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Posterior capsule opacification prevention by an intraocular lens incorporating a micropatterned membrane on the posterior surface

Ellis, Nathan MD; Werner, Liliana MD, PhD; Balendiran, Vaishnavi MD; Shumway, Caleb MD; Jiang, Bill; Mamalis, Nick MD

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Journal of Cataract & Refractive Surgery: January 2020 - Volume 46 - Issue 1 - p 102-107
doi: 10.1016/j.jcrs.2019.08.003
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Opacification within the capsular bag may involve the anterior or posterior capsules and can have a significant impact on visual function. Posterior capsule opacification (PCO) is the most common long-term complication of cataract surgery, resulting in visual impairment and necessitating additional procedures.1–3 Incorporation of features for the prevention of capsular bag opacification has become one of the goals of intraocular lens (IOL) and endocapsular device development. It has been hypothesized that an open or expanded capsular bag is associated with the longer retention of bag clarity.4 This might be due to mechanisms that include mechanical stretch of the bag, maintaining the overall bag contour and allowing a constant flow of aqueous fluid throughout the device.5 However, opacification prevention may also be enhanced through the modification of the surface of the IOL itself.

Engineered surface topographies, specifically geometries of ordered features designed with unique roughness properties such as the one seen in the Sharklet micropattern (Sharklet Technologies, Inc. and ClearSight LLC), elicit specific predictable biological responses and have been shown to control bioadhesion. Previous studies have shown this sharkskin-inspired microtopography inhibits bioadhesion more effectively than other ordered topographies (eg, pillars, channels, and other geometries).6–8

We have recently evaluated the outcome of capsular bag opacification with a new patterned protective membrane implanted in the bag with the secondary placement of an IOL in the rabbit eye for 4 weeks.9 This endocapsular device was shown to be effective in preventing postoperative capsular bag opacification; however, the study was unable to conclude whether the micropattern had any effect toward the outcome. To our knowledge, this is the first in vivo study evaluating an IOL incorporating the previously reported micropattern on the posterior surface and its ability to prevent postoperative capsular bag opacification in the rabbit model.

METHODS

Twelve New Zealand white rabbits of the same sex and weighing between 2.4 kg and 3.2 kg were acquired from the approved vendors and treated in accordance with the guidelines set forth by the Association for Research in Vision and Ophthalmology. Eight rabbit eyes received the unpatterned ClearSight IOL (Group 1), the Sharklet-patterned ClearSight IOL (Group 2),6–8 or the control, commercially available AcrySof IOL, SA60AT, Alcon Laboratories, Inc.) (Group 3). Figure 1 shows a schematic drawing of the IOL design in Groups 1 and 2. This is a 1-piece monofocal IOL with two haptics, manufactured from a proprietary glistening-free hydrophobic acrylic polymer (nanohybrid polymer). The IOL has a diameter of 13.5 mm haptic-to-haptic. The optic zone has a diameter of 5.5 mm, with a peripheral element referred to as a membrane, extending an additional 0.75 mm beyond the optic zone for a total optic membrane diameter of 7.0 mm and also featuring a lateral wall with a height of 0.59 mm. The IOL has a 7-degree posterior optic–haptic angulation. The IOL in Group 2 featured the new micropatterned design (Sharklet pattern), only on the posterior surface of the membrane, with no extension onto the optic zone and a slight extension to the optic–haptic junctions (Figure 2).

Figure 1
Figure 1:
Schematic drawing showing the 1-piece IOL design in Group 2 with the patterned membrane on the posterior surface. The design of the IOL in Group 1 was the same, without the pattern (IOL = intraocular lens).
Figure 2
Figure 2:
Scanning electron photomicrograph of an intraocular lens in Group 2 showing the details of the Sharklet-patterned membrane.

The placement of each IOL was distributed among the rabbit eyes in 2-by-2 combinations so that 4 animals had each combination. All surgeries were performed by the same surgeon (N.M.). The rabbit model was chosen for its accelerated development of PCO, in which 1 month of implant time is approximately equivalent to 1 to 2 years in humans for PCO development.10–13

Anesthesia, surgical preparation, and bilateral phacoemulsification with IOL implantation were performed as described in previous studies.10–13 Briefly, a fornix-based conjunctival flap was fashioned. A corneoscleral incision was then made using a crescent blade, and the anterior chamber was entered with a 3.0 mm keratome. A capsulorhexis forceps was used to create a well-centered continuous curvilinear capsulorhexis with a diameter of approximately 5.0 mm. After hydrodissection, the phacoemulsification handpiece (Alcon Infiniti System) was inserted into the posterior chamber for the removal of the IOL nucleus and cortical material. One-half milliliter of epinephrine 1:1000 and 0.5 ml of heparin (10 000 USP units/mL) were added to each 500 mL of irrigation solution to facilitate pupil dilation and control inflammation. The residual cortex was then removed with the irrigation/aspiration handpiece. An ophthalmic viscosurgical device (sodium hyaluronate 1.6% [Amvisc Plus]) was used to expand the capsular bag. The IOLs were then injected into the capsular bag using the corresponding recommended injection systems (Accujet 3.0 BL Injector set for IOLs in Groups 1 and 2 and Monarch III system with “C” cartridges for control Group 3). The wound was closed with a 10-0 monofilament nylon suture after the removal of the ophthalmic viscosurgical device using irrigation/aspiration.

Postoperative topical therapy included the combination of neomycin–polymyxin B sulfates–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 at 1, 2, 3, and 4 weeks (±2 days) postoperatively. 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 11 categories was used at each examination, including the assessment of corneal edema and the presence of cells and flare in the anterior chamber according to the previously described methods.10–13 Anterior capsule opacification (ACO) and PCO were also evaluated at each time point and scored from 0 to 4. Retroillumination images with the pupil fully dilated were obtained for photographic documentation.

After the final clinical examination at 4 weeks, the animals were anesthetized and then killed humanely 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 and photographs from the posterior aspect (Miyake-Apple view) were performed to assess the ACO and PCO development as well as IOL fixation. The extent and severity of ACO and PCO were scored according to the methods established at the Intermountain Ocular Research Center. After gross examination and photographs, all globes were sectioned and the anterior segments including the capsular bags processed for standard light microscopy and stained with hematoxylin–eosin.

RESULTS

All surgical procedures were overall uneventful, with the exception of 1 eye in the AcrySof control group, which exhibited a posterior capsule tear leading to decentration of the IOL at the end of the surgical procedure. Data from this eye were not included in capsular bag opacification evaluation.

Slitlamp examination at 1 week postoperatively showed a mild inflammatory reaction composed of aqueous cells in all rabbit eyes. Most eyes in the 3 IOL groups also exhibited mild fibrin formation either at the rhexis edge or in front of the IOL. The above-mentioned findings essentially subsided by the week 2 examination. At this time point, mild amounts of PCO started to be observed in some eyes of all IOL groups. Anterior proliferative pearl formation started to be observed in some eyes of Groups 1 and 2. At the week 3 examination, anterior proliferative pearl formation also started to be observed in the control group, Group 3. This anterior proliferation led to synechia formation in some eyes of all 3 groups, without any statistically significant difference among the groups (P = .77, one-way analysis of variance [ANOVA]).

Posterior capsule opacification was scored as follows at the week 4 examination: 1.93 ± 1.29 in Group 1, 1.07 ± 1.20 in Group 2, and 2.83 ± 0.93 in Group 3 (P = .11; one-way ANOVA) (Figure 3). It is noteworthy that the clinical assessment of PCO is limited to what can be observed behind the IOL optic through the pupil. Anterior capsule opacification was found to be mild in this study, scored as 0 to 1, with the exception of 1 eye in Group 3 , with ACO scored as 2 also showing the contraction of the capsulorhexis opening (phimosis). Overall, there was statistically more ACO in Group 3, in comparison with Groups 1 and 2 (P = .01; one-way ANOVA).

Figure 3
Figure 3:
Slitlamp photographs of eyes from all 3 groups taken 4 weeks postoperatively (A through C: Groups 1 through 3, respectively). The eye with the patterned IOL (B: Group 2) shows significantly less posterior capsule opacification than the unpatterned IOL (A: Group 1) and the control eye (C: Group 3) (IOL = intraocular lens).

Posterior capsule opacification formation was best assessed postmortem through the posterior or Miyake-Apple view. The mean postmortem central PCO was 1.87 ± 1.35 in Group 1, 1.06 ± 1.23 in Group 2, and 3.14 ± 0.89 in Group 3. When comparing central PCO between Groups 1 and 3, the difference was not statistically significant (Bonferroni-adjusted one-sided P-value = .05329). When comparing central PCO between Groups 2 and 3, the difference was statistically significant (Bonferroni-adjusted one-sided P-value = .00304). The mean postmortem peripheral PCO was 2.18 ± 1.36 in Group 1, 1.5 ± 1.03 in Group 2, and 3.57 ± 0.53 in Group 3. When comparing peripheral PCO between Groups 1 and 3, the difference was not statistically significant (P = .025, t test with Bonferroni correction). When comparing peripheral PCO between Groups 2 and 3, the difference was statistically significant (P = .0003, t test with Bonferroni correction). Soemmerring's ring formation was 5.12 ± 2.64 in Group 1, 5 ± 1.85 in Group 2, and 8.87 ± 3.52 in Group 3. When comparing Soemmerring's ring formation between Groups 1 and 3, the difference was not statistically significant (P = .03, t test with Bonferroni correction). When comparing Soemmerring's ring formation between Groups 2 and 3, the difference was statistically significant (P = .01, t test with Bonferroni correction) (Figure 4).

Figure 4
Figure 4:
Miyake-Apple view of the anterior segment of rabbit eyes from Group 2 (A) and Group 3 (B). The eye with the patterned membrane (A) showed less central and peripheral posterior capsule opacification as well as less Soemmerring's ring formation than the control eye (B).

Histopathological evaluation showed distinct difference in the amount of PCO as well as Soemmerring's ring formation and anterior cortical proliferation, with Elschnig pearl formation noted significantly more in Group 3 when compared with both Groups 1 and 2. There was no sign of untoward inflammation nor toxicity on all 3 groups (Figure 5).

Figure 5
Figure 5:
Light photomicrographs of histopathol-ogical sections cut from eyes in Group 2 (A) and Group 3 (B). A: Eye with the patterned IOL, showing minimal proliferative material along the posterior capsule (arrow). B: Eye with the control IOL, showing considerable Soemmerring's ring formation and posterior capsule opacification originating at the optic–haptic junctions (arrow). A and B: Composite of light photomicrographs; H&E staining; original magnification ×20 (IOL = intraocular lens).

DISCUSSION

Posterior capsule opacification or secondary cataract is a well-recognized complication of cataract surgery that dates to the first IOL.2 Although research has elucidated surgical and IOL-related mechanisms that are effective in its prevention, PCO remains the most common long-term postoperative complication of cataract surgery.1–3

The Sharklet pattern was previously described as a patterned silicone protective membrane implanted in the bag with the secondary placement of an IOL within it.9 The circular geometry of the protective membrane led to the expansion of the capsular bag and appeared to prevent capsular bag opacification according to an in vivo rabbit study performed in our laboratory. The same study, however, was unable to determine whether the pattern on the posterior surface of the protective membrane had a role in enhancing the prevention of PCO by limiting the posterior migration of residual lens epithelial cell (LEC), as some of the membranes were injected in an inverted position within the rabbit eye.

Engineered surface topographies, particularly geometries of ordered features designed with unique roughness properties, elicit specific predictable biological responses and have been shown to control bioadhesion in medical devices such as the endotracheal tube.6–8 The Sharklet micropattern used in this study and a previous rabbit study is one example of such surface topographies. Other studies in other medical specialties have shown this sharkskin-inspired microtopography inhibits bioadhesion more effectively than other ordered topographies (eg, pillars, channels, other geometries).

Cells interact with biomaterial interfaces through focal adhesions—protein assemblies embedded in the cell membrane.14 Micropatterns act to control cell migration by directing the placement of focal adhesions.14 The unique discontinuous features that comprise the Sharklet micropattern allow for focal adhesions to be precisely guided and, therefore, provide a high level of control over the migration orientation for a cell population. It was thus hypothesized that micropatterns could be optimized through altering dimensions of the pattern to the size scale of LECs to inhibit LEC migration. More recently, patterned protective membrane prototypes were tested in an in vitro PCO model for the reduction of cell migration behind an IOL vs unpatterned prototypes and IOLs with no membrane. Cell migration was analyzed with fluorescent microscopy, showing significant LEC migration reduction with patterned membranes.

This is the first study in which the Sharklet pattern has been directly placed on the posterior surface of the IOL, specifically onto a membrane (peripheral optic element) that surrounds the optic zone. Eyes that received the patterned IOL were associated with significantly less postmortem central and peripheral PCO than the control IOLs; however, PCO reduction related to IOLs without the pattern was not statistically significant when compared with the control IOL. This difference was not seen clinically at the week 4 slitlamp examination because of the limitation of the view through the pupil; therefore, PCO was best assessed postmortem through the posterior view of the anterior segment. When comparing postmortem Soemmerring's ring formation between groups, both patterned and unpatterned IOLs showed statistically less ring formation than the control IOL. This is likely due to the fact that the IOL design configuration in Groups 1 and 2 promotes a slight capsular bag expansion. Also, ACO was statistically higher in the control IOL when compared with the patterned and unpatterned IOLs, due to the fact that the lateral wall of IOLs in Groups 1 and 2 limited any contact between the anterior surface of the IOL and the inner surface of the anterior capsule.

The prevention of ACO and PCO and Soemmerring's ring formation with IOLs or devices maintaining the capsular bag open and/or expanded has been demonstrated in other studies by us and other groups. This can be seen in capsular tension ring–type devices, including the E-ring by Hara et al.,15–19 the capsular bending ring by Nishi et al.,20,21 and the capsular adhesion preventing ring by Nagamoto et al.22 The prevention of postoperative capsular opacification has been described in association with different IOLs as well, including the Concept 360 IOL (Corneal Laboratoire),23 the Synchrony IOL (Abbott Medical Optics, Inc.),24–28 the FluidVision IOL (Powervision, Inc.),12,13 and the disk-shaped 1-piece hydrophilic acrylic IOL suspended between two haptic rings connected by a pillar of haptic material (Zephyr, Anew Optics Inc.).11,12 It is noteworthy that PCO is a multifactorial factor, and the IOL optic diameter may play a role in its outcome. In a study with 3-piece AcrySof IOLs, PCO was less with the 6.0 mm optic IOL vs the 5.5 mm IOL.29 However, in another study using 1-piece AcrySof IOLs, PCO was less with the 5.5 mm optic IOL, in comparison with an experimental 7.0 mm optic IOL.30 In the current study, the total optic membrane diameter of the ClearSight IOL was 7.0 mm, whereas the optic diameter of the control IOL was 6.0 mm. Posterior capsule opacification was similar between the unpatterned ClearSight IOL and the control AcrySof SA60AT. It is however difficult to draw conclusions based on the optic size alone, as other design differences exist between the ClearSight IOLs and the AcrySof SA60AT. Our study nonetheless shows that the addition of the micropattern improved PCO prevention. Although not the objective of this report, studies are underway to ensure that the design features of the test IOL are not associated with dysphotopsia, considering the optic zone of 5.5 mm in diameter with the membrane peripheral element and the lateral wall with a height of 0.59 mm.

In conclusion, the implantation of an IOL with a Sharklet pattern incorporated on its posterior surface, on a membrane surrounding the optic, resulted in less PCO compared with a commercially available control IOL, whereas the implantation of an IOL with the same membrane design but without a micropattern did not. This is the first in vivo study, to our knowledge, demonstrating that the Sharklet pattern likely has a role in enhancing PCO prevention through the limitation of the posterior migration of residual LECs.

WHAT WAS KNOWN

  • A Sharklet micropattern used in medical devices allows for focal cell adhesions to be guided or inhibited, providing control over the migration orientation for a cell population.

WHAT THIS PAPER ADDS

  • The presence of the Sharklet micropattern on the posterior membrane surface of a new hydrophobic acrylic intraocular lens resulted in significantly less postoperative capsular bag opacification in comparison with control eyes in the rabbit model.

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