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

Outcome of strabismus surgery in Congenital Fibrosis of Extraocular Muscles (CFEOM)

E.C. S¸ ener, B.T. Öztürk*& A.S¸ . S¸ anaç

Hacettepe University, Faculty of Medicine, Department of Ophthalmology *Currently assigned at the Ankara Güven Hospital

ABSTRACT: CFEOM is one of the challenging topics in strabismus surgery. The data of 14 CFEOM patients who agreed to undergo strabismus surgery was retrospectively analysed. Twentythree operations on 19 eyes were evaluated in the study. All of the patients had significant restricted motility, nine had exotropia and hypotropia, 2 had esotropia and hypotropia, 1 had alternating esotropia, and 2 had hypertropia, one of them associated with exotropia. Recession of the horizontal or vertical recti were performed in all, together with resection in 5, transposition in 9 and conjunctival recession in one operation. Along the course of the follow-up of our patients, more common surgical doses were augmented because of the unsatisfactory outcome, in addition to the application of stay sutures in 6 patients. Large deviations of CFEOM patients with extreme restriction are difficult to overcome with even augmented surgery. Stay sutures can improve the results of augmented surgery in these cases.

1INTRODUCTION

CFEOM is one of the challenging topics in strabismus surgery. Functional recovery and cosmetic improvement are hard to achieve and multiple operations are usually needed. We herein report surgical results of our CFEOM patients.

2MATERIALS AND METHODS

Fiftysix CFEOM patients followed at one university hospital setting were included in the study. The data of 14 patients who agreed to undergo strabismus surgery was retrospectively analysed.

3RESULTS

At the time of the surgery the age of the patients ranged between 3–44 years. Two patients underwent 2 and one patient had 3 operations. Twenty-three operations on 19 eyes were evaluated in the study. All of the patients had significant restricted motility, nine had exotropia and hypotropia, 2 had esotropia and hypotropia, 1 had alternating esotropia, and 2 had hypertropia, one of them associated with exotropia. Recession of the horizontal or vertical recti were performed in all, together with resection in 5, transposition in 9 and conjunctival recession in one operation. Along the course of the follow-up of our patients, more common surgical doses were augmented because of the unsatisfactory outcome, in addition to the application of stay sutures in 6 patients.

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4CONCLUSIONS

Smaller deviations of CFEOM patients can be corrected by common recess-resect and transposition procedures, however larger deviations with extreme restriction are difficult to overcome with even augmented surgery, and reoperations are not rare. Stay sutures can improve the results of augmented surgery in these cases.

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

Surgical management in a newly identified CFEOM/postaxial oligo-syndactyly syndrome

Acun Gezer1 & Turgut Tükel2,3,4

1Istanbul University, Medical Faculty of Istanbul, Department of Ophthalmology, Itanbul, Turkey 2Departments of Human Genetics, Mount Sinai School of Medicine of New York University, New York, USA 3Istanbul University, Child Health Institute, Division of Medical Genetics, Istanbul, Turkey

4Istanbul University, Institute for Experimental Medicine, Department of Genetics, Istanbul, Turkey

ABSTRACT:

Objective: Surgical management of a newly identified syndrome consisting various forms of developmental anomalies of extraocular muscles innervated by the III. cranial nerve resembling CFEOM and oligodactyly is described.

Materials and Methods: Strabismus surgery is performed in four of the six members of the family. Two of the patients had clinical findings of double elevator palsy. On one of these patients an inferior rectus recession combined with superior rectus resection is performed, while the other patient underwent an inferior rectus recession. Superior oblique tenotomy and inferior rectus recession is performed in the third patient with clinical characteristics of Brown syndrome. Moderately affected fourth patient had the clinical presentation of a pseudo-Brown syndrome and exotropia and underwent merely a lateral rectus recession.

Results: All of the patients yielded satisfactory clinical results with reduction of the significant misalignment of their eyes.

Conclusions: The choice of procedure in CFEOM patients must be individualized according the preand peroperative findings.

1BACKGROUND

The combination of congenital blepharoptosis and restricted eye movements was first reported in 1879 by Heuk. In 1950, Brown described this group of ocular disorders in detail and subcategorized them into five distinct phenotypes: 1) horizontal retraction syndromes, 2) strabismus fixus, 3) vertical retraction syndromes, 4) superior oblique tendon sheath syndromes, and 5) a general fibrosis syndrome. Currently, the horizontal retraction syndromes are referred to as Duane syndrome, the superior oblique tendon sheath syndromes as Brown syndrome, and the remaining syndromes as congenital fibrosis of extraocular muscles (CFEOM)1.

Initially, these disorders were considered primarily due to fibrosis of the extraocular muscles (EOM). However, recent neuropathological studies revealed that some of the fibrosis syndromes resulted from defects in the development of particular brainstem alpha motor neurons and their corresponding axons2,3. To date, three inherited CFEOM syndromes have been mapped to different genetic loci. CFEOM1 (OMIM #135700), an autosomal dominant disorder, was mapped to 12q124, and the disease-causing gene was recently identified as KIF21A5. Affected individuals have bilateral ptosis and restrictive ophthalmoplegia, and their eyes are fixed below the horizontally neutral position with or without secondary esotropia or exotropia. Phenotypically, this syndrome is variable with some affected individuals having a milder phenotype, which resembles CFEOM3, but have been linked to CFEOM1 locus, and are referred to as CFEOM3A (OMIM %607034)6. The CFEOM2 locus (OMIM #602078), an autosomal recessive disorder, was mapped to chromosome

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11q13.3 in three consanguineous Saudi Arabian families7, and subsequently, mutations in ARIX gene were described8. Affected individuals with CFEOM2 have bilateral ptosis with the eyes fixed in abduction which virtually prevents voluntary eye movements. CFEOM3 (OMIM %600638, formerly #604361), an autosomal dominant disorder originally descibed in a large Canadian family was mapped to a 5.6 cM region on chromosome 16q24.29. The CFEOM3 phenotype of affected individuals was variable and ranged from bilateral ptosis with fixed eyes in an infraducted and exotropic position to normally positioned eyes with minimal limitation of vertical gaze and unilateral or absent ptosis. To date, the gene causing CFEOM3 has not been identified.

Here, we describe a new syndrome of CFEOM and ulnar abnormalities in a large consanguineous Turkish family and their surgical management.

2SUBJECTS AND METHODS

In five of the cases ocular studies and in four of them surgical treatment was performed. Histochemistry and electron microscopy of EOM, were performed in one patient, and genome-wide linkage analysis was made using DNA samples obtained from 13 individuals of the family.

3RESULTS

Six affected individuals spanning three generations, had mainly presented with right eye involvement and bilateral postaxial oligodactyly/oligosyndactyly of varying severity of the hands, with the right hand more severely affected.

Case #1 (II-7): 29 year old male. Bilaterally visual acuity was 10/10 and no remarkable refractive error was found. Slight chin up anomalous head posture was present. Right 14 pd exotropia and 25 pd hypotropia was found. The right eye had restricted elevation in both adduction and abduction. A slight pseudoptosis on the right eye existed. Forced duction test was found negative. MRI revealed a volume loss of the right SR and hypertrophy of the IR muscle. Patient had oligodactyly. His IR was recessed 5 mm and after 1 year of follow up his head posture were corrected with eyes rendered straight on the primary position.

Case #2 (II-12): 26 year old male with 1/10 OD and 10/10 OS visual acuity and a chin up head posture. Elevation of the right eye was restricted which was more significant on abduction. Right eye had a 12 pd exotropia and a 25 pd of hypotropia. Hemiptosis with no levator function and a poor Bell phenomenon was present. Forced duction test was negative. MRI showed light volume loss of the right SR and hypertrophy of IR. Oligodactyly was present. He firstly underwent a right IR recession and a SR resection 4 mm each. Three months later a frontalis suspension procedure performed which helped to correct ptosis with pupils free of lid intervention. After one year follow up patient is free of anomalous head posture with a 12 pd exotropia.

Case #3 (III-10): 4 year old female with 10/10 visual acuity bilaterally. She had restricted elevation on adduction in both eyes and a 16 pd right exotropia. A slight head tilt to the right shoulder occurred occasionally. MRI was normal and oligodactyly was present. Forced duction test was negative and 3-step test indicated a right IO dysfunction. This patient underwent a 5 mm LR recession and after one year she has a 10 pd exophoria.

Case #4 (III-11): 3 years old male with 1/10 OD and 10/10 OS visual acuity and no significant refractive errors. This patient had a 30 pd exotropia with 10 pd hypotropia on the right eye. Elevation was restricted and this was more marked in adduction than in abduction. A positive forced duction test showing a markedly restricted elevation in adduction resembling a Brown syndrome. He had a slight (pseudo)ptosis of the right eye and a slight head tilt towards the right side occurred intermittently. Three step test revealed a right IO defect. MRI was normal and oligodactyly also present. Firstly he underwent a right IR recession (4 mm) combined with SO tenotomy which resulted in A pattern exotropia, persistence of restricted elevation in adduction and

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restricted depression. Six months later a right SR resection performed which left the patient with a 25 pd exophoria and straight eyes in primary position, which helped his amblyopia to improve and occlusion therapy resulted in a visual acuity increase from 1/10 to 6/10.

Case #5 (IV-1): 2.5 years old female. She was the most severely affected member of the family. Total ptosis, enophthalmia, microcornea and tilted disc anomaly on the right side was found. Right eye movements were restricted in all directions, while they were normal on the left.

The MRI confirmed enophthalmia but did not reveal any additional abnormalities. Oligodactyly was also present. Her follow up and surgical management were done at another

institution and we had no opportunity to obtain further data.

On light microscopic examination right superior rectus muscle revealed primarily fibrous tissue and no muscle cells. In contrast, the inferior oblique muscle showed skeletal muscle with mild, non-specific variation in fiber size by routine light microscopy. No abnormalities were observed by histochemical analysis or electron microscopy

With the genomic scan of the family, the disease locus was mapped to 21q with a critical region of 1.5 cM between D21S1897 and the telomere of the long arm. A multipoint LOD score of 4.525 was obtained.

5CONCLUSION

The patients in this Turkish consanguineous pedigree define a new autosomal recessive syndrome of CFEOM with ulnar hand abnormalities. The five examined patients had CFEOM of varying severity, mainly confined to the right eye and postaxial oligodactyly/oligosyndactyly of both hands, more severly affecting the right hand . Although, clinical findings were variable between affected individuals, the penetrance was complete.

Clinically, two adult patients (#1, #2) had a double elevator palsy and ptosis of varying degree, most likely due to a N.III superior division defect. Younger patients (#3, #4) had more marked restriction of elevation in adduction. Patient #3 had a negative forced duction test, hence she is interpreted as a pseudo-Brown syndrome. Patient #4 was distinctive in having a more marked mechanical restriction to elevation in adduction resulting in a positive forced duction test, resembling a Brown syndrome. Histopathologically SR of Patient #4 was found fibrotic and IO was normal, raising the question if simply a secondary IO and/or IR contracture or a primary involvement may be the cause of restriction to elevation in adduction. The fifth patient had a more generalized pattern of extraocular muscle involvement with marked restriction of eye movements in all directions, total ptosis, enophtalmos, microcornea and disc anomaly10.

Our patients obviously represent an atypical form of CFEOM, by having clinical findings mostly consistent at least with the involvement of superior division of the N.III leading clinically to a double elevator palsy in different stages. The surgical management of patients with CFEOM is challenging. A staged approach to bring the eyes into a straight primary position with the order of first vertical, then horizontal and finally ptotic components is proposed11. In our study, moderate amount of surgery resulted in satisfactory results including normal head positions, better cosmesis and also improved vision in a young patient. We preferred an IR recession with/without a SR resection instead of a Knapp’s procedure because these patients had some degree of elevation above the midline. Supramaximal recessions12 are not always necessary because CFEOM phenotypes are highly variable13.

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