(Patney, S. A. : Strabismology Desk Reference, Chapter 41, Rajkot (India), JKAI Publications, pp.749-761).

NONPARALYTIC NONCOMITANT RESTRICTIVE STRABISMUS

CONGENITAL FIBROSIS OF EXTRAOCULAR MUSCLES (CFEOM)

Nonparalytic, noncomitant, restrictive strabismus is continued in this chapter. The next condition to be discussed is the rare but important congenital disorder of extraocular muscles called "Congenital Fibrosis of Extraocular muscles or CFEOM". It is one of the diseases affecting the extraocular muscles (EOM).

Definition

CFEOM is a rare congenital neuromuscular anomaly in which more than one muscle, sometimes more than three or possibly all the extraocular muscles are fibrosed. There is a ptosis in addition to hypotropia (the most common type of deviation in the patients suffering from this disorder) and/or other types of deviation.

The characteristic features of this anomaly are:

1. Compensatory head posture (elevation of chin)
2. Marked ptosis
3. Hypotropia due to downward fixation of one or both eyes
4. Anomalous convergent movements on attempted elevation or lateroversions
5. Familial or sporadic

History

• In 1840 Baumgarten seems to be the first to describe ptosis in association with restricted ocular motility.
• In 1879 Heuck for the first time reported a familial occurrence and also described postmortem findings in a case.
• In 1950 Brown¹ named the condition of fibrosis of three or more extraocular muscles as "General fibrosis syndrome".

Incidence and distribution

• Prevalence of the fibrosis syndrome in general or strabismic populations has not been reported.
• Cases have been reported from all over the world and
• From all communities and races.
• It seems that the generalized form of fibrosis syndrome is most common.
• But I think there is a possibility that cases in which there is fibrosis of a single isolated muscle it may not be recognized for what it is. Thus the case may get grouped under some other type of condition. For example, a mild form of inferior rectus fibrosis may be diagnosed as a contracture of the muscle secondary to congenital superior rectus palsy. The same thing happens when a bilateral case with severe involvement of one eye and only slight involvement of the other eye gets labeled as a unilateral case.

Etiology

There are various theories about the causation of CFEOM but the following are more popular:

The neurogenic theory

1. The myogenic theory

The neurogenic theory has more support and the neurologic cause is considered to be primary. The changes in the muscles that are found in cases of CFEOM are supposed to be secondary to the primary neurologic defect. Absence of superior division of oculomotor nerve and its alpha motoneurons was discovered in a case and generalized muscle fibrosis was found in the other three. In the latter there was a possibility of a primary myologic anomaly^7. It has been suggested that in CFEOM a primary developmental defect rules out normal neuronal connections⁸.

Classification

According to the classification by Harley et al² CFEOM is divided in to following types:

1. Generalized fibrosis of extraocular muscles
2. Fibrosis of inferior rectus with blepheroptosis
3. Strabismus fixus
4. Vertical retraction syndrome
5. Congenital unilateral fibrosis

Terminology

There are several names given to this condition by various authors at various times. Some of them are: generalized fibrosis of extraocular muscles, congenital ocular fibrosis, congenital ocular fibrosis syndrome, congenital fibrosis syndrome, syndrome of generalized fibrosis, congenital ophthalmoplegia, ophthalmoplegia imperfecta, hereditary congenital ophthalmoplegia, abiotrophic ophthalmoplegia externa, congenital external ophthalmoplegia with co-contraction and autosomal dominant congenital ophthalmoplegia.

Heredity and genetics

• Mode of transmission is often autosomal dominant³ but in my experience and others⁴ sporadic cases are more common.
• The gene for autosomal dominant CFEOM was mapped to chromosome 12 by Engle et al^{5, 6} but the gene has not been isolated so far and its function remains obscure.
• Evidence has been found that its gene may be involved in the development of the neurons of the III CN nucleus and probably also of other cranial nerves nuclei⁷.
• The expression of the gene is quite variable leading to a phenotype that is more severe and symmetric in some family members than in others. The resulting clinical picture may be quite variable with some cases being mild, some moderate and others severe in the same family. Also some may have symmetric anomalies in both eyes and others asymmetric.
• No chromosomal anomalies have been reported
• Autosomal recessive modes of transmission have also been reported⁴ with the anomaly affecting siblings and cousins in three Saudi Arabian families. The parents of affected individuals have consanguineous marriages and are themselves normal.

Symptomatology

According to Laughlin⁹ Congenital fibrosis syndrome consists of the following four components:

1. Blepheroptosis and chin elevation
2. Histopathologic evidence of fibrosis of the extraocular muscles
3. Absence of depression or elevation of the globe with the eyes fixed in 20-30 degrees depression
4. Little or no horizontal movements
5. A fifth feature that has been added¹⁰ is the absence of Bells phenomenon. It seems to be due to the mechanical restriction of elevation.

Other important features are given below:

• The cases of CFEOM may be symmetrically or asymmetrically bilateral. The asymmetry is sometimes so marked as to make the anomaly appear unilateral.
• The degree of involvement may vary from case to case from mild to severe.
• The number of muscles involved is also variable. In some cases all the extraocular muscles (EOM) are involved, in others only one may be affected.
• The patients of CFEOM are usually healthy but cases of rare associated ocular and systemic anomalies have been reported in sporadic cases.
• Some of the associated ocular anomalies reported are: chorioretinal coloboma, bilateral optic hypoplasia, retraction of the eyeball due to cocontraction, synergistic divergence due to neural misdirection, enophthalmos, microphthalmos and oculocutaneous albinism⁸ and Marcus Gunn jaw-winking phenomenon⁸.
• Some of the associated systemic anomalies reported are benign ethmoidal mesenchymoma, bilateral inguinal hernias.
• Unilateral cases of CFEOM may show facial asymmetry with the affected side of the face being smaller. Orbital anomalies may be present.
• The usual complaint is the strabismus and ptosis resulting in bad cosmesis.
• Orthoptic examination (ocular motility work-out) usually reveals following problems:

1. Amblyopia is common in one (strabismic/anisometropic/ametropic) or both eyes (ametropic). Upto 50% incidence of amblyopia has been reported in these cases with a constant strabismus and/or ptosis or both¹¹.
2. Refractive errors (hypermetropia and astigmatism) occur in 60% cases but occasionally visual acuity of 20/20 is possible¹¹. There may be significant changes in refractive errors post-operatively, possibly due to a change in the distribution of forces that are exerted on the globe by the tight fibrotic muscles^11,12.
3. Since the strabismus is constant in most of these cases there is no binocular vision. However, Binocular functions are preserved in some cases in which binocular single vision can be achieved by adopting compensatory head posture. These are usually cases of fibrosis of a single muscle. 40 degrees of stereopsis has been reported¹¹.
4. Progressive development of A pattern strabismus was reported in 8 patients of CFEOM¹³. This was explained by Traboulsi et al by the excessive convergence being exerted in elevation probably by the adductive effect of superior rectus muscle in elevation¹¹.
5. Ptosis with various degrees of severity is a common feature of CFEOM. However, it may be absent occasionally or it may be partially or totally a pseudoptosis because of hypotropia¹⁰. The false ptosis disappears when the affected eye is made to take up fixation but in a case of inferior rectus fibrosis the eye can not be brought to primary position as elevation function is absent. On recessing or tenotomising the fibrosed inferior rectus the pseudoptosis disappears. (see case report).
6. Retraction of eyeball may be observed in various directions because of the fibrosis of various muscles.

Investigations

1. Ophthalmologic examination:
   
   1. Complete ophthalmologic examination including fundus
   2. Refraction
   3. Orthoptic examination including measurement of deviation in various directions of gaze and assessment of binocular vision: One should be careful because mild cases of congenital fibrosis are liable to be missed. The degree of fibrosis may vary from case to case and from muscle to muscle.
   4. Forced duction test: It should be done in every case preoperatively, intraoperatively and postoperatively. If the test is positive the degree of tightness is assessed. In cases of severe fibrosis there is hardly any movement of the globe in the direction of action of the direct antagonist.

2. Special tests:
   
   1. CT scan (computed tomography) of orbits shows the fibrosed IR muscle or other affected EOM. The badly affected muscles are seen as thread like structures¹⁴. Other defects that may show up in CT scan are the atrophy, aplasia, and anomalous insertions¹⁵. A thickened muscle may stand out when compared with it normal counterpart.
   2. Histopathologic examination: Biopsy of the tenotomized IR shows replacement of muscle fibres by fibrous tissue. Fibrous infiltration of the muscles may be accompanied by the same in orbital tissue.
   3. Magnetic resonance imaging (MRI) may be more helpful in recognizing the affected muscles.
   4. Genetic testing if possible to locate the defective gene: At present this is being done only for research purposes. Engle and associates^{6, 7} have done the maximum amount of productive work on the genetics of congenital oculomotor anomalies.

Differential diagnosis

The following conditions can be confused with congenital oculomotor fibrosis syndromes. Forced duction test must be done in all cases to differentiate.

1. Brown’s syndrome
2. Double elevator palsy
3. Graves ophthalmopathy
4. Orbital floor fractures
5. Muscle entrapment in orbital wall fractures
6. Total or partial III CN palsy
7. Atypical Duane’s syndrome
8. Mobius syndrome
9. Chronic progressive external ophthalmoplegia (CPEO)
10. Kearns-Sayre syndrome
11. Myasthenia gravis
12. Orbital periostitis

Strabismus Fixus

This particular type of congenital fibrosis of extraocular muscles deserves special mention despite the fact that the condition is very rare. In more than four decades I have seen only about 7 cases of strabismus fixus, four of them convergent, one divergent and two verticals (one hypotropia and the other hypertropia).

In this condition the eye/eyes are anchored in a certain position, e.g., in adduction (convergent position), infraduction/depression (see case report 41-1), supraduction (elevation) or abduction (divergent position). Ocular motility is severely restricted in all the directions.

Classification

Strabismus fixus can be of two kinds:

1. Congenital type:
   The congenital type of strabismus fixus is due to a congenital fibrosis of the affected extraocular muscles. According to the direction of the deviation it can be divided into two types:

   A. Horizontal or
   B. Vertical
   

2. Acquired type is due to contracture/fibrosis of the direct (ipsilateral) antagonist of a palsied EOM or that of its contralateral synergist in a longstanding case.

Congenital strabismus fixus of the horizontal type

Medial rectus being the most commonly affected muscle, the most frequent type of congenital strabismus fixus is convergent On The main points regarding the congenital type of strabismus fixus are as follows:

• The condition can be bilateral or unilateral. If bilateral it causes severe disability.
• A positive family history must be excluded.
• The eye/eyes are fixed (anchored) in an extremely adducted (convergent) or rarely a divergent position.
• Divergent type of strabismus fixus has been reported but is extremely rare²⁰.
• Compensatory head posture is common as the eye is almost immobile and the patient has to adjust the head so that the better eye can be used to best advantage. An extreme degree of face turn is usually present in these cases to make it possible for them to move about and carry on with their daily activities.
• Amblyopia is common in the worse affected eye.
• The degree of deviation depends upon the severity of fibrosis but usually it is large. Extreme cases have been reported with eyes being so severely deviated that the cornea disappears from the view²⁰ (see case report 41-1).

• Ocular motility is severely restricted so as to be almost absent. The only movements that may be possible are some further adduction in convergent strabismus fixus and abduction in divergent strabismus fixus and slight vertical movements in the anchored position on attempted horizontal movements.
• Binocular functions are almost always absent.
• A case of convergent strabismus has been reported²⁵ in which there was ocular ischemia, central artery occlusion and optic atrophy due to due to mechanical stretching and torsion of the optic nerve causing strangulation of the blood supply to the eye.
• Computed tomography (CT) scan of the orbits might show the string like fibrosed and short medial or lateral recti, as the case may be.
• The only treatment is surgical, whereby a free tenotomy of the affected muscle is done with/without a resection of the normal antagonist. However, if the patient is old and not too keen on treatment one should leave such cases alone as the rate of complications is higher in them²¹ (see the surgical management of CFEOM on page
• It is preferable to take a small piece of the affected muscle for biopsy.

Congenital strabismus fixus of the vertical type

The main points are given below:

• The affected eye is fixed in a vertical position (supraduction or infraduction) due to the fibrosis of superior rectus or inferior rectus. The former leads to a large hypertropia and the latter causes a large hypotropia (see case report 41-1)

• Other features are similar to those in the horizontal variety.
• We treated one patient of the hypotropic strabismus fixus in whom the left eye was anchored in an extremely depressed and somewhat divergent position (see case report 41-1). The cornea could not be seen in the palpebral aperture (figure 41-2). A free tenotomy of inferior rectus resulted in a cosmetically acceptable result. About three decades ago we treated a case of vertical strabismus fixus with the left eye fixed in supraduction. A free tenotomy of the affected superior rectus resulted in an acceptable cosmetic appearance.

2. Acquired type of strabismus fixus

• Martinez described a case of acquired strabismus fixus (in 1948)²¹.
• Villaseca was of the opinion that the fibrosis of the medial rectus is secondary to the paralysis of lateral rectus leading to a contracture of the medial rectus²².
• A case was reported in which the strabismus fixus was due to amyloidosis²³.

Management of congenital fibrosis of extraocular muscles

(1) Nonsurgical treatment of congenital fibrosis of EOM:

Like that of most other types of strabismus, the non-surgical treatment of congenital fibrosis of EOM consists of the following:

1. Correction of refractive errors
2. Treatment of amblyopia should be carried out by occlusion of the eye with better visual acuity until the vision is equal in both eyes. However if the patient is an adult this is not possible and in the absence of fusion can result in (postoperative) diplopia.
3. Proper assessment of binocular functions
4. careful measurement of angle of deviation in various diagnostic positions of gaze.
5. Care of the ocular surface, especially the cornea: Lubricants are used if there is exposure keratitis. The eye has to be covered at night to prevent exposure.

(2) Surgical treatment of CFEOM

The following important points should be kept in mind before deciding on surgery:

• Surgery is not required and should not be carried out under the following circumstances:

1. If the patient is old, has strabismus fixus and is not keen about surgery, as the complication rate is higher in older people.
2. If the compensatory head posture is not significant.
3. If the pupil is not covered by drooping lid.
4. If fusion can be obtained in one or more directions without a significant head posture.

• The patient and his relatives should be warned about the uncertainty of the result, particularly of the postoperative movements. One may have to be satisfied with limited excursions because of the fibrosis of the muscles leading to their dysfunction.

• If the surgeon is going to operate on more than one member of a family, each case should be assessed fully and separately because of the variability of the severity of the condition in the same family. This is due to the expression of the phenotype being extremely variable^{6, 7}.

• The strabismus should be corrected first before ptosis surgery is carried out. Sometimes only a tenotomy or recession of the fibrosed inferior rectus gets rid of ptosis also. This is because the ptosis may be a false one (pseudoptosis due to hypotropia). In this case ptosis surgery will not be required.

• In most cases however, ptosis correction is required after strabismus surgery is completed.

• Each and every muscle should be given individual attention in these cases and assessed as to the degree of fibrosis and the function (underaction and overaction).

• The type of surgery and the amount of recession and resection to be done should be decided carefully after giving due attention to details given below:

1. Presence of binocular functions like fusion and its range
2. The angle of deviation in primary position and in various directions of gaze
3. The ocular motility in cardinal directions of gaze
4. The result of forced duction test and
5. The condition of the conjunctiva, which has to be taken into account. If it is contracted, as is the case when there has been a large strabismus for a long time or since birth particularly in cases of congenital fibrosis. For instance the nasal conjunctiva will be found contracted and non-elastic if there is marked esotropia.
   In such cases the conjunctiva has to be recessed after recessing or tonotomising the fibrosed muscle. This is especially true of cases of congenital fibrosis of EOM.

Surgical management:

Treatment of congenital fibrosis of extraocular muscles is basically surgical in most cases. It is difficult but careful planning and its execution often leads to a fairly successful result as regards the cosmetic result and improving the compensatory head posture. The aims of surgery are as follows:

1. Correction of the compensatory head posture (CHP) or at least improving it.
2. Removing obstacles to the visual axes in primary position, e.g., by ptosis correction.
3. Achieving binocular single vision in primary position with no or negligible CHP.

To accomplish the above, one or more of the following procedures may be required:

1. Total (free) tenotomy: It is advocated in cases of severe fibrosis when the eye is anchored in one position, e.g., in strabismus fixus with esotropia a free tenotomy of the fibrosed medial rectus is advocated^{16, 17, 18, 19}. After the tenotomy the eye may be anchored temporarily in abduction to keep it from going back to the adducted position. Particular indication of free tenotomy is Strabismus Fixus.
2. Recessions of the affected muscles, e. g., of the tight and fibrosed inferior rectus, medial rectus or any other muscle: The fibrosed muscles are non-elastic and tight. However, the degree of fibrosis may vary so much that mild cases of congenital fibrosis may be missed.
      The amount of recession mainly depends upon the angle of deviation in primary position, the severity of fibrosis and tightness of the affected muscle as determined by various tests particularly forced duction test.
   The recession can be either (a) Conventional or (b) The hang-back type, in which the muscle is allowed to hang back by the planned amount in mm and the sutures are placed at the site of the original insertion.
3. Recession of the conjunctiva covering the fibrosed muscle: It is not only a good idea but it is quite important to recess the conjunctiva after recessing or tenotomising the fibrosed tight muscles otherwise the desired result will not be achieved (see case report 41-2). Usual amount of recession is 4 mm. The sclera in this area is left bare.
   

4. Resection of the direct antagonist of the affected muscle along with recession/free tenotomy of the affected muscle has to be done in many cases. Many surgeons do it at the same sitting but I prefer to do it as a second stage procedure. This is because the result of the recession/free tenotomy can not be predicted with any certainty and one can plan the amount of resection of the antagonist better after assessing the result of the previous surgery.
5. Ptosis correction should only be done if it is severe and then one aims at under-correcting it because of the risk of exposure keratitis. The latter has to be kept in mind while correcting ptosis. An undercorrection is preferable, just sufficient to expose the pupil. Any of the frontalis suspension methods can be used. The material for the frontalis sling can be according to the surgeon’s choice, fascia lata being the most popular at present. However, I used retinal silicone bands in two patients years ago and the results were good.
      Use of lubricants is advised in the postoperative period even if the exposure is not much. In bad cases the lids should be taped at night.

Some important points concerning surgical management and postoperative care are given below:

1. Forced duction test is a good indicator of the severity of fibrosis and should be performed preoperatively, intraoperatively and immediately postoperatively.
2. During surgery if the muscle is found to be particularly stiff two hooks can be used to facilitate the placing of the sutures.
3. Thorough dissection of the muscle fascia, tenon’s membrane and intermuscular septum is a must otherwise even well planned surgery can fail. This is because the fascia is often not normal in these cases. It may be short and non-elastic and may pull the recessed muscle with it to an undesirable position. Even the tenotomized muscle may go on having an attachment that acts as its insertion.
4. It is possible to find anomalous insertions in these cases, particularly in the case of SR and SO²⁶. The muscle must be disinserted from all its insertions for the operation to be effective.
5. If more than two recti have been operated upon one should look for signs of anterior segment ischemia in the postoperative period.
6. Postoperative orthoptic exercises are a must in all strabismus cases, particularly in CFEOM. Ocular movements should be exercised on a regular basis for several weeks.
7. Regular follow-up for at least a year is important.
8. Patient must be made to understand the importance of always protecting the cornea in cases of exposure after ptosis surgery.

Complications

1. Overcorrection of ptosis can cause severe exposure keratitis. Lubricants must be used in such cases. Taping of the lids done at night helps.
2. Even without overcorrection of ptosis there may be incomplete closing of the lids leading to exposure keratitis. Absence of Bell’s phenomenon plays an important role. Night exposure is particularly to be prevented as already mentioned.
3. Anterior segment ischemia may occur if more than two rectus muscles are operated upon.
4. Operation may fail if all the insertions are not included in the procedures.
5. Failure to severe old fascial attachments and intermuscular septa may also lead to an unsatisfactory result.
6. Free tenotomy of medial recti may result in consecutive exotropia.
7. Too much resection of the antagonist may exacerbate the often-present look of slight enophthalmos in some cases.

References

1. Brown, H.W.: Congenital structural muscle anomalies. In Allen, J.H., editor: Symposium on Strabismus: Transactions of the New Orleans Academy of Ophthalmology, St. Louis, C.V. Mosby Company, 1950, p. 205.
2. Harley, R.D. et al: Congenital fibrosis of extraocular muscles, J. Pediatr. Ophthalmol. Strabismus 15:346, 1978.
3. Jaafar, M.S. and Traboulsi, E.I.: Clinical Strabismus Management: Principles and Surgical Techniques. Editors: Rosenbaum, A.L. and Santiago, A.P., chapter 27, 1998, Philadelphia, PA, W.B. Saunders Company, p. 363.
4. Noorden, G.K. von: Congenital hereditary ptosis with inferior rectus fibrosis, Arch. Ophthalmol. 83:378, 1970.
5. Engle, E.C. et al: Mapping a gene of congenital fibrosis of the extraocular muscles to the centrogenic region of the chromosome 12, Nat. Genet. 7:69, 1994.
6. Engle, E.C. et al: Congenital fibrosis of the extraocular muscles (autosomal dominant congenital external ophthalmoplegia): Genetic homogeneity, linkage refinement and physical mapping on chromosome 12, Am. J. Hum. Genet. 57:1086, 1995.
7. Engle, E.C. et al: Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles, Ann. Neurol. 41:314, 1997.
8. Brodsky, M.C. et al: Neural misdirection in congenital ocular fibrosis syndrome: Implications and pathogenesis, J. Pediatr. Ophthalmol. Strabismus 26:159, 1989.
9. Laughlin, R.C.: Congenital fibrosis of the extraocular muscles, Am. J. Ophthalmol. 41:432, 1956.
10. Jaafar, M.S. and Traboulsi, E.I.: Same as in ref. No. 3, P. 364.
11. Traboulsi, E.L. et al: Congenital fibrosis of the extraocular muscles: Report of 24 cases illustrating the clinical spectrum and surgical management, Am. Orthopt. J. 43:45, 1993.
12. Hertle, R.W. et al: Congenital unilateral fibrosis, blepharoptosis and enophthalmos syndrome, Ophthalmology 99:347, 1992.
13. Fells, P. et al: Progressive exaggerated A-Pattern strabismus with presumed fibrosis of the extraocular muscles. In Reinecke, R.D., editor, Strabismus II, Proceedings of the Fourth meeting of the International Strabismological Association, Asilomar, CA, 1982. Publisher: Grune & Stratton, 1984, Orlando, FL., p.335.
14. Jaafar, M.S. and Traboulsi, E.I.: Clinical Strabismus Management: Principles and Surgical Techniques. Editors: Rosenbaum, A.L. and Santiago, A.P., chapter 27, 1998, Philadelphia, PA, W.B. Saunders Company, p. 368 (fig. 27-5).
15. Hupp, S.L. et al: Computerized tomography in the diagnosis of general fibrosis syndrome, J. Clin. Neuroophthalmol. 19:135, 1990.
16. Apt, L. and Axelrod, R.L.: Generalized fibrosis of the extraocular muscles, Am J. Ophthalmol. 85: 822, 1978.
17. Crawford, J.S.: Congenital fibrosis syndrome, Can. J. Ophthalmol. 5:331, 1970.
18. Letson, R.D.: Surgical management of the congenital ocular fibrosis syndrome, Am. Orthopt. J. 30:97, 1980.
19. Traboulsi, E.I. et al: Congenital fibrosis of the extraocular muscles: Report of 24 cases illustrating clinical spectrum and surgical management, Am. Orthopt. J. 43:45, 1993.
20. Noorden, G.K. von: Binocular Vision and Ocular motility- Theory and Management of Strabismus, 5th edition, St. Louis, 1996, Mosby-Year Book, p. 443.
21. Martinez, L.: A case of fixed strabismus, Am. J. Ophthalmol. 31:80, 1948.
22. Villsecca, A.: Strabismus fixus, Am. J. Ophthalmol. 48:51, 1959.
23. Sharma, P. et al: Strabismus fixus convergens secondary to amyloidosis, J. Pediatr. Ophthalmol. Strabismus 28:236, 1991.
24. Prakash, P. et al: Myopic strabismus fixus convergens, Indian J. Ophthalmol. 37:24, 1989.
25. Mansour, A.M. et al: Ocular complications in strabismus fixus convergens, Ophthalmologica 195:161, 1987.
26. Jaafar, M.S. and Traboulsi, E.I.: Clinical Strabismus Management: Principles and Surgical Techniques, editors: Rosenbaum, A.L. and Santiago, A.P., 1998, Philadelphia, PA, W.B. Saunders Company, p. 369.