there was no silicone leakage noted the following day. There was, likewise no silicone leakage in the rabbit eyes, although their eyes are always positioned perpendicularly. This fact suggests that there might be no leakage, should the patient undergoing this procedure stand up immediately after surgery. Leakage can occur, when the accommodative IOL is forcibly pressed posteriorly mimicking the patient who will press or rub his eye vigorously.
When leakage did occur as a consequence of silicone injection, it was a small amount that could be easily aspirated or irrigated. Postoperatively, no leakage was noted in any of the rabbit eyes. Thus, this highly reproducible surgical technique using the accommodative IOL could successfully prevent leakage of the injectable silicone polymers.
From our early experience, silicone leakage could be successfully prevented through an upper mini-CCC (around 1.2 mm),7,8 when it was sealed by a single plate silicone plug slightly larger than the mini-CCC diameter. The principle of sealing of the CCC should be the same, independent of the CCC-size. That the anterior accommodative IOL seals such a large CCC opening preventing silicone leakage is consistent with our previous experience. Because the injected polymer presses the IOL from the inside of the capsular bag against the CCC and anterior capsule, and possibly due to 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 is excessively pushed posteriorly (Fig. 11).
Figure 11.
The principle of preventing leakage of injectable silicone. The injected silicone polymer presses the IOL from the inside of the capsular bag against the CCC and anterior capsule (arrows), and possibly due to 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 is excessively pushed posteriorly.
Similarly the invertedly implanted posterior accommodative IOL also sealed the posterior CCC preventing silicone leakage. The operative principle may be the same as for the anterior CCC. This general principle should be recognized in future development of capsular bag refilling.
The leakage of the injectable IOL was historically the paramount problem preventing clinical application, and therefore, its prevention has been crucial for developing a useful lens refilling procedure. We think the present technique could be a breakthrough in the lens refilling procedure and contribute to its future development.
Capsular opacification occurred 100 % in every refilled lens capsule in rabbits with a few exception in which lens epithelial cells were removed drastically.13 Although YAG laser posterior capsulotomy will not cause any herniation or leakage of the injected silicone,14 posterior capsulotomy may affect accommodation attained.
Attempting to prevent the migration of lens epithelial cells, we implanted a posterior accommodative IOL with sharp edges. In the posterior view, there was a distinct capsular bend at the sharp edge of the IOL in some eyes (Fig. 6, Fig. 7). But in the other eyes, the bend was not distinct and formed only partially throughout the circumference or not at all. In these eyes, a considerable migration of LECs had taken place. The bend formation may depend on the amount of silicone injected, which may, in turn, depend on the postoperative refraction that one wishes to create. Further evaluation will be needed whether this method will be capable to eliminating PCO.
In the eyes that underwent posterior CCC, no PCO was observed in any eye at least within the PCCC area, an expected outcome (Fig. 8– Fig. 10). There was also no leakage of the silicone noted.
Interestingly, anterior capsule opacification in the form of capsular fibrosis could not be seen even 8 weeks after surgery in rabbits (Fig. 10), in the slit lamp examination and apparently under stereo-microscopic observation. This may be due to the feature of the material used in the IOL. The posterior capsule opacification was observed in the form of LEC migration, but there was no fibrosis except apparently fine-fibrotic structure observed at the margin of PCCC (Fig. 8), although we have not performed any histological examination.
An arising question is whether the opacification observed in the periphery as the cell mass of migrating LECs significantly affects the accommodative response. These cell masses can be regarded as lens regenerates thus a rather physiological replacement for silicone, which might be expected not to interfer with the elastic properties of the residual lens capsule. However, the physical properties of these masses including the elastic property may significantly different from those in the physiological condition, possibly affecting the accommodative response. This may be one of the numerous questions in lens refilling to be answered in future studies.
The peripheral posterior capsule opacification may also affect visualization of the peripheral retina through a small PCCC. 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 have been proven to be easy, simple, safe and effective as a routine clinical procedure. In the event that an effective means will have been developed, the posterior accommodative IOL as well as PCCC in our procedure will become not necessary, rendering the procedure even more simple.
Another advantage of the second IOL, besides the prevention of PCO, may be that it could enhance the accommodation-amplitude being attained. The IOL can have a concave optic with minus dioptric power, which may imperatively give a greater power to the anterior accommodative optic, achieving emmetropia. During accommodation, an anterior optic with a greater power when it moves forward may enhance the accommodation-amplitude attained.
Anterior and posterior capsular opacifications in the visual axis and no silicone leakage were observed in this series. Anterior and posterior CCCs, however are a disadvantage in for optimal accommodative range. Change in the anterior capsule curvature including the fully-preserved elasticity of the lens capsule, which may be the main factor for accommodation may not be expected. Therefore, the proposed mechanism of accommodation in this procedure may be a dual-optic shift of the accommodative IOLs and possibly steepening of the anterior curvature of the IOL, when a very soft and primarily a very thin membranous accommodative IOL is used.
These problems and questions can be only answered by primate experiments. Since the present technique effectively solves the previously major setback to injectable IOLs, namely, leakage of the injectable silicone polymers, and is easy to perform and highly reproducible, we will soon perform the primate experiment, and the results will be reported elsewhere.
In conclusion, restoration of accommodation by refilling the lens capsule is a goal of refractive cataract surgery. Technical feasibility has been repeatedly demonstrated by obtaining some useful accommodation in primates. Leakage of the injectable materials and capsular opacification has hindered the development of the procedure in the past. The technique shown here may provide a future breakthrough for possible clinical application to the refilling of the lens capsule.
Figure 9.
Posterior view of an enucleated rabbit lens refilled with two accommodative IOLs with posterior CCC. Six weeks after surgery. L: The visual axis is PCO free due to both CCC, as the letters can be clearly seen. R: The arrows show the posterior CCC edge.
Table 1.
Results in the rabbits eyes refilled with 2 accommodating IOLs and enucleated.
| Rabbit | Postop Period (Wk) | Filling | Capsular Bend | PCO Degree* | PCO Within PCCC |
|---|---|---|---|---|---|
| R1 | |||||
| Without PCCC | 8 | Well refilled, no leakage | Circumferential | − | NA |
| With PCCC | Poorly refilled, no leakage | + | − | ||
| R2 | |||||
| Without PCCC | 6 | Well refilled, no leakage | Circumferential | − | NA |
| With PCCC | Well refilled, no leakage | + | − | ||
| R3 | |||||
| Without PCCC | 5 | Well refilled, no leakage | Partial | + | NA |
| With PCCC | Well refilled, no leakage | + | − | ||
| R4 | |||||
| Without PCCC | 7 | Well refilled, no leakage | Partial | + | NA |
| With PCCC | Well refilled, no leakage | + | − | ||
| R5 | |||||
| Without PCCC | 7 | Well refilled, no leakage | No bend | + + | NA |
| With PCCC | Well refilled, no leakage | + + | − |
NA = not applicable;
PCCC = posterior continuous curvilinear capsulorhexis;
PCO = posterior capsule opacification
− = no PCO;
+ = slight PCO;
+ + = moderate PCO;
+ + + = severe.
Biography
Footnotes
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Proprietary Interest: The authors have no proprietary interest in either the methods or products described in this paper.
Presented at the ASCRS, Charles Kelman Innovator’s Lecture in San Diego, California, USA April 2007.
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