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1From the Departamento de Oftalmologia and the 2Departamento de Anatomia Patológica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
| Abstract |
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METHODS. In an in vivo procedure, 120 superior recti muscles in New Zealand White rabbits were subjected to the posterior fixation procedure, at a distance of 6 mm from the insertion point of the muscle. They were divided into four groups of 30 muscles, according to the material used to perform a myopexy: group 1 (control): nonabsorbable 5-0 polyester sutures; group 2: n-butyl-2-cyanoacrylate adhesive; group 3: fibrin glue; group 4: gelatin-resorcin-formaldehyde-glutaraldehyde (GRFG) adhesive. The animals were examined at 1, 7, 14, and 21 days after surgery. Afterward, they were killed, and their eyes were enucleated to measure the distance between the myopexy and the anatomic insertion point and to assure the strength of the bond with a dynamometer. Finally, a histologic examination was performed.
RESULTS. Almost all eyes were clear after the third week, although group 4 presented the most intense inflammatory reaction. In histologic examination, groups 1 and 2 showed a chronic inflammatory reaction of the foreign-body type, with similar intensity. Fibrin glue induced minimal inflammation, but GRFG adhesive produced a pronounced reaction. Concerning the distance of the myopexy, groups 1 and 2 presented measures close to the expected distance of 6 mm, whereas groups 3 and 4 showed a greater variability. All groups performed well in the strength test, with no statistically significant differences among them.
CONCLUSIONS. n-Butyl-2-cyanoacrylate adhesive performed best in the sutureless Fadenoperation, characterized by precision in the expected distance of myopexy, sufficient resistance to separation, and acceptable inflammatory reaction.
The literature provides few and sporadic reports on the use of tissue adhesives in strabismus surgery. Most of them are experimental studies in animals. Ellis and Levine7 introduced the theme, mentioning the reinsertion of eight recti muscles of rabbits with methyl 2-cyanoacrylate adhesive; in 1969, Dunlap et al.8 were the first researchers to measure the tensile strength of rabbit muscles reattached with cyanoacrylates. Their report, discouraging the use of these substances in humans because of inadequate bond strength observed during the first days after surgery, may have influenced North American investigators, who have not published a single paper on this subject since then. Other researchers throughout the world have explored the topic. Munton9 asserted that cyanoacrylates would be satisfactory for squint operations, based on his experience with the gluing of pig and rabbit muscles. Although Flick and Tauchert10 reported insufficient tensile strength of rabbit muscles reattached with cyanoacrylate, Jung and Chang11 considered the outcome of glued muscles in the rabbit favorable, comparable to results in sutured muscles. Aichmair et al.12 were pioneers in using fibrin sealants for muscle surgery in rabbits and in recommending such a technique in humans. After them, other researchers experimented with fibrin adhesive for reattachment of rabbit muscles in different experimental designs (Erbil et al.,13 Spierer et al.,14 and Moreira et al.,15 ). Finally, investigators in Mexico (Villaseñor-Solares and Aguirre-Aquino16 ) reported good results with the use of cyanoacrylate in strabismus surgeries in 10 patients, and in Italy Ricci et al.17 experimented with octyl 2-cyanoacrylate to reattach rabbit muscles.
Nevertheless, only one study about the use of glue in the Fadenoperation has been reported. Flick18 described an experimental posterior fixation procedure with cyanoacrylate tissue adhesive in a group of 12 superior recti muscles of rabbits (four muscles for each period of follow-up). A case report on the use of such a technique in seven patients complemented his description. In this same article, the author mentioned 35 other surgeries in humans in which poor preliminary clinical results were achieved. Considering that such an experiment was accomplished with a single type of adhesive, without a control group or any objective analysis, we assumed that this subject was deserving of further evaluation.
| Methods |
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Sixty male New Zealand White rabbits (Oryctolagus cuniculus) were selected, with a healthy appearance and weight ranging from 1500 to 2500 g. The superior rectus muscles in both eyes were subjected to the Fadenoperation, in a randomized distribution among four groups of 30 muscles, classified according to the material used in the posterior fixation procedure: group 1 (control), two U-shaped nonabsorbable 5-0 polyester sutures (Mersilene; Ethicon, Piscataway, NJ); group 2, n-butyl-2-cyanoacrylate tissue adhesive (Histoacryl Blau; B. Braun AG, Melsungen, Germany); group 3, fibrin glue (Tissucol; Baxter AG, Vienna, Austria); and group 4, gelatin-resorcin-formaldehyde-glutaraldehyde (GRFG) biological adhesive (Colagel; Cirumédica SA, São Paulo, Brazil). Samples of these materials were generously provided by local distributors, in whose products the authors have no financial interest.
The surgical procedure was performed under optical microscopy with x10 magnification. The animals were anesthetized with an intramuscular combination of 5 mg/kg xylazine and 35 mg/kg ketamine. Immediately before surgery, a topical anesthetic (proxymetacaine 0.5%) was instilled in both eyes.
The conjunctiva was approached by limbic incision, exposing the superior rectus muscle and the reflex portion of the superior oblique tendon, which was resected. A cotton tip was applied beneath the superior rectus muscle to absorb the dampness. Then, with a Castroviejo caliper, two points were marked 6 mm distant from the insertion site, which was left untouched. This distance reached the equatorial region, sufficiently posterior to reproduce the usual difficulties characteristic of this surgery. The retroequatorial region was avoided due to the location of the retractor bulbi muscle insertion point.19 At the points marked, the posterior fixation procedure was accomplished in each of the four groups.
Group 1
Two U-shaped nonabsorbable 5-0 polyester sutures (Mersilene; Ethicon), covering the muscular fibers of both the nasal and temporal thirds, were used.
Group 2
Histoacryl blau (B. Braun AG) is presented in plastic ampoules containing 0.5 g n-butyl-2-cyanacrylate, blue stained. The ampoules have a tubular end that permits direct dropping (Fig. 1) .
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The animals were observed for 21 days, and a clinical examination under optical microscopy was performed at 1, 7, 14, and 21 days after surgery. At these time points, the conjunctivas inflammatory reaction was clinically graded from 1+ to 4+. On the 21st day after surgery, the rabbits were killed with an intracardiac pentobarbital sodium injection, after anesthesia was induced as already described. Afterward, their eyes were carefully enucleated, keeping the posterior myopexy intact. The distance of myopexy was measured with the Castroviejo caliper, from the original insertion to the most posterior point of gluing, at both margins of the superior rectus muscle (Fig. 4) .
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The aspects statistically assessed were (1) differences between inflammatory reactions clinically observed (the Kruskal-Wallis and Friedman tests), (2) distances from the myopexy to the anatomic insertion (Kruskal-Wallis test), and (3) resistance to the strength test (Fisher exact test).
| Results |
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Regarding the distance of the posterior fixation, it was observed that groups 1 and 2 had the best results, achieving the expected distance of 6 mm in both sides of the muscle, without significant deviation. Groups 3 and 4 showed a greater variability, and the distances observed were more frequently less than expected (Tables 1 2) . It is interesting to point out that the whole arc of contact of the operated-on muscles was noted to adhere to the sclera in all eyes of the four groups under study.
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| Discussion |
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Among the adhesives available for medical use, cyanoacrylates have been extensively investigated in most surgical specialties. They have also been examined experimentally in different fields of ophthalmology: corneal surgery, glaucoma filtering surgery, conjunctiva synthesis, oculoplastics, and orbital and posterior segment surgeries. Their best performance, however, was established in the treatment of small corneal perforations and descemetoceles.27 Since the first studies about their toxicity were performed, it has been known that cyanoacrylates with longer chains, such as butyl- or octyl-cyanoacrylates, were shown to have better tolerance.28 29 30 This fact is related to the velocity of polymer degradationthe slower its degradation, the lower its toxicity. Moreover, long-term studies on the use of cyanoacrylates in dogs, rats, mice,31 and chimpanzees29 have failed to reveal any evidence of carcinogenicity, contrasting with other acrylic nonabsorbable substances.32 In experimental studies on the use of cyanoacrylates for muscle surgery, their toxicity, once detected, has not been reported as a limiting factor.8 9 10 11 17 18 When used for squint operation in humans, observations have shown good tolerance that was inversely proportional to the amount of adhesive applied.16
Fibrin glue, however, has been pointed to as the most biocompatible adhesive, but it is not at all devoid of disadvantages. The great concern about this sealant is its potential risk of being a vehicle for blood-transmitted diseases, because it is composed of blood derivatives. The possibility of obtaining its components from a single selected donor33 34 or, preferably, from the patient,35 36 may resolve this problem. Nevertheless, the fibrin sealants commercially available to date are obtained from pools of donors, which calls for rigorous donor selection, reliable serologic tests, and well-established methods for sterilization. Furthermore, the literature provides reports of fatal reactions secondary to the use of fibrin adhesives.37 38 39 Today, with the substitution of bovine thrombin for human thrombin in the fibrin glues makeup, these rare accidents may be avoided. However, the mechanisms of such serious or even fatal reactions are not completely understood, and anaphylaxis related to aprotininemia has also been reported.40 Fibrin sealants, although studied for use in surgery since 1940,41 were first used experimentally in muscles operations only in 1988.12 Among four experimental studies on this subject,12 13 14 15 two had promising results,12 15 and the other two had discouraging outcomes.13 14
GRFG adhesive is the least studied in ophthalmology. To our knowledge, a single experimental study42 on its use has been reported, and significant toxicity was observed at the site of application (rabbit sclera). This biological glue has been used in cardiovascular surgery, although late complications secondary to its use have been reported.43
These data suggest a well-defined field for research. The possibility of using glue in a sutureless Fadenoperation has been poorly explored; moreover, this technique, among other surgical methods for strabismus, seems to be the one that would most benefit from the use of sealants, due to its particularities. This subject demands investigation of all common tissue adhesives available, since their potentials and usefulness in strabismus surgery has not been definitely established.
The present study is a pioneer in assessing the posterior myopexy with tissue adhesives through an analysis of objective parameters, notably the expected position of gluing and its tensile strength. Concerning the former, n-butyl-2-cyanoacrylate produced adherence at the expected distance, with a performance comparable to the control group of sutures. The other substances showed inadequate results, as the adherences between muscle bellies and sclera were found at lesser distances than were intended. Data in the literature poorly describe such aspects. When used in other strabismus surgeries, cyanoacrylate adhesives are reported to produce an imprecise final position of reinserted rabbit muscle, because of the growth of muscle fibers anterior to the point of gluing.8 Other investigators have asserted that rabbit muscles recessed with cyanoacrylate adhesives were found "approximately" at the distance expected,17 whereas significant slippage of the muscles occurred in recessions inferior to 6 mm14 when fibrin glue was used. It has been postulated that the insufficient distances observed in the groups of fibrin and GRFG adhesives is due to a partial slippage of the myopexy that occurred during the period before the third week. If this hypothesis is correct, it means there was an insufficient bond strength in these groups, probably during the first days after surgery.
An unexpected result was the complete adherence of the whole arc of contact in all eyes from all groups observed, a fact that had already been verified in traditional Fadenoperations performed on rabbit muscles.44 45 It is well known that rabbits possess a strong "healing nature," notably evidenced in intraocular surgeries, when intense tissue organization may occur, related to the existence of fibrinogen in the aqueous humor. Nevertheless, no adhesions were reported in rabbit muscles that have been simply manipulated, but not sutured (control group for the traditional Fadenoperation).45 Hence, such a tendency for robust healing, alone, seems not to be sufficient to amplify the muscle scaring in this technique. In group 1, it was speculated that extended adherence resulted from ultrastructural changes in the muscle fibers, induced by the sutures themselves, which could be responsible for innervational and/or ischemic alterations, as reported elsewhere.45 In groups 2 and 3, however, this fact could be explained by the spread of adhesives beneath the arc of contact, by capillarity, considering that these substances are liquid. In group 4, this wide adherence could be due to the intense fibrosis produced by the GRFG adhesive.
As for the strength of the bond, all groups showed firm adhesion at the third week after surgery. This fact has been shown to be in accordance with reports on reattachments of rabbit muscles with cyanoacrylates11 17 and fibrin glue,15 at this point in the follow-up.
These three classes of tissue adhesives have never been compared before in ophthalmology. Histologic examination showed that n-butyl-2-cyanoacrylate adhesive induced an inflammatory reaction of a type and intensity similar to that in the suture group. The fibrin adhesive showed the best tissue performance, confirming that it is the adhesive with the best biocompatibility. The GRFG adhesive produced an excessive inflammatory response, affecting grossly the sclera up to the choroid, a fact that had already been observed in another experimental study in rabbits.42 Hence, the use of GRFG in the Fadenoperation or any other strabismus surgery should be discouraged.
Through analysis of the findings mentioned herein, we may conclude that the n-butyl-2-cyanoacrylate adhesive showed the best performance in a sutureless Fadenoperation in a rabbit model, characterized by precision in the expected distance of the myopexy, sufficient resistance to the effects of tension, and an acceptable inflammatory reaction. Although the conclusions drawn from such a model cannot be directly applied to humans because of anatomic differences, these observations could guide further studies to recommend this technique in the surgical treatment of strabismus. The reproduction of this experiment in human eyes that are scheduled for enucleation (for instance, atrophic eyes) would provide a good experimental setup for future investigations. Besides avoiding the risks related to the traditional posterior fixation procedure, another great advantage of testing adhesives for sutureless Fadenoperation is the impossibility of losing a muscle, as would occur if glue were used for reinsertions. Hence, such an experiment should also represent a preliminary step in the investigations into the use of tissue adhesives for other strabismus surgery.
| Acknowledgements |
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| Footnotes |
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Disclosure: E. Tonelli, Jr, None; H. Celestino de Almeida, None; E.A. Bambirra, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C.
1734 solely to indicate this fact.
Corresponding author: Edward Tonelli, Jr, Rua Professor Otaviano de Almeida, 131/1304, Belo Horizonte, MG, Brazil CEP 30260-020; tonellijunior{at}click21.com.br.
| References |
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y mi
êsni ocznych. Klin Oczna. 1954;24:407410.
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