Posterior capsule opacification (PCO) is the most common long-term complication of cataract surgery, resulting in visual impairment and necessitating additional procedures.1,2 The material opacifying the posterior capsule may have cortex/pearl and fibrotic components,1,2 whereas anterior capsule opacification (ACO) is essentially a fibrotic entity.3,4 Prevention of overall capsular bag opacification has become a primary goal of intraocular lens (IOL) design and development, especially in specialized IOLs such as multifocal or accommodating models.5 Prevention of any form of fibrosis in the capsular bag is particularly important for accommodating IOLs, which are generally designed to move within the bag or have the optical shape altered in response to accommodating stimuli.5–14
Studies of IOLs that maintain an open or expanded capsular bag7–17,A,B describe the relative lack of PCO and ACO in association with those designs. In this study, we evaluated the outcome of capsular bag opacification with a new accommodating IOL that incorporates large haptic elements.
Materials and methods
The relatively large haptic elements of the study IOL (Fluidvision, Powervision, Inc.) keep the anterior and posterior capsules apart. This IOL is composed of a hollow fluid-filled hydrophobic acrylic optic and oversized hollow fluid-filled haptics. The fluid in the optic and haptics is an index-matched silicone oil that flows back and forth between the haptics and optic to change the curvature, and hence the power of the optic (Figure 1). An initial clinical evaluation of an earlier prototype of this IOL performed in a limited number of sighted-eye subjects showed the potential to achieve more than 5.0 diopters of power change.A The control IOL was the U.S. Food and Drug Administration–approved and commercially available single-piece Acrysof SA60AT (Alcon Laboratories, Inc.).
Six New Zealand white male rabbits weighing 3.4 to 3.6 kg were acquired from approved vendors and treated in accordance with the guidelines set forth by the Association for Research in Vision and Ophthalmology and the Animal Welfare Act regulations. They had bilateral phacoemulsification with IOL implantation. The right eye was randomized to receive a study IOL or a control IOL, and the contralateral eye received the other IOL. All surgeries were performed by the same surgeon (N.M.) and recorded on a video system.
Anesthesia, surgical preparation, and bilateral phacoemulsification with IOL implantation were performed as described in previous studies.18,19 In brief, a fornix-based conjunctival flap was fashioned. An initial 3.0 mm limbal incision was made using a 3.0 mm keratome. A capsulorhexis forceps was used to create a well-centered continuous curvilinear capsulotomy (CCC) approximately 5.0 mm in diameter. After hydrodissection, the phacoemulsification handpiece (Infiniti, Alcon Laboratories, Inc.) was inserted into the posterior chamber for removal of the lens nucleus and cortical material. One milliliter of epinephrine 1:1000 and 0.5 mL of heparin (10 000 USP units/mL) was added to each 500 mL of irrigation solution to facilitate pupil dilation and control inflammation. After removal of the lens, sodium hyaluronate 1.6% (Amvisc Plus) was used to inflate the capsular bag. The incision was then extended to 5.2 mm with a blade. The IOLs were implanted in the capsular bag using the corresponding recommended injection system. The wound was closed with 10-0 monofilament nylon suture after removal of ophthalmic viscosurgical device by irrigation/aspiration. Appropriate in-the-bag placement of the IOL, IOL centration, and coverage of the IOL optic by the capsulorhexis were verified at the end of the procedure.
Postoperative topical therapy included combination neomycin, polymyxin B sulfates, and dexamethasone ointment during the first postoperative week and prednisolone acetate drops during the second postoperative week.
The eyes were dilated and evaluated by slitlamp examination for ocular inflammatory response and capsular bag opacification on 1 day postoperatively and then weekly for 6 weeks. Clinical color photographs of each eye at each time point were obtained with a digital camera attached to the slitlamp. A standard scoring method in specific categories was used at each examination, including assessment of corneal edema and the presence of cell and flare in the anterior chamber. Retroillumination images with the pupil fully dilated were obtained for photographic documentation of capsular bag opacification.
After the final clinical examination at 6 weeks, the animals were anesthetized and then humanely killed with a 1 mL intravenous injection of pentobarbital sodium–phenytoin sodium. Their globes were enucleated and placed in 10% neutral buffered formalin for at least 24 hours. The globes were then bisected coronally just anterior to the equator. Gross examination with photographs from the posterior aspect (Miyake-Apple view) was performed to assess capsular bag opacification and IOL fixation. The extent and severity of ACO and PCO were scored according to previously described methods.18,19 Basically, the intensity of ACO was scored from grades 0 to 4; this analysis was performed in the areas of capsulorhexis coverage of the IOL optic. The intensity of central PCO (behind the central 3.0 mm of the IOL optic), peripheral PCO (behind the periphery of the IOL optic), and Soemmerring ring formation (outside the IOL optic area) was also scored from grades 0 to 4, according to previous studies. The area of Soemmerring ring formation was graded from 0 to 4 (according to the number of quadrants involved).
After gross examination, all globes were sectioned and the anterior segments, including the capsular bags, were processed for standard light microscopy and stained with hematoxylin–eosin (H&E).
All surgical procedures were uneventful. In 3 rabbits, the study IOL was implanted in the right eye and the control IOL was implanted in the left eye. In the other 3 rabbits, the study IOL was implanted in the left eye and the control IOL was implanted in the right eye. In general, the leading haptic and the optic of the study IOL were injected directly into the capsular bag, while the trailing haptic was rotated inside the bag with a collar button hook. The control IOLs were injected directly into the capsular bag. In all eyes (study and control), 100% coverage of the IOL optic periphery by the CCC was observed at the end of the surgical procedure.
Slitlamp examination 1 day postoperatively showed a mild degree of conjunctival injection, corneal edema (generally limited to the incision site), aqueous flare, aqueous cells, and iris hyperemia in all eyes in both IOL groups. The eyes showed a mild amount of fibrin and blood in the anterior chamber; both resolved by the 2-week examination. At the 3-week examination, trace to mild PCO was observed in all eyes; this finding remained stationary in the study group but progressively increased in the control group, especially at the level of the optic–haptic junctions. At the 6-week examination, the mean PCO score was 0.5 ± 0.3 (SD) in the study group and 3.0 ± 0.9 in the control group (P=.001, 2-tail paired t test). Proliferative material in the study group was generally limited to the gap spaces between the haptics. Anterior capsule opacification was practically absent in the study group and mild in the control group (Figure 2). Starting at the 4-week examination, mild degrees of giant cell formation were observed in both IOL groups. Mild degrees of posterior synechiae were also observed in both groups, generally associated with Soemmerring ring protruding anteriorly.
Additional findings included posterior capsule striae in the control group starting at the 1-day examination and progressively decreasing thereafter. The distal part of 1 haptic of a study IOL was anterior to the optic periphery, and the IOL appeared to be slightly tilted. Review of the surgical video showed that this haptic was anterior to the optic periphery at the end of the surgery.
Gross examination under the Miyake-Apple posterior view of the anterior segment confirmed the slitlamp findings (Table 1 and Figure 3). The mean central PCO score was 0 ± 0 in the study group and 3.0 ± 1.1 in the control group (P=.001, 2-tail paired t test). The mean peripheral PCO score was 0.7 ± 0.4 in the study group and 3.5 ± 0.8 in the control group (P=.0006, 2-tail paired t test). The mean Soemmerring ring intensity × area score was 2.3 ± 0.8 in the study group and as 7.0 ± 2.8 in the control group (P=.01, 2-tail paired t test).
Two control IOLs were slightly decentered. Glistenings were also observed within the optic of some control IOLs under gross examination. Examination of multiple histopathologic sections from each eye showed that the anterior segments of the globes had no signs of untoward inflammation or toxicity in the study eyes or the control eyes. The study eyes showed proliferation of lens cortical material limited to the fornix, particularly in the area of the gaps between the IOL haptics. The posterior capsule usually remained clear in the study eyes (Figure 4). In addition, the anterior capsule was relatively clear. Virtually all eyes with control IOLs showed proliferation of cortical material in the fornix forming a Soemmerring ring with extensive extension of cortex along the posterior capsule as well as some areas of cortex extending anterior to the IOL optic and mild fibrosis of the anterior capsule.
Cellular proliferation within the capsular bag after implantation of an accommodating IOL could potentially impair its function. Postoperative fibrosis with contraction of the capsular bag could also be detrimental. Therefore, we assessed postoperative capsular bag opacification and fibrosis with the Fluidvision accommodating IOL in an animal model. Rabbit eyes show exacerbated inflammatory reactions and proliferative lens epithelial cell (LEC) capacity, which make these eyes a useful model to evaluate new IOLs in a relatively short period.20
It has been hypothesized that IOL designs that maintain an open or expanded capsular bag are associated with bag clarity.7–17,B This may be due to mechanisms that include mechanical compression of the capsular bag by a relatively bulky device or IOL with overall inhibition of residual LEC metaplasia and migration and proliferation. Another factor may be mechanical stretch of the bag at the level of the equatorial region, which maintains the overall bag contour. Constant irrigation of the inner capsular bag compartment by the aqueous humor may also have an influence on the prevention of proliferation of residual LECs.21–23,B Prevention of capsular bag collapse has been described with various devices and IOLs, such as the capsular bending ring of Menapace et al.,24 Hara et al.’s25 and Hashizoe et al.’s26 equator ring, Nagamoto et al.’s27 acrylic capsular adhesion prevention ring, a poly(methyl methacrylate)–polyvinylidene fluoride dual-optic accommodating IOL with spring action also designed by Hara et al.,7,8 the Concept 360 IOL (Corneal),17 and the Synchrony IOL (Abbott Medical Optics).9–14 We have also evaluated in rabbit studies15,16 2 versions of a modified disk-shaped single-piece hydrophilic acrylic IOL suspended between 2 complete haptic rings connected by a pillar of the haptic material. By maintaining an open capsular bag and enhancing endocapsular inflow of aqueous, this disk-shaped IOL was associated with remarkable capsular bag clarity compared with commercially available standard single-piece acrylic IOLs.15,16
Figures 3 and 4 show that the Fluidvision IOL practically fills the entire capsular bag, with significant bag expansion. It is unlikely in this configuration that constant irrigation of the inner compartment of the capsular bag by aqueous humor occurs and plays any role in preventing LEC proliferation. Other factors, such as mechanical compression and/or stretching of the capsular bag, are probably responsible for the significant prevention of capsular bag opacification compared with that in the control eyes. Mild amounts of proliferative material limited to the fornix of the capsular bag were seen in some instances in eyes with the Fluidvision IOL. The presence of the haptics generally blocked extension of the proliferative material toward the optic, with the exception of the haptic gap sites. In those 2 areas, there was a lack of mechanical compression of the inner surface of the capsular bag; the shape/contour of the bag was also not maintained. However, the optic edge blocked access of the material to the posterior capsule.
Previous studies3,4 describe that ACO and fibrosis tend to occur in areas where the anterior capsule comes in contact with the IOL optic. This was particularly observed with silicone IOLs and accounts for large amounts of ACO developing with plate silicone IOLs.3,4 The anterior capsule remained clear with the Fluidvision IOL throughout the study. The only contact between the study IOL and the anterior capsule was at the periphery of the capsular bag, at the level of the haptic components. Fine wrinkling of the anterior capsule was observed in some instances at that area (eg, Figure 2, D). The anterior capsule at and around the capsulorhexis edge was generally devoid of any fibrosis because it was kept at a distance from the anterior IOL surface. Intraocular lenses such as the Concept 360,17 the Synchrony,9–14 and the disk-shaped IOL evaluated in our laboratory (Zephyr, Anew Optics)15,16 also have design features that prevent significant contact between the anterior capsule inner surface and the anterior IOL surface. A relative lack of ACO was described in association with those IOL designs in animal and clinical studies.B,C
In conclusion, the clarity of the capsular bag with the silicone oil-filled IOL 6 weeks postoperatively was remarkable in the rabbit model, both clinically and pathologically. This is in marked contrast to the control IOLs, which showed a large amount of proliferative material with significant PCO, generally starting at the optic–haptic junctions. The study IOL we describe here is another example of an IOL design maintaining an expanded capsular bag. Further research on the proposed mechanisms of capsular bag opacification prevention by such IOLs or devices is warranted.
What Was Known
- A shrink-wrap effect of the IOL by the capsular bag is a significant factor that can enhance prevention of PCO.
What This Paper Adds
- A new silicone oil–filled accommodating IOL incorporating large haptic elements appears to prevent capsular bag opacification by keeping the anterior capsule at a distance from the anterior optic surface and maintaining an expanded capsular bag.
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Other Cited Material
A. Roux P, Nichamin LD, “Early Implantation Results of Shape-Changing Accommodating IOL in Sighted Eyes,” presented at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, April 2010
B. Werner, 2010B. Werner L, “IOL Designs Maintaining an Open or Expanded Capsular Bag,” presented at the XXVIII Congress of the European Society of Cataract & Refractive Surgeons, Paris, France, September 2010
C. McGrath D, “New IOL Tackles Anterior-Capsule-Related Complications,” EuroTimes, September 2003, page 12. Available at: http://www.escrs.org/eurotimes/September2003/5.asp
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