Polydiaxonon Prevents Adhesions in the Rabbit Model: A Pilot Report Naval Sondhi, M D , a Selim T. Koseoglu, M D , a Jose M. Bonnin, M D , b - and Badia Fahad, M D a
Purpose:Restrictive strabismus is a common and difficult problem confronted by strabismologists. Several materials have been used to minimize the formation of adhesions after strabismus surgery with varying degrees of success. Pelydiaxonon (PDS, Ethicon)is an absorbable, nontoxic, nonporous material. We used it as 25 and 50 gm thick sleeves to study its effectiveness in the prevention of adhesions. Method: Eight eyes of four adult New Zealand White rabbits were used. To simulate the adhesions, a raw scleral bed was created under the superior rectus insertion in study animals and the muscle capsule facing the sclera was opened. Four study eyes had PDS sleeves inserted around the superior rectus; the other four served as controls. After 4 months the animals were killed. The surgical sites were inspected for adhesions. Light microscopy was also performed. Results: Virtually no adhesion formation was noted in the study eyes. In the control group, however, dense adhesions were seen. Light microscopy confirmed these results. No significant amount of foreign material was found. There was no toxicity resulting from PDS. Conclusions: This demonstrated nearly complete prevention of adhesions in the rabbit model. PBS sleeves appear to have potential in surgery for restrictive strabismus. (J AAP0S 1998;2:214-7)
estrictive strabismus is a common and difficult problem confronted by strabismologists. Adhesions between raw surfaces occur after various surgical procedures or trauma. Even after routine extraocular muscle surgery, it is common to see relatively severe adhesions in the area where the surgery was performed. These adhesions can result in restrictive strabismus or make subsequent surgeries more difficult. They also limit the period of adjustment to the first 24 to 48 hours after adjustable muscle operations. In an effort to minimize this problem, many materials have been tried: Vicryl mesh (Ethicon, Somerville, NJ), Supramid mesh (Jackson, Alexandria, Va), Interceed oxidized regenerated cellulose sleeve (Johnson & Johnson Medical, Arlington, Tex), 1, 2 Healon (Pharmacia), and recently mitomycin and 5-fluorouracil (5-FU). Healon was shown to have limited success. 3 Mitomycin and 5-FU also appear to prevent adhesions, 4, s but they are highly toxic substances that act by permanently destroying the fibroblasts that they contact. It has been hypothesized by one of us (N.S.) that the ideal material to serve this goal would be absorbable, nontoxic, and nonporous. We therefore decided to try a new material
R
From the Division of Pediatric Ophthalmology, Department of Ophthalmology, Indiana University, e and the Department of Pathology, Methodist Hospital of Indiana, b Indianapolis, Indiana. Submitted April 6, 199Z RevMon acceptedffanua) 7 20, 1998. Reprint requests: Selim 77 Koseoglu, MD, Akatlar Maya Sitesi J1 D11, 80630 Istanbul, Turkey. Copyright © 1998 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8Y31/98 SY.o0 + 0 75/1/90040
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made of polydiaxonon (PDS). This is supplied in sheets of 25-and 50-gin thickness by Ethicon. This material is particularly appealing because sutures made from it are available for human use. PDS is completely absorbable in 6 months and, unlike Vicryl mesh, it is not thought to induce inflammation. METHOD A total of eight eyes of four adult New Zealand White rabbits were used. The study protocol was approved by Indiana University Laboratory Animal Research Center. The animals were also housed and operated on at the same facility. To be able to compare our results with prior results, the technique described by Sondhi et al 1 was used to create adhesions. After anesthesia was achieved with intramuscular ketamine 75 mg/kg, acepromazine 5 mg/kg, atropine 0.02 mg/kg, and topical proparacaine, both eyes of the rabbit were prepared and draped by standard technique for extraocular surgery. The superior rectus muscle was isolated with use of a limbal approach and disinserted after securing it at the insertion with 6-0 Vicryl suture with locking bites. The superior oblique muscle was cut and allowed to retract. Then in two of the animals the muscle capsule on the inferior aspect was opened 5 mm from the insertion and a partial-thickness 4 x 4 mm sclerectomy was performed with an I-Knife (AlconPharmaceuticals) under the muscle insertion. This created two raw surfaces. The sleeve made of 50-gin PDS was cut to the appropriate size and the free edges were sutured together with 6-0 PDS suture. The sleeve was passed over the right superior rectus muscle. A similar procedure was performed on the left Journal of AAPOS
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FIG 1. PDS sheet.
FIG 2. PDS sleeve ready to be placed around superior rectus.
superior rectus, and this was covered with a 25-btm sleeve.
TABLE. Procedures done on each rabbit and grade of adhesions formed
The muscles were reattached at the insertion and the conjunctiva was closed with the 6-0 Vicryl suture. Two eyes of one rabbit were used as PDS-only controls and the 50-btm PDS sheet was wrapped around the right superior rectus and the 25-btm sheet around the left superior rectus without taking the muscle off the sclera. No trauma to the muscle capsule or sclera was created. Only surgery was done to the two eyes of another rabbit: the right eye had the superior rectus muscle disinserted then reattached and the left eye had the muscle procedure and the flap like the study eyes but not the PDS sleeve. (See the Table for a summary and Figure 1 for the illustration of PDS in sheet and Figure 2 in sleeve form.) All animals woke up spontaneously without problems. After 2 months the surgeryonly rabbit 881 was anesthetized according to the above technique, the conjunctiva was opened, the superior rectus muscles were isolated, and the different surfaces were inspected for adhesions. These were then graded according to the system of Yaacobi et al,2 where 0 = no adhesions, 1 = filmy adhesions easily separable by blunt dissection, 2 = mild to moderate adhesions with freely dissectable plane, and 3 = moderate to dense adhesions with difficult dissection or nondissectable plane. Afterward, the eyes were enucleated. The superior rectus muscle was cut near its entry to the Tenon's capsule and the globe was placed in Preferred, a solution that the Department of Pathology at the Methodist Hospital of Indiana uses for light microscopy. Then the rabbit was killed by intracardiac pentobarbital injection while it was still under anesthesia. After a total of 4 months, the same procedure was performed on the rest of the rabbits. Light microscopy was performed on the sections containing the superior rectus attachment site. ~S~TS
Macroscopy In the positive control animal, number 881, adhesions were noted between the muscle and the sclera, as expect-
No.
Eye
Procedure done
Grade of adhesion
880
Right 50 #m PDS with scleral flap 1 Left 25 ~zm PDS with sclera[ flap 1 881 Right Regular muscle operation 2 Left Muscle with scleral flap, no PDS 3+ 882 Right 50 pm PDS, no flap 0 Left 25 ~tm PDS, no flap 0 883 Right 50 #m PDS with scleral flap 1 Left 25 ~m PDS with scleral flap 1 Gradingof adhesionsin each rabbitwith the system of Yaacobiwere 0 = no adhesions, 1 = filmy adhesionseasily separableby blunt dissection,2 = mild to moderate adhesionswith freely dissectableplane,and 3 = moderateto denseadhesionswith difficult dissectionor nondissectableplane.
ed. The left eye of this animal had grade 3+ adhesions; the right eye, which had regular surgery, also had grade 2 adhesions near the insertion site. In the eyes in which the PDS sleeve was used there was virtually no adhesion between the two raw surfaces. There were no changes around the muscles of the negative control rabbit. After 4 months there was no evidence of PDS either. (See Table 1 for a summary of the results with the grading system of Yaacobi et al.) Figures 3 and 4 demonstrate that the muscle hook cannot be pulled forward in the control animal, in contrast to the study animal in which PDS prevented adhesions. Figures 5 and 6 show the sclera under the muscle attachment. In Figure 5 the sclerectomy site is covered with adhesions and cannot be seen. In Figure 6 the sclerectomy site is clearly visible and well healed.
Microscopy Microscopy confirmed the above results. A few strands of Vicryl with inflammation surrounding them were visible. There were a few fibers of foreign material that could be seen only after polarization under the insertion the superior rectus muscles. These are assumed to be PDS. Compare Figure 7, showing that the muscle is adherent to the sclera in the control animal, with Figure 8, showing the clear
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FI6 3. In control eye (left eye of rabbit 881) Jameson hook cannot be pulled up to insertion because of grade 3+ adhesions to sclerectomy site. SR, Superior rectus.
FI6 4. In study eye (right eye of rabbit 880) no adhesions formed under muscle. Muscle hook can easily reach insertion. SR, Superior rectus.
FI6 6. Minimal (grade 1) scar in sclerectomy area in study eyes (right eye of rabbit 880). Muscle can be easily lifted toward insertion. SR, Superior rectus.
FIG 5. Dense adhesions between sclera and muscle in control eye (left eye of rabbit 881), Muscle insertion cannot be seen. SR, Superior rectus.
FIG 7. Low-power photomicrograph of control eye showing that muscle fibers are totally adherent to sclera.
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1=16 8. Low-power photomicrograph of study eye showing clear
space around muscle with virtually no adhesions and no PDS.
space between the muscle and the sclera and the conjunctiva and the muscle where PDS used to be in the study animal. Interestingly, all muscles other than the ones in the PDS-only control rabbit (including the muscle that had the regular operation) showed some inflammation as well as degenerating and regenerating cells. These changes were ascribed to the effects of surgical trauma. The muscles in control rabbit 882, which only had PDS wrapped around them, looked very healthy. There was no microscopic evidence of toxicity. DISCUSSION
AND CONCLUSIONS
This pilot study demonstrated nearly complete prevention of adhesions after extraocular muscle surgery even in areas heavily traumatized, as in the Sondhi rabbit model. Different materials were tried in the past to achieve the same purpose. Absorbable materials such as Vicryl mesh did not prevent the adhesions between the muscle and the sclera. 1 Interceed oxidized regenerated cellulose actually increased the formation of postoperative adhesions. 2 Gelatin sponges had a similar problem. Permanent materials such as Supramid mesh may erode through the tissues, cause a foreign body reaction, and still not prevent the adhesions. Healon mesh prevented the formation of .adhesions in the Sondhi model in the study by Yaacobi et al 2 but was not very successful in another study that used the less rigorous test of superior rectus resection. 3 Mitomycin and 5-FU have been shown to reduce adhesions; however, the model used to simulate adhesions in the mitomycin study involved only a 2 mm recession 4 and the adhesions in the 5-FU study were not graded. 5 In another study done by Brooks et al6 mitomycin did not
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have a beneficial effect in the prevention of fat adhesion. T h e toxicity of these medications is well known and their effect is permanent. Late-onset scleritis is reported after their adjunctive use in optic nerve sheet fenestration. 7 N o animal model can exactly duplicate the fat adherence syndrome in humans. In the Sondhi model the adhesions formed between the muscle and the sclera. This model is easy to standardize and consistently forms strong adhesions. Brooks et al 6 simulated the adhesions by opening the Tenon's capsule anteriorly. Their model causes the adhesions to occur between the muscle and the fibrovascular metaplastic fat in 75 % of the cases, but they had to place a suture between the muscle and the periosteum. We used only eight eyes of four rabbits. T h e results cannot be interpreted by statistical methods. We did not use one eye of each animal as a control because the strength of the adhesions formed by the Sondhi model is well established in prior studies J, 2 T h e same specimens were used both for macroscopy and microscopy and the authors were not blinded. We do not think that these factors affected the results because of the marked difference between the amount of adhesions. T h e amount of adhesions formed in the eyes with PDS were so minimal that this material has potential in surgery for restrictive strabismus. The authors believe that the success of PDS is the result of its being nonporous, nontoxic, and totally absorbable. Further study will be necessary in establishing its role in the adhesion syndrome in humans because the anatomy of the rabbit is different and the healing response in rabbits with use of this model may not simulate similar problems observed in humans. References
1. Sondhi N, Ellis FD, Hamed LM, HelvestonEM. Evaluationof an absorbable musclesleeveto limit postoperativeadhesionsin strabismus surgery.Ophthal Surg 1987;18:441-3. 2. YaacobiY, Hamed LM, Kaul KS, Fanous MM. Reductionof postoperative adhesions secondary to strabismus surgery in rabbits. Ophthal Surg 1992;23:123-8. 3. Searl SS, Metz H, Lindahl KJ. The use of sodiumhyaluronateas a biologic sleeve in strabismus surgery. Ann Ophthalmol 1987;19: 259-68. 4. Cruz OA, Matkovitch L. Effects of intraoperative topical mitomycin-c on strabismus surgery in the rabbit: a preliminarystudy. Ophthal Surg 1995;26:237-9. 5. Mora JS, Sprunger DT, Helveston EM, Evan AP. Intraoperative sponge 5-fluorouracil to reduce scarring in strabismus surgery.J AAPOS 1997;1:92-7. 6. BrooksSE, Ribeiro GB, Archer SM, Elner VM, Del Monte MA. Fat adherence syndrometreatedwith intraoperativemitomycin-c:a rabbit model.J Pediatr OphthalmolStrabismus 1996;33:21-7. 7. Kersten RC, Kulwin DR. MMC in ONS decompression [letter]. Ophthalmology1996;103:864-5.