New Endoscopic Technique to Analyze Various Modern Specialized Intraocular Lenses in Research Eyes and Human Eyes Obtained Postmortem

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New Endoscopic Technique to Analyze Various Modern Specialized Intraocular Lenses in Research Eyes and Human Eyes Obtained Postmortem Guy Kleinmann, MD, David J. Apple, MD, Jesse Chew, MD, Nick Mamalis, MD Purpose: To describe a new modification of the Miyake–Apple posterior video photographic technique and its 2 variations. We have developed a new endoscopic technique that is especially amenable for observation of modern specialized intraocular lenses (IOLs). Design: Laboratory study. Participant: Three cadaver eyes obtained postmortem. Methods: Human eyes obtained postmortem were prepared according to our modified preparation technique used for analyses of whole globes. An intraocular endoscope was utilized to demonstrate all aspects of the interior of an experimentally implanted IOL, with specialized reference to anterior segment structures, obtaining posterior, oblique, and side view images. Main Outcome Measures: Different interior dynamic views of the anterior segment structures before and after implantation of an IOL. Results: High-magnification images of different intraocular structures both before and after device insertion as well as the device itself were obtained. Oblique and side view images from different locations were also available and informative. These images helped to create a 3-dimensional view of these objects and their relations to the surrounding structures. Conclusion: The combination of the intraocular endoscope with the closed-system technique is a useful addition to our 3 previously described techniques: (1) the original Miyake–Apple posterior video/photograph technique and the (2) closed system and (3) side/oblique view (keyhole technique) modifications. Ophthalmology 2006;113:591–597 © 2006 by the American Academy of Ophthalmology.

The analysis of eyes obtained postmortem, both human clinical cases and experimental animal eyes, has been the cornerstone of our intraocular lens (IOL)/biodevices research since its beginning in 1982. Irrefutable information regarding the good and bad of surgical techniques and IOL designs, as well as hints regarding the pathologies of complications, can be discerned by such techniques, and appropriate analysis can thus be made. Because of a plethora of Originally received: March 22, 2005. Accepted: October 31, 2005. Manuscript no. 2005-297. From the David J. Apple, MD, Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah. The authors have no financial or proprietary interest in any product mentioned in the article. Dr Kleinmann is the recipient of a fellowship from The American Physicians Fellowship for Medicine in Israel, Boston, Massachusetts. Correspondence and reprint requests to Guy Kleinmann, MD, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, 50 North Medical Drive, Salt Lake City, UT 84132. E-mail: [email protected]. © 2006 by the American Academy of Ophthalmology Published by Elsevier Inc.

new, specialized IOLs and devices, for purposes ranging from accommodative to telescopic lenses for age-related macular degeneration correction, it will be useful if the techniques can be enhanced. Three major techniques used today for research on different surgical techniques and IOLs using experimental animal or human eyes obtained postmortem include: 1. The Miyake–Apple posterior video/photographic technique, which is the most commonly used and most popular. In this technique, the eyes are bisected through the equator and glued to a glass slide. Posterior images can be obtained by placing an extra microscope (placed upside down) that is connected to a camera recorder below the eye. Procedures are usually done with an open sky preparation. It is the easiest one to do and provides a wide spectrum of information. This technique was first described in a single eye in 1985 by Miyake and Miyake1 and was modified and popularized in 1990 by Apple et al2 (Fig 1); Davis et al3 have reported a means to simplify this procedure. ISSN 0161-6420/06/$–see front matter doi:10.1016/j.ophtha.2005.10.058

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Figure 1. The standard Miyake–Apple posterior video photographic technique. A, One-piece all–polymethyl methacrylate intraocular lens (IOL) (Advanced Medical Optics, Santa Ana, CA) implanted experimentally into a human eye obtained postmortem. B, Hydrophilic acrylic IOL (Rayner Intraocular Lenses Ltd.) implanted experimentally into a rabbit eye. C, Silicone IOL (Advanced Medical Optics) implanted clinically into a human eye and obtained after the death of the patient. D, Hydrophobic acrylic IOL (the 1-piece AcrySof lens [Alcon Laboratories, Fort Worth, TX]) implanted clinically into a human eye and obtained after the death of the patient. Figure 2. The side/oblique view (keyhole) technique. A, Three-piece intraocular lens (IOL). B, One-piece IOL.

2. The second technique is the closed-system procedure, developed by Auffarth et al4 in our laboratory in 1996. In this technique, the cornea of a human eye obtained postmortem is dehydrated using a hyperos-

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molar dextran solution, which clarifies the cornea for several hours. This technique can be used on autopsy eyes up to 4 days postmortem without other fixation. This technique is excellent not only for research, but

Kleinmann et al 䡠 Endoscopic Technique to Analyze Specialized IOLs also for teaching young ophthalmologists in training. Many young surgeons at our institution have had their first experience at entering an eye and doing the cataract IOL operation with this technique. 3. Dr Ehud Assia, Tel-Aviv, Israel, developed in 1992 the third technique in this series—namely, the side view or keyhole technique, also while working in our laboratory.5,6 In this technique, an oblique or side view is achieved by creating an uveoscleral window. This technique provided for the first time an opportunity to study far peripheral structures and to do side view analyses of eyes obtained postmortem (Fig 2). As mentioned, we are now entering a new and exciting era in which various specialized intraocular biodevices and IOLs are being tested (e.g., accommodative IOLs, telescopic IOLs). Implantation of a myriad of IOL/device designs has increased so rapidly in the past decade that tens of thousands are immediately available for manufacturing. To date, there is no good technique for analyzing the function and 3-dimensional anatomical relationship to the surrounding anatomical structures of these in postmortem eyes, either human or experimental animal. In our laboratory, we have come up with a fourth new variation, utilizing a combination of Auffarth’s closedsystem technique with an intraocular endoscope, with which we can observe intraocular structures through a closed eye. This is efficacious for posterior and side view imaging. The addition of this fourth technique to our laboratory armamentarium will be useful in detailed analyses of these new designs. We describe this technique for the first time here.

Materials and Methods Human eyes obtained postmortem were prepared according to the modified preparation technique used for Auffarth’s closed-system technique.4 Briefly, the technique consisted of removing the corneal epithelial cells and placing the globe in a hyperosmolar dextran solution (Swinger–Kornmehl solution, Pfizer Inc., New York, NY) for 12 to 24 hours before the study/operation. The intraocular endoscope (Medtronic Ophthalmics, Jacksonville, FL) was used to visualize the anterior segment from posterior, oblique, and side views. The intraocular endoscope was introduced into the eyes through a 1.1-mm incision made with a microvitreoretinal blade (Alcon Surgical, Fort Worth, TX) next to the optic nerve (posterior view), at the equator (oblique view), and at the pars plana (side view) (Fig 3). In the first stage, the normal anatomy of a human cadaver eye was demonstrated. In a second stage, the crystalline lenses of 2 other cadaver eyes were evacuated with phacoemulsification using a standard stop-and-chop technique, and an IOL (C-flex, Rayner Intraocular Lenses Ltd., Hove, United Kingdom) was implanted into the capsular bag. The intraocular endoscope was used to demonstrate the relationship between the IOL and the surrounding structures from posterior, oblique, and side views. For the normal anatomy, one incision was created for each view (posterior, oblique, and side). For the eye implanted with the IOL, several incisions were made at the equator and pars plana to enable views of the IOL from different angles. A digital video camera recorder was connected to the endoscope and used to record the images.

Figure 3. Schematic illustration of the various insertion locations of the endoscope used to achieve the different views. A, The posterior view was achieved by inserting the endoscope adjacent to the optic nerve. B, The oblique view was achieved by inserting the endoscope through the equator, pointing toward the anterior segment of the eye. C, The side view was achieved by inserting the endoscope through the pars plana/ciliary body.

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Figure 4. Low-power images recorded by the endoscope from the posterior view aspect using the closed-system technique. A, Cataractous crystalline lens and surrounding structures. B, Direct posterior view of a well-centered 1-piece intraocular lens experimentally implanted into the capsular bag. Arrows indicate the optic– haptic junction. Intraocular lens courtesy of Rayner Intraocular Lenses Ltd.

Figure 5. High-magnification images recorded through the endoscope, viewed from the posterior aspect with the closed-system technique. A, Demonstration of an evacuated capsular bag (arrows indicate its equator) and adjacent ciliary processes (CP). B, Demonstration of the haptic (H) of a capsular fixated intraocular lens and the surrounding structures.

Results Images of the different anterior segment intraocular structures were available as shown in Figures 4 to 7 and Videos 1 and 2 (available at http://aaojournal.org). It was possible to obtain an overview of images, including a nonoperated crystalline lens (Fig 4A, Video 1) and the direct posterior aspect of an implanted IOL (Fig 4B, Video 2), as well as high magnification of the desired area of interest like the ciliary process or IOL haptics (Fig 5, Video 2). High-magnification images of oblique and side views from different locations were also available and informative (Figs 6, 7; Video 2).

Discussion

Figure 6. Oblique image recorded through the endoscope with a closedsystem technique showing a 1-piece foldable hydrophilic acrylic lens implanted in-the-bag. CP ⫽ ciliary processes; H ⫽ haptic; O ⫽ optic. Arrow, O–H junction. Intraocular lens courtesy of Rayner Intraocular Lenses Ltd.

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Significant improvements in cataract surgical techniques and IOL technology have been obtained from cadaver eye studies, ranging from basic improvements in lens fixation7 to advances against posterior capsule opacification.8 –10 With the myriad of new IOLs and biodevices now being marketed and tested, responsible postimplantation pathological evaluations are even more important than before. These will be enhanced by the techniques described in this report. In this study, we present the advantages of adding an intraocular endoscope to the closed-system technique. Each

Kleinmann et al 䡠 Endoscopic Technique to Analyze Specialized IOLs

Figure 7. Side view images recorded by the endoscope with a closed-system technique. A, Normal nonoperated crystalline lens equator (arrows) and ciliary processes (CP). B, Ciliary processes and a side view of the peripheral posterior capsular bag. The arrows indicate the equator of the evacuated lens after removal of the crystalline lens. Some peripheral cortical material (C) was left in the capsular bag. C, In-the-bag fixation of an intraocular lens (IOL). We focused on the square edge of the IOL (small arrows). O ⫽ optic. Large arrows, haptic outline margin. D, Ophthalmic viscoelastic device (OVD) between the distal optic (O)– haptic (H) junction of the IOL and the posterior capsule (arrows) can be seen. E, Residual cortical material can be seen peripherally to the implanted IOL (large arrow). Small arrow, O–H junction.

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Ophthalmology Volume 113, Number 4, April 2006 of the 3 techniques that are in use today has specific advantages and disadvantages. The original Miyake–Apple video/ photograph posterior view technique provides an excellent 2-dimensional overview image of the implanted IOL, but it is difficult to achieve high magnification of special structures of interest. Oblique and side view images are not possible, unless the side view technique is being implemented. Applying pressure to these eyes is problematic due to the fear that they will be detached from the glass slide. The closed-system technique is excellent for residency training and postgraduate wet laboratories, but is also a viable tool for research purposes. Basic surgical steps such as incision techniques, capsulorrhexis, phacoemulsification, and IOL implantation, as well as other surgical procedures such as glaucoma surgery, transscleral fixation of posterior chamber lenses, and vitrectomies can be performed. Neodymium:yttrium–aluminum– garnet laser capsulotomies or other laser surgical procedures are also possible. The only major disadvantage of this technique is that it lacks the posterior/side view demonstration. The side view technique provides a clear 3-dimensional view of such structures as the crystalline lens, zonular apparatus, and ciliary body, but this technique reduces the integrity of the eye and is challenging to perform. It provides only one possible view—namely, only in the quadrant where the uveoscleral window was created. Furthermore, it may disrupt the relationships of the zonules to the ciliary body and also affect the integrity of the globe. An intraocular endoscope has been reported for use in diagnosis, treatment, and surgeries of glaucoma,11–14 IOL fixation,15–18 the retina,19 –24 and oculoplastic disorders.25 This is the first application of this technique for use in cadaver eyes. The combination of an intraocular endoscope with the closed system is not suggested to replace the Miyake–Apple video/photograph posterior view technique, but as an adjunct tool. It allows posterior, oblique, and side view imaging in cases were the closed system is needed. This modification enables demonstration of such views of the anterior segment and ensures that the adjacent structures remain intact. The images are dynamic and can be taken from different angles, so 3-dimensional perception of the structures investigated can be achieved easily—an important feature in evaluating several forms of modern specialized IOLs (e.g., the motile accommodative IOLs that are now being researched). The technique is simple, and there is a minimal learning curve. It is also provides the possibility to overcome limited media opacities. The only significant disadvantage of this modification is the high cost of the endoscope. In summary, this modification of the closed-system technique enables different posterior, oblique, and side view imaging of the anterior segment. The importance of this modification is especially significant as we proceed into the 21st century, an era of rapidly developing ocular devices. Some of these are already being investigated with the closed system without the ability to look at these devices from posterior, oblique, and side views. Examination of these specialized devices with the intraocular endoscope has the

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potential to teach us much more about these devices and to facilitate and improve their development. To date, we have examined ⬎7000 IOLs in our Miyake– Apple laboratory database. The number of implantations of standard and experimental specialized IOLs and devices has increased exponentially. The technique described in this report will be useful in confirming these important evaluations. Acknowledgments. The authors acknowledge Medtronic Ophthalmics for providing the intraocular endoscope and Rayner Intraocular Lenses Ltd. for providing the intraocular lenses (C-flex).

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Kleinmann et al 䡠 Endoscopic Technique to Analyze Specialized IOLs 16. Althaus C, Sundmacher R. Endoscopically controlled optimization of trans-scleral suture fixation of posterior chamber lenses in the ciliary sulcus [in German]. Ophthalmologe 1993; 90:317–24. 17. Tsunoda K, Migita M, Nakashizuka T, Kohzuka T. Treatment of anterior vitreous before suturing an intraocular lens to the ciliary sulcus. J Cataract Refract Surg 1996;22:222– 6. 18. Jurgens I, Lillo J, Buil JA, Castilla M. Endoscope-assisted transscleral suture fixation of intraocular lenses. J Cataract Refract Surg 1996;22:879 – 81. 19. Terasaki H, Miyake Y, Awaya S. Fluorescein angiography of peripheral retina and pars plana during vitrectomy for proliferative diabetic retinopathy. Am J Ophthalmol 1997;123: 370 – 6.

20. Hammer ME, Grizzard WS. Endoscopy for evaluation and treatment of the ciliary body in hypotony. Retina 2003;23:30 – 6. 21. Norris JL, Cleasby GW, Nakanishi AS, Martin LJ. Intraocular endoscopic surgery. Am J Ophthalmol 1981;91:603– 6. 22. Norris JL, Cleasby GW. Intraocular foreign body removal by endoscopy. Ann Ophthalmol 1982;14:371–2. 23. Eguchi S, Araie M. A new ophthalmic electronic videoendoscope system for intraocular surgery. Arch Ophthalmol 1990; 108:1778 – 81. 24. Eguchi S, Kohzuka T, Araie M. Stereoscopic ophthalmic microendoscope system. Arch Ophthalmol 1997;115:1336 – 8. 25. Sandler NA, Carrau RL, Ochs MW, Beatty RL. The use of maxillary sinus endoscopy in the diagnosis of orbital floor fractures. J Oral Maxillofac Surg 1999;57:399 – 403.

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