Age-related cataract accounts for half the blindness worldwide. Over 25 million people are blind from cataract (<20/400); 110 million are severely visually impaired (<20/200).1 Most cataract patients seen today, especially in the industrialized world, have soft to semisoft nuclei. In developing countries, mature, hypermature, and brunescent cataracts are commonly seen. The treatment methods include surgical removal of the opaque lens by extracapsular cataract extraction (ECCE) or phacoemulsification (PE).
In the present era of reimbursement changes and cutbacks, as well as dwindling numbers of patients available for resident training, it is sometimes difficult to attain systematic teaching of ECCE and PE procedures. This is important since teaching surgeons now represents a high priority, especially in the developing world. To reduce the learning curve and enhance the margin of safety before operating on patients, it is useful to practice ECCE and nuclear emulsification techniques in a “wet laboratory” setting. The available models consist of animal eyes (pig, rabbit)2–4 and the use of “synthetic cataracts”5 and “pseudonuclei.”6 However, with these models, it is sometimes difficult to reproduce the conditions in human eyes. The best model is, of course, the use of human eyes obtained postmortem with cataracts closely resembling the types seen clinically.
At the Center for Research on Ocular Therapeutics and Biodevices, postmortem human phakic eyes are commonly used for practicing ECCE/PE procedures with the Miyake–Apple posterior video/photographic technique7–9 (or 1 of its modifications10–12). Most of the eyes are noncataractous or precataractous, often with soft to semisoft nuclei. They are usually not suitable for ECCE and some 2-handed PE procedures. Since most patients in the United States have cataract surgery at relatively early stages, it is difficult to obtain postmortem human phakic eyes with advanced nuclear sclerosis.
We have developed a technique to create cataracts of varying degrees of hardness by injecting a mixture of paraformaldehyde and glutaraldehyde (Karnovsky's solution13) into the lens nucleus of nonfixated human cadaver eyes. Using this procedure in association with the Miyake–Apple posterior video/photographic technique is effective for practicing various ECCE and PE maneuvers.
Materials and Methods
Postmortem human eyes (N = 20) obtained within 4 days of death from eye banks nationwide were used. The eyes were forwarded to our laboratory in moist gauze wraps without formalin fixation. Karnovsky's solution13 was prepared by mixing 8 g of paraformaldehyde with 50 mL of distilled water in a 125 mL Erlenmeyer flask. The mixture was heated at 60°C on a stir plate to dissociate the paraformaldehyde to formaldehyde. Once moisture formed on the sides of the flask, 1 M sodium hydroxide (2 to 4 drops) were added and stirred until the solution cleared. After the solution cooled and was filtered, 40 mL of 25% glutaraldehyde and 40 mL of 0.2 M cacodylate buffer were added. The pH of Karnovsky's solution should be 7.2 to 7.4. Pre-mixed Karnovsky's solution can also be purchased (e.g., Electron Microscopy Sciences).
All eyes used for the induction of hard nuclear cataracts had soft (grade 1, Emery–Little classification14) nuclei. They were prepared according to the Miyake–Apple posterior video/photographic technique.7,8 After the cornea and iris were removed, a 5.0 to 5.5 mm continuous curvilinear capsulorhexis (CCC) was performed with a 26 gauge needle cystotome. Complete cortical cleaving hydrodissection was performed by injecting balanced salt solution (BSS®) between the lens capsule and cortex with a 27 gauge cannula. This was followed by hydrodelineation. Placing a 27 gauge cannula deep in the nucleus and injecting BSS created the surge of a small fluid wave, marking the separation of the nucleus and epinucleus. With a tuberculin syringe, 0.2 cc of Karnovsky's solution was carefully injected within the crystalline lens nucleus. The needle tip was shaken side to side at the center of the nucleus to create space to inject the solution. To determine the optimal time for the creation of nuclear cataracts of grade 2 to 5 hardness (Emery–Little classification14), ECCE or PE maneuvers were performed 5, 10, 15, 20, 25, and 30 minutes after the injection (2 globes at each time). Phacoemulsification was initially attempted in all globes, but when maximum ultrasonic energy was unable to emulsify the harder nuclei, they were delivered using manual ECCE techniques.
Extracapsular cataract extraction was performed using hydroexpression and viscoexpression maneuvers for nucleus expression.15,16 The epinucleus and cortex were aspirated manually. Phacoemulsification was performed with 2-handed maneuvers (Alcon Legacy 20,000). Nuclear fragmentation techniques included Gimbel's divide and conquer,17 Nagahara's nonstop chop (K. Nagahara, MD, “Phaco-Chop,” film presented at the 3rd American–International Congress on Cataract, IOL and Refractive Surgery, Seattle, Washington, USA, May 1993), Shepherd's 4-quadrant in situ fracture,18 Koch's stop and chop,19 and Vasavada's chop in situ.20 The epinucleus and cortex were removed with the irrigation/aspiration tip. In both ECCE and PE, the procedure was completed by filling the capsular bag with a viscoelastic substance and implanting a posterior chamber intraocular lens (IOL).
In 8 eyes, an ab externo injection was made in addition to the direct intralenticular injection. In these eyes, 0.2 mL of Karnovsky's solution was injected into the nucleus at the equator of the crystalline lens using a 26 gauge needle attached to a tuberculin syringe. The injection was made 2.0 mm posterior to the limbus, with the needle tip directed horizontally (parallel to the plane of the surgical table) and toward the center. We used the Miyake–Apple posterior video/photographic technique to guide the needle track, but the technique allows the practice of ECCE and PE maneuvers in unopened eyes in closed-system ocular surgery.12 Two-handed PE maneuvers were also performed 15 minutes after the injection.
Hard nuclear cataracts were successfully induced in all globes. The degree of nuclear hardness varied with the time since the injection (Figure 1). Uniform semisoft nuclei (grade 2) were created after 5 to 10 minutes and medium-hard nuclei (grade 3) after 15 minutes (Figure 1, B). Hard nuclei (grade 4) were obtained after 20 to 25 minutes (Figure 1, C). It was very difficult to perform 2-handed maneuvers with these nuclei. Rock-hard nuclei (grade 5) were obtained after 30 minutes (Figure 1, D). Grades 4 and 5 eyes were used for practicing manual ECCE (hydroexpression/viscoexpression) (Figure 2) and grade 3 eyes for practicing 2-handed PE maneuvers such as divide and conquer nucleofractis and chopping (Figure 3).
Injecting Karnovsky's solution within the crystalline lens after CCC and hydrodissection/delineation had the advantage of sparing the fixation of the CCC margin and the superficial cortex; thus, these steps could be performed in conditions similar to those of “real” surgery. By waiting more than 15 minutes after the injection, slight fixation of the capsular bag and superficial cortex was achieved. It prevented complete cleaning of the capsular bag, as some cortical fibers remained firmly attached (Figure 4).
The suitable injection dose of Karnovsky's solution was 0.2 mL. When higher doses were injected, the solution leaked from the capsular bag through the CCC opening, over the anterior capsule, leading to capsule–cortical fixation.
Ab externo injection of Karnovsky's solution through the limbus within the lens equator (for closed-system ocular surgery) led to slight fixation of the entire capsular bag after 15 minutes, making CCC difficult (Figure 5). Tear formation from the capsular injection site was also observed during manipulations within the capsular bag.
The Miyake–Apple posterior video/photographic technique (or 1 of its modifications) has been used to evaluate new surgical techniques, IOL designs, as well as to carry out research and educational activities.7–12,21,22 This technique has also been established as a means of assessing aspects of surgical techniques, such as trauma to zonules, the capsular bag, and other structures, during ECCE and PE as well as IOL implantation itself. Karnovsky's solution, a mixture of paraformaldehyde and glutaraldehyde commonly used for electron microscopy, is routinely used in our laboratory to prepare postmortem human eyes for the Miyake–Apple posterior video/photographic technique. It is used to fixate the sclera to facilitate sectioning the eye at the equator. Formaldehyde penetrates rapidly but does not preserve the tissue well; glutaraldehyde fixes well but does not penetrate very fast. Karnovsky's solution combines the fixation and penetration properties of these 2 fixatives, with a buffer for their diluent.23 Thus, we could obtain uniform, reproducible, hardened lens nuclei. The mixture of formalin and alcohol proposed by Sugiura et al.3 may represent an alternative to Karnovsky's solution, as the authors demonstrate that this mixture uniformly penetrates and fixates the lens of pig eyes.
Until now, it has been difficult to obtain a cataract model with characteristics similar to those seen in the real surgical situation. Animal eyes (e.g., pigs and rabbits) used for experimental cataract surgery have highly elastic anterior capsules. This renders the CCC difficult for the beginner in comparison with the conditions in human eyes. Furthermore, animal crystalline lenses do not undergo a process of cataractogenesis, hence their soft nuclei are not suitable for practicing ECCE and 2-handed PE maneuvers.3 Recently, there have been reports of hardening the crystalline lens in animal eyes. To induce cataract in postmortem pig eyes, van Vreeswijk and Pameyer2 put them in a microwave oven for 9 seconds. They obtained hard nuclei, but the capsule and zonules became weak, rendering the surgery difficult. Sugiura et al.3 injected a mixture of formalin, ethanol, and 2-propanol into the lens (3.0 mm from the limbus) in pig eyes. Besides obtaining harder nuclei, the elasticity of the anterior capsule was closer to that in human eyes. However, tear formation was observed from the injection site during capsule manipulations. Mekada et al.6 used chestnuts of various hardness as “pseudonuclei” of pig eyes, but the preparations for this technique may be complicated and time consuming for inexperienced surgeons.
The use of a synthetic surgical training system including head, bilateral globes, removable corneas, and replaceable synthetic cataracts of varying density has also been described.5 The consistency of the materials, however, is different from that of a human lens, and the cost of these models may be prohibitive.
We performed CCC and hydrodissection/delineation prior to using Karnovsky's solution to fix the crystalline lens (and thus make it harder) in 12 eyes; if one waits more than 15 minutes, the capsular bag is usually fixed by the solution, rendering these steps difficult. In these cases, it is not possible to clean the capsular bag completely without tear formation, as some cortical fibers remain firmly attached. The 0.2 mL dose of Karnovsky's solution for the intralenticular injection was defined after preliminary studies, which demonstrated leakage of the solution from the capsular bag through the CCC opening with higher doses. If leakage occurs, it is better to irrigate the CCC opening to avoid its excessive fixation.
In closed-system surgeries, injecting 0.2 mL of the solution into the nucleus at the lens equator, 2.0 mm posterior to the limbus, can be performed similarly to the technique proposed by Sugiura et al.3 This is technically more difficult, and the novice surgeon can damage the lens capsule or zonules. Using the Miyake–Apple posterior video/photographic technique for controlling and guiding the needle track, we practiced ab externo injection of Karnovsky's solution within the lens nucleus in 8 eyes, before applying it in closed-system surgery. The drawback of this technique is the possibility of enlarging the injection site during manipulations of the relatively fixated capsular bag. The consistency of the anterior capsule also changes because of slight fixation, which was useful for practicing CCC in pig eyes,3 but it is not suitable in human eyes. Thus, the injection of fixative solutions is preferably performed in human eyes after CCC and hydrodissection/delineation.
The creation of cataracts with varying degrees of hardness with the technique we describe is excellent for training in both classical ECCE and PE. Extracapsular cataract extraction (with or without IOL implantation) remains an important procedure of cataract surgery in the developing world. It is essential that surgeons learn the basic ECCE technique, especially in the developing world where modern instrumentation may not be available. Even in the industrialized world, some training in ECCE is important to manage PE patients presenting a large posterior capsule tear, for example, in whom conversion to ECCE is the safest option to minimize the risk of nucleus drop in the vitreous cavity.
Use of PE has markedly increased during the past 3 decades, especially in the industrialized world. Many modifications, including the use of CCC, hydrodissection, and hydrodelineation have been added.24–27 It has evolved into a common and effective surgical method that allows implantation of foldable IOLs through a small incision. Therefore, there is substantial interest among surgeons practicing ECCE and residents-in-training to learn PE. In a recent survey,28 the choice of PE for cataract surgery had increased as follows: 12% in 1985, 66% in 1990, 79% in 1992, and 97% in 1998. The transition to PE can be difficult, with a relatively high incidence of intraoperative complications (posterior capsule tear, vitreous loss, dislocation of nucleus in the vitreous cavity) in the early learning period.29–32 To reduce the learning curve (and thus avoid complications), practice in a wet laboratory before performing real surgery is recommended.9,33
In summary, practicing various ECCE and PE techniques using postmortem human or animal eyes in a wet laboratory helps surgeons reduce the learning curve and thus enhance the safety margin in the clinical setting. Most animal eyes (and also randomly accessioned postmortem human eyes) have soft, flexible lens nuclei, which are not suitable for practicing ECCE or 2-handed PE maneuvers. The use of Karnovsky's solution to harden the crystalline lens nucleus for practice of various ECCE or 2-handed PE (cracking/chopping) maneuvers was valuable for residents in training and surgeons in transition.
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