Journal of Neuro-Ophthalmology, March 2013, Volume 33, Issue 1

Long-Term Follow-Up of Strabismus Surgery for Patients With Ocular Myasthenia Gravis

Patients with ocular myasthenia gravis (OMG) may develop strabismus and diplopia. We completed a retrospective observational case series to evaluate long-term surgical outcomes in patients with OMG. The medical records of all patients with OMG who underwent strabismus surgery with at least 6 months of postoperative follow-up were reviewed. Nine patients met the study inclusion criteria. The main outcomes, including ocular alignment, number of surgeries, and sensory status were evaluated. Of these patients, initially 2 had horizontal strabismus alone, 3 had vertical strabismus alone, 3 had both vertical and horizontal strabismus, and 1 patient had vertical and torsional strabismus. The length of preoperative stability was 2.0 - 2.5 years (range: 0.1-8.0 years). The mean preoperative horizontal and vertical deviations were 40.5-32.5 prism diopters (PD; range: 0-90 PD) and 25.6-36.7 PD (range: 0-120 PD), respectively. The average length of the follow-up after the first surgery was 5.7-4.2 years (range: 0.7 0.6 years). Four patients (44%) underwent 2 operations. For patients requiring a second operation, the time to second operation was 2.3 years (range: 0.4-5.0 years). Six patients (67%) were within 10 PD of orthotropia at distance in primary position at the final visit. Five patients (55%) had single vision after their surgeries. Strabismus surgery can achieve good long-term binocular alignment in patients with OMG.

Long-Term Follow-Up of Strabismus Surgery for Patients With Ocular Myasthenia Gravis Jason H. Peragallo, MD, Federico G. Velez, MD, Joseph L. Demer, MD, PhD, Stacy L. Pineles, MD Background: Patients with ocular myasthenia gravis (OMG) may develop strabismus and diplopia. We completed a retrospective observational case series to evaluate long-term surgical outcomes in patients with OMG. Methods: The medical records of all patients with OMG who underwent strabismus surgery with at least 6 months of postoperative follow-up were reviewed. Nine patients met the study inclusion criteria. The main outcomes, including ocular alignment, number of surgeries, and sensory status were evaluated. Results: Of these patients, initially 2 had horizontal strabismus alone, 3 had vertical strabismus alone, 3 had both vertical and horizontal strabismus, and 1 patient had vertical and torsional strabismus. The length of preoperative stability was 2.0 ± 2.5 years (range: 0.1-8.0 years). The mean preoperative horizontal and vertical deviations were 40.5 ± 32.5 prism diopters (PD; range: 0-90 PD) and 25.6 ± 36.7 PD (range: 0-120 PD), respectively. The average length of the follow-up after the first surgery was 5.7 ± 4.2 years (range: 0.7-10.6 years). Four patients (44%) underwent 2 operations. For patients requiring a second operation, the time to second operation was 2.3 years (range: 0.4-5.0 years). Six patients (67%) were within 10 PD of orthotropia at distance in primary position at the final visit. Five patients (55%) had single vision after their surgeries. Conclusion: Strabismus surgery can achieve good long-term binocular alignment in patients with OMG. Journal of Neuro-Ophthalmology 2013;33:40-44 doi: 10.1097/WNO.0b013e318280d630 © 2013 by North American Neuro-Ophthalmology Society Myasthenia gravis is an autoimmune disorder in which autoantibodies to the neuromuscular junction result in neuromuscular blockage leading to striated muscle fatigability (1). Myasthenia gravis can be generalized or may involve only the extraocular muscles, designated as ocular myasthenia gravis (OMG). Establishing the diagnosis of OMG may be difficult as negative serologies do not rule out the disease, and, at times, the diagnosis is made on clinical grounds. Intravenous edrophonium and single-fiber electromyography are diagnostic studies with the greatest sensitivity. Involvement of the extraocular muscles may lead to strabismus and diplopia. Strabismus tends to be variable during the active phase of disease (2), and most clinicians agree that strabismus surgery is not indicated during this time. Patients are usually treated with parasympathomimetic and immunosuppressive medications until the disease has stabi-lized. Some patients may be tapered off medication, and progress into a phase of remission and decreased disease sever-ity (3).While the clinical course of myasthenia gravis is unpre-dictable, substantial improvement or spontaneous remission is often seen after the second year of disease (3). Once ocular alignment in patients with OMG is stable, strabismus surgery may be undertaken (4,5). While previ-ous studies have demonstrated the feasibility of performing both strabismus surgery and botulinum toxin injection for patients with OMG (5-9), long-term outcomes are unclear. The purpose of our study is to provide additional data regarding the role and long-term follow-up of eye muscle surgery in patients with OMG. METHODS This study was approved by the University of California, Los Angeles, Institutional Review Board and conformed to the requirements of the Declaration of Helsinki and the United States Health Insurance Portability and Accountability Act. A retrospective review was performed of the clinical records of all patients in 2 tertiary care strabismus practices (Arthur L. Department of Ophthalmology (JHP, FGV, JLD, SLP), Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California; and Department of Ophthalmology (FGV), Olive View, UCLA Medical Center, Sylmar, California. Supported by NIH/NEI K23EY021762 (S.L.P.), EY08313 (J.L.D.), Knights Templar Eye Foundation (S.L.P.), Oppenheimer Family Foundation (S.L.P.), Leonard Apt Fellowship (J.H.P.), and Adelaide Stein Fellowship (J.H.P.). The authors report no conflicts of interest. Address correspondence to Stacy L. Pineles, MD, Department of Ophthalmology, Jules Stein Eye Institute, University of California Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095; E-mail: [e-mail] 40 Peragallo et al: J Neuro-Ophthalmol 2013; 33: 40-44 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Rosenbaum, MD, Joseph L. Demer, MD) at the Jules Stein Eye Institute between 1980 and 2011 with the diagnosis of OMG and strabismus. None of the patients in the current study were included in a previous report from this institution (6). Patients who had previously undergone strabismus surgery prior to diagnosis of OMG were excluded. The following preoperative and postoperative character-istics were recorded: age at presentation, age at first surgery, duration of stability of ocular alignment, preoperative alignment at distance and near in cardinal gaze positions, medications for myasthenia used immediately preopera-tively and in the postoperative period, surgical procedures performed, use of adjustable sutures, initial postoperative deviation achieved following adjustable suture technique, ocular alignment determined at the last visit or immediately prior to reoperation, ocular alignment after second surgery, history of thymectomy, presence or absence of acetylcholine receptor antibodies (binding, blocking, and/or modulating), development of generalized myasthenia gravis, and presence of diplopia with or without prisms at final visit. The amount of strabismus surgery was based upon ocular alignment in primary gaze at distance. Surgical information was retrieved from operative reports, including results of forced duction testing, which was performed in every case. Ocular alignment with spectacle correction was measured in prism diopters (PD) either using cover/uncover and alternate cover testing at distance (3-4 m) in cardinal gaze positions or by Krimsky light reflex testing. Alignment was also assessed in primary position at near (36 cm). For the purposes of analysis, the preoperative ocular deviation was given a positive (+) value and overcorrections were assigned a negative (2) value. For example, if a patient had 25 PD of esotropia preoperatively, this would be denoted as a deviation of +25. If that patient had postoperative overcorrection result-ing in 10 PD of exotropia, that deviation would be designated TABLE 1. Characteristics of patients with ocular myasthenia gravis undergoing strabismus surgery Demographic (Total n = 9) Number (%) Women 5 (55%) Age at first surgery 49.9 yrs (range 9.7-74.2) Length of preoperative stability of deviation 2.0 yrs (range 0.1-8.0) Time to second surgery (n = 4)* 2.3 yrs (range 0.4-5.0) Initial horizontal deviation 40.5 PD (range 0-90) Initial vertical deviation 25.6 PD (range 0-120) Final horizontal deviation 12.7 PD (range 24 to 35) Final vertical deviation 7.4 PD (range 0-20) Length of follow-up 5.7 yrs (range 0.7-10.7) Thymectomy (n = 8)† 2 (25%) AchR Ab (+) or edrophonium (+) (n = 8)† 6 (75%) *n = number of patients who underwent a second surgery. †n = number of patients for whom data were recorded. AchR Ab, acetylcholine receptor antibodies. TABLE 2. Characteristics of patients with myasthenia gravis undergoing strabismus surgery Pt Age at Surgery (Yrs) Length of Follow-Up (Yrs) Length of Disease Stability (yrs) Thymectomy Performed Method of Diagnosis Preop Meds* Postop Meds Development of Generalized MG After Initial Presentation 1 73.9 3.3 0.38 No Edrophonium (+) None Pyridostigmine No 2 9.7 10.7 1.26 Not recorded Edrophonium (+) Pyridostigmine Pyridostigmine No 3 55.6 10.6 1.84 No Edrophonium (+) None None No 4 62.7 3.1 0.58 No Clinical examination Prednisone None Not recorded 5 22.3 10.3 8.01 Yes AchRAb+ None Pyridostigmine Yes 6 74.2 2.7 3.74 No Clinical examination None None No 7 72.6 1.5 0.10 No AchRAb+ Pyridostigmine Pyridostigmine Yes 8 39.1 8.1 2.00 Yes AchRAb+ Pyridostigmine Pyridostigmine Yes 9 38.5 0.7 0.16 No Clinical examination Pyridostigmine Pyridostigmine, prednisone No *Include only the medications the patient was taking immediately preoperatively. AchR Ab, acetylcholine receptor antibody; MG, myasthenia gravis. Peragallo et al: J Neuro-Ophthalmol 2013; 33: 40-44 41 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. as 210. Successful treatment results were defined as freedom from diplopia and alignment within 10 PD of orthotropia in primary position at distance at the final visit. RESULTS Table 1 summarizes demographic data for 9 patients who met inclusion criteria. All were adults with the exception of a single child, aged 9.7 years. The characteristics of each patient's myasthenia gravis are presented in Table 2. Table 3 summarizes the individual preoperative devia-tions, results of surgery performed, and final ocular deviation at last recorded visit. Adjustable sutures were utilized in all adult cases. Two of 8 patients (25%) required adjustment at first surgery, while 2 of 4 (50%) required adjustment at second surgery. Of the 3 patients with unacceptable align-ment results (heterotropia .10 PD deviation at the last visit), 2 had generalized MG, 2 were over 70 years of age, and all 3 had evidence of restriction on forced duction test-ing. Two of 3 patients who underwent surgery with eye position stable for ,6 months, either had unrecognized TABLE 3. Eye position and surgical outcomes in patients with ocular myasthenia gravis Pt Preoperative Deviation (PD) Initial Procedure* Forced Duction Test Residual Horizontal Deviation (PD)† Residual Vertical Deviation (PD)† 1 65 XT RLRc 8.5, BMRs 7 OD mild restriction to adduction, OU mild restriction to supraduction 0 10 2 16 LHT RSRs 4, LIRs 4 (2) 0 0 3 20 LHT RSRs 6.5 (2) 0 5 4 20 XT, 27.5 RHT LSRs 4.5, BLRc 5.5 (2) 26 0 5 28 XT, 25 LHT LMRs 10, LSRc 8 OS mild restriction to adduction, moderate restriction to depression 210 6 6 40 ET, 8 RHT BMRc 5.5 (transp. Inf ½ TW), LIRc 3 (2) 4 0 7 120 LHT RIRc 7, LSRc 10 OD moderate limit to supraduction, mild limit to infraduction, OS severe limit to infraduction 0 50 8 90 XT BLRc 8, BMRs 6 Limit to adduction OU 0 2 9 14 RHT LSO Sp 4, LIRc 4 (2) 0 0 Pt Second Preop Horizontal Deviation (PD) Second Preop Vertical Deviation (PD) Second Procedure Second Residual Horizontal Deviation (PD)‡ Second Residual Vertical Deviation (PD)‡ Final Horizontal Deviation (PD)§ Final Vertical Deviation (PD)§ 1 242.5 0 RMRs 5, RLR advanced from 14 to 8 mm from limbus 0 23.5 35 10 2 10 245 LIRc 4.5, LSRs 4.75 0 0 0 10 3 0 4 4 26 10 RSRc 3.5 0 0 0 3 5 12 10 6 8 0 7 0 50 LIR plication 10 0 0 25 20 8 15 25 LIRc 5, BMRs 4 8 10 24 10 9 0 0 *Procedures: RLRc, right lateral rectus muscle recession; BMRs, bilateral medial rectus muscle resection; RSRs, right superior rectus muscle resection; LIRs, left inferior rectus muscle resection; LSRs, left superior rectus muscle resection; BLRc, bilateral lateral rectus muscle recession; LMRs, left medial rectus muscle resection; LSRc, left superior rectus muscle recession; BMRc, bilateral medial rectus muscle recession; LIRc, left inferior rectus muscle recession; RIRc, right inferior rectus muscle recession; LSO Sp, left superior oblique muscle spacer; RSRc, right superior rectus muscle recession; Inf transp. ½ TW, inferior transposition one-half tendon width for V-pattern. All the procedures are amount of surgery performed prior to adjustment. †On postoperative day 1 after initial surgery and after adjustment (if performed). ‡On postoperative day 2 after second surgery if performed, and after adjustment (if performed). §On the final recorded visit. 42 Peragallo et al: J Neuro-Ophthalmol 2013; 33: 40-44 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. OMG (patient 9) or profound ocular misalignment (patient 7). Patient 7 had previous bilateral orbital decompression for thyroid eye disease and scleral buckling procedure for retinal detachment in the right eye. No other patient had a diagnosis of coexistent thyroid eye disease or previous ocular surgery. Four patients (44%) underwent a second surgery. Time to second surgery was 2.3 ± 2.0 years (range: 0.4-5.0 years). No patients underwent .2 surgeries. For the 6 patients who initially had, or developed, horizontal deviations, the average preoperative horizontal deviation was 40.5 ± 32.5 PD (range: 0-90 PD), while horizontal deviation at final visit was 12.7 ± 14.9 PD (range: 4-35 PD). Three patients (50%) were within 10 PD of orthotropia horizontally. All patients initially had, or developed, vertical devia-tions. The average preoperative vertical deviation was 25.6 ± 36.7 PD (range: 0-120 PD), while final vertical deviation was 7.4 ± 6.4 PD (range: 0-20 PD). Eight patients (89%) were within 10 PD of orthotropia vertically postoperatively. Regarding sensory status, patient 2 had childhood myasthenia gravis with treated amblyopia and was capable of suppression of 1 eye. Of the patients (n = 4) who con-tinued to have diplopia after surgical intervention, all were taking medications for myasthenia gravis postoperatively, 2 (50%) underwent 2 surgeries, and all had either positive AChR Abs or edrophonium testing, and 3 (75%) developed generalized MG after initial presentation of ocular MG. Two patients had ptosis preoperatively. A total of 6 patients had ptosis at some point postoperatively, 2 of which required medication, for MG. Eight of 9 patients (89%) had initial postoperative alignment within 10 PD of orthotropia. At the final visit, 5 patients (56%) had a successful result as defined by freedom from diplopia and heterotropia #10 PD. Three of these patients underwent a single surgery, and 2 required a second surgical procedure. All the patients who failed treatment in this study were women and had positive forced ductions. Of the patients whose AchR Ab status was known, 3 with positive antibodies failed treatment with strabismus surgery. One of 4 patients with negative AchR Ab results also failed treatment. Two patients who underwent thy-mectomy in this study did not have a successful result. DISCUSSION Patients with OMG and variable eye position are not considered appropriate candidates for extraocular muscle surgery (6). However, once ocular alignment and disease course stabilize, an appropriate surgical plan may be imple-mented (4-6,10). Previous reports of patients with OMG undergoing strabismus surgery are summarized in Table 4. Our study includes the largest number of patients with OMG who underwent strabismus surgery with adjustable suture technique and without botulinum toxin injections. It also has the longest reported average length of follow-up, TABLE 4. Summary of previous studies evaluating strabismus surgery in patients with myasthenia gravis Author, Year N Surgical Procedures Use of Botulinum Toxin Adjustable Sutures Follow-Up Definition of Success Success Rate Acheson et al (5) 5 Horizontal muscle faden (n = 1), horizontal rectus muscle surgery (n = 5), superior oblique tenotomy (n = 2) No Yes 6 mos to 6 yrs Not defined Not defined Davidson et al (6) 6 Horizontal rectus muscle surgery (n = 6), vertical rectus muscle surgery (n = 1), superior oblique tenotomy (n = 2) No Yes 4 mos to 16 yrs ,10 PD of ocular misalignment 4/6 (67%) Bentley et al (7) 9 Horizontal rectus muscle surgery (n = 9), vertical rectus muscle surgery (n = 1), inferior oblique surgery (n = 1) Yes (n = 6) Yes 6 mos to 5 yrs Symptom-free 6/9 (67%) Ohtsuki et al (8) 4 Horizontal rectus muscle surgery (n = 3), vertical rectus muscle surgery (n = 3) No Yes 8 mos to 2.5 yrs Single binocular vision 3/4 (75%) Morris and O'Day (9) 2 Horizontal rectus muscle surgery (n = 1), vertical rectus muscle surgery (n = 1) No Yes 3-6 mos Not defined Not defined N, number of patients. Peragallo et al: J Neuro-Ophthalmol 2013; 33: 40-44 43 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 5.7 ± 4.2 years, and the highest percentage of patients followed beyond 1 year (89%). In our series, all the patients experienced an improvement in ocular alignment from ini-tial deviation. At the final visit, 56% of the patients were within 10 PD of orthotropia. Other reports have shown that the use of adjustable sutures can improve surgical out-comes (11). In our series, adjustable sutures were utilized in all cases. However, 44% of patients continued to have dip-lopia after surgery; the remainder either suppressed diplopia (patient 2), or achieved single binocular vision. We searched for factors affecting the surgical outcome (Table 5). Strabismus surgery was less successful in older patients and those with OMG and thymectomy, positive AchR Abs, and generalized disease. We did not find a cor-relation between length of stability of preoperative ocular alignment and long-term success. Several of our patients with positive forced ductions had a poor outcome. Restric-tion on forced duction testing could have been due to undiagnosed thyroid eye disease or muscle contracture and atrophy associated with chronic strabismus including myasthenia (12,13). We acknowledge the limitations of our study. It was retrospective and subject to biases in both patient selection and follow-up. Our sample size was small, and establishing the diagnosis of OMG was not standardized but rather based on results of clinical examination, serologic tests, and intravenous edrophonium. Single-fiber electromyography testing was not utilized in our patients. Our results suggest that extraocular muscle surgery is a viable option for patients with OMG and stable ocular alignment. However, these patients should be counseled regarding the possibility of multiple surgeries, especially in those with more severe disease, older age, and coexistent restrictive strabismus. ACKNOWLEDGMENTS The authors would like to thank Dr. Arthur L. Rosenbaum for his dedication to his patients included in this study, and for years of thoughtful discussion that led to the inception and implementation of this study. REFERENCES 1. Pal J, Rozsa C, Komoly S, Illes Z. Clinical and biological heterogeneity of autoimmune myasthenia gravis. J Neuroimmunol. 2011;231:43-54. 2. Oosterhuis HJ. The ocular signs and symptoms of myasthenia gravis. Doc Ophthalmol. 1982;52:363-378. 3. Oosterhuis HJ. The natural course of myasthenia gravis: a long term follow up study. J Neurol Neurosurg Psychiatry. 1989;52:1121-1127. 4. Haines SR, Thurtell MJ. Treatment of ocular myasthenia gravis. Curr Treat Options Neurol. 2012;14:103-112. 5. Acheson JF, Elston JS, Lee JP, Fells P. Extraocular muscle surgery in myasthenia gravis. Br J Ophthalmol. 1991;75:232-235. 6. Davidson JL, Rosenbaum AL, McCall LC. Strabismus surgery in patients with myasthenia. J Pediatr Ophthalmol Strabismus. 1993;30:292-295. 7. Bentley CR, Dawson E, Lee JP. Active management in patients with ocular manifestations of myasthenia gravis. Eye (Lond). 2001;15:18-22. 8. Ohtsuki H, Hasebe S, Okano M, Furuse T. Strabismus surgery in ocular myasthenia gravis. Ophthalmologica. 1996;210:95-100. 9. Morris OC, O'Day J. Strabismus surgery in the management of diplopia caused by myasthenia gravis. Br J Ophthalmol. 2004;88:832. 10. Elrod RD, Weinberg DA. Ocular myasthenia gravis. Ophthalmol Clin North Am. 2004;17:275-309. 11. Nihalani BR, Hunter DG. Adjustable suture strabismus surgery. Eye (Lond). 2011;25:1262-1276. 12. Chan J, Orrison W. Ocular myasthenia: a rare presentation with MuSK antibody and bilateral extraocular muscle atrophy. Br J Ophthalmol. 2007;91:842-843. 13. Okamoto K, Ito J, Tokiguchi S, Furusawa T. Atrophy of bilateral extraocular muscles. CT and clinic features of seven patients. J Neuroophthalmol. 1996;16:286-288. TABLE 5. Factors associated with surgical outcome in patients with ocular myasthenia gravis* Successful (N = 5) Failure (N = 4) Age (mean, median) 48.1 yrs 52.0 Sex (F) 1/5 (20%) 4/4 (100%) Thymectomy 0/4 2/4 AchR Ab 0/3 3/4 Generalized MG after initial presentation 0/4 3/4 (+) Forced ductions 0/5 4/4 Size of horizontal deviation 30 PD 45.8 PD Size of vertical deviation 17.1 PD 36.25 PD Presence of initial horizontal deviation 2/5 3/4 Presence of initial vertical deviation 5/5 2/4 Presence of initial horizontal and vertical deviation 2/5 1/4 *Treatment failure defined as continued diplopia or deviation beyond 10 PD of orthotropia in primary gaze. AchR Ab, acetylcholine receptor antibody positive; PD, prism diopter. 44 Peragallo et al: J Neuro-Ophthalmol 2013; 33: 40-44 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. [VBstrabismus]