CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES* BY R. D. Harley, MD, M.M. Rodrigues, MD (BY INVITATION), ANDJ.S. Crawford, MD CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES IS characterized by the replacement of normal contractile muscle tissue by fibrous tissue or fibrous bands in varying degrees. The clinical entities which result from this alteration of normal muscle tissue presents a varying clinical picture depending on the number of muscles affected, the degree of fibrosis, and whether the involvement is unilateral or bilateral. Genetic factors may or may not be apparent. One of our pedigrees with the general fibrosis syndrome was traced through five generations.

Congenital fibrosis of the extraocular muscles has been described in the literature under the following headings: General Fibrosis Syndrome, Congenital Fibrosis of the Inferior Rectus with Blepharoptosis, Strabismus Fixus, Congenital Enophthalmos with Ocular Muscle Fibrosis and Blepharoptosis, and the Vertical Retraction Syndrome. The purpose of this paper is to briefly review the various forms of congenital fibrosis of the extraocular muscles, summarize the clinical findings and surgical management of twenty-eight patients and present the histopathological and electron microscopy findings in five patients. GENERAL FIBROSIS SYNDROME

This clinical entity represents the most severe form of the condition. Brown' reported three cases under the title of "General Fibro*From the Department of Pediatric Ophthalmology, Wills Eye Hospital and Saint Christopher's Hospital for Children, Philadelphia, Pennsylvania (Dr Harley); the National Eye Institute, National Institutes of Health, Bethesda, Maryland (Dr Rodrigues); and the Hospital for Sick Children, Toronto, Ontario (Dr Crawford). Supported in part by the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Inc. and Fight for Sight, Inc.

TR. AM. OPHTH. SOC., vol LXXVI, 1978

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sis Syndrome." All three patients showed complete bilateral ptosis, as well as paralysis of all the ocular muscles and represented an extensive involvement of these muscles. He observed that all the muscles including the levator muscle were involved in this bilateral condition. The inferior recti muscles are usually most prone to maximal involvement which causes the eyes to assume a hypotropic-position. Blepharoptosis is present in all of the patients with severe involvement. In this characteristic downward fixed position of the eyes of 20 to 30 degrees, patients generally adopt a chin-up position in order to fixate objects in front of them (Figure 1). In some patients on attempt to look upward, there is a jerky convergent movement. Forced ductions demonstrate a marked resistence to passive movement, especially in abduction. Horizontal movements may be absent or limited to a few degrees in either lateral direction. Binocular vision is rare and the exotropic position seems to be more frequent than the esotropic. Visual acuity seldom can be improved to 20/20 even in the fixing eye and amblyopia is common. Significant refractive errors with high astigmatism are frequent findings. The condition is present from birth and a family history is often present. Male and female individuals are equally affected and the condition occurs in each generation. Several large pedigrees indicate autosomal dominant inheritance. Parks2 illustrates such a pedigree through five generations. However, Waardenburg3 has indicated that the autosomal recessive mode does occur, but less commonly. CONGENITAL FIBROSIS OF THE INFERIOR RECTUS MUSCLE

Congenital fibrosis of the inferior rectus is probably a variant of the general fibrosis syndrome (Figure 2). The inferior rectus alone or the inferior rectus together with the levator may be involved with little or no involvement of the other extraocular muscles.4 The condition may be unilateral or bilateral and asymmetrical. Since the patient cannot elevate the eyes even to the midline, vision in the primary position is achieved by means of a compensatory backward head tilt. Binocular vision is often present. The familial and hereditary pattern so often present in the general fibrosis syndrome is rarely encountered. We have observed a number of ocular and systemic anomalies in conjunction with the fibrosis condition which is interesting and possibly significant. (Figure 3A, 3B, Figure 4, Figure 5)

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FIGURE 3 A: Patient before surgery. B: Patient after surgery.

STRABISMUS FIXUS

Strabismus fixus is a rare congenital disorder in which the eyes may be observed in a markedly fixed position of esotropia or exotropia, although the former is far more common. The extreme tightness of the medial or lateral bands indicates that the medial or lateral recti have been replaced by fibrous tissue and this observation has been made at the time of surgery.5 6 The eyes are so firmly fixed that they cannot be actively or passively moved in a horizontal direction; however, vertical movement is possible. This disorder is probably a variant of the congenital fibrosis group, although it has been considered to have occurred secondary to lateral rectus palsy. Villaseca7 has concluded from his study of three cases that there are forms of congenital strabismus fixus that can be reversed during the first few months of life suggesting that the spastic medial rectus muscle undergoes a fibrotic change with time. VERTICAL RETRACTION SYNDROME

Vertical retraction which was well described in two siblings by Khodadoust and von Noorden8 may be an additional expression of

202

Harley, Rodrigues, and Crawford

FIGURE 4

Pedigree chart showing inheritance through five generations.

the congenital fibrosis syndrome. This condition was reported as the ability to depress either eye in abduction and with resistance encountered on attempted elevation. One patient exhibited a pronounced exotropia in upgaze; the other patient had an exotropia in downgaze. Forced ductions were positive in the vertical direction, but the horizontal movements were not impaired which indicated that the fibrosis involved both vertical recti. There was retraction of the globe on attempted downgaze which suggests that the fibrosis was principally confined to the superior rectus.

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Harley, Rodrigues, and Crawford

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Case 2. Replacement of striated muscle by dense fibrous tissue (*) (Toluidine blue, x 500).

Tirelli 1935,1f Brown 1950,1 Holmes 1956,'7 Laughlin 1956,18 Garzino 1956,19 Goldstein 1964,20 Hansen 1968,21 Paolillo and Burch 1969,22 Knapp 1969,23 Lyle 1970,24 Leone and Weinstein 1972,7 and Prieto-Diaz and Laguens 1973.25 Crawford described sixteen cases and reported on the surgical results of fourteen in 1970.26 Rumpf studied six generations of a family consisting of twenty-eight persons, among whom sixteen individuals had congenital fibrosis in 1974.27 The affected persons consisted of eight male and eight female individuals. Electromyographic studies were unable to demonstrate any neuro-muscular response but the author noted that the electrode insertion was uncertain.

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FIGURE 7

A: Case 3. Interlacing bundles of smooth muscle (arrows) with adjacent connective tissue (Masson trichrome, x 200). B: Electron micrograph showing replacement of skeletal muscle by collagen fibrils with a 45-50 nm period (x 37, 660). C: Electron micrograph showing a fibroblast (F) with prominent rough-surfaced endoplasmic reticulum. Adjacent collagen fibrils (arrows) are present (x 9,000).

SUBJECTS AND METHODS

We have combined the experiences of three investigators on the subject of congenital fibrosis of the extraocular muscles in order to present an overview of the subject to include clinical findings, surgical management, and the histopathology. Twenty-eight patients have been selected including sixteen patients previously reported by one of us (J.S.C.) together with variations of the fibrosis

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Harley, Rodrigues, and Crawford

A~~ FIGURE 8 A: Case 4. Replacement of the medial rectus muscle by fibrous tissue. (Toluidine blue, x 500). B: Striations (arrows) are still evident in some. areas of partly degenerated striated muscle from the lateral rectus muscle (Masson trichrome, x 500).

condition such as four cases of fibrosis of the inferior rectus and one case each of strabismus fixus, the vertical retraction syndrome, and the combination of unilateral congenital fibrosis of the extraocular muscles, enophthalmos, and ptos is. In five patients the muscle biopsies (approximately 10 mm from the tendonous insertion) were taken from areas where one would assume normal muscle tissue to be present. The specimens were bisected in the operating room and half of the specimen was fixed in formalin, embedded in parafin, and stained with hematoxylin and eosin in addition to Masson trichrome. The other half was fixed in 2.5% phosphate buffered glutaraldehyde, dehydrated through ascending concentrations of alcohol, and embedded in epon. Thin sections were stained with uranyl acetate and lead citrate and examined with a Siemens 101 electron microscope. CASE REPORTS CASE1

A typical case history was that of a 52-year-old man who had severe

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FIGURE 9 A: Case 4. Electron micrograph demonstrating myofibrils (*), mitochondna (M) and prominent z-bands (arrows) (x 13,030). Relatively normal lateral rectus muscle. B: Prominent glycogen particles (arrows), mitochondria and myofibrils (x 60,200). Lateral rectus. C: Well defined triads (T-tubes) (arrows) bounded by electron dense sacs of sarcoplasmic reticulum (x 60,200). Lateral rectus muscle. D: Scattered lipid material. Lateral rectus muscle.

bilateral blepharoptosis since birth. The patient had found reading tiresome and stopped school after the ninth grade. He drove a truck for 15 years but driving with his head tilted back and his chin elevated to see caused tension and pain in the neck muscles. Visual acuity was right eye 20/100 corrected to 20/30 with +1.00 +2.00 x 90, and left eye 20/200 corrected to 20/60 with + 1.50 +2.00 x 90. There was a right hypotropia of 20 degrees below the midline and left hypotropia of 15 degrees together with an exotropia of twenty prism diopters. Attempts to elevate his eyes produced slow jerky spasms of convergence. The remainder of the eye examination was normal. A family history disclosed that the father, sister, and son had a similar condition. The surgical management consisted of a bilateral complete tenotomy of the inferior recti at their scleral insertion. No muscle tissue was observed and in its place was inelastic fibrous tissue.

208

Harley, Rodrigues, and Crawford Both eyes were elevated by means of a suture secured into the remaining tendonous stump of the sclera and brought out through the lower lids. Both inferior recti were permitted to retract and re-attach posterior to the former insertion. Following this procedure there was still a small residual hypotropia. Six months later a bilateral frontalis suspension using facia lata was performed. In addition an ellipse of skin from both upper eye lids was excised in order to remove excess skin and create a lid fold. When the patient attempted to look up he still had jerky convergent eye movements. On reconsideration of this surgical approach, a large six or seven millimeter recession of the inferior recti might be preferable to the free tenotomy of the inferior recti although the clinical improvement was apparent with the former method. A histopathologic report on the inferior rectus biopsy showed "fibrous tissue." CASE 2

A 4-year-old white boy was first examined at age one and demonstrated a marked congenital bilateral blepharoptosis, bilateral hypotropia and a 35 prism diopter esotropia associated with a pronounced backward head tilt. A cycloplegic refraction showed OD +2.00 +1.50 x 90 20/60; OS +2.50 +2.00 x 90 20/60. The remainder of the eye examination was normal. No similar condition was known to be present in any family member or relative. Forced duction maneuvers indicated a complete immobility to passively move either eye upward, but voluntary horizontal movements appeared unaffected. Occlusion therapy improved the visual acuity of the left eye which had been amblyopic. The following surgical procedures were performed: 1) A bilateral maximal levator resection was followed by a bilateral frontalis suspension since the former procedure proved in-

adequate. 2) A bilateral recession of the inferior recti 5 mm each. 3) A bilateral recession of the medial recti 5 mm each. Three years postoperatively the eyes appear straight and the lids have been sufficiently elevated to permit the head to be held in a straight frontal position. HISTOPATHOLOGY

Microscopic examination revealed total replacement of muscle by fibrous tissue in the biopsies from the inferior recti (Figure 6). A biopsy from the left levator tissue exhibited similar findings. There was a complete absence of skeletal muscle by light or electron microscopy. CASE 3

A 3-year-old black girl presented with a bilateral congenital blepharoptosis, bilateral hypotropia, and a backward head tilt with elevation of the chin. The refractive error was OD -0.50; OS -5.00 x 180. Fixation and

209 Congenital Fibrosis following movements were equal in each eye and although amblyopia was suspected in the left eye, a satisfactory visual assessment could not be definitely recorded at this time. No familial history of a similar situation could be elicited. A complete immobility of the eyes for upward gaze was present but horizontal movement seemed unimpaired. The remainder of the eye examination was normal. Under anesthesia, forced ductions showed complete restriction of elevation. Surgery consisted of two proce-

dures two months apart: 1) A 5 mm recession of the right inferior rectus and a frontalis sling of the right upper lid. 2) A 6 mm recession of the left inferior rectus and frontalis sling of the left upper lid. Six months postoperatively the head was straight in the primary position, but a slight residual head tilt persisted. Abduction and adduction were normal but marked limitation of depression and elevation persisted. Mild residual ptosis of the left upper lid was evident. Biopsies of both inferior recti and levators were taken. HISTOPATHOLOGY

The levator specimen was composed primarily of fibrous tissue except for an area of smooth muscle. (Figure 7A) The inferior recti were replaced by collagen. Electron microscopy demonstrated collagen fibrils with prominent 45-50 nm banding. (Figure 7B) Fibroblasts showed prominent rough endoplasmic reticulum and adjacent collagen fibrils. (Figure 7c) There was no evidence of skeletal muscle. CASE 4

A 17-year-old white man presented with a right esotropia of 40 prism diopters which was noted at age one. The family history was negative for similar eye defects. A surgical correction for esotropia had been performed at five years of age, but the records indicated a persistent esotropia. No abduction was present and abduction was limited in the right eye but vertical movements were full and normal. Cycloplegic refraction showed OD +1.50 +1.00 x 90 20/40; OS +1.75 +0.75 x 90 20/40. Normal movements were present in the left eye. The remainder of the right eye examination was within normal limits. A partial right facial weakness and a bilateral talipes equinovalgus were present. The surgical management consisted of a 5.5 mm recession of the right medial rectus and a 7 mm resection of the right lateral rectus. Biopsies were taken of the medial and lateral muscles. Postoperatively there was some residual right esotropia of 10 prism diopters. No adduction was present, but abduction was considerably improved but limited. HISTOPATHOLOGY

The medial rectus biopsy specimen revealed total fibrous tissue. (Figure 8A). The lateral rectus which did not appear clinically involved had nega-

210

Harley, Rodrigues, and Crawford tive forced ductions and showed evidence of striations (Figure 8B) in some muscles. Electron microscopy demonstrated myofibrils, z-bands (Figure 9A), moderate numbers of mitochondria and considerable glycogen accumulation (Figure 9B). The sarcoplasmic reticulum showed prominent transverse systems of tubules (T-tubes) (Figure 9c) and triads (T-tubes bounded by electron-dense lateral sacs on either side). Lipid material was present (Figure 9D) and vacuolar degeneration was noted in some areas. Myelinated nerves were observed adjacent to skeletal muscle. CASE 5

A 6-year-old white girl presented with a blepharoptosis and an exotropia of 35 prism diopters of the right eye since birth. There was no history of similar eye defects in the family. A cycloplegic refraction showed OD + 1.50 + 1.50 x 135 20/80; OS + 1.50 + 1.00 x 135 20/80. No horizontal gaze movement of the right eye was possible on voluntary gaze. The left eye was normal. The remainder of the eye examination was within normal limits. At surgery, forced ductions indicated fixation of the globe in the divergent position. A 7 mm resection of the right medial rectus was performed. Biopsies of the horizontal muscles were taken as well as a small portion of the superior rectus muscle. HISTOPATHOLOGY

Microscopic examination of the medial and lateral recti revealed only fibrous tissue with no evidence of skeletal muscle. This finding was confirmed by electron microscopy. The superior rectus biopsy showed mostly fibrous tissue and a small area of degenerated skeletal muscle. CASE 6

A 2-year-old white male was referred with a marked congenital esotropia measuring approximately 65 prism diopters by the Krimsky method. The child was unable to fixate light in the primary position, but found it necessary to turn his head to see right or left. Examination disclosed an esotropia of each eye but no abduction movement even on occlusion. A diagnosis of strabismus fixus was made. The cycloplegic refraction indicated OD + 0.75; OS + 1.00. The fundi were negative and the remainder of the eye examination was normal. At surgery, an attempt at forced ductions indicated complete immobility of the medial recti. A 6 mm bilateral recession of the medial recti was performed with considerable technical difficulty. Postoperatively the esotropia was considerably undercorrected, and at reoperation a complete bilateral tenotomy of the medial recti tendons was required. The eye was held in the primary position with fixation sutures and the final result was cosmetically acceptable. No horizontal movements were observed and the vertical movements were normal. HISTOPATHOLOGY

Microscopic examination of the medial recti disclosed fibrous tissue only and no evidence of skeletal muscle.

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CASE 7

A 4-year-old white girl was first seen at the age of six months with a right hyperesotropia, enophthalmos, and partial blepharoptosis with extremely limited motility of the right eye in all directions of gaze, especially abduction. The right esotropia measured 40 prism diopters and the right hypertropia 15 prism diopters. The right eye was preferred for fixation. Atropine sulfate 1% and a patch were instituted for the right eye to improve fixation of the left eye. Two months later the right esotropia had decreased to 15 prism diopters, although the hypertropia persisted. Limitation of abduction persisted. Latent nystagmus was present bilaterally. Ocular motility was otherwise entirely normal in the left eye. Roentgenograms of the orbits were normal. A cycloplegic refraction showed OD +2.00 +1.00 x 90 6/12; OS +2.50 +1.50 x 90 6/18. Bilateral hypoplasia of the optic disc was present and may account for the reduced visual acuity. A distinct enophthalmos was now evident with persistent abducting and elevating paresis.

Under anesthesia forced ductions were not possible in any direction and all muscles appeared involved. Surgical management at age five consisted of a 4 mm recession of the right superior rectus and a 4 mm resection of the right inferior rectus. Biopsies were taken of both muscles. Surgical manipulation was difficult due to inadequate exposure as a result of ocular immobility. Blepharoptosis correction with a frontalis suspension will be required. HISTOPATHOLOGY

Light and electron microscopy showed replacement of skeletal muscle by collagen.

REVIEW OF HISTOPATHOLOGY

Normal extraocular muscle exhibits prominent z-lines, occasional electron-dense rods, and myofibrils. In degenerating muscle, myelin bodies, membranous bodies, mitochondrial changes, damage to myofibrils, and increased accumulation of glycogen and lipid are frequently present. In all of our patients, the muscle biopsies were taken at least 10 mm or more above the tendonous insertions of the involved muscles. The structure of muscles of the upper eyelid in the normal and diseased state has been described by Kuwabara and associates.31 In 28 patients with congenital ptosis they observed considerable reduction or lack of the normal striations of the levator muscle, about

Harley, Rodrigues, and Crawford 1 cm superior to the tarsus. Absence of z-bands and vacuolation of muscle cells were also noted but the smooth muscle cells of Muller appeared intact. This was also observed in our patients in which associated congenital ptosis was present. Pachter and associates32 216

reported a case of congenital total external ophthalmoplegia and infantile spinal muscular atrophy. They analyzed 50 end plates by electron microscopy and attempted to differentiate neurogenic and myopathic atrophy. In our cases, neural elements appeared normal and the pathologic alterations were suggestive of myopathic rather than neuropathic abnormalities. Progressive external ophthalmoplegia may be associated with a defect in pyruvate metabolism and is characterized by degeneration of both muscle and nerve cells as well as abnormal mitrochondria. Laughlin18 reported six cases of this entity and noted that bundles of collagen were enclosed in dense fibrous tissue but no muscle tissue was seen. In four patients with unilateral congenital fibrosis and enophthalmos described by Leone and Weinstein, the condition was nonfamilial and the surgical treatment was only partially successful. Rumpf27 reported a light and electron microscopy examination on biopsied specimens taken from an involved inferior rectus and a normal medial rectus in congenital fibrosis of the inferior rectus. The medial rectus showed normal muscle fibers. However the inferior rectus exhibited an absence of muscle cells and replacement by collagen fibers. Anomalous posterior tendonous insertions and an absent lateral rectus were reported in a survey of six generations in which the transmission was autosomal dominant. Prieto-Diaz and Laguens25 described three patients with congenital fibrosis of the inferior rectus muscle. In two patients, light and electron microscopy of biopsy specimens showed changes compatible with muscle dystrophy. There were small areas of muscle fibers surrounded by dense connective tissue. The myofibrils appeared abnormal and the mitochondria displayed degenerative changes. In some areas disrupted myofibrils and lipid vacuoles were observed. They assumed that the pathologic changes were myopathic rather than neuropathic. Frazzetto33 and co-workers made an extensive study of three cases from the same family and arrived at the same conclusion. Hornblass and associates34 recently described a clinical and electron microscopic study of 33 biopsy specimens of the anterior levator, excised from patients with congenital and acquired ptosis.

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They noted a direct correlation between the severity of the ptosis and the atrophy of the levator muscle. They also confirmed earlier observations by Isaksson that congenital ptosis probably represents a myogenic disease rather than a neurogenic alteration. In summary, microscopic examination of biopsied material from 14 of our patients revealed total replacement of muscle by fibrous tissue in all specimens. There was no evidence of skeletal muscle by light or electron microscopy. Four additional levator muscle biopsy specimens were found to be composed of fibrous tissue primarily except for small areas of smooth muscle.

ASSOCIATED DEFECTS

Certain ocular conditions and systemic defects were observed among our congenital fibrosis patients and concurrent defects were also encountered in the literature. The ocular defects included a high incidence of hyperopic astigmatism, subnormal visual acuity, amblyopia and strabismus. Hypotropia was regularly observed in all the general fibrosis patients as well as those in which the fibrosis was primarily confined to inferior rectus muscle. Exotropia was somewhat more frequently encountered than esotropia. Other anomalies which have been reported consist of unilateral enophthalmos (Leone and Weinstein 4 cases) and our Case 7, the Marcus-Gunn jaw wink in two cases (Vossius and Rumpf), ventricular septal defect (Hansen), anomalous posterior tendonous insertions and an absence of the lateral rectus (Rumpf), choroidal coloboma and secondary fibrous bands (Brown), pendular nystagmus and bilateral optic disc hypoplasia (Case 7) and talipes equinovalgus and unilateral fascial palsy (Case 4). The fibrosis of the medial rectus in Case 4 may be secondary to a neurological defect since the possibility of a congenital sixth and seventh nerve defect must be considered. Histologically only minimal changes are to be observed in the lateral rectus but abduction was limited suggesting a neurological defect. Situs inversus of the left optic nerve head, right fascial asymmetry, and ptosis were present in one child with the vertical retraction syndrome (Khodadoust and von Noorden). Patients with sporadic Duane's retraction syndrome (congenital aberrant innervation) appear to have a significant increase in the number of associated congenital malformations.30

218

Harley, Rodrigues, and Crawford The ocular defects were noted predominantly among patients with autosomal dominant inheritance whereas the other anomalies occurred in the sporadic cases without a known genetic background. DISCUSSION

A review of our patients with congenital fibrosis of the extraocular muscles suggests that while the underlying pathology and physiology in all were quite similar, the clinical manifestations often varied from complete involvement of all the extraocular muscles, including the levator, to specific muscles, bilateral as well as unilateral. In the general fibrosis syndrome characterized by involvement of all the extraocular muscles the similarity of the twenty-one cases observed by one of us U.S.C.) was striking. Twenty-one of the twenty-eight patients were classified as having the general fibrosis syndrome. Inheritance through five generations in one family is typical of autosomal dominant inheritance in which half of the offspring remain unaffected with normal offspring. An anomalous feature of the pedigree of this family was that the parents of the 2-1 were first cousins and reportedly unaffected. In three of the nine families examined there was clear evidence of autosomal dominant inheritance. Brown1 reported three cases of general fibrosis syndrome in which he found abnormal fibrous bands, abnormal tendonous insertions, and extensive secondary attachments but no familial history. Reports from other workers emphasize the frequency of factors which have been encountered that cause altered or restricted motility.28'29 Other patients demonstrated variations of the congenital fibrosis condition. We have observed six patients who exhibited primarily fibrosis of the inferior rectus and levator with minimal involvement of the other extraocular muscles. These patients had the classical findings of a backward head tilt, ptosis, and a horizontal deviation. Only four of these patients were included in this reported series. Another variant of the congenital fibrosis syndrome involves the horizontal muscles primarily such as observed in strabismus fixus. Congenital unilateral fibrosis of the ocular muscles with ptosis and enophthalmos and the vertical retraction syndrome are additional examples of the fibrosis group. In our patient with strabismus fixus (Case 6), the marked esotropic position required a horizontal head turn in order to fixate objects

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directly in front of him. There was no evidence of diplopia. The lateral field was reinforced by cross fixation. A large recession of the medial recti was insufficient since a reoperation disclosed a continuing positive response to forced ductions. In addition to replacement of the medial rectus muscle by fibrous tissue, numerous abnormal fibrous bands were observed to restrict abduction. Adequate surgical exposure was difficult. Unilateral congenital fibrosis of the ocular muscles with enophthalmos and blepharoptosis represents a recently recognized manifestation of the fibrosis condition (Case 7). Leone and Weinstein9 reported four patients with unilateral congenital fibrosis, enophthalmos, and blepharoptosis and no family history of the disorder. Each of the cases illustrated the following features: 1) Congenital: nonfamilial. 2) Unilateral. 3) Marked limitation of motility. 4) Blepharoptosis. 5) Fibrosis of ocular muscles and fascia. 6) Enophthalmos. 7) Surgical management difficult. We have added an additional case to this study which resembled in all respects their four reported case studies. The extensive fibrosis apparently involves all the orbital soft tissues causing a secondary retraction of the globe. A vertical retraction syndrome was present in both eyes of two children of a sibship of five. Ocular motility was normal in all other members of the family. In one child with the vertical retraction syndrome an incomplete situs inversus of the optic nerve head was present. We have observed a similar patient who8 exhibited marked resistance to elevation and depression, especially in abduction and to a much lesser extent on adduction. Our patient had unilateral involvement while the reported cases were bilateral. Horizontal movements were unaffected and since the eyes appeared straight, no further treatment was advised. The results of the forced duction tests indicate that structural rather than neurogenic anomalies are probably the basis for the vertical retraction syndrome in these patients. MANAGEMENT

The surgical management of congenital fibrosis of the extraocular muscles and levator must aim for functional readjustment and im-

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proved appearance. In those patients with hypotropia, a pronounced backward head tilt and chin-up position, a maximal recession of the inferior recti is indicated and relieves the exaggerated, uncomfortable position. However, elevation of the hypotropic eye accentuates the ptosis problem to the extent that a frontalis suspension is required at the same time or soon following the motility correction. The horizontal deviation can be adjusted subsequently. In our experience, levator resection for correction of ptosis is effective only in mild cases so that a frontalis suspension is generally the procedure of choice. Correction of ptosis by brow suspension for patients without Bell's phenomenon produces a significant lagophthalmos which can produce corneal complications. In such patients the lid is elevated only to the upper pupillary border and no complications have been encountered with this procedure. Twenty-two patients had a marked hypotropia indicating that the inferior rectus is the most affected muscle. Eleven patients had an exotropia and five exhibited an esotropia. Twenty-seven of the patients required surgical correction and 17 had correction of the ptosis. The frontalis sling using fascia lata was the operation of choice. Two corneal problems were encountered; one was a prolonged exposure keratopathy and the other was a corneal leukoma. Operative procedures of various types offer much for the patients. However, the responsibility of the ophthalmologist is not only correction of strabismus and ptosis. Many of these individuals require genetic counselling and this service should be made available. SUMMARY

Congenital fibrosis of the extraocular muscles is characterized by the replacement of normal contractile muscle tissue by fibrous tissue or fibrous bands in varying degrees. The clinical entities which result from the fibrous replacement can be classified under the following headings: general fibrosis syndrome, congenital fibrosis of the inferior rectus muscle with blepharoptosis, strabismus fixus, vertical retraction syndrome and congenital unilateral fibrosis, enophthalmos and blepharoptosis. Genetic factors may or may not be apparent. One pedigree with general fibrosis syndrome was traced through five generations. Light and electron microscopy demonstrated replacement of nor-

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mal muscle by collagen and dense fibrous tissue with occasional areas of degenerated skeletal muscle. The surgical mangement attempts to achieve some functional readjustment of the ocular and lid position as well as the abnormal head posture. The surgical results were considered satisfactory when compared with the original position of the eyes and the backward head tilt.

REFERENCES 1. Brown HW: Congenital Structural Muscle Anomalies. Strabismus Ophthalmic Symposium. Ed Allen JH. St Louis, CV Mosby, 1950, p 205. 2. Parks M: Ocular Motility and Strabismus, Fibrosis Syndrome. Hagerstown, Harper and Row, 1975, pp 170-172. 3. Waardenburg PJ: Ueber eine recessive Form Angeborener Ophthalmolplegie. Genetica 6:487, 1924. 4. von Noorden GK: Congenital hereditary ptosis with inferior rectus fibrosis. Arch Ophthalmal 83:378, 1970. 5. Bielschowsky A: Lectures on Motor Anomalies. Hanover, Dartmouth Press, 1940, p 71. 6. Duke-Elder S, Wybar K: Ocular Motility and Strabismus. Chapter VI, St Louis, CV Mosby, 1973, p 476. 7. Villaseca A: Strabismus Fixus. Am J Ophthalmal 48:751, 1959. 8. Khodadoust AA, von Noorden GK: Bilateral vertical retraction syndrome. Arch Ophthalmal 78:606, 1967. 9. Leone CR, Weinstein GW: Orbital fibrosis with enophthalmos. Ophthal Surg 3:71, 1972. 10. Baumgarten: Cited by Henck G. 11. Heuck G: Ueber angeborene vererbte Beweglichkeitsdefekte der Augen. Klin Monatsbl Augenheilk 17:253, 1879. 12. Lawford JB: Congenital hereditary defect of ocular movements. Trans Ophthalmol Soc UK 8:262, 1888. 13. Vossius A: Zwei Fiille von angeborener, fast vollstandiger Unbeweglichkeit beider Augen und der oberen Augenlider - Beitr Augenheilk 5:1, 1892. 14. Westfall W: Ueber einen Befund der Augenmuskeln bei Ophthalmoplegie. Munch Med Wochensch r 11:30, 1888. 15. Fuchs E: Uber isolierte doppelseitige Ptosis. Albrecht von Graefes Arch Klin Ophthalmol 36:234, 1890. 16. Tirelli G: Sulla Ptosi Congenita Creditaria della palpebre superiore. Ross Ital Ottal 4:224, 1935. 17. Holmes WJ: Hereditary congenital ophthalmolplegia. Trans Am Ophthalmol Soc 53:245, 1956. 18. Laughlin RC: Congenital fibrosis of the extraocular muscles. Am J Ophthalmol 41:432, 1956. 19. Garzino A: Ptosis palpebrale ed oftalmolplegia estema congenite e familiari in clinque gererazione. Ross Ital Ottal 26:436, 1957. 20. Goldstein JH: The intraoperative forced duction test. Report of a case of congenital fibrous brands. Arch Ophthalmol 72:647, 1964. 21. Hansen E: Congenital general fibrosis of the extraocular muscles. Acta Ophthalmologica 46:469, 1968.

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22. Paolillo R, Burch P: Infantile contracture of the inferior rectus muscle. Am J Ophthalmol 68:1057, 1969. 23. Knapp P: The surgical treatment of double elevator paralysis. Trans Am Ophthalmol Soc 67:204, 1969. 24. Lyle TK: Surgical management of congenital muscle-fascial anomalies in strabismus. St Louis, CV Mosby, 1970. 25. Prieto-Diaz J, Laguens R: Fibrosis congenita del recto inferior. Arch Oftalmol. (Buenos Aires) 48:301, 1973. 26. Crawford JS: Congenital fibrosis syndrome. Can J Ophthalmol 5:331, 1970. 27. Rumpf M: Fibrose du muscle droit inferieur etc (Six Cases) Ann d'Oculist (Paris) 207:831, 1974. 28. McNeer KW, Jampolsky A; Double elevator palsy caused by anomalous insertion of the inferior rectus. Am J Ophthalmol 59:317, 1965. 29. Fink WH: A study of the anatomical variations in the attachment of the Oblique Muscles of the Eyeball. Trans Am Acad Ophthalmol Otolaryngol 51:500, 1947. 30. Pfaffenback DD, Cross HE, Keams TP: Congenital Anomalies in Duane's retraction syndrome. Arch Ophthalmol 88:635, 1972. 31. Kuwabara T, Cogan DG, Johnson CC: Structure of the muscles of the upper eyelid. Arch Ophthalmol 93:1184, 1975. 32. Pachter BR, Pearson J, Davidowitz J, et al: Congenital total external ophthalmolplegia associated with infantile, spinal muscular atrophy. Fine structure of extraocular muscle. Invest Ophthalmol 15:320, 1976. 33. Frazzetto F, Streiff EB, Forssmann WG: L'Ophthalmomyopathie congenitale. Ann Oculist (Paris) 12:1217, 1969. 34. Hornblass A, Adachi M, Wolintz A, et al: Clinical and ultrastructural correlation in congenital and acquired ptosis. Ophthalmic .'urg 7:69, 1976.

DISCUSSION

DR MARSHALL M. PARKS. The autosomal dominant entity of congenital fibrosis of the extraocular muscles does exist and apparently the authors have shown the extraocular muscle tissue is replaced with noncontractile collagen. The severity of involvement of the various extraocular muscles varies among afflicted family members but the inferior recti invariably are tighter than other muscles causing the eyes to be held downward. Hence, the neck must be extended to see straight ahead which with increasing age causes a sore neck. This symptom is helped or avoided by recessions of the inferior rectus muscles, but now the pupils are displaced upward under the ptotic lids. A frontalis suspension procedure raises the ptotic lids above the pupils. Since the Bell's phenomena is lacking in these patients, it is wise to use a suture that is easily removable such as Supramid as opposed to fascia lata, in case the ptosis surgery must be reversed because of complication resulting from corneal exposure. I do the combined bilateral strabismus surgery and bilateral ptosis surgery at the same operation as illustrated in the following case. In November 1969 a 1-year-old male with bilateral ptosis and chin elevation presented with his mother who obviously had the same disorder. The mother was very knowledgeable about her family background and

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assisted in preparing a pedigree that identified family members with bilateral congenital fibrosis of the extraocular muscles in five successive generations. The mother's bilateral ptosis was symmetrical and total. Her eyes were practically immobile and fixed in a 30 degree downturned position that forced her to maintain a 30 degree chin up position. She volunteered that she had a "sore neck" caused by the persistent abnormal head posture. The patient had asymmetrical bilateral ptosis, greater on the left than the right, with symmetrically fixed 25 degree downturned eyes. The principle eye movement was approximately 45 degrees of abduction of the left eye. Associated with the fixed downturned eyes was 30 prism diopter of exotropia that decreased on attempted upgaze since the eyes converged (the left more than the right) rather than upturned. Occlusion between 18 months of age and 4 years of age and prescription of glasses at 4 years of age controlled the amblyopia of the left eye. In August 1970 the traction test revealed positive resistence to passive ductions of both eyes except abduction of the left eye. An 8 mm recession of each inferior rectus muscle and an 8 mm recession of the right lateral rectus was performed along with bilateral frontalis suspension procedure of both upper lids using 4-0 Supramid suture. A 5 mm elipse of skin was excised from the left upper lid. The chin-up head posture and appearance were improved. By 1976, 40 prism diopters of exotropia returned and a 25 prism diopter right hypertropia appeared. In January 1977 an 8 mm recession of the left lateral rectus and an additional 7 mm recession of the previously 8 mm left inferior rectus (total of 15 mm recession) was performed. The previously recessed left inferior rectus was extremely tight. The child still maintains 20 degrees chin elevation. The lid levels are symmetrical and satisfactory in appearance and the eyes appear horizontally and vertically straight when last examined in January 1978. The above example of a documented congenital fibrosis syndrome well illustrates (1) the autosomal dominant inheritance of the disorder and (2) the variable involvement of the various extraocular muscles with increasing age and among various afflicted family members. However, it is reasonable to assume that possibly formes frustes of this disorder would result in less clear hereditary patterns and less severe degree of involvement among the 14 intraorbital muscles. Apparently, the authors use this tactic to link together the various disorders discussed in this paper. However, is this a valid tactic? One would suspect that if the other disorders discussed by the authors were merely less involved forms of the full-blown general fibrosis syndrome that not all cases of congenital fibrosis of the inferior rectus muscle, strabismus fixus, vertical retraction syndrome, and congenital unilateral fibrosis with enophthalmos and ptosis would be sporadic. Instead, I would anticipate some evidence at least that they also are autosomal dominant disorders like the general fibrosis syndrome. In the absence of support for a genetic cause of these disorders discussed by the authors I wonder if they actually are formes frustes of the general fibrosis

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syndrome. Could not these other disorders just as well be unrelated sporadic separate components within the spectrum of extraocular myopathies characterized by collagen replacement of normal contractile tissue? The authors are congratulated for studying so thoroughly the clinical and histological aspects of such a volume of patients with extraocular myopathies. Surely this study will be identified as a noteworthy contribution to the field of myopathies and attract much attention by subsequent investigators for a long time to come. DR THOMAS P. KEARNS. As you know, I'm not a strabismus surgeon, but I do know about chronic progressive external ophthalmoplegia in which similar lid problems are present. I would like to reiterate that point that Doctor Parks made about using the Supramid suture or some other similar technique. I believe that we should not do cosmetic lid surgery on these patients but do visual lid surgery. If you get the lid too high there is going to be a problem with exposure keratitis. The combination of lagophthalmos from overzealous surgery for ptosis and the lack of a Bell's phenomena is a treacherous one. DR JOHN W. HENDERSON (ANN ARBOR). I would like to make a few comments. For the last year or year and a half I've been struggling with a patient who came to me in his early 40's with a combination of what I at that time called strabismus fixus. Both eyes were pointed down and were just about as far in as they could go. In addition, he also was developing cataracts. He also had complete ptosis and was going around with his head tipped backward and was using one eye at a time. Idiscovered that his mother had had exactly the same problem and had been treated in Philadelphia. Two or three things about him I learned the hard way. He does not have fibrotic muscles. He doesn't have muscles. He has fibrotic tissue bands not ncessarily in muscle positions. The only one in his right eye that I'm working on now is a band where the superior rectus should be. His eye was turned down with no evidence of anything below that could be a recognizable remnant or fibrotic alteration of an inferior rectus muscle. I had a problem with him in treating his cataract in trying to move his eye into a position where we could then fit him with an aphakic correction. I didn't feel that he needed an intraocular lens with all of his other problems. He has single vision lenses for distance and near with a good visual recovery to about 20/40. After the cataract extraction the ptosis was treated by Supramid slings with the problem of no Bell's phenomenon for protection. He still is caring for his eyes very carefully because his eye that I previously operated upon is still turned down and in, but he can now see through his aphakic correction. We are now starting with his second eye.

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His mother had exactly the same strabismus fixus with cataracts which were removed successfully in Philadelphia as noted earlier. When I began operating upon the muscles of his second eye, I recessed his conjunctiva. This I thought should be done because the tissue was very short. However, when you have a fixed eyeball and recess the conjunctiva, you may end up with a symblepharon unless you're very careful about using a glass rod and freeing it up. I learned this the hard way on his first visit back to the office. I found a total adhesion across where I had recessed his conjunctiva as part of the procedure. DR MICHEL MATHIEU. Once in a while one must not be too serious. Such is my intention at this time. I do not know if you were as impressed as I was by the fact that in all pictures shown, every one affected had a large smile. I would like to know if this gaiety is part of the syndrome. In fact on one particular picture only a dog was not really smiling.

DR JOHN S. CRAWFORD. I would like to thank the discussors. This is a very interesting syndrome. I have followed a number of these patients over a long period of time and have performed ptosis surgery on 16 of these patients. I have only had problems in one patient who developed an exposure keratitis. We must teach these patients how to tape their lower lid up at night and keep their corneas moistened until they can stand the exposure. Doctor Parks mentioned the fact that we group all these cases together and I'm inclined to agree with him because I think that the congenital fibrosis syndrome has its own unique characteristics that are different from the other conditions mentioned. In one paper by Doctor George Weinstein published in 1972 in Ophthalmic Surgery, he described unilateral involvement where there was fibrosis around the muscles and around the rest of the orbit. I never found this in these bilateral examples that I operated upon. In my patients the extraocular muscles could be dissected out quite easily, but the muscle was a fibrous band and would not stretch when pulled with a muscle hook. I would like to make one other interesting observation and that is in the family tree that Doctor Harley described. In the beginning when I was studying this family with 5 generations involved, I went back and looked at the grandparents of the proband who appeared to be normal from their picture. The picture came from an old Russian newspaper. We thought there must be something wrong, so I took this picture to our photographic department. When it was enlarged, we found the old lady in the first generation had her eyes painted in. The photographer had touched up the photograph to make her ptotic lids appear normal. I think it's important as Doctor Parks has stated that all the surgery be done at one time because with the last child in this family (fifth generation) I did a recession of the inferior recti and resected the superior recti. This raised the eyes to a good primary position, and the poor child was walking

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around holding his upper lids up with his fingers until I repaired the ptosis with fascia lata. That is the only patient I corrected in two stages. The rest of them I corrected the strabismus and ptosis in one operation. Doctor Phil Knapp mentioned that it's difficult to take a biopsy. In order to do a biopsy we put a hook under the inferior rectus muscle and pull it up as far as we can. We then put in a retractor and get well down on the muscle to take the biopsy. It may not have been 10 mm but it was certainly not in the muscle tendon. Thank you.