Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia

Alexander Matthew Jones, MSc, MA, MB BChir; Julia Starte, BSci (Adv), MBBS; Hamish Dunn, B Lib Stud, MBBS (Hons); Kate Ahmad, MBBS, FRACP; Kimberley Tan, BSc (Med), MBBS, FRANZCO

Abstract

The authors describe three examples of “pulled in two syndrome” (PITS) from a series of 13 patients undergoing strabismus surgery with underlying chronic progressive external ophthalmoplegia (CPEO) and illustrate techniques for recovery of the “pulled in two” extraocular muscle should the complication arise. In all cases, a rectus muscle snapped under minimal tension while held on a strabismus hook during strabismus surgery. Two patients suffered from CPEO as a result of genetic mitochondrial disease, whereas one resulted from presumed mitochondrial toxicity induced by HAART. In cases 1 and 3, the proximal medial rectus segment was retrieved and reattached. In case 2, the fragmented superior rectus muscle was too friable to be reattached. All three patients were satisfied with the outcome, having reduced their angles of misalignment postoperatively. All three had improved cosmesis, and the two who had complained of diplopia preoperatively found their diplopia to be eliminated or improved. With anticipation of muscle friability in patients with previous extraocular surgery or degenerative muscle changes such as CPEO, the likelihood of the complication arising may be reduced. Should it occur, the loss of a snapped rectus muscle may be avoided through careful manipulation of the globe. [J Pediatr Ophthalmol Strabismus. 2017;54:e83–e87.]

Abstract

The authors describe three examples of “pulled in two syndrome” (PITS) from a series of 13 patients undergoing strabismus surgery with underlying chronic progressive external ophthalmoplegia (CPEO) and illustrate techniques for recovery of the “pulled in two” extraocular muscle should the complication arise. In all cases, a rectus muscle snapped under minimal tension while held on a strabismus hook during strabismus surgery. Two patients suffered from CPEO as a result of genetic mitochondrial disease, whereas one resulted from presumed mitochondrial toxicity induced by HAART. In cases 1 and 3, the proximal medial rectus segment was retrieved and reattached. In case 2, the fragmented superior rectus muscle was too friable to be reattached. All three patients were satisfied with the outcome, having reduced their angles of misalignment postoperatively. All three had improved cosmesis, and the two who had complained of diplopia preoperatively found their diplopia to be eliminated or improved. With anticipation of muscle friability in patients with previous extraocular surgery or degenerative muscle changes such as CPEO, the likelihood of the complication arising may be reduced. Should it occur, the loss of a snapped rectus muscle may be avoided through careful manipulation of the globe. [J Pediatr Ophthalmol Strabismus. 2017;54:e83–e87.]

Introduction

“Pulled in two syndrome” (PITS) is a rare complication of strabismus surgery characterized by rupture of the extraocular muscle under minimal tension and not through inappropriate excess force.1–4 This rare occurrence is described predominantly in cases in which there is preexisting extraocular muscle pathology, although the muscle can appear macroscopically normal.3,5 Reported risk factors include previous strabismus surgery, extraocular muscle palsy, thyroid eye disease, or metastatic infiltration.6,7

Surgical outcome depends on retrieval of the dehisced muscle, which can be either sutured to the sclera7 or re-anastomosed with the proximal section of muscle.5 Should the muscle prove irretrievable, a transposition procedure can be performed,3 although this can have disappointing results.7,8

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease, most commonly the result of mitochondrial DNA deletion.9 It has also been reported as a result of mitochondrial toxicity related to long-term use of nucleoside reverse transcriptase inhibitors.10–12 A clinical diagnosis of CPEO can be considered when a patient presents with progressive bilateral ptosis and ophthalmoplegia.13 On examination, limited ductions in all directions of gaze may be noted, along with slow saccades.9 Excluding fatigability, restriction, and supranuclear features can rule out key differential diagnoses, such as myasthenia gravis, thyroid-associated ophthalmopathy, Miller Fisher syndrome, and cranial dysinnervation syndromes, and central causes of eye movement disorders, such as progressive supranuclear palsy.9

Orbital magnetic resonance imaging (MRI) has been reported to demonstrate a bright “spongiform” signal in the extraocular muscle bellies.14 A definitive diagnosis may be made by detection of a genetic abnormality. Deletions of mitochondrial DNA are most reliably detected on analysis of muscle tissue; mitochondrial DNA and nuclear DNA mutations may be detected in urine and blood, respectively.15,16

This case series highlights the association between PITS and CPEO before commenting on and illustrating surgical techniques used to prevent rectus muscle loss. In particular, these involve globe counter-rotation and avoidance of pulling on the Tenon's capsule when trying to retrieve the muscle.

Case Reports

Patients were retrospectively identified from the set of patients who underwent strabismus surgery with CPEO from the Neuro-Ophthalmology Clinic at the Royal North Shore Hospital, Sydney, between 2003 and 2016. All patients had strabismus surgery performed by the same experienced strabismus surgeon (KT).

Thirteen patients with CPEO had strabismus surgery during the nominated period. Three patients experienced PITS intraoperatively.

Case 1

A 54-year-old man presented with a 10-year history of bilateral progressive ptosis and a 5-year history of horizontal binocular diplopia. He had also noted difficulty with night vision, glare, and afterimages. He was diagnosed as having human immunodeficiency virus (HIV) and hepatitis C in 1989. His HIV was initially treated with tenofovir, but he had changed medication to ritonavir and abacavir + lamivudine due to development of Fanconi syndrome (renal tubular dysfunction) as a result of a drug reaction. At the time he was referred, his HIV was well controlled (CD4+ count = 400; viral load < 37).

On examination, his best corrected visual acuity (BCVA) was 6/5 in the right eye and 6/6 in the left eye. There was a moderate bilateral ptosis (levator function = 11; 12 mm, margin to reflex distance 1 mm in both eyes). Ocular motility examination showed a large left exotropia (45 prism diopters) with moderate limitation of ductions in all directions bilaterally. Horizontal and vertical saccades were slow. Anterior segment examination was unremarkable and funduscopy revealed a fine pigmentary retinopathy.

Clinical and serological testing for myasthenia gravis was negative. An MRI (Figure 1) of the orbits was unremarkable and an electroretinogram was within normal ranges. A clinical diagnosis of CPEO was made and thought likely to be secondary to nucleoside/nucleotide analogue reverse transcriptase inhibitor treatment (tenofovir + abacavir).

Case 1. Coronal T1-weighted magnetic resonance imaging of (A) retro-orbital, (B) middle, and (C) deep orbit. Patchy signal in multiple extraocular muscles particularly in the (B) middle and (C) deep orbit.

Figure 1.

Case 1. Coronal T1-weighted magnetic resonance imaging of (A) retro-orbital, (B) middle, and (C) deep orbit. Patchy signal in multiple extraocular muscles particularly in the (B) middle and (C) deep orbit.

Bilateral lateral rectus muscle recessions and medial rectus muscle resections were planned to correct a large left exotropia. Right lateral rectus recession by 8 mm was routine. The right medial rectus muscle was then isolated via a limbal-based peritomy. A Moorfields strabismus hook was used to isolate the muscle, then replaced with a Chavasse hook to spread the muscle. However, with minimal traction, the strabismus hook tore through the muscle. The muscle was friable and relatively atonic, so it did not retract significantly. The proximal end was able to be retrieved and sutured to sclera. Left medial rectus resection (6 mm) and lateral rectus recession (10 mm) proceeded as planned. Due to the abnormal macroscopic muscle appearance and behavior, bilateral medial rectus resection specimens were sent in formalin for histopathology. Two months postoperatively, he showed 2.00 diopters of esophoria, no diplopia, and excellent cosmesis.

Histopathology reported predominantly collagenous, fibrous tissue resembling ligamentous tissue with some adjacent vascular adipose tissue. Only a small cluster of skeletal muscle fibers were seen in each sample. No inflammatory cell infiltration or scarring was noted.

Case 2

A 63-year-old woman presented with ophthalmoplegia, retinopathy, and right exposure keratopathy secondary to ectropion. She had previously undergone multiple eyelid operations for ptosis and ectropion. She had been formally diagnosed as having mitochondrial myopathy and associated CPEO through muscle biopsy of the right quadriceps in 2004. She had undergone genetic testing for 22 common mitochondrial DNA mutations and mutations in the Polymerase Gamma POLG gene, but these were negative. Complications of mitochondrial myopathy were exertional dyspnea, bulbar dysarthria and dysphagia, short-term memory loss, and fecal incontinence. She also suffered from urinary incontinence, migraine, L4/5 prolapse, and pancreatitis.

On examination, her BCVA was 6/9 in the right eye and 6/9 in the left eye. Ptosis persisted in the right eye. Ocular motility examination showed a large right hypertropia (approximately 45 prism diopters) and the right eye fixed in up gaze, with movement limitation in all directions bilaterally. Forced duction testing was strongly positive trying to rotate the right eye down, suggesting a tight superior rectus muscle, which would not usually be expected in CPEO. Anterior segment examination showed right exposure keratopathy and funduscopy confirmed pigmentary retinopathy bilaterally.

A right superior rectus recession and inferior rectus resection were planned to correct the right hypertropia. Forced duction intraoperatively again showed the tight superior rectus muscle. The superior rectus muscle was isolated via a limbal-based peritomy. It was identified as friable and atrophic. Indeed, we noted during dissection that the muscle itself was more friable than the Tenon's capsule itself. A strabismus hook was inserted to lift the muscle, but the hook pulled through the muscle and the proximal end retracted. The end was retrieved before loss, but appeared ragged. Forced duction test was still positive with the superior rectus muscle free, indicating more extensive connective tissue restriction. As such, the planned recession was converted to a tenotomy and an attempt was made to free as much connective tissue and check ligaments around the muscle superonasally and superotemporally as possible. After careful isolation, the inferior rectus muscle appeared to be similarly atrophic and lax. The planned resection was changed to a 10-mm tuck using 5-0 polyester to suture the muscle to the sclera. The polyester suture was also used to suture the check ligament to the tucked inferior rectus muscle to help rotate the globe inferiorly. Further, the extraconal fat was opened inferiorly to encourage fat adherence syndrome in an attempt to stick the globe in some degree of relative down gaze. Postoperatively, the right hypertropia has halved to approximately 25 prism diopters, with no diplopia. The angles have been stable after 1 year of follow-up, and the patient is satisfied with the outcome. There has been no deterioration of the ocular surface due to exposure keratopathy.

Case 3

A 51-year-old woman presented with external ophthalmoplegia, ptosis, and exposure keratopathy. She also suffered from weakness of the facial muscles and proximal limb muscles. She complained of ocular irritation and binocular diplopia. She had previously been diagnosed as having mitochondrial myopathy and had undergone two ptosis repairs and bilateral cataract extraction.

On examination, her BCVA was 6/12 in the right eye and 6/9 in the left eye. Ptosis remained with encroachment of both upper eyelids on the visual axis. Her ocular ductions were moderately restricted in all positions of gaze, with slightly better preserved abduction in each eye. She demonstrated a right exotropia of 14.00 diopters at distance and 25.00 diopters at near. She had right anterior capsular phimosis. Funduscopy demonstrated prominent optic nerve cupping that was worse on the left side, but no focal neural rim defects to indicate glaucoma. She had no retinopathy.

Bilateral medial rectus resection was planned to correct the exotropia. Intraoperative forced duction testing was negative. Left medial rectus resection of 4.5 mm was routine. The right medial rectus muscle was isolated via limbal peritomy. A Moorfields strabismus hook was used to isolate the muscle, and then a Chavasse hook was placed to stabilize the muscle for suture placement. However, the Chavasse hook snapped through the muscle with minimal traction (Figure 2). Globe traction was immediately released and the Tenon's capsule carefully explored to identify the proximal end of the muscle tendon. Only once the proximal end was secured with two forceps was the globe again rotated back laterally and the Tenon's capsule retracted to allow muscle exposure. A further 4-mm resection was performed with a direct globe suture using 6-0 polyglactin 910. On day 1 postoperatively, her eyes had improved to be orthotropic. Follow-up over the first 4.5 years showed stability with only a tiny exophoria. When reviewed for ptosis at 6 years postoperatively, she was experiencing intermittent near diplopia, which was relieved with a prism in her reading glasses. She remains satisfied with the surgical outcome (Figure 3).

Case 3. Intraoperative photograph showing “pulled in two syndrome.” Torn medial rectus muscle with distal insertion fragment several millimeters back from insertion. A 6-0 polyglactin 910 suture has been placed into the proximal segment of the medial rectus muscle.

Figure 2.

Case 3. Intraoperative photograph showing “pulled in two syndrome.” Torn medial rectus muscle with distal insertion fragment several millimeters back from insertion. A 6-0 polyglactin 910 suture has been placed into the proximal segment of the medial rectus muscle.

Case 3. (A) Positions of gaze preoperatively and (B) postoperative orthotropia.

Figure 3.

Case 3. (A) Positions of gaze preoperatively and (B) postoperative orthotropia.

Discussion

PITS describes snapping of a rectus muscle with normal macroscopic appearance and bulk, under minimal tension, often while held on a strabismus hook.1–4 Occurrence is difficult to predict, but has been linked to muscles with previously diagnosed degenerative processes.6,7 These three cases demonstrate the possibility of PITS occurring during strabismus surgery for patients with CPEO.

Case 1 provides further evidence for the development of CPEO as a complication of nucleoside reverse transcriptase inhibitor treatment. As life expectancy increases for those receiving HAART, treatment, side effects could become more common.10 Strabismus surgeons may encounter more patients with strabismus in CPEO after antiretroviral therapy, and need to be aware of the potential challenges intraoperatively. In cases 2 and 3, CPEO developed due to genetic mutation.

PITS can lead to loss of an extraocular muscle. Surgical outcome after PITS usually depends strongly on retrieval and reattachment of the snapped muscle. The most frequently snapped muscle is the inferior rectus,3 but the most frequently lost muscle is the medial rectus.7 It is theorized that this relates to attachments of the other rectus muscles to oblique muscles, which limits slippage of the muscle.7 Loss in muscle integrity can be anticipated in advanced age, previous extraocular muscle surgery, and degenerative conditions of the muscle. Greater care should be taken when manipulating the extraocular muscle in these cases.6 Our 3 cases suggest that CPEO should be explicitly included as a risk for PITS. Given the muscle atrophy in our cases, retrieval was facilitated by less dramatic proximal end retraction than would be expected if performing surgery on normal muscles. Cases 1 and 3 involved PITS of the medial rectus muscle, and in both cases the muscle remnants were retrieved through careful manipulation of the globe and handling of the Tenon's capsule.

MacEwen et al.7 recommended the following techniques for muscle retrieval. Orbital exploration should be done posteriorly through the fascial planes, with careful avoidance of the optic nerve. Avoidance of the fascial planes is encouraged to reduce fat adherence and scarring. Should the muscle be irretrievable, the adjacent fascia can be attached to the globe and the ipsilateral antagonist recessed.7 Location of the missing muscle can be assisted though the oculocardiac reflex by applying traction to the suspected piece of tissue and observing a slowing of the pulse. Computed tomography or MRI imaging have been used to locate the muscle.7

Standard practice in routine strabismus surgery is to rotate the globe away from the muscle of interest and to retract the Tenon's capsule off the muscle. Both of these maneuvers are used to expose the extraocular muscle. The surgeon's first instinct on snapping of the rectus muscle is commonly to rotate the globe away from the affected side even further. However, the attachment of the Tenon's capsule to the globe and of the proximal rectus to the annulus causes this maneuver to encourage withdrawal inside the connective tissue sheath. Instead, the globe should be rotated toward the affected side to encourage the muscle to not retract any further inside the sheath. The second erroneous maneuver after rectus muscle snapping is to pull up on the Tenon's capsule with no muscle inside. Pursuing this temptation will also cause further retraction of the proximal muscle as the Tenon's capsule is pulled up and around the unattached muscle, increasing the likelihood of loss (Figure 4).

(A) “Pulled in two syndrome”with proximal fragment retracting into the muscle sheath. (B) Unintended pulling on the Tenon's capsule, causing retraction of the muscle. (C) INCORRECT MANEUVER: Rotation of the globe away from affected side, causing retraction of muscle. (D) CORRECT MANEUVER: Rotation of the globe toward the affected side resulting in relaxation of the proximal muscle, facilitating retrieval.

Figure 4.

(A) “Pulled in two syndrome”with proximal fragment retracting into the muscle sheath. (B) Unintended pulling on the Tenon's capsule, causing retraction of the muscle. (C) INCORRECT MANEUVER: Rotation of the globe away from affected side, causing retraction of muscle. (D) CORRECT MANEUVER: Rotation of the globe toward the affected side resulting in relaxation of the proximal muscle, facilitating retrieval.

We acknowledge the limitations of a simple case series, which is prone to selection bias.17 However, the rarity of this syndrome makes other study methods impractical. We believe the risk of PITS in patients with CPEO needs to be highlighted. Further, given increasing numbers of patients who have survived long term with antiretroviral therapy for HIV, strabismus surgeons may find increasing numbers of patients with CPEO induced by antiretroviral therapy.

PITS is a devastating complication regardless of etiology. Patients with CPEO present many challenges for the strabismus surgeon and the possible increased risk of PITS should probably be added to the list. Larger case series, likely across multiple centers, are required to verify the association. We have also highlighted two crucial maneuvers in globe rotation and Tenon's capsule handling to facilitate muscle retrieval if PITS does occur.

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Authors

From the University of Cambridge School of Medicine, Cambridge, United Kindome (AMJ); Departments of Ophthalmology (JS, HD, KT) and Neurology (KA), Royal North Shore Hospital, Sydney, Australia, University of Sydney, Sydney, Australia; and the Department of Ophthalmology, Royal North Shore Hospital, Sydney, Australia (KT).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Kimberley Tan, BSc (Med), MBBS, FRANZCO, Department of Ophthalmology, Royal North Shore Hospital, Sydney, Australia. E-mail: kimberleytan123@gmail.com

Received: April 25, 2017
Accepted: June 15, 2017
Posted Online: November 17, 2017

10.3928/01913913-20171017-01

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