Transactions 29th European Strabismological Association Meeting – de Faber (ed) © 2005 European Strabismological Association, ISBN 04 1537 211 9

Efficacy of the anterior transposition of the inferior oblique as a secondary procedure in cases of recurrent DVD

V. Paris

Liège University, Belgium

ABSTRACT: Twenty one patients, presenting a residual manifest DVD, after one to three procedures to control it, were retrospectively studied. They were treated by anterior transposition of the inferior oblique muscle (ATPIO) at zero, 1 or 2, in association with a resection of the proximal part of the IO tendon in three cases and with a re-recession of the superior rectus (SR) in three other cases. The mean age at surgery was 8.4 years (1.5–42). No patient had any ATIO before and they were all operated by the same surgeon (VP). Preoperatively, a residual vertical lateral incomitance was present in 24% of the cases and a V pattern in 19%. A latent DVD was finally obtained in all cases but two. One of these two cases was reoperated 3 years later in the same manner on the other eye and led to a stable good result. The mean follow up is 4 years (0.6–7). No significant side effect was observed. However, a residual upgaze limitation was small in three cases and mild in one case without provoking any chinup head posturing.

1INTRODUCTION

DVD remains one of our most difficult challenge because of its various clinical aspects: latent or manifest, variable, recurrent, pseudo or really asymmetric, sometimes even unilateral. ATIO is an old method which proved its efficacy for treating DVD (Mims 1989, Krats 1989,) but less stable to control the largest ones ( 15 PD) (Burke 1993). These authors performed this technique bilaterally, always for incomitant DVD and never combined with SR recessions (SRR). In 1997, Varn (Varn 1997) demonstrated the efficacy of a combined procedure in “pure” DVD but, again, proposed bilaterally in all cases but one.

This study wants to demonstrate the efficacy of a graded, almost unilateral (77%), ATIO as a combined and “staged” procedure in a population presenting recurrent DVD, almost operated bilaterally (86%) before.

2METHOD

We have retrospectively studied twenty one consecutive patients aged from 1.5 to 42 years (mean: 8.4) presenting a recurrent manifest DVD operated once (66%), twice (29%) or three times (5%) before, by the same surgeon (VP). In 24% of the cases, an additional vertical lateral incomitance (termed incomitant DVD) was present. A V pattern was measured in 90% of the cases but no A pattern was noticed. All patients were esotropic with the clinical signs of early onset strabismus. A SRR was initially performed in 14 patients (66%), combined with an IO recession ( IOR ) in 6 patients (29%).

One patient underwent a simple bilateral IOR. As already mentioned, the majority of the cases was initially operated on both eyes. In all cases but one, our previous surgery was based on a classical, graded, almost asymmetric recession of the SR without using “hang back” technique to avoid any forward postoperative gliding. The amount of SRR was limited to 8 mm in order to eliminate any risk of lid retraction or limitation of elevation. According to the size of the DVD, we have

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Table 1. Quantification of the DVD.

Table 2. Quantification of the technique (* recession of the contral at IO).

planed a simple SRR or a combined surgery ( SRR IOR ) as a single or a staged procedure. The amount of IOR was 8 to 10 mm.

As described in table 1, the initial DVD was large and asymmetric in most of the cases. It is interesting to notice that only one of the three cases presumed unilateral at first remained like that during the follow up. At the time of the ATIO, all patients but one had an asymmetric deviation. Most of them were considered as unilateral (80%) and remained unilateral after the follow up, except for one single case.

We have used a graded technique of AT. The IO was attached to the globe at the temporal edge of the insertion of the inferior rectus (IR) muscle (AT at zero), 1 or 2 mm anteriorly (AT 1, 2), never more. Using the Gobin’s technique for many years, we are used to bunch the new insertion of the IO so that we have never taken any risk of upgaze restriction due to the spread of this insertion (Mims 1999). Nevertheless, some cases underwent a small additional anterior displacement of the posterior part of the IO tendon in order to reinforce the mechanical action of the global anteriorization, as proposed by Kratz (Kratz 1989). For the same reason, as described in table 2, we also performed a resection of the proximal part of the IO tendon (limited to 4 mm) in three cases. One case for a hyperelasticity of the IO muscle, one for a persisting unilateral DVD after a maximal combined procedure. The last case presented a residual incomitant DVD with a large V pattern and so, underwent a bilateral resection associated with an ATIO 2.

Finally, we performed in some cases a re-recession of the SR (RRSR), respecting the limit of a total amount of 8 mm.

3RESULTS

The result was considered as good when manifest DVD became latent or 4 PD, either eye fixing. This result was obtained in all cases but two. A moderate lateral incomitance was persisting in 2 cases (symmetric 1) and a significant V pattern in 1 case. This latter patient can be considered as a bad result in term of horizontal incomitance but the DVD was latent and 5 PD. The 2 patients with a small incomitant DVD had only a latent vertical deviation 5 PD in primary position. Finally, a residual manifest DVD was only present in 2 cases as summarized in table 3.

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Table 3. Results.

Our graded technique of anteriorization of the IO was then efficient enough to control the residual DVD in 95% of the cases. One of the 2 failures was considered as good during a period of 3 years….. then he started to present a manifest DVD on the contralateral eye. He was treated with an unilateral ATIO 2 with success (follow up: 3 years). This patient was the only “false unilateral” case out of the 16 patients diagnosed preoperatively as unilateral in this study (see table 1). We proposed a fourth step of surgery to the other patient. His parents refused because they were satisfied of the cosmetic aspect. However, the residual DVD (10 PD) was not compatible with a good binocular sensorial result, which is much more important than the cosmetic appearance. The mean follow up is 4 years (0.6–7). We didn’t measure any significant side effect. However, an upgaze limitation was found in 4 patients: small in 3 patients and mild in 1 patient. This latter patient was the only one who underwent a bilateral resection of the IO associated with an anteriorization of 2. He didn’t adopt any chinup posturing anyway. We observed no lid retraction, no A pattern and no postoperative overcorrection.

4DISCUSSION

According to the fact that spontaneous evolution of the DVD is not easily predictable, the duration of the follow up takes a great importance. To our knowledge, it is the first time that ATIO is proposed, almost unilaterally, as a combined procedure. The main problem of using an unilateral or an asymmetric surgery of the DVD is to increase the DVD on the non operated eye and to provoke a hypotropia on the operated eye. This overcorrection has no correlation with the amount of SRR (Schwartz & Wilson 1991) but is related to the presence of an increasing DVD on the less operated eye (Can et al 1997). One of the most plausible explanation of these frequent clinical facts is to accept the following hypothesis: DVD doesn’t violate Hering’s law all the time as already mentioned by Guyton’s findings (Guyton et al 1998). Guyton described a supraversion impulse coming from the SR of the fixing eye, succeeding to an initial vertical vergence phase, to elucidate the mechanism of DVD. We propose that, in some asymmetric cases, the persistence of SR contracture on the fixing eye can provoque an infraversion impulse on the non fixing eye as already assessed by the persistence of hypotropia under general anesthesia in highly asymmetric DVD (Paris 1998). This hypothesis is clinically correlated by the efficacy of an unilateral procedure in large bilateral DVD and the efficacy of bilateral symmetric SRR in cases of apparent asymmetric DVD.

This «hypotropic» effect represents the principle trap of the surgical management of the DVD. Taking this observation into account we think that the hypotropic effect of the IO on the contralateral eye in abduction is not systematically valid to differentiate DVD and IOOA. We have enough clinical clues such as; presence of V pattern, lateral incomitance, to do that.

Based on the hypothesis that oblique muscles were primary concerned by the DVD process, it would be attractive to propose a “magic formula” to control it, which could be a bilateral recession of the four oblique muscles. Guyton was disappointed by this procedure but Gamio’s results are encouraging (Gamio 2002).

5CONCLUSIONS

Because ATIO causes an anti-elevating force vector resulting from the fibrous nature of the neurovascular bundle of the IO (Stager 1997), it is very efficient to control vertical deviations.

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Waiting for more clinical experiences about the use of a standard formula in all kind of DVD, we can perform a combined procedure, single or staged, symmetric or not, but always graded proportionally to the estimate of the DVD deviation.

Respecting some surgical limitations and technical details we can obtain good stable results in most of the difficult cases without provoking any significant side effects.

REFERENCES

1.Burke J., Scott W., Kutschke P. 1993. Anterior Transposition of the Inferior Oblique Muscle for Dissociated Vertical Deviation. Ophtalmology. 100(2): 245–250.

2.Can D., Özkan S.B., Kasim R., Duman S. 1997. Surgical results in highly asymmetric dissociated vertical deviations. Strabismus. 5(1): 21–26.

3.Gamio S. 2002. A Surgical Alternative for Dissociated Vertical Deviation Based on New Pathologic Concepts: Weakening All Four Oblique Eye Muscles. Outcome and Results in 9 Cases. Binocular Vision & Strabismus. 17(1): 15–23.

4.Guyton D.L., Cheesman E.W., Ellis F.J., Starutmann D., Zee D. 1998. DVD: An exaggerated normal eye movement used to damp cyclovertical latent nystagmus. Trans Am Ophtalm Soc. 96: 390–429.

5.Kratz R.E., Rogers G.L., Bremer D.L., Leguire L.E. 1989. Anterior tendon displacement of the inferior oblique for D.V.D. JPOS: 212–217.

6.Mims J.L., Wood R.C. 1989. Bilateral anterior transposition of the inferior oblique. Arch. Ophthalm.1 (107): 41–44.

7.Mims J.M., Wood R.C. 1999. Antielevation Syndrome After Bilateral Anterior Transposition of the Inferior Oblique Muscles: Incidence and Prevention. J. AAPOS. 3(6): 333–336.

8.Paris V. 1998. Reality of vertical deviation asymmetry in early onset strabismus: observation during general anesthesia as a predictive sign. Proceedings of the VIIth Meeting of the ISA. Maastricht, 10–12 September, The Nederland. : 357–360.

9.Schwartz T., Scott W. 1991. Unilateral Superior Rectus Recession for the Treatment of Dissociated Vertical Deviation. JPOS. 28(4): 219–222.

10.Stager D.R. 1997. The Neurofibrovascular Bundle of the Inferior Oblique Muscle as the Ancillary Origin of that Muscle. J AAPOS. 1(4): 216–225.

11.Varn M.M., Saunders R.A., Wilson M.R. 1997. Combined Bilateral Superior Rectus Muscle Recession and Inferior Oblique Muscle Weakening for D.V.D. J. AAPOS 1(3): 134–137.

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Transactions 29th European Strabismological Association Meeting – de Faber (ed) © 2005 European Strabismological Association, ISBN 04 1537 211 9

Mechanical and histopathological effects of ADCON – L, conventional and polymer coated liposomes in an experimental strabismus

surgery model

B. Sönmez

Department of Ophthalmology, Military Hospital, Malatya, Turkey

S¸ . Gedik

Department of Ophthalmology, Bas¸ kent University, Ankara, Turkey

Ç. Karaca, E.C. S¸ ener & A.S¸ . S¸ anaç

Department of Ophthalmology, Hacettepe University, Ankara, Turkey

T. Eldem

Department of Pharmaceutical Biotechnology, Hacettepe University, Ankara, Turkey

ABSTRACT:

Aim: To investigate the effect of ADCON – L, conventional and polymer coated liposomes on the formation of scar tissue following strabismus surgery.

Methods: Thirty-six eyes of 18 rabbits underwent 5 mm superior rectus recessions. One eye of each rabbit was used as control. ADCON – L, conventional and polymer coated liposomes were applied to five, six, seven eyes respectively. For all eyes, preoperative, early postoperative late postoperative quantitative forced duction measurements were carried out. At the postoperative 6th week surgical region was explored and histopathological specimens for light and electron microscopy were prepared.

Results: The administration of ADCON – L was associated with less adhesion formation. Both liposome groups showed less restriction in quantitative forced duction compared to the control group. Conclusion: ADCON – L is an effective anti-adhesive barrier gel which can be used in prevention of adhesions caused by strabismus surgery.

Adhesions arising between sclera, conjunctiva and extra ocular muscles have a negative impact on the success of strabismus surgery. Avoiding traumatic surgical techniques, control of excessive hemorrhage, suppression of postoperative infection and inflammation and avoiding multiple surgical interventions are frequently employed to prevent adhesion formation following strabismus surgery. Wagner & Nelson (1985).

Many kinds of synthetic and biological membranes and implants were used experimentally to prevent the development and spread of fibrotic scar tissue. Synthetic and biological implants act as mechanical barriers whereas antifibrotic drugs act on several steps of wound healing pharmacologically. Among these materials are tissue implants such as Tenon’s capsule, Amnioplastin, egg membrane and peritoneum Berens (1943); and plastic implants such as pig gelatin, polyester film and silicon. Polyglactin mesh sleeves placed over extraocular muscles also have been tried Dunlap (1976).

In our study, ADCON – L, which is a bioabsorbable barrier gel shown to be effective experimentally in preventing postlaminectomy peridural fibrosis in rabbits and conventional and polymer coated liposomes were used in an experimental model of strabismus surgery to observe their mechanical and histopathological effects on the development of fibrosis.

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1METHODS

The study was conducted at Hacettepe University School of Medicine and School of Pharmacy. Thirty-six eyes of 18 rabbits were included in the study. One eye of each rabbit was used as control. After intramuscular anesthesia with Ketalar (Ketamine Hydrochloride 40 mg/kg, Parke Davis) and Rompun (Xylazine Hydrochloride 4 mg/kg, Bayer) quantitative forced duction (QFD) measurements were done via a traction suture piercing sclera partially at 12 o’clock quadrant with a Pesola dynamometer. Passive traction forces against the superior rectus muscle were recorded for each 1 mm movement as grams. The superior rectus muscles were recessed 5.0 mm in all eyes. In control group surgical field was washed with 0.9% NaCl. 1 ml of ADCON – L was applied to the surface of the superior rectus muscle and the surgical field after recession in 5 eyes. ADCON – L is a polyglycan formed by repeat sequences of poly-sulpho-alpha(1→6)–D-glucan Fredericson (1996). Two types of liposomes were prepared at the department of pharmacy namely conventional and polymer coated liposomes Table 1.

0.1 ml of conventional liposomes were used in 6 eyes and polymer coated liposomes in 7 eyes. Liposomes were injected into the superior rectus muscle with a 26 gauge needle and the surgical field was washed with the rest. After closure of the conjunctiva with 7/0 vicryl sutures the QFD test was repeated. No other topical medications were used postoperatively. After a six week period the rabbits were anesthetized again and QFD test repeated by the same examiner. The surgical field was explored and adhesions between conjunctiva, superior rectus muscle and the sclera were evaluated and graded Table 2.

Thereafter 5.0 mm muscle tissue specimens with adjacent conjunctiva and sclera were prepared and the rabbits were sacrificed with intravenous pentobarbital. All of the surgeries and the quantitative forced duction measurements were done by the same examiner.

Tissue specimens were fixated with 2.5% gluteraldehyde solution and treated with Sorensen’s phosphate buffer and 1% osmium tetroxide solution. After dehydration with alcohol and treatment with propylene oxide specimens were embedded in epoxy-resin material and 2 thick sections were cut with ultramicrotome (LKB – Nova Ultratome). Sections were stained with methylene blue for 200 magnification observation with light microscopy. For electrone microscopy 60 nm thick sections were cut and evaluated with 10000 and 120000 magnification after staining with uranyl acetate and lead citrate. The sections were analyzed by the same anatomo-pathologist.

Table 1. Materials used for the preparation of the liposomes.

DSPG (Distearoyl phosphatidyl glycerol) (Genzyme Corporation)

MPEG-DSPE (2000) (Distearoyl-N-monomethoxypolyethileneglycol phosphatidyl ethanolamine) (Molecular Weight 2000) (Genzyme Corporation)

CHOL (Cholesterol) (Sigma)

HSPC (Semi-hydrogenised phosphatidylcholine) (Lipoid AG) HEPES (n-2-hydroxypiperazine-N -2-ethanesulphonic acid) CHCl3 (Chloroform) (Sigma)

MeOH (Methanol) (Sigma) NaCl (Sodium chloride) Deionized water

Table 2. Grading of the adhesions after surgical exploration.

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Data obtained from the quantitative forced duction tests at preoperative, early postoperative and late postoperative measurements are evaluated with Mann-Whitney U test statistically and ingroup and intergroup comparisons were used. Findings from the surgical exploration at the sixth week which were evaluated as gradings are analyzed as percentages in groups.

2RESULTS

At the postoperative 6th week surgical field was explored and adhesions between conjunctivamuscle and adhesions between muscle-sclera were evaluated and graded. In the control group; 94.5% of adhesions between conjunctiva and the superior rectus muscle were grade 1 (55.6%) and grade 2 (38.9%). 100% of adhesions between muscle and sclera were in grade 1 (44.4%) and grade 2 (55.6%). In the ADCON – L group; 100% of adhesions between conjunctiva and muscle were in grade 0 (60%) and grade 1 (40%). Also 100% of the adhesions between the muscle and the sclera were grade 0 (20%) and grade 1 (80%). In conventional liposome group 100% of adhesions between the conjunctiva and the muscle were in grade 0 (16.7%) and grade 1 (83.3%); also 100% of adhesions between the muscle and the sclera were grade 1 (16.7%) and grade 2 (83.3%). In polymer coated liposome group 100% of adhesions between conjunctiva and muscle were grade1, and 100% of adhesions between the muscle and the sclera were in grade 1 (42.9%) and grade 2 (51.7%).

When compared to the control group and both liposome groups both conjunctiva-muscle adhesions and muscle-sclera adhesions were less severe in the ADCON – L group. There were no significant differences in terms of surgical findings between the control and both liposome groups.

Mean values for QFD measurements were 6.12 gr for 1 mm and 19.22 gr for 6 mm in control group preoperatively. Early postoperative values were 5.42 gr for 1 mm and 17.97 gr for 6 mm, late postoperative values 6.33 gr and 19.22 gr for 1 and 6 mm respectively. The differences were not statistically significant. In the ADCON – L group preoperative QFD measurements were 6.36 gr for 1 mm and 18.8 gr for 6 mm. The mean early postoperative values were 5.76 and 18.0 gr and late postoperative values were 6.32 gr and 18.64 gr for 1 and 6 mm respectively. When we compared the QFD values of the ADCON – L group with the control group, no statistically significant difference was found. The QFD measurements of the conventional liposome group showed statistically significant differences compared to the control group at the early postoperative 2,4 and 6 mm measurements and at all values of the late postoperative measurements. Also in the polymer coated liposome group there were statistically significant differences at early postoperative 2 mm and late postoperative all measurements compared to the control group.

Figure 1a and 1b. Fibroblastic proliferation and collagen deposition was more pronounced in the control group (1a). The muscle fibers were more preserved in the ADCON – L group (1b).

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On histopathological sections less amount of fibrotic tissue were observed between the muscle fibers in ADCON – L group compared to the control group. Also the bulk of muscle tissue was better preserved compared to the control group (Figure1a, 1b). In both of the liposome groups the muscle tissue was not well preserved as in the ADCON – L group. Also in the electron microscopic sections of the liposome groups intracytoplasmic and mitochondrial edema was noticed which was not seen both in the control and the ADCON – L groups.

3DISCUSSION

ADCON – L is a drug of polyglycan formed by repeat sequences of poly-sulpho-alpha(1 → 6) – D-glucan Fredericson (1996). It is a clinically safe drug with bioabsorbtion and antiadhesive barrier gel properties. First use of ADCON – L was in experimental neurosurgical laminectomy procedures for the prevention of postoperative peridural adhesions after laminectomy procedures Robertson 1993. Later on it was also shown to be effective in adjustable suture surgery for the prevention of adhesions histopathologically Choi 2001. Our results on the effects of ADCON – L were similar to the findings of Choi and friends. On histopathological sections with light microscopy less amount of fibroblastic tissue were observed between the muscle fibers in ADCON – L group compared to the control group, also the bulk of muscle tissue appeared to be well preserved. On electron microscopy, less amount of collagen bundles were appearent between the muscle fibers compared to the control group. These histopathological findings were not supported with the quantitative forced duction measurements in our study. There were no statistically significant differences between the ADCON – L and control groups in the preoperative, early and late postoperative quantitative forced duction test results.

Liposomes are global structures formed by a liquid phase in the middle covered by one or more lipid bilayers mainly formed by cell membrane components, phospholipids and cholesterol. They are usually used as adjuvants or carriers for drugs in chemotherapy, immunization or diagnostic imaging. To the best of our knowledge, liposomes have not been used in strabismus surgeries, neither alone nor combined to any antifibrotic drug. In our study, quantitative forced duction measurements showed less restriction in both of the liposome groups compared to the control group especially in the late postoperative values. Whereas these findings were not supported by the histopathological data. The sections for light microscopy showed increased amount of fibrotic tissue and decreased amount of muscle tissue compared to the control group. In the electron microscopic sections intracytoplasmic and intramitochondrial edema was observed, especially in the polymer coated liposome group.

As a result ADCON – L decreased postoperative fibrosis and adhesions in our experimental strabismus surgery model. Neither conventional nor polymer coated liposomes decreased postoperative fibrosis but they seemed to be safe for the future combinations with antifibrotic drugs.

REFERENCES

Berens C & Romina HH. 1943. Postoperative cicatricial strabismus, results of the transplantation of the Tenon’s capsule. Transactions of the American Academy of Ophthalmology 47:183–205

Choi MY. 2001. Effect of ADCON – L on adjustable strabismus surgery in rabbits. Br J Ophthalmol 2001. 85:80–84

Dunlap EA. 1976. Plastic implants. Int Ophthalmol Clin 16:221–227

Frederickson RC. 1996. ADCON – L: a review of its development, mechanism of action, and preclinical data.

Eur Spine J 5:7–9

Robertson JT. 1993. The reduction of postlaminectomy peridural fibrosis in rabbits by a carbohydrate polymer. J Neurosurgery 75:89–95

Wagner RS & Nelson LB. 1985. Complications following strabismus surgery. Int Ophthalmol Clin 25:171

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