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Initial treatment outcomes in chronic sixth nerve palsy
Initial Treatment Outcomes in Chronic Sixth Nerve Palsy Jonathan M. Holmes, BM, BCh,a David A. Leske, BS,a and Stephen P. Christiansen, MDb Introduction: We conducted a prospective multi-center, nonrandomized, data-collection study of patients with chronic sixth cranial nerve palsy. We evaluated success rates with conservative nonsurgical management, botulinum toxin (botox) treatment, strabismus surgery, and a combination of botox treatment and surgery. Methods: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American NeuroOphthalmology Society were invited to enroll patients with sixth nerve palsy or paresis of more than 6 months duration over a 2-year period (between March 1998 and February 2000). The botox and surgical groups received intervention within 3 months of enrollment. Success at 6 months from enrollment was defined as absence of diplopia in primary position and no more than 10 prism diopters (pd) distance esotropia in primary position. Patients with no follow-up were excluded. Results: Fifty-six eligible patients were enrolled by 33 investigators. Eighteen (32%) were traumatic in etiology, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were other. Twenty (35%) were managed conservatively without surgery, 10 (18%) with botox treatment, 19 (33%) with surgery, and 8 (14%) with a combination of botox treatment and surgery. Success at 6 months from enrollment was 15% in the conservatively managed cases, 10% with botox alone, 39% with surgery alone, and 25% with a combination of botox and surgery. Conclusions: This study demonstrates that management of chronic sixth nerve palsy and paresis remains challenging. Spontaneous recovery occurs but is uncommon. Botox treatment alone was rarely successful, and a single surgical procedure had a lower-than-expected success rate. Care should be taken in directly comparing success rates between treatment groups because of bias in patient selection. (J AAPOS 2001;5:370-6) ew studies have been conducted on the outcome of patients with chronic sixth nerve palsy and paresis. Chronic will be defined, for the present study, as longer than 6 months in duration since onset. There is controversy about the optimum timing and mode of treatment for these patients. In a survey of 201 pediatric ophthalmologists and neuro-ophthalmologists regarding the timing of strabismus surgery in acute traumatic sixth nerve palsy, 26% would wait more than 6 months from onset before performing surgery, expecting further recovery (J. M. Holmes, unpublished survey data, 1996). Although some physicians advocate continued conservative management at 6 months from onset, others advocate botulinum toxin (botox) injection to the ipsilateral medial rectus1 or
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Presented in part at the annual meeting of the American Association for Pediatric Ophthalmology and Strabismus, Orlando, Florida, March 25, 2001. Supported by NIH EY11578, Research to Prevent Blindness, Inc (J.M.H. as Olga Keith Wiess Scholar and an unrestricted grant to the Mayo Clinic Department of Ophthalmology), and the Mayo Foundation. aDepartment of Ophthalmology, Mayo Clinic, Rochester, Minnesota. bDepartment of Ophthalmology, University of Minnesota, Minneapolis. Submitted March 30, 2001. Revisions accepted August 24, 2001. Reprint requests: Dr Jonathan M. Holmes, Department of Ophthalmology W7, Mayo Clinic, Rochester, MN 55905; e-mail, [email protected]. Copyright © by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2001/$35.00 + 0 75/1/120176 doi:10.1067/mpa.2001.120176
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strabismus surgery (with or without botox).2 Knowledge of success rates for each of these treatment modalities will help guide treatment decisions. This study was designed to assess current practice patterns in management of chronic sixth nerve palsy and to report on 6-month outcomes.
METHODS Since chronic sixth nerve palsy and paresis are uncommon conditions, we used a prospective multi-center data collection study design that has been successful in collecting data for acute traumatic sixth nerve palsy.3,4 For brevity, we will refer to sixth nerve palsy whether it was a complete palsy or an incomplete paresis. All members of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) and the North American Neuro-Ophthalmology Society (NANOS) were invited to enroll patients with chronic sixth nerve palsy during a 2-year period (between March 1998 and February 2000). Inclusion criteria were chosen to parallel those that might be used for a future randomized treatment trial (Table 1). Data collected at enrollment included date of onset, date of birth (age), sex, ethnicity, etiology of sixth nerve palsy, degree of monocular abduction deficit, and angle of deviation (in prism diopters [pd] measured by simultaneous prism and cover test in the primary position at distance Journal of AAPOS
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fixation). The etiology of the palsy was classified according to the investigator’s best judgment at the time of enrollment as traumatic, diabetic, neoplastic, unknown (including hypertensive), or other. Because it is difficult to be certain that hypertension is the cause of a sixth nerve palsy, those cases were classified in the “unknown” category. Monocular abduction deficit was recorded on the scale described by Scott and Kraft5: zero (normal); –1 (to 75% full rotation); –2 (to 50% full rotation); –3 (to 25% full rotation); –4 (to midline); and –5 (inability to abduct to the midline). A complete palsy was defined as a -4 or -5 abduction deficit, and incomplete as –1, –2, or –3. For purposes of analysis, in bilateral cases, the severity of the palsy was defined as the abduction deficit of the worst eye. A reminder was sent to each participating investigator 6 months after enrollment to obtain follow-up data on treatment (if any), diplopia, abduction deficit, and angle of deviation. No window was specified, except that the examination should be as close to, but at least, 6 months after enrollment. Investigators chose a specific treatment and arranged intervening follow-up visits according to their usual clinical practices. For analysis, patients were classified into 1 of 4 treatment groups: (1) conservative, which included prisms or patching; (2) botox; (3) surgery; and (4) botox plus surgery. The botox, surgery, and botox-plus-surgery groups included the patients who received that intervention within 3 months of enrollment. Of 66 initially eligible patients, 8 had no follow-up after the enrollment visit and therefore could not be classified into a treatment group. These patients were excluded from further analysis. Another patient in the botox-plus-surgery group had no follow-up after surgery and was also excluded from the analysis. Patients with a fourth nerve palsy were not explicitly excluded because a small hypertropia due to loss of fusion (secondary to the large esotropia) cannot be easily distinguished from a hypertropia secondary to a fourth nerve palsy. The only exception was a patient who was believed to have bilateral fourth nerve palsy at enrollment and underwent bilateral inferior oblique recessions as part of the initial management. This patient was excluded from the analysis, leaving 56 patients. Of these, only 15 patients had a hypertropia at enrollment, ranging from 1 to 8 pd (median, 3 pd). Regarding classification of outcome, 39 of the 56 patients had a follow-up examination at or beyond the planned 6-month outcome, without an intervening alternative or additional management (range, 180-357 days; median, 211 days; quartiles, 195 and 228.5 days). Success was defined as the absence of diplopia in primary position and no more than 10 pd distance esotropia in primary position. The latter criterion was used to prevent patients with residual moderate esotropia but suppression, ie, no diplopia, from being classified as successes.
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TABLE 1. Inclusion criteria Six months from onset Inability to fully abduct 1 or both eyes Diplopia in primary position at distance fixation Visual acuity at least 20/200 in each eye Distance esotropia more than 10 pd Absence of a third nerve palsy No previous treatment with botox or surgery
Of the remaining 17 patients, 8 received a change in management or an additional intervention before the 6month outcome, and 9 had incomplete follow-up. Those who had changes in management were defined as failures and retained their original assigned treatment group. Specifically, 3 patients had an intervention after 3 months from enrollment, were considered in the conservatively managed group, and classified as failures. Five patients in an intervention group received a second intervention before the 6-month outcome; they were similarly classified as failures. The only exception to this classification was a patient who underwent surgery a month after a botox injection; because this was planned, the patient was classified in the botox-plus-surgery group. All other patients in the botox-plus-surgery group received botox on the same day as surgery. For the 9 patients with incomplete follow-up, the outcome was defined as the status at the last follow-up. These 9 patients had incomplete follow-up less than the planned 180 days (range, 44-147 days). Five of these patients had an intervention (4 had surgery, and 1 had botox plus surgery) and had postintervention follow-ups of 37 to 109 days. We believe that including patients with incomplete follow-up reduced the potential bias of the study toward failure at 6 months. In contrast, excluding surgical patients who had been seen, eg, 1 month after surgery but did not return 6 months after surgery might have biased the entire surgical group toward failure, because nonreturning patients might have been more likely to have been surgical successes. We assumed, for incomplete follow-up, that status at last follow-up would approximate status at the planned 6-month primary outcome. Proportions were compared using Fisher exact tests or χ2 tests, and exact 95% confidence intervals of proportions were calculated. Continuous data (eg, ages) were compared using analysis of variance (ANOVA) if normally distributed, or nonparametric Kruskal-Wallis tests if nonnormal. Institutional review board approval was obtained at the data-coordinating center (Mayo Clinic, Rochester, Minn). Data that could identify a specific patient were confidential and not transmitted from the study ophthalmologist to the data-coordinating center.
RESULTS Description of the Cohort Fifty-six eligible patients were enrolled by 33 investigators (see acknowledgements). Ages ranged from 5 to 87
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TABLE 2. Patient demographics, palsy characteristics, treatment groups, and outcomes Conservative (n = 20) overall success
failure
Botox (n = 10)
Botox + Surgery (n = 8)
overall success failure
overall success failure
Surgery (n = 18) overall
success
failure
Gender Male Female
12 8
2 1
10 7
3 7
0 1
3 6
2 6
0 2
2 4
9 9
4 3
5 6
Race White non-white
18 2
2 1
16 1
10 0
1 0
9 0
8 0
2 0
6 0
15 3
7 0
8 3
Age mean (years) SD < 50 > 50
52 23 9 11
44 23 2 1
53 24 7 10
69 12 0 10
64 NA 0 1
70 12 0 9
42 15 7 1
34 18 2 0
45 15 5 1
42 19 11 7
46 22 3 4
40 17 8 3
Duration median (days) < 1 year > 1 year
456 6 14
322 2 1
602 4 13
269.5 6 4
204 1 0
301 5 4
263.5 6 2
227.5 2 0
296 4 2
272.5 12 6
296 4 3
240 8 3
Etiology Neoplastic Other Traumatic Unknown Diabetic
7 2 4 5 2
1 0 1 0 1
6 2 3 5 1
4 1 1 4 0
1 0 0 0 0
3 1 1 4 0
1 1 6 0 0
0 0 2 0 0
1 1 4 0 0
2 3 7 6 0
0 2 2 3 0
2 1 5 3 0
Laterality Unilateral Bilateral
17 3
3 0
14 3
9 1
1 0
8 1
7 1
2 0
5 1
13 5
6 1
7 4
7 5 3 1 4
2 0 0 0 1
5 5 3 1 3
0 0 6 0 4
0 0 1 0 0
0 0 5 0 4
0 0 0 3 5
0 0 0 0 2
0 0 0 3 3
5 4 4 2 3
2 2 2 1 0
3 2 2 1 3
15 5
2 1
13 4
6 4
1 0
5 4
0 8
0 2
0 6
13 5
6 1
7 4
8 8 2 0 2
2 1 0 0 0
6 7 2 0 2
4 0 2 2 2
1 0 0 0 0
3 0 2 2 2
0 0 2 1 5
0 0 1 0 1
0 0 1 1 4
6 5 2 3 2
3 2 1 1 0
3 3 1 2 2
Abduction deficit -1 -2 -3 -4 -5 Completeness Incomplete Complete Angle of deviation 11-20 pd 21-30 pd 31-40 pd 41-50 pd > 50 pd
years (median, 51 years); 54% were female, and 91% were white (Table 2). Regarding etiology of the chronic sixth nerve palsy, 18 (32%) were traumatic, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were
other (Table 2). The other causes included 2 cases of aneurysm, 1 vascular, 2 ischemic, 1 pontine arteriovenous malformation, and 1 pontine hemorrhage. Further etiological details were not specifically requested, such as whether the neoplastic cases were postneurosurgery. Ten
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(18%) were bilateral, and 34 (61%) of the palsies were incomplete. There appeared to be no relationship between laterality and etiology. Regarding chronicity, the median time from onset to enrollment was 327.5 days (range, 181 days-364 months; quartiles, 226 and 640.5 days). Treatment Groups According to our study criteria, 20 patients (36%) were managed conservatively, 10 (18%) with botox, 8 (14%) with botox plus surgery, and 18 (32%) with surgery alone. For the botox-treated patients, there was a median delay of 7.5 days between the enrollment visit and the botox injection (range, 0-56 days; quartiles, 0 and 47 days). The median dose was 5 units (range, 2.5-7.5 units). All but 1 botox case received just 1 injection before the 6-month outcome. The patient who received 2 injections of botox was still a failure after the second injection, so the second intervention definition of failure did not adversely bias against botox. For the patients treated with botox plus surgery, there was a median delay of 10 days between the enrollment visit and the treatment (range, 1-69 days; quartiles, 1 and 36.5 days). For the patients treated with surgery, there was a median delay of 19 days between the enrollment visit and the treatment (range, 1-66 days; quartiles, 7 and 43.5 days). There were differences between cases in each treatment group; this is a clear indication of bias when comparing outcomes (Table 2). The most notable differences were the unequal distributions of complete palsies (P = .002, χ2 test) and age (P = .005, ANOVA). All the patients treated with botox plus surgery were complete palsies, and the botox patients were older. The mean age (±SD) of the botox patients was 69 ± 12 years, compared with the conservative group (mean, 52 ± 23 years), the surgery group (mean, 42 ± 19 years), and the botox-plus-surgery group (mean, 42 ± 15 years). The absence of statistical significance of other factors (such as etiology of the palsy) does not exclude other possible sources of bias. This is particularly true because the number of cases per group was small, and therefore we had low statistical power to detect these differences. Success Rates Success at 6 months from enrollment occurred in 3 (15%; 95% CI, 3%-38%) of 20 cases managed conservatively, 1 (10%; 95% CI, 0%-45%) of 10 cases treated with botox, 7 (39%; 95% CI; 17%-64%) of 18 cases treated with surgery, and 2 (25%; 95% CI, 3%-65%) of 8 cases treated with a combination of botox and surgery. Caution should be used when comparing these proportions because of certain bias in treatment selection.
DISCUSSION In this prospective multi-center study of chronic sixth nerve palsy or paresis, the 6-month success rates ranged from 10% to 39% (95% CI, 0%-45% and 17%-64%).
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Such a low success rate is somewhat surprising in the surgery and botox-plus-surgery groups, and is less than the commonly stated success rate of 80% in strabismus surgery. The reasons for the lower overall success rate in our study are likely to be multifactorial. Our study was prospective, thus reducing the possibility of selecting cases based on outcome or completeness of follow-up. Our criteria for success were strict, requiring single vision in the primary position at distance fixation, without a head turn and without a residual esodeviation accompanied by suppression. Our outcome was measured at a clearly defined time, and the definition of failure included a second intervention or a change in management. Continued follow-up of these patients with subsequent interventions will most likely result in a higher long-term success rate. It is unwise to directly compare the success rates between our groups because there were clear differences between groups in the demographic and palsy characteristics (Table 2). For example, patients in the botox-plussurgery group were more likely to have had a complete palsy. This difference would tend to bias towards a lower success rate in that group. There are almost certainly other differences between groups; these, although not statistically significant because of low statistical power, may well have influenced success rates. Additional potential sources of bias are less likely to have influenced our results. Lack of masking would tend to bias toward an inflated success rate in some groups, but the number of cases from an individual investigator ranged from 1 to 11; this would make it less likely that the results of 1 investigator could influence the overall results. Exclusion of patients with no follow-up would have been unlikely to influence our results, because they could not be assigned to a treatment group for analysis. Even if these 8 cases were all conservatively managed, the success rate in the conservative group would range from 11 (39%) of 28, if all recovered, to 3 (11%) of 28, if they did not recover. Our sample size in each treatment group was clearly small; this led to wide 95% confidence intervals and some uncertainty as to the accuracy of our point estimates of success. Nevertheless, all groups had low success rates. Regarding spontaneous recovery, we reported on 3 cases (15%; 95% CI, 3%-38%) of chronic sixth palsy that were successful with conservative management. Two patients—1 diabetic and 1 traumatic—showed evidence of recovery up to and including the enrollment examination. The third case (postneurosurgery for neoplasia) declined the offer of eye muscle surgery and subsequently recovered over the next 6 months. Our data suggest that patients who undergo spontaneous recovery had smaller angles of deviation (Table 2), but we did not have sufficient statistical power to formally test this hypothesis. Our study suffered from a bias against success in the conservatively managed patients because we included those with very
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chronic sixth nerve palsy (up to 3 years from onset). These chronic cases had to some extent already failed conservative management. If we consider only chronic cases that were enrolled 6 to 12 months from onset, the spontaneous recovery rate increases to 2 (33%) of 6 cases, but the 95% confidence intervals are wide (4%-78%). The literature has few examples of late spontaneous recovery from sixth nerve palsy. King et al6 reported that 10 (5%) of 213 cases of sixth nerve palsy (excluding traumatic etiology) recovered between 6 and 12 months from onset. Savino et al7 reported that 17 (45%) of 38 chronic sixth nerve palsy cases spontaneously recovered, but chronic was defined as more than 3 months from onset. Thirteen of these cases recovered before 6 months from onset (and would not have been defined as chronic in the present study), and 4 cases resolved between 10 and 15 months from onset. For other cranial nerve palsies, late recovery has also been reported. Golnik and Miller8 described 3 patients with third nerve palsy—1 posttrauma, 1 postneurosurgery, and 1 postorbital hemorrhage—who recovered 3, 4, and 2 years after onset, respectively. Those patients were believed to be stable and nonresolved more than 6 months after onset. It appears that late spontaneous recovery in cases of cranial nerve palsy is a real but rare event. Botox injected into the ipsilateral medial rectus has been advocated, in selected patients, for treating chronic sixth nerve palsy.1 Our results provide little support for this recommendation, because treatment in only 1 (10%) of 10 patients was successful after botox alone (95% CI, 0%-45%). This patient was in the neoplastic group, 204 days from onset, and had a partial paresis with only 18 pd of esotropia in primary position at distance fixation. Forty percent of the patients in the botox group were classified as neoplastic, suggesting a patient-selection bias. More neoplastic cases were treated with botox alone than with any other modality (Table 2), potentially biasing against success. It is tempting to compare the botox group with the conservative group and declare that conservative management was more successful; however, the differences in patient and palsy demographics between these groups (Table 2) make them uncomparable. Repka et al1 reported success in 9 (41%) of 22 patients with chronic sixth nerve palsy of 5 or more months duration (95% CI, 21%-64%) but defined success somewhat differently; they included patients who had 50% improvement in their esotropia. Even excluding these cases, Repka et al1 reported a 32% success rate in restoring single binocular vision in primary position. Their patients received 1 to 5 injections of botox and were followed for an unspecified, but doubtless longer, time. In a discussion of Repka’s article, Biglan9 abstracted chronic sixth nerve palsy patients from a previous article10 and reported that 5 (45%) of 11 did not need surgery after botox injection. In another small series, Murray11 used botox in 10 cases of sixth nerve palsy. Four of these were longer than 6 months’ duration. None of these chronic patients was restored to
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single vision in primary position on follow-up. Taken together, the results of botox injection alone for chronic sixth nerve palsy are less than encouraging. Because the complication rate is reportedly low1 and the treatment can be given in an office setting, it may be reasonable to offer botox injections to selected patients with the knowledge that it may delay more definitive incisional surgical intervention. It would be helpful if the patients who might respond to botox injection could be distinguished by history and baseline characteristics from those who would not. No clear patterns have been identified in this study. However, it is possible that chronic sixth nerve palsy patients with mild contracture of the medial rectus and recovered lateral rectus function who still have limited abduction and esotropia in primary position might be the best candidates for botox injection. Preoperative force generation tests, forced ductions, and saccadic velocity tests would help to distinguish such patients. We had incomplete data for these potentially predictive factors, and our sample size was small, so that we could not test these hypotheses in our study. Nevertheless, it is inconceivable that a patient with a truly complete sixth nerve palsy would have significant longterm benefit from botox injection alone to the ipsilateral medial rectus. Regarding surgical intervention, it is generally accepted that, for complete palsies, some form of transposition procedure is indicated and, for partial pareses, a recess-resect procedure is performed.12 Indeed, of the 26 patients undergoing surgery and botox plus surgery, our investigators chose a transposition procedure in 11 (85%) of 13 complete cases and 1 (8%) of 13 incomplete cases. A recess-resect procedure was chosen for the vast majority (92%) of incomplete palsies, as expected. It is possible that the 2 cases of complete palsy treated with a recess-resect procedure were actually incomplete and that the failure to abduct past the midline (hence their classification as complete) might have been due to a tight medial rectus. For the surgery only group, the success rate was 7 (50%) of 14 recess-resect procedures and 0% of 4 transposition procedures. Again, care should be taken in comparing these small groups, and the reader should be aware of the clear bias in case selection, including completeness of the palsy. The differences between our success rate with surgery and other reported series might be explained partly by our stringent definition of success, ie, no diplopia in primary position. For complete chronic palsies, Cline and Scott13 reported on 20 (77%) of 26 patients with at least 60 sec of arc of stereopsis on the Titmus test postoperatively after a Jensen transposition procedure. Nevertheless, 58% of their patients had no face turn postoperatively, so some of the successfully treated patients were fusing with a face turn. Our criteria for success would not have included these patients. In Jensen’s original report,14 12 patients would probably have met our inclusion criteria; 6 (50%) of them were aligned to less than 10 pd of orthophoria in primary
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position with a single transposition procedure combined with a medial rectus recession. Again, it is difficult make a direct comparison with our series because data on diplopia were not described. For botox plus surgery, our 10 cases had a success rate of 25%. It is possible that our defined window for outcome examination at 6 months biased this group against our definition of success, because in some cases the effects of botox take many months to wear off. 12 Nevertheless, the follow-up interval from intervention to outcome examination ranged from 85 to 265 days in this group. Two of the 8 cases had persistent overcorrections, 1 of which prompted a take-down of the transposition. We compared these botox-plus-surgery cases with similar series in the literature. Rosenbaum et al2 reported on 8 of 10 patients with excellent alignment in primary position postoperatively, but 2 needed either additional surgery or reinjection of botox. Fitzsimons et al15 reported success in 3 (37%) of 8 unilateral cases and 3 (30%) of 10 bilateral cases with a single botox-plus-surgery intervention. As we have described, all our cases were complete palsies; this presumably biases against success. Taken together, it is clear that there is a high likelihood of needing more than 1 surgery in complete chronic sixth nerve palsy. In Fitzsimons’ series,15 the final status of the patient was more encouraging, with 63% obtaining fusion and “a satisfactory field of single binocular vision” after additional surgery when necessary. Longer-term follow-up continues in our current series; this will enable us to report on final outcome, particularly after additional surgical procedures are performed. Regarding augmented transpositions, 5 of our patients initially had an augmentation of the transposition as described by Foster. 16 Interestingly, 1 of these also received botox to the medial rectus at the time of surgery, in contrast to Foster’s original recommendations.16 One conservatively managed case was also subsequently managed with an augmented transposition. The 5 cases undergoing the Foster procedure alone were slightly undercorrected and had a small residual esotropia of 8 to 18 pd. Three were later treated with either ipsilateral or contralateral medial rectus recessions. Although our numbers were small, they suggest that undercorrection is a common outcome after the Foster augmented transposition. Our study could have been improved with data on field of single binocular vision, pre- and postoperatively. Nevertheless, participation in such multi-center data collection studies is enhanced by limiting data to what can be routinely obtained. We believe that recruitment would have been adversely affected by requiring such a test in this study. Although we have shown relatively low success rates with surgery, botox plus surgery, and botox alone, we have not addressed the symptomatic benefits of these treatments. Reduction of the angle of deviation and improve-
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ment in abduction might allow a patient to fuse with a slight face turn and improve quality of life. Nevertheless, our data suggest that it is highly likely that at least 2 procedures are necessary to regain single binocular vision in chronic sixth nerve palsy. These data are important in addressing physician and patient expectations, and will help guide the timing and choice of intervention. Our study also provides useful pilot data on success rates for planning future multi-center treatment trials in chronic sixth nerve palsy. The authors wish to thank the following investigators for their participation in this study: Brian Arthur, MD, Wilkes-Barre, Pa; William Astle, MD, Calgary, Alberta, Canada; Sandra Brown, MD, Lubbock, Tex; David Coats, MD, Houston, Tex; Oscar Cruz, MD, St Louis, Mo; Sean Donahue, MD, PhD, Nashville, Tenn; Mark Dorfman, MD, Hollywood, Fla; Patrick Droste, MD, Grand Rapids, Mich; W. Keith Engel, MD, Minneapolis, Minn; Robert Enzenauer, MD, MPH, Chattanooga, Tenn; Balaji Gupta, MD, Chicago, Ill; David Johnson, MD, Wichita, Kan; David Katz, MD, Rockville, Md; John Mumma, MD, San Antonio, Tex; Anthony Murray, MD, Cape Town, South Africa; Mary O’Hara, MD, San Antonio, Tex; Miguel Paciuc, MD, Mexico City, Mexico; Earl Palmer, MD, Portland, Ore; Evelyn Paysse, MD, Houston, Tex; Maria Pesheva, MD, Dallas, Tex; Jan Pott, MD, Groningen, The Netherlands; Michael Repka, MD, Baltimore, Md; Nicholas Sala, DO, Erie, Pa; David Silbert, MD, Lancaster, Pa; Naval Sondhi, MD, Indianapolis, Ind; David Stager, MD, Dallas, Tex; D. Brian Stidham, MD, Houston, Tex; Gail Summers, MD, Minneapolis, Minn; Michael Vaphiades, DO, Little Rock, Ark; David Wheeler, MD, Portland, Ore; and Robert Wiggins, MD, Asheville, NC.
References 1. Repka MX, Lam GC, Morrison NA. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. J Pediatr Ophthalmol Strabismus 1994;31: 79-83. 2. Rosenbaum AL, Kushner BJ, Kirschen D. Vertical rectus muscle transposition and botulinum toxin (Oculinum) to medial rectus for abducens palsy. Arch Ophthalmol 1989;107:820-3. 3. Holmes JM, Droste PJ, Beck RW. The natural history of acute traumatic sixth nerve palsy or paresis. J AAPOS 1998;2:265-8. 4. Holmes JM, Beck RW, Kip KE, Droste PJ, Leske DA, Pediatric Eye Disease Investigator Group. Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. J AAPOS 2000;4:145-9. 5. Scott AB, Kraft SP. Botulinum toxin injection in the management of lateral rectus paresis. Ophthalmology 1985;92:676-83. 6. King AJ, Stacey E, Stephenson G, Trimble RB. Spontaneous recovery rates for unilateral sixth nerve palsies. Eye 1995;9:476-8. 7. Savino PJ, Hilliker JK, Casell GH, Schatz NJ. Chronic sixth nerve palsies: are they really harbingers of serious intracranial disease? Arch Ophthalmol 1982;100:1442-4. 8. Golnik KC, Miller NR. Late recovery of function after oculomotor nerve palsy. Am J Ophthalmol 1991;111:566-70. 9. Biglan AW. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy: discussion. J Pediatr Ophthalmol Strabismus 1994;31:84. 10. Biglan AW, Burnstine RA, Rogers GL, Saunders RA. Management of strabismus with botulinum A toxin. Ophthalmology 1989;96: 935-43.
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11. Murray AD. Early and late botulinum toxin treatment of acute sixth nerve palsy. Aust N Z J Ophthalmol 1989;17:239-45. 12. Holmes JM. Surgical management of abduction deficits. Am Orthoptic J 2000;50:36-41. 13. Cline RA, Scott WE. Long-term follow-up of Jensen procedures. J Pediatr Ophthalmol Strabismus 1988;25:264-9. 14. Jensen CDF. Rectus muscle union: a new operation for paralysis of
Journal of AAPOS Volume 5 Number 6 December 2001 the rectus muscles. Trans Pacific Coast Otolaryngol Ophthalmol Soc 1964;45:359-87. 15. Fitzsimons R, Lee JP, Elston J. Treatment of sixth nerve palsy in adults with combined botulinum toxin chemodenervation and surgery. Ophthalmology 1988;95:1535-42. 16. Foster RS. Vertical muscle transposition augmented with lateral fixation. J AAPOS 1997;1:20-30.
An Eye on the Arts – The Arts on the Eye According to Trevor-Roper, there is a myopic personality that artists, mathematicians, and bookish people tend to share. They have “an interior life different from others,” a different personality, because only the close-up world is visually available to them. The imagery in their work tends to pivot around things that “can be viewed at very close range,” and they’re more introverted. Of Degas’s myopia, for example, he says: As time passed he was often reduced to painting in pastel rather than oil as being an easier medium for his failing sight. Later, he discovered that by using photographs of the models or horses he sought to depict, he was able to bring these comfortably within his limited focal range. And finally he fell back increasingly on sculpture where at least he could be sure that his sense of touch would always remain true, saying, ‘I must learn a blind man’s trade now,’ although he had always in fact had an interest in modeling. —Diane Ackerman (from A Natural History of the Senses)
F
Presented in part at the annual meeting of the American Association for Pediatric Ophthalmology and Strabismus, Orlando, Florida, March 25, 2001. Supported by NIH EY11578, Research to Prevent Blindness, Inc (J.M.H. as Olga Keith Wiess Scholar and an unrestricted grant to the Mayo Clinic Department of Ophthalmology), and the Mayo Foundation. aDepartment of Ophthalmology, Mayo Clinic, Rochester, Minnesota. bDepartment of Ophthalmology, University of Minnesota, Minneapolis. Submitted March 30, 2001. Revisions accepted August 24, 2001. Reprint requests: Dr Jonathan M. Holmes, Department of Ophthalmology W7, Mayo Clinic, Rochester, MN 55905; e-mail, [email protected]. Copyright © by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2001/$35.00 + 0 75/1/120176 doi:10.1067/mpa.2001.120176
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strabismus surgery (with or without botox).2 Knowledge of success rates for each of these treatment modalities will help guide treatment decisions. This study was designed to assess current practice patterns in management of chronic sixth nerve palsy and to report on 6-month outcomes.
METHODS Since chronic sixth nerve palsy and paresis are uncommon conditions, we used a prospective multi-center data collection study design that has been successful in collecting data for acute traumatic sixth nerve palsy.3,4 For brevity, we will refer to sixth nerve palsy whether it was a complete palsy or an incomplete paresis. All members of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) and the North American Neuro-Ophthalmology Society (NANOS) were invited to enroll patients with chronic sixth nerve palsy during a 2-year period (between March 1998 and February 2000). Inclusion criteria were chosen to parallel those that might be used for a future randomized treatment trial (Table 1). Data collected at enrollment included date of onset, date of birth (age), sex, ethnicity, etiology of sixth nerve palsy, degree of monocular abduction deficit, and angle of deviation (in prism diopters [pd] measured by simultaneous prism and cover test in the primary position at distance Journal of AAPOS
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fixation). The etiology of the palsy was classified according to the investigator’s best judgment at the time of enrollment as traumatic, diabetic, neoplastic, unknown (including hypertensive), or other. Because it is difficult to be certain that hypertension is the cause of a sixth nerve palsy, those cases were classified in the “unknown” category. Monocular abduction deficit was recorded on the scale described by Scott and Kraft5: zero (normal); –1 (to 75% full rotation); –2 (to 50% full rotation); –3 (to 25% full rotation); –4 (to midline); and –5 (inability to abduct to the midline). A complete palsy was defined as a -4 or -5 abduction deficit, and incomplete as –1, –2, or –3. For purposes of analysis, in bilateral cases, the severity of the palsy was defined as the abduction deficit of the worst eye. A reminder was sent to each participating investigator 6 months after enrollment to obtain follow-up data on treatment (if any), diplopia, abduction deficit, and angle of deviation. No window was specified, except that the examination should be as close to, but at least, 6 months after enrollment. Investigators chose a specific treatment and arranged intervening follow-up visits according to their usual clinical practices. For analysis, patients were classified into 1 of 4 treatment groups: (1) conservative, which included prisms or patching; (2) botox; (3) surgery; and (4) botox plus surgery. The botox, surgery, and botox-plus-surgery groups included the patients who received that intervention within 3 months of enrollment. Of 66 initially eligible patients, 8 had no follow-up after the enrollment visit and therefore could not be classified into a treatment group. These patients were excluded from further analysis. Another patient in the botox-plus-surgery group had no follow-up after surgery and was also excluded from the analysis. Patients with a fourth nerve palsy were not explicitly excluded because a small hypertropia due to loss of fusion (secondary to the large esotropia) cannot be easily distinguished from a hypertropia secondary to a fourth nerve palsy. The only exception was a patient who was believed to have bilateral fourth nerve palsy at enrollment and underwent bilateral inferior oblique recessions as part of the initial management. This patient was excluded from the analysis, leaving 56 patients. Of these, only 15 patients had a hypertropia at enrollment, ranging from 1 to 8 pd (median, 3 pd). Regarding classification of outcome, 39 of the 56 patients had a follow-up examination at or beyond the planned 6-month outcome, without an intervening alternative or additional management (range, 180-357 days; median, 211 days; quartiles, 195 and 228.5 days). Success was defined as the absence of diplopia in primary position and no more than 10 pd distance esotropia in primary position. The latter criterion was used to prevent patients with residual moderate esotropia but suppression, ie, no diplopia, from being classified as successes.
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TABLE 1. Inclusion criteria Six months from onset Inability to fully abduct 1 or both eyes Diplopia in primary position at distance fixation Visual acuity at least 20/200 in each eye Distance esotropia more than 10 pd Absence of a third nerve palsy No previous treatment with botox or surgery
Of the remaining 17 patients, 8 received a change in management or an additional intervention before the 6month outcome, and 9 had incomplete follow-up. Those who had changes in management were defined as failures and retained their original assigned treatment group. Specifically, 3 patients had an intervention after 3 months from enrollment, were considered in the conservatively managed group, and classified as failures. Five patients in an intervention group received a second intervention before the 6-month outcome; they were similarly classified as failures. The only exception to this classification was a patient who underwent surgery a month after a botox injection; because this was planned, the patient was classified in the botox-plus-surgery group. All other patients in the botox-plus-surgery group received botox on the same day as surgery. For the 9 patients with incomplete follow-up, the outcome was defined as the status at the last follow-up. These 9 patients had incomplete follow-up less than the planned 180 days (range, 44-147 days). Five of these patients had an intervention (4 had surgery, and 1 had botox plus surgery) and had postintervention follow-ups of 37 to 109 days. We believe that including patients with incomplete follow-up reduced the potential bias of the study toward failure at 6 months. In contrast, excluding surgical patients who had been seen, eg, 1 month after surgery but did not return 6 months after surgery might have biased the entire surgical group toward failure, because nonreturning patients might have been more likely to have been surgical successes. We assumed, for incomplete follow-up, that status at last follow-up would approximate status at the planned 6-month primary outcome. Proportions were compared using Fisher exact tests or χ2 tests, and exact 95% confidence intervals of proportions were calculated. Continuous data (eg, ages) were compared using analysis of variance (ANOVA) if normally distributed, or nonparametric Kruskal-Wallis tests if nonnormal. Institutional review board approval was obtained at the data-coordinating center (Mayo Clinic, Rochester, Minn). Data that could identify a specific patient were confidential and not transmitted from the study ophthalmologist to the data-coordinating center.
RESULTS Description of the Cohort Fifty-six eligible patients were enrolled by 33 investigators (see acknowledgements). Ages ranged from 5 to 87
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TABLE 2. Patient demographics, palsy characteristics, treatment groups, and outcomes Conservative (n = 20) overall success
failure
Botox (n = 10)
Botox + Surgery (n = 8)
overall success failure
overall success failure
Surgery (n = 18) overall
success
failure
Gender Male Female
12 8
2 1
10 7
3 7
0 1
3 6
2 6
0 2
2 4
9 9
4 3
5 6
Race White non-white
18 2
2 1
16 1
10 0
1 0
9 0
8 0
2 0
6 0
15 3
7 0
8 3
Age mean (years) SD < 50 > 50
52 23 9 11
44 23 2 1
53 24 7 10
69 12 0 10
64 NA 0 1
70 12 0 9
42 15 7 1
34 18 2 0
45 15 5 1
42 19 11 7
46 22 3 4
40 17 8 3
Duration median (days) < 1 year > 1 year
456 6 14
322 2 1
602 4 13
269.5 6 4
204 1 0
301 5 4
263.5 6 2
227.5 2 0
296 4 2
272.5 12 6
296 4 3
240 8 3
Etiology Neoplastic Other Traumatic Unknown Diabetic
7 2 4 5 2
1 0 1 0 1
6 2 3 5 1
4 1 1 4 0
1 0 0 0 0
3 1 1 4 0
1 1 6 0 0
0 0 2 0 0
1 1 4 0 0
2 3 7 6 0
0 2 2 3 0
2 1 5 3 0
Laterality Unilateral Bilateral
17 3
3 0
14 3
9 1
1 0
8 1
7 1
2 0
5 1
13 5
6 1
7 4
7 5 3 1 4
2 0 0 0 1
5 5 3 1 3
0 0 6 0 4
0 0 1 0 0
0 0 5 0 4
0 0 0 3 5
0 0 0 0 2
0 0 0 3 3
5 4 4 2 3
2 2 2 1 0
3 2 2 1 3
15 5
2 1
13 4
6 4
1 0
5 4
0 8
0 2
0 6
13 5
6 1
7 4
8 8 2 0 2
2 1 0 0 0
6 7 2 0 2
4 0 2 2 2
1 0 0 0 0
3 0 2 2 2
0 0 2 1 5
0 0 1 0 1
0 0 1 1 4
6 5 2 3 2
3 2 1 1 0
3 3 1 2 2
Abduction deficit -1 -2 -3 -4 -5 Completeness Incomplete Complete Angle of deviation 11-20 pd 21-30 pd 31-40 pd 41-50 pd > 50 pd
years (median, 51 years); 54% were female, and 91% were white (Table 2). Regarding etiology of the chronic sixth nerve palsy, 18 (32%) were traumatic, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were
other (Table 2). The other causes included 2 cases of aneurysm, 1 vascular, 2 ischemic, 1 pontine arteriovenous malformation, and 1 pontine hemorrhage. Further etiological details were not specifically requested, such as whether the neoplastic cases were postneurosurgery. Ten
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(18%) were bilateral, and 34 (61%) of the palsies were incomplete. There appeared to be no relationship between laterality and etiology. Regarding chronicity, the median time from onset to enrollment was 327.5 days (range, 181 days-364 months; quartiles, 226 and 640.5 days). Treatment Groups According to our study criteria, 20 patients (36%) were managed conservatively, 10 (18%) with botox, 8 (14%) with botox plus surgery, and 18 (32%) with surgery alone. For the botox-treated patients, there was a median delay of 7.5 days between the enrollment visit and the botox injection (range, 0-56 days; quartiles, 0 and 47 days). The median dose was 5 units (range, 2.5-7.5 units). All but 1 botox case received just 1 injection before the 6-month outcome. The patient who received 2 injections of botox was still a failure after the second injection, so the second intervention definition of failure did not adversely bias against botox. For the patients treated with botox plus surgery, there was a median delay of 10 days between the enrollment visit and the treatment (range, 1-69 days; quartiles, 1 and 36.5 days). For the patients treated with surgery, there was a median delay of 19 days between the enrollment visit and the treatment (range, 1-66 days; quartiles, 7 and 43.5 days). There were differences between cases in each treatment group; this is a clear indication of bias when comparing outcomes (Table 2). The most notable differences were the unequal distributions of complete palsies (P = .002, χ2 test) and age (P = .005, ANOVA). All the patients treated with botox plus surgery were complete palsies, and the botox patients were older. The mean age (±SD) of the botox patients was 69 ± 12 years, compared with the conservative group (mean, 52 ± 23 years), the surgery group (mean, 42 ± 19 years), and the botox-plus-surgery group (mean, 42 ± 15 years). The absence of statistical significance of other factors (such as etiology of the palsy) does not exclude other possible sources of bias. This is particularly true because the number of cases per group was small, and therefore we had low statistical power to detect these differences. Success Rates Success at 6 months from enrollment occurred in 3 (15%; 95% CI, 3%-38%) of 20 cases managed conservatively, 1 (10%; 95% CI, 0%-45%) of 10 cases treated with botox, 7 (39%; 95% CI; 17%-64%) of 18 cases treated with surgery, and 2 (25%; 95% CI, 3%-65%) of 8 cases treated with a combination of botox and surgery. Caution should be used when comparing these proportions because of certain bias in treatment selection.
DISCUSSION In this prospective multi-center study of chronic sixth nerve palsy or paresis, the 6-month success rates ranged from 10% to 39% (95% CI, 0%-45% and 17%-64%).
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Such a low success rate is somewhat surprising in the surgery and botox-plus-surgery groups, and is less than the commonly stated success rate of 80% in strabismus surgery. The reasons for the lower overall success rate in our study are likely to be multifactorial. Our study was prospective, thus reducing the possibility of selecting cases based on outcome or completeness of follow-up. Our criteria for success were strict, requiring single vision in the primary position at distance fixation, without a head turn and without a residual esodeviation accompanied by suppression. Our outcome was measured at a clearly defined time, and the definition of failure included a second intervention or a change in management. Continued follow-up of these patients with subsequent interventions will most likely result in a higher long-term success rate. It is unwise to directly compare the success rates between our groups because there were clear differences between groups in the demographic and palsy characteristics (Table 2). For example, patients in the botox-plussurgery group were more likely to have had a complete palsy. This difference would tend to bias towards a lower success rate in that group. There are almost certainly other differences between groups; these, although not statistically significant because of low statistical power, may well have influenced success rates. Additional potential sources of bias are less likely to have influenced our results. Lack of masking would tend to bias toward an inflated success rate in some groups, but the number of cases from an individual investigator ranged from 1 to 11; this would make it less likely that the results of 1 investigator could influence the overall results. Exclusion of patients with no follow-up would have been unlikely to influence our results, because they could not be assigned to a treatment group for analysis. Even if these 8 cases were all conservatively managed, the success rate in the conservative group would range from 11 (39%) of 28, if all recovered, to 3 (11%) of 28, if they did not recover. Our sample size in each treatment group was clearly small; this led to wide 95% confidence intervals and some uncertainty as to the accuracy of our point estimates of success. Nevertheless, all groups had low success rates. Regarding spontaneous recovery, we reported on 3 cases (15%; 95% CI, 3%-38%) of chronic sixth palsy that were successful with conservative management. Two patients—1 diabetic and 1 traumatic—showed evidence of recovery up to and including the enrollment examination. The third case (postneurosurgery for neoplasia) declined the offer of eye muscle surgery and subsequently recovered over the next 6 months. Our data suggest that patients who undergo spontaneous recovery had smaller angles of deviation (Table 2), but we did not have sufficient statistical power to formally test this hypothesis. Our study suffered from a bias against success in the conservatively managed patients because we included those with very
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chronic sixth nerve palsy (up to 3 years from onset). These chronic cases had to some extent already failed conservative management. If we consider only chronic cases that were enrolled 6 to 12 months from onset, the spontaneous recovery rate increases to 2 (33%) of 6 cases, but the 95% confidence intervals are wide (4%-78%). The literature has few examples of late spontaneous recovery from sixth nerve palsy. King et al6 reported that 10 (5%) of 213 cases of sixth nerve palsy (excluding traumatic etiology) recovered between 6 and 12 months from onset. Savino et al7 reported that 17 (45%) of 38 chronic sixth nerve palsy cases spontaneously recovered, but chronic was defined as more than 3 months from onset. Thirteen of these cases recovered before 6 months from onset (and would not have been defined as chronic in the present study), and 4 cases resolved between 10 and 15 months from onset. For other cranial nerve palsies, late recovery has also been reported. Golnik and Miller8 described 3 patients with third nerve palsy—1 posttrauma, 1 postneurosurgery, and 1 postorbital hemorrhage—who recovered 3, 4, and 2 years after onset, respectively. Those patients were believed to be stable and nonresolved more than 6 months after onset. It appears that late spontaneous recovery in cases of cranial nerve palsy is a real but rare event. Botox injected into the ipsilateral medial rectus has been advocated, in selected patients, for treating chronic sixth nerve palsy.1 Our results provide little support for this recommendation, because treatment in only 1 (10%) of 10 patients was successful after botox alone (95% CI, 0%-45%). This patient was in the neoplastic group, 204 days from onset, and had a partial paresis with only 18 pd of esotropia in primary position at distance fixation. Forty percent of the patients in the botox group were classified as neoplastic, suggesting a patient-selection bias. More neoplastic cases were treated with botox alone than with any other modality (Table 2), potentially biasing against success. It is tempting to compare the botox group with the conservative group and declare that conservative management was more successful; however, the differences in patient and palsy demographics between these groups (Table 2) make them uncomparable. Repka et al1 reported success in 9 (41%) of 22 patients with chronic sixth nerve palsy of 5 or more months duration (95% CI, 21%-64%) but defined success somewhat differently; they included patients who had 50% improvement in their esotropia. Even excluding these cases, Repka et al1 reported a 32% success rate in restoring single binocular vision in primary position. Their patients received 1 to 5 injections of botox and were followed for an unspecified, but doubtless longer, time. In a discussion of Repka’s article, Biglan9 abstracted chronic sixth nerve palsy patients from a previous article10 and reported that 5 (45%) of 11 did not need surgery after botox injection. In another small series, Murray11 used botox in 10 cases of sixth nerve palsy. Four of these were longer than 6 months’ duration. None of these chronic patients was restored to
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single vision in primary position on follow-up. Taken together, the results of botox injection alone for chronic sixth nerve palsy are less than encouraging. Because the complication rate is reportedly low1 and the treatment can be given in an office setting, it may be reasonable to offer botox injections to selected patients with the knowledge that it may delay more definitive incisional surgical intervention. It would be helpful if the patients who might respond to botox injection could be distinguished by history and baseline characteristics from those who would not. No clear patterns have been identified in this study. However, it is possible that chronic sixth nerve palsy patients with mild contracture of the medial rectus and recovered lateral rectus function who still have limited abduction and esotropia in primary position might be the best candidates for botox injection. Preoperative force generation tests, forced ductions, and saccadic velocity tests would help to distinguish such patients. We had incomplete data for these potentially predictive factors, and our sample size was small, so that we could not test these hypotheses in our study. Nevertheless, it is inconceivable that a patient with a truly complete sixth nerve palsy would have significant longterm benefit from botox injection alone to the ipsilateral medial rectus. Regarding surgical intervention, it is generally accepted that, for complete palsies, some form of transposition procedure is indicated and, for partial pareses, a recess-resect procedure is performed.12 Indeed, of the 26 patients undergoing surgery and botox plus surgery, our investigators chose a transposition procedure in 11 (85%) of 13 complete cases and 1 (8%) of 13 incomplete cases. A recess-resect procedure was chosen for the vast majority (92%) of incomplete palsies, as expected. It is possible that the 2 cases of complete palsy treated with a recess-resect procedure were actually incomplete and that the failure to abduct past the midline (hence their classification as complete) might have been due to a tight medial rectus. For the surgery only group, the success rate was 7 (50%) of 14 recess-resect procedures and 0% of 4 transposition procedures. Again, care should be taken in comparing these small groups, and the reader should be aware of the clear bias in case selection, including completeness of the palsy. The differences between our success rate with surgery and other reported series might be explained partly by our stringent definition of success, ie, no diplopia in primary position. For complete chronic palsies, Cline and Scott13 reported on 20 (77%) of 26 patients with at least 60 sec of arc of stereopsis on the Titmus test postoperatively after a Jensen transposition procedure. Nevertheless, 58% of their patients had no face turn postoperatively, so some of the successfully treated patients were fusing with a face turn. Our criteria for success would not have included these patients. In Jensen’s original report,14 12 patients would probably have met our inclusion criteria; 6 (50%) of them were aligned to less than 10 pd of orthophoria in primary
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position with a single transposition procedure combined with a medial rectus recession. Again, it is difficult make a direct comparison with our series because data on diplopia were not described. For botox plus surgery, our 10 cases had a success rate of 25%. It is possible that our defined window for outcome examination at 6 months biased this group against our definition of success, because in some cases the effects of botox take many months to wear off. 12 Nevertheless, the follow-up interval from intervention to outcome examination ranged from 85 to 265 days in this group. Two of the 8 cases had persistent overcorrections, 1 of which prompted a take-down of the transposition. We compared these botox-plus-surgery cases with similar series in the literature. Rosenbaum et al2 reported on 8 of 10 patients with excellent alignment in primary position postoperatively, but 2 needed either additional surgery or reinjection of botox. Fitzsimons et al15 reported success in 3 (37%) of 8 unilateral cases and 3 (30%) of 10 bilateral cases with a single botox-plus-surgery intervention. As we have described, all our cases were complete palsies; this presumably biases against success. Taken together, it is clear that there is a high likelihood of needing more than 1 surgery in complete chronic sixth nerve palsy. In Fitzsimons’ series,15 the final status of the patient was more encouraging, with 63% obtaining fusion and “a satisfactory field of single binocular vision” after additional surgery when necessary. Longer-term follow-up continues in our current series; this will enable us to report on final outcome, particularly after additional surgical procedures are performed. Regarding augmented transpositions, 5 of our patients initially had an augmentation of the transposition as described by Foster. 16 Interestingly, 1 of these also received botox to the medial rectus at the time of surgery, in contrast to Foster’s original recommendations.16 One conservatively managed case was also subsequently managed with an augmented transposition. The 5 cases undergoing the Foster procedure alone were slightly undercorrected and had a small residual esotropia of 8 to 18 pd. Three were later treated with either ipsilateral or contralateral medial rectus recessions. Although our numbers were small, they suggest that undercorrection is a common outcome after the Foster augmented transposition. Our study could have been improved with data on field of single binocular vision, pre- and postoperatively. Nevertheless, participation in such multi-center data collection studies is enhanced by limiting data to what can be routinely obtained. We believe that recruitment would have been adversely affected by requiring such a test in this study. Although we have shown relatively low success rates with surgery, botox plus surgery, and botox alone, we have not addressed the symptomatic benefits of these treatments. Reduction of the angle of deviation and improve-
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ment in abduction might allow a patient to fuse with a slight face turn and improve quality of life. Nevertheless, our data suggest that it is highly likely that at least 2 procedures are necessary to regain single binocular vision in chronic sixth nerve palsy. These data are important in addressing physician and patient expectations, and will help guide the timing and choice of intervention. Our study also provides useful pilot data on success rates for planning future multi-center treatment trials in chronic sixth nerve palsy. The authors wish to thank the following investigators for their participation in this study: Brian Arthur, MD, Wilkes-Barre, Pa; William Astle, MD, Calgary, Alberta, Canada; Sandra Brown, MD, Lubbock, Tex; David Coats, MD, Houston, Tex; Oscar Cruz, MD, St Louis, Mo; Sean Donahue, MD, PhD, Nashville, Tenn; Mark Dorfman, MD, Hollywood, Fla; Patrick Droste, MD, Grand Rapids, Mich; W. Keith Engel, MD, Minneapolis, Minn; Robert Enzenauer, MD, MPH, Chattanooga, Tenn; Balaji Gupta, MD, Chicago, Ill; David Johnson, MD, Wichita, Kan; David Katz, MD, Rockville, Md; John Mumma, MD, San Antonio, Tex; Anthony Murray, MD, Cape Town, South Africa; Mary O’Hara, MD, San Antonio, Tex; Miguel Paciuc, MD, Mexico City, Mexico; Earl Palmer, MD, Portland, Ore; Evelyn Paysse, MD, Houston, Tex; Maria Pesheva, MD, Dallas, Tex; Jan Pott, MD, Groningen, The Netherlands; Michael Repka, MD, Baltimore, Md; Nicholas Sala, DO, Erie, Pa; David Silbert, MD, Lancaster, Pa; Naval Sondhi, MD, Indianapolis, Ind; David Stager, MD, Dallas, Tex; D. Brian Stidham, MD, Houston, Tex; Gail Summers, MD, Minneapolis, Minn; Michael Vaphiades, DO, Little Rock, Ark; David Wheeler, MD, Portland, Ore; and Robert Wiggins, MD, Asheville, NC.
References 1. Repka MX, Lam GC, Morrison NA. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. J Pediatr Ophthalmol Strabismus 1994;31: 79-83. 2. Rosenbaum AL, Kushner BJ, Kirschen D. Vertical rectus muscle transposition and botulinum toxin (Oculinum) to medial rectus for abducens palsy. Arch Ophthalmol 1989;107:820-3. 3. Holmes JM, Droste PJ, Beck RW. The natural history of acute traumatic sixth nerve palsy or paresis. J AAPOS 1998;2:265-8. 4. Holmes JM, Beck RW, Kip KE, Droste PJ, Leske DA, Pediatric Eye Disease Investigator Group. Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. J AAPOS 2000;4:145-9. 5. Scott AB, Kraft SP. Botulinum toxin injection in the management of lateral rectus paresis. Ophthalmology 1985;92:676-83. 6. King AJ, Stacey E, Stephenson G, Trimble RB. Spontaneous recovery rates for unilateral sixth nerve palsies. Eye 1995;9:476-8. 7. Savino PJ, Hilliker JK, Casell GH, Schatz NJ. Chronic sixth nerve palsies: are they really harbingers of serious intracranial disease? Arch Ophthalmol 1982;100:1442-4. 8. Golnik KC, Miller NR. Late recovery of function after oculomotor nerve palsy. Am J Ophthalmol 1991;111:566-70. 9. Biglan AW. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy: discussion. J Pediatr Ophthalmol Strabismus 1994;31:84. 10. Biglan AW, Burnstine RA, Rogers GL, Saunders RA. Management of strabismus with botulinum A toxin. Ophthalmology 1989;96: 935-43.
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11. Murray AD. Early and late botulinum toxin treatment of acute sixth nerve palsy. Aust N Z J Ophthalmol 1989;17:239-45. 12. Holmes JM. Surgical management of abduction deficits. Am Orthoptic J 2000;50:36-41. 13. Cline RA, Scott WE. Long-term follow-up of Jensen procedures. J Pediatr Ophthalmol Strabismus 1988;25:264-9. 14. Jensen CDF. Rectus muscle union: a new operation for paralysis of
Journal of AAPOS Volume 5 Number 6 December 2001 the rectus muscles. Trans Pacific Coast Otolaryngol Ophthalmol Soc 1964;45:359-87. 15. Fitzsimons R, Lee JP, Elston J. Treatment of sixth nerve palsy in adults with combined botulinum toxin chemodenervation and surgery. Ophthalmology 1988;95:1535-42. 16. Foster RS. Vertical muscle transposition augmented with lateral fixation. J AAPOS 1997;1:20-30.
An Eye on the Arts – The Arts on the Eye According to Trevor-Roper, there is a myopic personality that artists, mathematicians, and bookish people tend to share. They have “an interior life different from others,” a different personality, because only the close-up world is visually available to them. The imagery in their work tends to pivot around things that “can be viewed at very close range,” and they’re more introverted. Of Degas’s myopia, for example, he says: As time passed he was often reduced to painting in pastel rather than oil as being an easier medium for his failing sight. Later, he discovered that by using photographs of the models or horses he sought to depict, he was able to bring these comfortably within his limited focal range. And finally he fell back increasingly on sculpture where at least he could be sure that his sense of touch would always remain true, saying, ‘I must learn a blind man’s trade now,’ although he had always in fact had an interest in modeling. —Diane Ackerman (from A Natural History of the Senses)