“Pathological Assessment of the First Human Eyes Obtained Postmortem Implanted with the Bag-In-The-Lens Design” Liliana Werner, MD, PhD 1 Marie-José Tassignon, MD, PhD, FEBO 2 Brian Zaugg, MS 1 1 John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA 2 Department of Ophthalmology, Antwerp University Hospital, Belgium -Tassignon is the inventor of the bag-in-the-lens IOL. The other authors have no financial or proprietary interest in any product mentioned in this poster. -Supported in part by the Research to Prevent Blindness Olga Keith Wiess Scholar Award, and a Funding Incentive Seed Grant of the University of Utah Research Foundation (Liliana Werner, MD, PhD), as well as by the Funds for Research in Ophthalmology, Belgium (Marie-José Tassignon, MD, PhD, FEBO). -The Bag-In-The-Lens IOL is not FDA approved.

Background The “bag-in-the-lens” (BIL) concept involves the use of a twin capsulorhexis lens design, and performance of anterior and posterior capsulorhexes of the same size (Figure 1). According to this concept, if both capsules are well stretched around the optic of the lens, any remaining lens epithelial cells (LECs) will be captured within the remaining space of the capsular bag, and their proliferation will be limited to this space, so the visual axis will remain clear. 1-9 The BIL has been patented in Europe and in the United States. It received European CE mark approval in 2004 and it has been implanted in over 2,000 eyes in Europe, India, and South Africa ( ). BIL LECs The aim of this study was to describe, for the first time, clinico- pathological findings of human eyes obtained postmortem implanted with the foldable hydrophilic acrylic BIL design. 10 Fig. 1

Patient #Eye #Age at implantation GenderDate of implantation Date of death Postoperative time Cause of death 11 (OD)86Male5-Jun-0712-Oct-074 monthsLung cancer 22 (OD)59Female13-Apr-065-Jul-0827 monthsBreast cancer 33 (OD)66Female20-May-0512-Jul-0838 monthsOvarian cancer 34 (OS)65Female11-Apr-0512-Jul-0839 monthsOvarian cancer Eye #Antero- posterior length (mm)* Keratometry (D) Anterior chamber depth (mm) Type of cataract Densitometry Preop. BCVA** Subjective refraction Postop. BCVA × nuclear20/ °)20/ × posterior subcapsular cataract20/50-320/ × cortical cataract20/ °)20/ × cortical cataract20/ °)20/20 Patients and Methods: 1 * Measured with IOL Master (Zeiss, Germany). ** BCVA = Best-corrected visual acuity.

Patients and Methods: 2 All lenses were the Morcher (Stuttgart, Germany) type 89A, single- piece, hydrophilic acrylic BIL (28% water content); the surgical procedure was described elsewhere; 1-8 The eyes were enucleated, immersed in 10% neutral buffered formalin, and sent to the John A. Moran Eye Center; They underwent anterior segment scanning with a very-high frequency ultrasound system with digital enhancement (Artemis, Ultralink LLC, St. Petersburg, FL, USA) (Figure 2); After coronal section, gross analyses were done from the posterior or Miyake-Apple view; Photographs were analyzed for BIL centration with the Matlab 6.5 (MathWorks, MA, USA); After histopathological processing, sections were stained with Masson’s trichrome stain. Fig. 2

Results: 1 In each case, ultrasound examination revealed the presence of a well- fixated, well-centered IOL located at the level of the capsular bag (Figure 3). Eye #1 Eye #3 Eye #2 Eye #4 Fig. 3

Results: 2 Gross examination showed fibrosis of the rhexis edges, more prominently in eyes number 2-4 (postoperative time: 27 to 39 months). The overall round shape of the capsular bag was maintained in each case, without any distortion or ovalization. The central area delimitated by the rhexis openings remained perfectly clear in all eyes. Progressively larger amounts of Soemmering’s ring formation were observed from eyes 1 to 4 (Figure 4). Fig. 4 Eye #1 Eye #3 Eye #2 Eye #4

Results: 3 Analyses of the gross photographs with the Matlab 6.5* showed minimal degrees of BIL decentration in relation to the capsular bag and the pupil (Figure 5). Eye #Capsular bag diameter Pupil diameter Average space in the capsular bag periphery Decentration in relation to the capsular bag Decentration in relation to the pupil *All measurements in mm. Fig. 5

Results: 4 Although some degree of artifactual disruption of the relationship between the lens and the capsular bag due to tissue processing and sectioning was observed in each case, histopathological sections passing through the center of the capsular bag showed anterior and posterior capsule openings directed to the groove at the periphery of the lens (Figures 6-8). Anterior capsule Posterior capsule BIL Fig. 6; Eye number 1

Results: 5 Progressively larger amounts of Soemmering’s ring formation, composed of cortical material and pearls were observed in the eyes with longer follow up. However, any regenerative/proliferative material would remain confined to the intercapsular space of the capsular bag remnant outside the optic rim/groove (Figures 7 and 8). Fig. 7; Eye number 2 BIL Anterior capsule Posterior capsule Soemmering’s ring

Results: 6 A tissue composed of LECs and fibrosis was present on the inner surface of the anterior capsule, apparently mediating adhesion between anterior and posterior capsules at the rhexis sites (more clearly observed in eyes number 2-4) (Figure 8). Fig. 8; Eye number 3 BIL Soemmering’s ring Anterior capsule Posterior capsule Site of adhesion between capsules

Discussion / Conclusions The donor eyes analyzed in our study, which represent unique specimens had different postoperative times after BIL implantation. Our results confirm the BIL concept: 1.The special design of the BIL renders its centration and postoperative stability primarily dependent on the position of the 2 capsulorhexes. Decentration of the lens in relation to the center of the capsular bag, and to the center of the pupil was insignificant in the specimens described here, but can be improved by new alignment devices. 2.It appears that a fibrocellular tissue develops during the first postoperative year on the inner surface of the anterior rhexis margin (rhexis fibrosis), which mediates adhesion between anterior and posterior capsules at that site, inside the IOL groove. This probably helps enhancing the postoperative stability of the lens. 3.When anterior and posterior capsules are properly secured in the peripheral groove of the IOL, any proliferative/regenerative material remains confined to the intercapsular space of the capsular bag remnant outside the optic rim. Therefore, the visual axis remains clear.

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