- Email: [email protected]
Use of bipolar diathermy to prevent posterior capsule opacification1
Use of bipolar diathermy to prevent posterior capsule opacification Randolph H. Bretton, PhD, Roger L. Kash, David J. Schanzlin, MD
Purpose: To determine the feasibility of using directed bipolar diathermy to eliminate or reduce the formation of new cortical lens material following phacoemulsification in a rabbit model. Setting: Department of Research & Development, Bausch & Lomb Surgical, and Department of Ophthalmology, St. Louis University, St. Louis, Missouri, USA. Methods: A rabbit model for posterior capsule opacification (PCO) was used. A continuous curvilinear capsulorhexis was performed followed by phacoemulsification to remove cortical lens material. In 2 experimental groups, modified bipolar instruments were used to apply diathermy to residual lens epithelial cells using an intracapsular or extracapsular method of application. Postoperative clinical examinations were at 1, 3, and 7 days and then weekly up to 60 days. Selected animals were followed for a longer period. Capsule integrity was evaluated by measuring the pressure required to rupture the capsule in similarly treated porcine eyes. Results: Diathermy prevented PCO in 4 of 4 eyes in the intracapsular treatment group and 4 of 5 in the extracapsular group. Eyes remained free of new lens cortex for the life of the animal, which was as long as 18 months. New cortical material was detected after 35 days in 1 animal in the extracapsular group. Mean time for the formation of observable cortical material was 29 days ⫾ 5 (SD) in the control animals. Physical measurements did not detect a reduction in capsule integrity with diathermy treatment. The extracapsular treatment method resulted in fewer iris complications. Conclusions: Directed diathermy has the potential to eliminate secondary cataract formation with minimal damage to collateral tissues. J Cataract Refract Surg 2002; 28:866 – 873 © 2002 ASCRS and ESCRS
P
osterior capsule opacification (PCO), also referred to as secondary cataract and after-cataract, is 1 of the few remaining complications of modern cataract surgery. The frequency of PCO ranges from 10% to 50% depending on the surgical technique, intraocular lens (IOL) design, and patient age.1–5 The incidence in pediatric patients exceeds 80% to 90%6,7 and presents the greatest challenge to treatment. The accepted procedure for treating PCO is to open the posterior capsule with a neodymium:YAG (Nd: Accepted for publication October 10, 2001. Reprint requests to Randolph H. Bretton, PhD, 2440 Pro Tour Drive, Belleville, Illinois 62220, USA. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
YAG) laser. Complications of an Nd:YAG capsulotomy include damage to the IOL,8 cystoid macular edema,9 and retinal detachment,10 as well as discomfort and inconvenience to the patient. The procedure is also expensive. The cost has been estimated at $250 million annually.11 The number of cataracts surgeries has been increasing, with an estimated 2.5 million IOLs implanted in the United States in 1999.12 An Nd:YAG capsulotomy may also be incompatible with new IOLs and surgical techniques such as those being developed for accommodative IOLs. It is clear that a therapy to prevent PCO would be preferable to the current laser therapy. Both surgical and chemical preventive therapies for PCO have been inves0886-3350/02/$–see front matter PII S0886-3350(01)01256-1
LABORATORY SCIENCE: BIPOLAR DIATHERMY FOR PCO PREVENTION
tigated.13 Surgical methods are the most cost effective. A primary goal of surgical prevention has been to remove all viable lens epithelial cells (LECs) at the time of the initial surgery. In this study, we looked at diathermy instruments and procedures that may be used to destroy remaining LECs. These methods will reduce or eliminate the occurrence of PCO and are not dependent on patient age or IOL design.
Materials and Methods Experimental Instruments The initial diathermy instrument, referred to as the multidirectional instrument, is an 18-gauge coaxial bipolar pencil modified by exposing approximately 3.0 mm of additional electrode area on 2 opposing surfaces at the instrument tip. Polishing is done to remove sharp edges. The instrument emits energy in almost all directions away from the tip and is operated from positions within the lens capsule. This is referred to as the intracapsular method (Figure 1,A). A 20-gauge coaxial bipolar pencil was modified by exposing approximately 4.0 mm of additional electrode area on 1 surface only at the instrument tip. The instrument emits energy predominately in 1 direction perpendicular to the shaft and is referred to as the unidirectional instrument. It is operated from positions between the iris and the anterior capsule so energy is directed into the capsule and away from the iris. This is referred to as the extracapsular method (Figure 1,B). The Storz Premiere was used as a power source for both instruments. A typical power setting was 20%. The duration of each application was limited to 1 second using proprietary software.
Surgical Procedures The rabbits used in this study were cared for and treated in accordance with the ARVO Statement for Use of Animals in Ophthalmic and Vision Research. They were anesthetized and lens extraction was performed using a continuous curvilinear capsulorhexis (CCC) followed by a small-incision phacoemulsification technique and irrigation/aspiration to remove remaining cortical material. After the lens was removed, the capsular bag and anterior chamber were filled with hydroxypropyl methylcellulose (HPMC) 2% (Ocucoat威). Animals then received no treatment (controls, n ⫽ 4), treatment from within the capsule by means of the multidirectional instrument (intracapsular treatment group, n ⫽ 4), or treatment from the anterior chamber using the unidirectional instrument (extracapsular treatment group, n ⫽ 6). The experimental instruments were inserted through a 3.0 mm opening that was enlarged from the original stab incision and also from a second incision opposite the original. It was necessary to use 2 incisions to achieve access to all areas
Figure 1. (Bretton) A: In the intracapsular treatment method, a multidirectional diathermy instrument, produced by modifying a bipolar pencil to emit energy in almost all directions from the tip, is operated from positions within the lens capsule. B: In the extracapsular treatment method, a unidirectional diathermy instrument, produced by modifying a bipolar pencil to emit energy in 1 direction primarily, is operated from positions between the iris and anterior lens capsule so energy is directed away from the iris and through the anterior lens capsule membrane.
of the lens capsule and ensure complete treatment. The experimental instrument was held in contact with the lens capsule and energized via a footswitch. The instrument was then moved to an adjacent area where treatment was again applied. This process was repeated in an overlapping pattern until all areas were treated, typically requiring 12 to 16 applications. Treatment was concentrated in the periphery of the lens capsule. The incision was then opened to 6.0 mm, and a poly(methyl methacrylate) IOL was placed in the lens capsule. The wounds were closed, and injectable antibiotic and steroid agents were administered subconjunctivally.
Clinical Observations Clinical observations were conducted by slitlamp examination for conjunctival congestion, corneal clarity, hyperemia and entrapment (fibrin) of the iris, anterior chamber flare, and lens cortical regrowth. These clinical assessments were performed preoperatively and repeated at 3, 7, 14, 21, 28, 35, 42, 49, and 56 days. The animals were then examined twice monthly. Animals were killed once cortical regrowth had opacified the optical zone.
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Capsule Integrity Destructive testing. Lens extraction as described was performed in 14 porcine eyes obtained from a local slaughterhouse within hours of the animal’s death. The lens capsules of 7 eyes were treated using the unidirectional diathermy instrument and the extracapsular method except that the power was increased to 60%. This ⫻3 increase in power was used to demonstrate a worst-case or overtreatment scenario. The mechanical integrity of the capsules was determined by increasing pressure in the vitreous chamber and measuring the pressure at the time of rupture. The cornea and iris were removed. A 25-gauge needle was inserted through the optic nerve and secured with a suture. An intravenous (IV) line supplied pressure from a reservoir of a balanced salt solution, which was elevated 6.0 m above the eye. When the IV line was unclamped, pressure in the vitreous chamber increased until the lens capsule ruptured. The pressure was monitored with a corneal pneumotonometer held against the lens capsule throughout the procedure. During the initial method optimization, experimental pressure in the vitreous chamber was determined by raising or lowering the reservoir until a distinct and reproducible endpoint was observed. Because of the large number of eyes required to make this initial determination, it was necessary to use readily available porcine eyes.
Results Clinical Observations Clinical and slitlamp examinations revealed between-group differences in inflammatory responses such as hyperemia and entrapment of the iris, anterior chamber flare, and lens cortical regrowth. Since new lens cortex was found in only 1 treated eye, the postoperative times at which new lens cortex was first observed is reported rather than the severity of the PCO. Examination photographs are shown at 1 month in all groups and at 2 and 15 months in control and treatment groups, respectively. Control. Control animals exhibited postoperative inflammation in the form of iris hyperemia and anterior chamber flare, which peaked on day 3 and resolved in 7 to 14 days. With the appearance of new lens cortex, most animals exhibited recurrent inflammation as well as iris entrapment due to fibrin (Figure 2,A). Cortical regrowth was observed in 100% of control eyes. The mean postoperative time of the first observation of new lens cortex via a clinical slitlamp examination was 29 days ⫾ 5 (SD) (n ⫽ 4) (Figure 2,B, example 28 days). Hyperemia and entrapment wors868
ened as cortical regrowth increased (Figure 2,C). By 60 days, new lens cortical growth had clearly progressed to the extent that it opacified the optical zone (Figure 2,D). Multidirectional intracapsular diathermy treatment. All animals treated with the multidirectional instrument and intracapsular method exhibited elevated levels of postoperative anterior chamber flare and iris hyperemia, which peaked on day 3 and resolved in 21 to 28 days. Some damage to the iris was noted in the form of localized points of ischemia and possible dehydration. Increased levels of fibrin were attached to the iris (Figure 3,A). Cortical regrowth was prevented in 4 of 4 eyes treated. An absence of new cortical material was apparent at 1 month (Figure 3,B). Ischemia and iris entrapment were noted as early as 14 days and persisted over the life of the animal (Figure 3,C). Iris entrapment by fibrin was likely a continuing source of irritation and may have been responsible for continuing low levels of anterior chamber flare. All animals in this group remained free of new lens cortex throughout their lives (Figure 3,D). These animals were killed after approximately 18 months. Unidirectional extracapsular diathermy treatment. To reduce iris damage and anterior segment inflammation, treatment was applied through the anterior capsule membrane using an instrument and method that directed energy away from the iris. The treated animals exhibited slightly more inflammation than seen in the controls but less than seen in the intracapsular treatment group. Hyperemia and anterior chamber flare peaked on day 3 and took 7 to 21 days to resolve. The most significant difference was the absence of ischemic areas on the iris and reduced levels of fibrin (Figure 4,A). Cortical growth was detected 35 days after surgery in 1 of the 6 eyes treated. One animal was lost to follow-up after 29 days because of unrelated health problems. The eye was free of new lens cortex during that time but is not included in further analysis. Cortical regrowth was prevented in 4 of 5 treated eyes evident at 1 month (Figure 4,B). The iris remained free from entrapment throughout the 15-month observation period (Figure 4,C). Eyes were free of new lens cortex at the time of death. One animal died after 243 days from unrelated causes. Three eyes remained clear at the time the rabbits were killed 15 months later (Figure 4,D).
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Figure 2. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification without diathermy treatment. A: Clinical examination shows iritis and iris entrapment in a control eye at 1 month. B: Slitlamp retroillumination of A shows new lens cortical material on the IOL. C: Iritis and iris entrapment has increased at 2 months concurrent with extensive growth of cortical lens material. D: Slitlamp retroillumination of C shows that cortical epithelial growth has become substantial.
Capsule Integrity Destructive testing. The hydraulic pressure required to rupture the lens capsule or zonular fibers was measured to determine whether extracapsular diathermy treatment reduced the strength of these structures. There was no significant difference in capsule strength between nontreated and treated porcine eyes as indicated by the pressure at which the capsules ruptured (Figure 5). In both groups, rupture occurred in a similar manner, centrally, on the posterior capsule.
Discussion Rapid and aggressive cortical regrowth makes the rabbit eye a challenging model for the prevention of PCO. In nontreated rabbit eyes, we consistently see evidence of cortical regrowth by 4 weeks, which proceeds to obstruct the optical path by 8 weeks. Further progres-
sion will eventually displace the IOL. For this reason, control animals were killed after 60 days. In all the intracapsular eyes and 80% of the extracapsular eyes, PCO was essentially prevented for the life of the animal. Prevention was absolute in that no new cortical material could be detected at the time the animals were killed. We attribute the cortical regrowth detected in 1 extracapsular eye at 35 days to incomplete treatment of the capsule. This was evident from the videorecording of the surgical procedure made through the operating microscope. The major difference between treatment groups was fewer iris complications in the extracapsular group. The multidirectional instrument and intracapsular method was our original approach and used a diathermy instrument that emitted energy in all directions from the tip to deliver it directly to the residual cortex and epithelial cells from within the lens capsule. This procedure was
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Figure 3. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification and intracapsular multidirectional diathermy treatment. A: Clinical examination shows a scalloped pupil at 1 month because of iris entrapment by fibrin. B: Slitlamp retroillumination of A shows no cortical material around the IOL. C: Fibrin entrapment of the iris persists at 15 months. D: Slitlamp retroillumination of C shows no cortical material.
effective; however, sufficient energy passed through the lens capsule to damage the iris. Since the lens capsule appeared to be unchanged by this treatment, we believed that energy could be delivered from the anterior surface through the anterior capsule to the target cells. Using this application route, energy might be directed away from the iris. When this extracapsular procedure was performed using a diathermy instrument designed to direct energy in 1 direction only, PCO was effectively prevented and iris complications were reduced almost to the levels in nontreated eyes. Since the unidirectional instrument does not enter the capsule, this procedure is compatible with future accommodative lens materials that might be injected into the lens capsule through a small capsulorhexis. The accommodative mechanism and lens capsule can be left intact. A disadvantage of this approach is that care must be taken not to insert the instrument into the ciliary 870
body during treatment. Although the results suggest that the unidirectional instrument and extracapsular method are superior, it may be possible to develop a diathermy instrument that operates using the intracapsular method by precisely controlling the direction of energy from the tip. Regardless of the application route, the iris must be protected. Destructive testing of the lens capsule was performed to determine whether damage was caused by the diathermy treatment. By pressurizing the vitreous chamber, we were able to measure the physical strength of the lens capsule as well as other structural elements including the zonules. The requirement of a large number of eyes made it necessary to use porcine eyes for destructive testing. Porcine lens capsules are slightly thicker than rabbit capsules. However, based on previous observations of diathermy in the rabbit eye, we are confident that the porcine capsules received adequate treatment or
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Figure 4. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification and extracapsular unidirectional diathermy treatment. A: Clinical examination shows an almost normal iris at 1 month. B: Slitlamp retroillumination of A shows no cortical material near the IOL. C: The iris remains free of entrapment by fibrin at 15 months. D: Slitlamp retroillumination of C shows no cortical material.
overtreatment as intended by the increased power setting. We found no significant difference between nontreated porcine and diathermy-treated porcine lens capsules. The capsules ruptured in the same manner, at approximately the same pressure, and in the center region of the posterior capsule. It has long been known that diathermy will destroy living cells. The significant finding in this study is that bipolar diathermy can be applied to the lens capsule without destructive consequences. The lens capsule is a highly permeable hydrated structure, which may present minimal resistance to electric current. The lens cortex, in contrast, is a nonpermeable dense tissue that would probably provide resistance to electric current and absorb energy. This procedure was performed with a viscoelastic agent, HPMC 2%, in a balanced salt solution. A solution of HPMC will increase in viscosity with an increase in temperature. This may have provided added
protection by preventing intimate contact between the tip and the lens capsule. Under different conditions, diathermy has been used to cut the lens capsule and perform the anterior capsulotomy.14,15 Morgan and coauthors16 report a reduction in strength when the capsulotomy is produced by diathermy, as opposed to a CCC. Delcoigne and Hennekes17 report no significant difference between a diathermy capsulotomy and the CCC method. In our study, only a CCC was used. Diathermy was applied later solely to eliminate residual LECs. The capsulorhexis did not appear to be affected by diathermy in the intracapsular or extracapsular group. No damage became evident during destructive testing. Diathermy instruments used for cutting have been sharp-tipped instruments designed to focus the flow of current to a single point on the tissue. In contrast, modifications to our instruments were done to increase the electrode area
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Figure 5. (Bretton) Destructive testing of control and diathermytreated lens capsules. The structural integrity of nontreated and extracapsular-diathermy-treated porcine lens capsules was measured by determining the hydraulic pressure required to rupture the capsule. There was no significant difference in the ability of the lens capsule to withstand pressure after diathermy treatment. Bars ⫽ 1 standard deviation; n ⫽ 7.
and disperse the flow of current. The use of diathermy to prevent PCO may result in an increase in temperature in the anterior chamber. However, this increase should be transitory as viscoelastic material is replaced with a balanced salt solution as the procedure is completed. No corneal opacities or indications of endothelial damage were seen in treated eyes. Antimetabolites, cytotoxins, cell release agents, and physical barriers have been used to prevent PCO. Many of these approaches show promise but have not made it into clinical use. This is the subject of several reviews.18 –20 Truncated IOLs also reduce the incidence of PCO by creating a sharp bend at the juncture of the lens capsule and the IOL.21,22 However, these lenses have been associated with undesirable optical effects such as negative dysphotopsia and glare.23–25 It is estimated that through efforts in surgical technique and the use of truncated IOLs, PCO may be reduced to less than 10%.1 A major effort in surgical prevention is directed at removing all viable epithelial cells from the lens capsule. An in vitro study suggests that almost all LECs may have to be removed to prevent PCO.26 This is a difficult task, especially important in younger patients who have the 872
highest rates of PCO. Since diathermy may make it possible to physically destroy and effectively eliminate all viable LECs, efficacy should not differ among age groups. This procedure is also not dependent on IOL design. Application of the procedure described in this study requires 2 entries into the eye and takes about 3 minutes to perform. An instrument in development will require only 1 incision and will reduce procedure time to less than 1 minute. A previous study reported the use of a targeted cytotoxin, polylysine-saporin, for the prevention of PCO.13 The work reported here was concurrent with that study as part of a 2-pronged approach to the problem of PCO. The advantages of using a pharmaceutical in solution or absorbed to an IOL are ease of application for the surgeon primarily. The advantages of a surgical approach are greatly reduced costs and in this specific example, a high likelihood of achieving prevention. Whether a method of PCO prevention is adopted into mainstream use will likely depend on these factors.
References 1. Apple DJ, Ram J, Foster A, Peng Q. Posterior capsule opacification. (secondary cataract). Surv Ophthalmol 2000; 45(suppl 1):S100 –S130 2. Hollick EJ, Spalton DJ, Ursell PG, et al. The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery. Ophthalmology 1999; 106: 49 –54; discussion by RC Drews, 54 –55 3. Schaumberg DA, Dana MR, Christen WG, Glynn RJ. A systematic overview of the incidence of posterior capsule opacification. Ophthalmology 1998; 105:1213–1221 4. Sundelin K, Sjo¨ strand J. Posterior capsule opacification 5 years after extracapsular cataract extraction. J Cataract Refract Surg 1999; 25:246 –250 5. Ninn-Pedersen K, Bauer B. Cataract patients in a defined Swedish population 1986 –1990; VI: YAG laser capsulotomies in relation to preoperative and surgical conditions. Acta Ophthalmol Scand 1997; 75:551–557 6. Malukiewicz-Wisniewska G, Kaluzny J, Lesiewska-Junk H, Eliks I. Intraocular lens implantation in children and youth. J Pediatr Ophthalmol Strabismus 1999; 36:129 – 133 7. Eckstein M, Vijayalakshmi P, Killedar M, et al. Use of intraocular lenses in children with traumatic cataract in south India. Br J Ophthalmol 1998; 82:911–915 8. Chehade M, Elder MJ. Intraocular lens materials and styles: a review. Aust NZ J Ophthalmol 1997; 25:255– 263
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9. Steinert RF, Puliafito CA, Kumar SR, et al. Cystoid macular edema, retinal detachment, and glaucoma after Nd: YAG laser posterior capsulotomy. Am J Ophthalmol 1991; 112:373–380 10. Ninn-Pedersen K, Bauer B. Cataract patients in a defined Swedish population, 1986 to 1990; V: postoperative retinal detachments. Arch Ophthalmol 1996; 114:382–386 11. Steinberg EP, Javitt JC, Sharkey PD, et al. The content and cost of cataract surgery. Arch Ophthalmol 1993; 111:1041–1049 12. Apple DJ, Peng Q, Visessook N, et al. Surgical prevention of posterior capsule opacification. Part 1: progress in eliminating this complication of cataract surgery. J Cataract Refract Surg 2000; 26:180 –187 13. Bretton RH, Swearingen A, Kash RL, Cooley R. Use of a polylysine-saporin conjugate to prevent posterior capsule opacification. J Cataract Refract Surg 1999; 25:921–929 14. Sugimoto Y, Kubo E, Tsuzuki S, et al. Histology of anterior capsule edges produced by CCC and DC. Jpn J Ophthalmol 1997; 41:77– 80 15. Findl O, Amon M. Anterior capsulotomy created by radiofrequency endodiathermy and continuous curvilinear posterior capsulorhexis in a patient with intumescent cataract and primary capsular fibrosis. J Cataract Refract Surg 1998; 24:870 – 871 16. Morgan JE, Ellingham RB, Young RD, Trmal GJ. The mechanical properties of the human lens capsule following capsulorhexis or radiofrequency diathermy capsulotomy. Arch Ophthalmol 1996; 114:1110 –1115 17. Delcoigne CD, Hennekes R. Circular continuous anterior capsulotomy with high frequency diathermy. Bull Soc Belge Ophtalmol 1993; 249:67–72 18. Nishi O. Posterior capsule opacification. Part 1: experimental investigations. J Cataract Refract Surg 1999; 25: 106 –117 19. Tetz MR, Nimsgern C. Posterior capsule opacification.
20. 21.
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Part 2: clinical findings. J Cataract Refract Surg 1999; 25:1662–1674 Spalton DJ. Posterior capsular opacification after cataract surgery. Eye 1999; 13:489 – 492 Ursell PG, Spalton DJ, Pande MV, et al. Relationship between intraocular lens biomaterials and posterior capsule opacification. J Cataract Refract Surg 1998; 24:352– 360 Nishi O, Nishi K, Wickstro¨ m K. Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 2000; 26:1543– 1549 Holladay JT, Lang A, Portney V. Analysis of edge glare phenomena in intraocular lens edge designs. J Cataract Refract Surg 1999; 25:748 –752 Tester R, Pace NL, Samore M, Olson RJ. Dysphotopsia in phakic and pseudophakic patients: incidence and relation to intraocular lens type. J Cataract Refract Surg 2000; 26:810 – 816 Davison JA. Positive and negative dysphotopsia in patients with acrylic intraocular lenses. J Cataract Refract Surg 2000; 26:1346 –1355 Davidson MG, Morgan DK, McGahan MC. Effect of surgical technique on in vitro posterior capsule opacification. J Cataract Refract Surg 2000; 26:1550 –1554
From Bausch & Lomb Surgical (Bretton) and Anheuser-Bush Eye Institute, St. Louis University (Kash, Schanzlin), St. Louis, Missouri, USA. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Ft. Lauderdale, Florida, USA, May 1996. Supported in part by a research grant from Bausch & Lomb Surgical to the Department of Ophthalmology, St. Louis University. Dr. Bretton is an employee of Bausch & Lomb. Neither of the other authors has a financial interest in any product mentioned. Mary Kay Harmon assisted with the animals.
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Purpose: To determine the feasibility of using directed bipolar diathermy to eliminate or reduce the formation of new cortical lens material following phacoemulsification in a rabbit model. Setting: Department of Research & Development, Bausch & Lomb Surgical, and Department of Ophthalmology, St. Louis University, St. Louis, Missouri, USA. Methods: A rabbit model for posterior capsule opacification (PCO) was used. A continuous curvilinear capsulorhexis was performed followed by phacoemulsification to remove cortical lens material. In 2 experimental groups, modified bipolar instruments were used to apply diathermy to residual lens epithelial cells using an intracapsular or extracapsular method of application. Postoperative clinical examinations were at 1, 3, and 7 days and then weekly up to 60 days. Selected animals were followed for a longer period. Capsule integrity was evaluated by measuring the pressure required to rupture the capsule in similarly treated porcine eyes. Results: Diathermy prevented PCO in 4 of 4 eyes in the intracapsular treatment group and 4 of 5 in the extracapsular group. Eyes remained free of new lens cortex for the life of the animal, which was as long as 18 months. New cortical material was detected after 35 days in 1 animal in the extracapsular group. Mean time for the formation of observable cortical material was 29 days ⫾ 5 (SD) in the control animals. Physical measurements did not detect a reduction in capsule integrity with diathermy treatment. The extracapsular treatment method resulted in fewer iris complications. Conclusions: Directed diathermy has the potential to eliminate secondary cataract formation with minimal damage to collateral tissues. J Cataract Refract Surg 2002; 28:866 – 873 © 2002 ASCRS and ESCRS
P
osterior capsule opacification (PCO), also referred to as secondary cataract and after-cataract, is 1 of the few remaining complications of modern cataract surgery. The frequency of PCO ranges from 10% to 50% depending on the surgical technique, intraocular lens (IOL) design, and patient age.1–5 The incidence in pediatric patients exceeds 80% to 90%6,7 and presents the greatest challenge to treatment. The accepted procedure for treating PCO is to open the posterior capsule with a neodymium:YAG (Nd: Accepted for publication October 10, 2001. Reprint requests to Randolph H. Bretton, PhD, 2440 Pro Tour Drive, Belleville, Illinois 62220, USA. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
YAG) laser. Complications of an Nd:YAG capsulotomy include damage to the IOL,8 cystoid macular edema,9 and retinal detachment,10 as well as discomfort and inconvenience to the patient. The procedure is also expensive. The cost has been estimated at $250 million annually.11 The number of cataracts surgeries has been increasing, with an estimated 2.5 million IOLs implanted in the United States in 1999.12 An Nd:YAG capsulotomy may also be incompatible with new IOLs and surgical techniques such as those being developed for accommodative IOLs. It is clear that a therapy to prevent PCO would be preferable to the current laser therapy. Both surgical and chemical preventive therapies for PCO have been inves0886-3350/02/$–see front matter PII S0886-3350(01)01256-1
LABORATORY SCIENCE: BIPOLAR DIATHERMY FOR PCO PREVENTION
tigated.13 Surgical methods are the most cost effective. A primary goal of surgical prevention has been to remove all viable lens epithelial cells (LECs) at the time of the initial surgery. In this study, we looked at diathermy instruments and procedures that may be used to destroy remaining LECs. These methods will reduce or eliminate the occurrence of PCO and are not dependent on patient age or IOL design.
Materials and Methods Experimental Instruments The initial diathermy instrument, referred to as the multidirectional instrument, is an 18-gauge coaxial bipolar pencil modified by exposing approximately 3.0 mm of additional electrode area on 2 opposing surfaces at the instrument tip. Polishing is done to remove sharp edges. The instrument emits energy in almost all directions away from the tip and is operated from positions within the lens capsule. This is referred to as the intracapsular method (Figure 1,A). A 20-gauge coaxial bipolar pencil was modified by exposing approximately 4.0 mm of additional electrode area on 1 surface only at the instrument tip. The instrument emits energy predominately in 1 direction perpendicular to the shaft and is referred to as the unidirectional instrument. It is operated from positions between the iris and the anterior capsule so energy is directed into the capsule and away from the iris. This is referred to as the extracapsular method (Figure 1,B). The Storz Premiere was used as a power source for both instruments. A typical power setting was 20%. The duration of each application was limited to 1 second using proprietary software.
Surgical Procedures The rabbits used in this study were cared for and treated in accordance with the ARVO Statement for Use of Animals in Ophthalmic and Vision Research. They were anesthetized and lens extraction was performed using a continuous curvilinear capsulorhexis (CCC) followed by a small-incision phacoemulsification technique and irrigation/aspiration to remove remaining cortical material. After the lens was removed, the capsular bag and anterior chamber were filled with hydroxypropyl methylcellulose (HPMC) 2% (Ocucoat威). Animals then received no treatment (controls, n ⫽ 4), treatment from within the capsule by means of the multidirectional instrument (intracapsular treatment group, n ⫽ 4), or treatment from the anterior chamber using the unidirectional instrument (extracapsular treatment group, n ⫽ 6). The experimental instruments were inserted through a 3.0 mm opening that was enlarged from the original stab incision and also from a second incision opposite the original. It was necessary to use 2 incisions to achieve access to all areas
Figure 1. (Bretton) A: In the intracapsular treatment method, a multidirectional diathermy instrument, produced by modifying a bipolar pencil to emit energy in almost all directions from the tip, is operated from positions within the lens capsule. B: In the extracapsular treatment method, a unidirectional diathermy instrument, produced by modifying a bipolar pencil to emit energy in 1 direction primarily, is operated from positions between the iris and anterior lens capsule so energy is directed away from the iris and through the anterior lens capsule membrane.
of the lens capsule and ensure complete treatment. The experimental instrument was held in contact with the lens capsule and energized via a footswitch. The instrument was then moved to an adjacent area where treatment was again applied. This process was repeated in an overlapping pattern until all areas were treated, typically requiring 12 to 16 applications. Treatment was concentrated in the periphery of the lens capsule. The incision was then opened to 6.0 mm, and a poly(methyl methacrylate) IOL was placed in the lens capsule. The wounds were closed, and injectable antibiotic and steroid agents were administered subconjunctivally.
Clinical Observations Clinical observations were conducted by slitlamp examination for conjunctival congestion, corneal clarity, hyperemia and entrapment (fibrin) of the iris, anterior chamber flare, and lens cortical regrowth. These clinical assessments were performed preoperatively and repeated at 3, 7, 14, 21, 28, 35, 42, 49, and 56 days. The animals were then examined twice monthly. Animals were killed once cortical regrowth had opacified the optical zone.
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Capsule Integrity Destructive testing. Lens extraction as described was performed in 14 porcine eyes obtained from a local slaughterhouse within hours of the animal’s death. The lens capsules of 7 eyes were treated using the unidirectional diathermy instrument and the extracapsular method except that the power was increased to 60%. This ⫻3 increase in power was used to demonstrate a worst-case or overtreatment scenario. The mechanical integrity of the capsules was determined by increasing pressure in the vitreous chamber and measuring the pressure at the time of rupture. The cornea and iris were removed. A 25-gauge needle was inserted through the optic nerve and secured with a suture. An intravenous (IV) line supplied pressure from a reservoir of a balanced salt solution, which was elevated 6.0 m above the eye. When the IV line was unclamped, pressure in the vitreous chamber increased until the lens capsule ruptured. The pressure was monitored with a corneal pneumotonometer held against the lens capsule throughout the procedure. During the initial method optimization, experimental pressure in the vitreous chamber was determined by raising or lowering the reservoir until a distinct and reproducible endpoint was observed. Because of the large number of eyes required to make this initial determination, it was necessary to use readily available porcine eyes.
Results Clinical Observations Clinical and slitlamp examinations revealed between-group differences in inflammatory responses such as hyperemia and entrapment of the iris, anterior chamber flare, and lens cortical regrowth. Since new lens cortex was found in only 1 treated eye, the postoperative times at which new lens cortex was first observed is reported rather than the severity of the PCO. Examination photographs are shown at 1 month in all groups and at 2 and 15 months in control and treatment groups, respectively. Control. Control animals exhibited postoperative inflammation in the form of iris hyperemia and anterior chamber flare, which peaked on day 3 and resolved in 7 to 14 days. With the appearance of new lens cortex, most animals exhibited recurrent inflammation as well as iris entrapment due to fibrin (Figure 2,A). Cortical regrowth was observed in 100% of control eyes. The mean postoperative time of the first observation of new lens cortex via a clinical slitlamp examination was 29 days ⫾ 5 (SD) (n ⫽ 4) (Figure 2,B, example 28 days). Hyperemia and entrapment wors868
ened as cortical regrowth increased (Figure 2,C). By 60 days, new lens cortical growth had clearly progressed to the extent that it opacified the optical zone (Figure 2,D). Multidirectional intracapsular diathermy treatment. All animals treated with the multidirectional instrument and intracapsular method exhibited elevated levels of postoperative anterior chamber flare and iris hyperemia, which peaked on day 3 and resolved in 21 to 28 days. Some damage to the iris was noted in the form of localized points of ischemia and possible dehydration. Increased levels of fibrin were attached to the iris (Figure 3,A). Cortical regrowth was prevented in 4 of 4 eyes treated. An absence of new cortical material was apparent at 1 month (Figure 3,B). Ischemia and iris entrapment were noted as early as 14 days and persisted over the life of the animal (Figure 3,C). Iris entrapment by fibrin was likely a continuing source of irritation and may have been responsible for continuing low levels of anterior chamber flare. All animals in this group remained free of new lens cortex throughout their lives (Figure 3,D). These animals were killed after approximately 18 months. Unidirectional extracapsular diathermy treatment. To reduce iris damage and anterior segment inflammation, treatment was applied through the anterior capsule membrane using an instrument and method that directed energy away from the iris. The treated animals exhibited slightly more inflammation than seen in the controls but less than seen in the intracapsular treatment group. Hyperemia and anterior chamber flare peaked on day 3 and took 7 to 21 days to resolve. The most significant difference was the absence of ischemic areas on the iris and reduced levels of fibrin (Figure 4,A). Cortical growth was detected 35 days after surgery in 1 of the 6 eyes treated. One animal was lost to follow-up after 29 days because of unrelated health problems. The eye was free of new lens cortex during that time but is not included in further analysis. Cortical regrowth was prevented in 4 of 5 treated eyes evident at 1 month (Figure 4,B). The iris remained free from entrapment throughout the 15-month observation period (Figure 4,C). Eyes were free of new lens cortex at the time of death. One animal died after 243 days from unrelated causes. Three eyes remained clear at the time the rabbits were killed 15 months later (Figure 4,D).
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Figure 2. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification without diathermy treatment. A: Clinical examination shows iritis and iris entrapment in a control eye at 1 month. B: Slitlamp retroillumination of A shows new lens cortical material on the IOL. C: Iritis and iris entrapment has increased at 2 months concurrent with extensive growth of cortical lens material. D: Slitlamp retroillumination of C shows that cortical epithelial growth has become substantial.
Capsule Integrity Destructive testing. The hydraulic pressure required to rupture the lens capsule or zonular fibers was measured to determine whether extracapsular diathermy treatment reduced the strength of these structures. There was no significant difference in capsule strength between nontreated and treated porcine eyes as indicated by the pressure at which the capsules ruptured (Figure 5). In both groups, rupture occurred in a similar manner, centrally, on the posterior capsule.
Discussion Rapid and aggressive cortical regrowth makes the rabbit eye a challenging model for the prevention of PCO. In nontreated rabbit eyes, we consistently see evidence of cortical regrowth by 4 weeks, which proceeds to obstruct the optical path by 8 weeks. Further progres-
sion will eventually displace the IOL. For this reason, control animals were killed after 60 days. In all the intracapsular eyes and 80% of the extracapsular eyes, PCO was essentially prevented for the life of the animal. Prevention was absolute in that no new cortical material could be detected at the time the animals were killed. We attribute the cortical regrowth detected in 1 extracapsular eye at 35 days to incomplete treatment of the capsule. This was evident from the videorecording of the surgical procedure made through the operating microscope. The major difference between treatment groups was fewer iris complications in the extracapsular group. The multidirectional instrument and intracapsular method was our original approach and used a diathermy instrument that emitted energy in all directions from the tip to deliver it directly to the residual cortex and epithelial cells from within the lens capsule. This procedure was
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Figure 3. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification and intracapsular multidirectional diathermy treatment. A: Clinical examination shows a scalloped pupil at 1 month because of iris entrapment by fibrin. B: Slitlamp retroillumination of A shows no cortical material around the IOL. C: Fibrin entrapment of the iris persists at 15 months. D: Slitlamp retroillumination of C shows no cortical material.
effective; however, sufficient energy passed through the lens capsule to damage the iris. Since the lens capsule appeared to be unchanged by this treatment, we believed that energy could be delivered from the anterior surface through the anterior capsule to the target cells. Using this application route, energy might be directed away from the iris. When this extracapsular procedure was performed using a diathermy instrument designed to direct energy in 1 direction only, PCO was effectively prevented and iris complications were reduced almost to the levels in nontreated eyes. Since the unidirectional instrument does not enter the capsule, this procedure is compatible with future accommodative lens materials that might be injected into the lens capsule through a small capsulorhexis. The accommodative mechanism and lens capsule can be left intact. A disadvantage of this approach is that care must be taken not to insert the instrument into the ciliary 870
body during treatment. Although the results suggest that the unidirectional instrument and extracapsular method are superior, it may be possible to develop a diathermy instrument that operates using the intracapsular method by precisely controlling the direction of energy from the tip. Regardless of the application route, the iris must be protected. Destructive testing of the lens capsule was performed to determine whether damage was caused by the diathermy treatment. By pressurizing the vitreous chamber, we were able to measure the physical strength of the lens capsule as well as other structural elements including the zonules. The requirement of a large number of eyes made it necessary to use porcine eyes for destructive testing. Porcine lens capsules are slightly thicker than rabbit capsules. However, based on previous observations of diathermy in the rabbit eye, we are confident that the porcine capsules received adequate treatment or
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Figure 4. (Bretton) Continuous curvilinear capsulotomy followed by phacoemulsification and extracapsular unidirectional diathermy treatment. A: Clinical examination shows an almost normal iris at 1 month. B: Slitlamp retroillumination of A shows no cortical material near the IOL. C: The iris remains free of entrapment by fibrin at 15 months. D: Slitlamp retroillumination of C shows no cortical material.
overtreatment as intended by the increased power setting. We found no significant difference between nontreated porcine and diathermy-treated porcine lens capsules. The capsules ruptured in the same manner, at approximately the same pressure, and in the center region of the posterior capsule. It has long been known that diathermy will destroy living cells. The significant finding in this study is that bipolar diathermy can be applied to the lens capsule without destructive consequences. The lens capsule is a highly permeable hydrated structure, which may present minimal resistance to electric current. The lens cortex, in contrast, is a nonpermeable dense tissue that would probably provide resistance to electric current and absorb energy. This procedure was performed with a viscoelastic agent, HPMC 2%, in a balanced salt solution. A solution of HPMC will increase in viscosity with an increase in temperature. This may have provided added
protection by preventing intimate contact between the tip and the lens capsule. Under different conditions, diathermy has been used to cut the lens capsule and perform the anterior capsulotomy.14,15 Morgan and coauthors16 report a reduction in strength when the capsulotomy is produced by diathermy, as opposed to a CCC. Delcoigne and Hennekes17 report no significant difference between a diathermy capsulotomy and the CCC method. In our study, only a CCC was used. Diathermy was applied later solely to eliminate residual LECs. The capsulorhexis did not appear to be affected by diathermy in the intracapsular or extracapsular group. No damage became evident during destructive testing. Diathermy instruments used for cutting have been sharp-tipped instruments designed to focus the flow of current to a single point on the tissue. In contrast, modifications to our instruments were done to increase the electrode area
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Figure 5. (Bretton) Destructive testing of control and diathermytreated lens capsules. The structural integrity of nontreated and extracapsular-diathermy-treated porcine lens capsules was measured by determining the hydraulic pressure required to rupture the capsule. There was no significant difference in the ability of the lens capsule to withstand pressure after diathermy treatment. Bars ⫽ 1 standard deviation; n ⫽ 7.
and disperse the flow of current. The use of diathermy to prevent PCO may result in an increase in temperature in the anterior chamber. However, this increase should be transitory as viscoelastic material is replaced with a balanced salt solution as the procedure is completed. No corneal opacities or indications of endothelial damage were seen in treated eyes. Antimetabolites, cytotoxins, cell release agents, and physical barriers have been used to prevent PCO. Many of these approaches show promise but have not made it into clinical use. This is the subject of several reviews.18 –20 Truncated IOLs also reduce the incidence of PCO by creating a sharp bend at the juncture of the lens capsule and the IOL.21,22 However, these lenses have been associated with undesirable optical effects such as negative dysphotopsia and glare.23–25 It is estimated that through efforts in surgical technique and the use of truncated IOLs, PCO may be reduced to less than 10%.1 A major effort in surgical prevention is directed at removing all viable epithelial cells from the lens capsule. An in vitro study suggests that almost all LECs may have to be removed to prevent PCO.26 This is a difficult task, especially important in younger patients who have the 872
highest rates of PCO. Since diathermy may make it possible to physically destroy and effectively eliminate all viable LECs, efficacy should not differ among age groups. This procedure is also not dependent on IOL design. Application of the procedure described in this study requires 2 entries into the eye and takes about 3 minutes to perform. An instrument in development will require only 1 incision and will reduce procedure time to less than 1 minute. A previous study reported the use of a targeted cytotoxin, polylysine-saporin, for the prevention of PCO.13 The work reported here was concurrent with that study as part of a 2-pronged approach to the problem of PCO. The advantages of using a pharmaceutical in solution or absorbed to an IOL are ease of application for the surgeon primarily. The advantages of a surgical approach are greatly reduced costs and in this specific example, a high likelihood of achieving prevention. Whether a method of PCO prevention is adopted into mainstream use will likely depend on these factors.
References 1. Apple DJ, Ram J, Foster A, Peng Q. Posterior capsule opacification. (secondary cataract). Surv Ophthalmol 2000; 45(suppl 1):S100 –S130 2. Hollick EJ, Spalton DJ, Ursell PG, et al. The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery. Ophthalmology 1999; 106: 49 –54; discussion by RC Drews, 54 –55 3. Schaumberg DA, Dana MR, Christen WG, Glynn RJ. A systematic overview of the incidence of posterior capsule opacification. Ophthalmology 1998; 105:1213–1221 4. Sundelin K, Sjo¨ strand J. Posterior capsule opacification 5 years after extracapsular cataract extraction. J Cataract Refract Surg 1999; 25:246 –250 5. Ninn-Pedersen K, Bauer B. Cataract patients in a defined Swedish population 1986 –1990; VI: YAG laser capsulotomies in relation to preoperative and surgical conditions. Acta Ophthalmol Scand 1997; 75:551–557 6. Malukiewicz-Wisniewska G, Kaluzny J, Lesiewska-Junk H, Eliks I. Intraocular lens implantation in children and youth. J Pediatr Ophthalmol Strabismus 1999; 36:129 – 133 7. Eckstein M, Vijayalakshmi P, Killedar M, et al. Use of intraocular lenses in children with traumatic cataract in south India. Br J Ophthalmol 1998; 82:911–915 8. Chehade M, Elder MJ. Intraocular lens materials and styles: a review. Aust NZ J Ophthalmol 1997; 25:255– 263
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9. Steinert RF, Puliafito CA, Kumar SR, et al. Cystoid macular edema, retinal detachment, and glaucoma after Nd: YAG laser posterior capsulotomy. Am J Ophthalmol 1991; 112:373–380 10. Ninn-Pedersen K, Bauer B. Cataract patients in a defined Swedish population, 1986 to 1990; V: postoperative retinal detachments. Arch Ophthalmol 1996; 114:382–386 11. Steinberg EP, Javitt JC, Sharkey PD, et al. The content and cost of cataract surgery. Arch Ophthalmol 1993; 111:1041–1049 12. Apple DJ, Peng Q, Visessook N, et al. Surgical prevention of posterior capsule opacification. Part 1: progress in eliminating this complication of cataract surgery. J Cataract Refract Surg 2000; 26:180 –187 13. Bretton RH, Swearingen A, Kash RL, Cooley R. Use of a polylysine-saporin conjugate to prevent posterior capsule opacification. J Cataract Refract Surg 1999; 25:921–929 14. Sugimoto Y, Kubo E, Tsuzuki S, et al. Histology of anterior capsule edges produced by CCC and DC. Jpn J Ophthalmol 1997; 41:77– 80 15. Findl O, Amon M. Anterior capsulotomy created by radiofrequency endodiathermy and continuous curvilinear posterior capsulorhexis in a patient with intumescent cataract and primary capsular fibrosis. J Cataract Refract Surg 1998; 24:870 – 871 16. Morgan JE, Ellingham RB, Young RD, Trmal GJ. The mechanical properties of the human lens capsule following capsulorhexis or radiofrequency diathermy capsulotomy. Arch Ophthalmol 1996; 114:1110 –1115 17. Delcoigne CD, Hennekes R. Circular continuous anterior capsulotomy with high frequency diathermy. Bull Soc Belge Ophtalmol 1993; 249:67–72 18. Nishi O. Posterior capsule opacification. Part 1: experimental investigations. J Cataract Refract Surg 1999; 25: 106 –117 19. Tetz MR, Nimsgern C. Posterior capsule opacification.
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Part 2: clinical findings. J Cataract Refract Surg 1999; 25:1662–1674 Spalton DJ. Posterior capsular opacification after cataract surgery. Eye 1999; 13:489 – 492 Ursell PG, Spalton DJ, Pande MV, et al. Relationship between intraocular lens biomaterials and posterior capsule opacification. J Cataract Refract Surg 1998; 24:352– 360 Nishi O, Nishi K, Wickstro¨ m K. Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 2000; 26:1543– 1549 Holladay JT, Lang A, Portney V. Analysis of edge glare phenomena in intraocular lens edge designs. J Cataract Refract Surg 1999; 25:748 –752 Tester R, Pace NL, Samore M, Olson RJ. Dysphotopsia in phakic and pseudophakic patients: incidence and relation to intraocular lens type. J Cataract Refract Surg 2000; 26:810 – 816 Davison JA. Positive and negative dysphotopsia in patients with acrylic intraocular lenses. J Cataract Refract Surg 2000; 26:1346 –1355 Davidson MG, Morgan DK, McGahan MC. Effect of surgical technique on in vitro posterior capsule opacification. J Cataract Refract Surg 2000; 26:1550 –1554
From Bausch & Lomb Surgical (Bretton) and Anheuser-Bush Eye Institute, St. Louis University (Kash, Schanzlin), St. Louis, Missouri, USA. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Ft. Lauderdale, Florida, USA, May 1996. Supported in part by a research grant from Bausch & Lomb Surgical to the Department of Ophthalmology, St. Louis University. Dr. Bretton is an employee of Bausch & Lomb. Neither of the other authors has a financial interest in any product mentioned. Mary Kay Harmon assisted with the animals.
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