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Show Comparison of Primary Position Measurements and Abduction Deficit Between Type 1 Duane Syndrome and Sixth Cranial Nerve Palsy Noopur Nikki Batra, CO, Kyle Arnoldi, CO, COMT, James D. Reynolds, MD, Mitchell B. Strominger, MD Background: Unilateral Duane retraction syndrome type 1 (DRS-I) and unilateral sixth nerve palsy (6NP) present with limitation of abduction, incomitant eso-tropia, and frequently, a compensatory head turn. The purpose of this study was to compare the mean primary position measurement and to correlate this with the ab-duction deficit to determine if these measurements may be used to differentiate between the 2 conditions when other clinical signs of DRS-I (globe retraction, changes in lid fissure height, and upshoots/downshoots) are subtle. Methods: A database search of patients examined over a 5-year period revealed 69 cases of DRS-I and 62 cases of unilateral 6NP. Primary position measurements both at distance and near and limitation of abduction on version testing were recorded and compared. Results: Mean abduction deficit was 23.5 6 0.1 for DRS-I and 22.6 6 0.2 for 6NP (P = 0.0004). Mean esotropia at near was 8.4 6 1.1 prism diopters (PD) for DRS-I and 27.2 6 2.4 PD for 6NP (P , 0.0001). Mean esotropia at distance was 10.3 6 1.3 PD for DRS-I and 36.4 6 2.4 PD for 6NP (P , 0.0001). The mean distance-near disparity for DRS-I was 1.946 0.62 PD and 9.1961.28 PD for 6NP (P , 0.0001). The age-group of #2 years consisted of 23 DRS-I and only 2 6NP cases. The age-group between .2 years and ,18 years had 41 DRS-I and 16 6NP cases, respectively. Finally, the age-group of $18 years had only 5 DRS-I and 44 6NP cases (P , 0.0001). Conclusion: Patients with DRS-I showed greater abduc-tion deficit yet significantly less esotropia in primary po-sition than those with 6NP. Patients with 6NP were more likely to have a significant distance-near disparity. In addition, patients with DRS-I tended to be younger than those with 6NP. This report documents that DRS-I and 6NP can be differentiated based on magnitude of primary position esotropia, comparison of primary position eso-tropia with severity of abduction deficit, distance-near disparity, and patient age. Journal of Neuro-Ophthalmology 2011;31:117-120 doi: 10.1097/WNO.0b013e3182059ebf 2011 by North American Neuro-Ophthalmology Society Type 1 Duane retraction syndrome (DRS-I) is a con-genital disorder of ocular motility characterized by the following features: 1) marked limitation or absence of ab-duction, 2) variable limitation of adduction, 3) narrowing of the palpebral fissure on attempted adduction, 4) re-traction of the globe on attempted adduction, and 5) upshoot or downshoot on adduction. Autopsies of patients with DRS-I have shown absence of the abducens nerve causing the abduction deficiency. However, aberrant in-nervation occurs via the third cranial nerve, which branches to innervate both the medial rectus muscle and the ipsi-lateral lateral rectus muscle. Globe retraction and limitation of adduction are believed to be caused by the cocontraction of the lateral and medial rectus muscles on attempted ad-duction (1,2). Engle et al (3) have done extensive work on the genetic basis of isolated Duane retraction syndrome (DRS) and looked at its 1 genetic locus, the DURS2 locus on chromosome 2. DRS is now noted as one of the most common congenital cranial dysinnervation disorders. Sixth nerve palsy (6NP) can be congenital or acquired. The etiology of most cases includes trauma, inflammation or infection, neoplasm, microvascular disease, hydroceph-alus or shunt malfunction, and pseudotumor cerebri (4). 6NP results in an abduction deficiency of variable degree usually causing esotropia (ET). Recovery rate of 6NP is highly variable and dependant on the cause of the paresis with tumor having the lowest recovery rate in children (4). Differentiating DRS-I from 6NP is very important be-cause the workup and management are different for each Department of Ophthalmology (NNB, MBS), Tufts Medical Center, Boston, Massachusetts; and Ross Eye Institute (KA, JDR), University at Buffalo, Buffalo, New York. Supported by an unrestricted award from the Research to Prevent Blindness, New York, New York. Address correspondence to Noopur Nikki Batra, CO, University of Chicago Medical Center, Eye Center MC 9005 DCAM 1B, 5841 S. Maryland Ave., Chicago, IL 60637; E-mail: nnagarwa@yahoo.com Batra et al: J Neuro-Ophthalmol 2011; 31: 117-120 117 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. condition (5). Differentiating these 2 entities is usually straightforward. Acquired 6NP produce new onset diplopia in older children and adults with no history of a motility disorder dating from early childhood. However, pre-sentation in young children may be accompanied by an incomplete historical observation that fails to note the congenital onset, inadequate evidence of diplopia vs sup-pression, and clinical features that are subtle or difficult to detect. Caputo et al (6) studied 24 patients with abduction deficits before 36 months of age and found that classic findings of DRS, such as lid fissure narrowing on adduction, upshoots or downshoots, and globe retraction in adduction, may not manifest until early childhood. The purpose of this retrospective study was to compare the mean primary position strabismus measurement at distance and near and to correlate this with the abduction deficit to determine if these measurements may be used to differentiate between DRS-I and 6NP. METHODS Patients diagnosed and treated for unilateral DRS-I and unilateral 6NP within a 5-year period at the Floating Hospital for Children at Tufts Medical Center in Boston, MA, and at the Ross Eye Institute in Buffalo, NY, were included in this retrospective chart review. At the Ross Eye Institute, data were collected on patients diagnosed with DRS-I or 6NP consecutively with no selection bias. At Tufts Medical Center, 9 DRS-I cases were excluded because both distance and near measurements were not recorded. Six unilateral 6NP patients were excluded due to the lack of distance or near measurements, and 10 cases were omitted because they had been treated for the initial 6NP elsewhere and had been referred for possible surgery for a long-standing partially resolved paresis. All patients with a history of eye muscle surgery were excluded. The records of a total of 131 subjects were identified: 69 DRS-I patients and 62 6NP patients. Each patient underwent a complete ophthalmologic and orthoptic examination. Sex, age at first visit with accurate measurements, degree of version restrictions, side of the affected eye, and strabismic meas-urements in primary position at both distance and near were recorded in each case. Measurements in primary position were determined by Krimsky or Hirschberg method, or prism cover test. To simplify analysis, patients were only included if the records included all these required fields of data. Since the quantification of the degree of version re-striction is subjective, the degree number obtained at the first visit was usually compared to other consecutive visits to compare and judge for reliability of the assessment during the initial visit. The same pediatric ophthalmologist con-firmed the abduction deficit in the charts to ensure intra-observer reliability. Abduction deficits were graded on a 0 to 25 scale with 0 equaling no observable abduction deficit and 25 equaling an inability to achieve even the midline. We grouped the size of the abduction deficit into 3 cate-gories: severe (greater than 23), intermediate (23), and mild (less than 23). All statistical comparisons were performed using the SAS system for Windows (version 9.2) (SAS Institute, Cary, NC). Primary position measurements at near and distance for DRS-I were compared to 6NP measurements using the Wilcoxon 2-sample test. Distance-near disparity between the 2 groups was also compared using the Wilcoxon 2-sample test. The x2 tests were used to assess age dis-tributions between DRS-I and 6NP patients in 3 different age-groups: 2 years or younger, older than 2 years and younger than 18 years, and 18 years and older. Finally, we used logistic regression models to evaluate the magnitude of associations, as estimated by odds ratios (ORs) and 95% confidence intervals (CIs), between near or distance meas-urements and age and the 2 conditions. RESULTS Among the 131 unilateral cases evaluated, 69 cases wereDRS-I and 62 cases were 6NP. Of DRS-I cases, 42 (61%) were women and 27 (39%) were men. Of the 6NP cases, 34 (55%) were women and 28 (45%) men. The left eye was involved in 52 (75%) and the right eye in 17 (25%) of the DRS-I cases. In the 6NP cases, the left eye was involved in 34 (55%) and the right eye in 28 (45%) of cases. The age distribution of patients with DRS-I ranged from 7 months to 34 years (median = 4 years), and the mean (6SE) age was 6.6 6 0.9 years. The mean age for 6NP patients was 46.9 6 3.7 years with a range of 7 months to 87 years (median = 54 years). The age-group of #2 years consisted of 23 DRS-I and 2 of 6NP cases. The age-group between .2 years and ,18 years consisted of 41 DRS-I and 16 6NP cases. The age-group of $18 years had 5 DRS-I and 44 6NP cases (Table 1). Calculated by x2 test, the P value was ,0.0001, indicating that the age distribution of DRS-I and 6NP cases is significantly different. In evaluating the abduction deficit in DRS-I cases, 51 (74%) were in the severe category, 10 (14%) were in the intermediate category, and 8 (12%) were in the mild category. For the 6NP cases, 24 (39%) were in the severe category, 10 (16%) were in the intermediate category, and 28 (45%) were in the mild category. There were a significantly larger number of severe and intermediate cases with DRS-I (61 [88%]), than TABLE 1. Age group distribution within DRS-I and 6NP patients DRS-I (n = 69) 6NP (n = 62) #2 years 23 (33.3) 2 (3.2) 2-18 years 41 (59.4) 16 (25.8) $18 years 5 (7.3) 44 (71.0) Values represent n (%). 118 Batra et al: J Neuro-Ophthalmol 2011; 31: 117-120 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. with 6NP (34 [55%]). The mean (6SE) degree of abduction deficit in DRS-I cases was 23.5 6 0.1, and the median (interquartile range) was 24.0 (24.0 to 23.0). For 6NP cases, the mean deficit was -2.6 6 0.2 and the median was 23.0 (24.0 to 21.0). Using the Wilcoxon 2-sample test, the P value equaled 0.0004. The mean (6SE) primary position measurement at near for DRS-I was 8.4 6 1.1 prism diopters (PD) (range, 1 PD exophoria to 30 PD of esotropia). At distance, the mean was 10.3 6 1.3 PD (range, orthophoria to 35 PD of esotropia). For 6NP, the near mean was 27.2 6 2.4 PD (range, or-thophoria to 90 PD of esotropia). At distance for 6NP, the mean was 36.4 6 2.4 PD (range, 6 PD to 90 PD of esotropia). The P value for near measurements between the 2 groups was ,0.0001 and for distance was ,0.0001. From a logistic regression model, which included eye position near measurements and age as covariates, the ORs and 95% CIs for DRS-I and 6NP were 1.14 (1.07-1.23) and 1.10 (1.06-1.15), respectively. A model including distance measurements and age produced similar results (OR, 1.15; 95% CI, 1.07-1.22 and OR, 1.09; 95% C1, 1.05-1.14, respectively). When comparing the distance-near disparity between DRS-I and 6NP by Wilcoxon 2-sample test, we found that the difference was significant with P , 0.0001. The mean (6SE) distance-near disparity for DRS-I was 1.94 6 0.62 PD (median = 0 PD) and 9.19 6 1.28 PD (median = 9.5 PD) for 6NP. The maximum disparity in DRS-I cases was 16 PD. The maximum disparity in 6NP was 40 PD, more than double the DRS-I disparity. There was a disparity of 5 diopters or less in 52 (75%) of DRS-I cases and only 21 (34%) of 6NP cases. Our data suggest that there is definite overlap between the 2 conditions. To better understand if this is significant, we looked at the mean 6 SD for both near and distance within the 3 abduction deficit categories: mild, intermediate, and severe (Table 2). Then, the OR could be calculated with regards to the abduction deficit categories. When looking at the effect betweenmild and severe, the point estimate equaled 7.437. Therefore, without other information, if a patient's abduction deficit is between 22.5 and 0, then the odds of being 6NP is 7.43 times to a patient whose abduction deficit is between 25 and 23.5 (P , 0.0001). However, if the patient's abduction deficit is23, then the odds of being 6NP is only 2.12 times to the patient whose abduction deficit is between 23.5 and 25, and this was not significant (P = 0.1403) (Table 3). To go one step further, we looked at 6 groups by ab-duction deficit (mild, intermediate, and severe) and near primary measurements with a cutoff at the median or 14 PD (ie, 21#near ET#14 and 14,near ET#90). We then calculated OR estimates using the reference group as 14,near ET#90 and 25.0#abduction deficit#23.5 (Table 4). DISCUSSION The mean primary position deviations for near and distance measurements were significantly different between patients with DRS-I and 6NP. The mean measurements for 6NP exceeded DRS-I measurements for primary position eso-tropia at near by 18 PD and 26 PD at distance. Wagner et al studied patients who presented with an abduction deficiency during infancy. Their patients were followed until a diagnosis of either DRS-I or 6NP was established. They found that of the 24 patients younger than 2 years, 13 were diagnosed with DRS-I, only 1 was diagnosed with 6NP and 10 had an uncertain diagnosis. The average esotropia in DRS-I cases was 18 PD and 80 PD in 6NP cases. Of the 10 uncertain cases, 8 developed narrowing of the palpebral fissure, retraction of the globe, and upshoots or downshoots on adduction by 35 months of age. The remaining 2 patients still had uncertain diagnosis. Wagner et al concluded, ‘‘Other findings suggestive of DRS include a smaller angle of esotropia and adduction deficits manifesting as exotropia in contralateral gaze and conver-gence insufficiency'' (5). Our study also shows smaller angles of esotropia for DRS-I (maximum 35 PD) vs 6NP (maximum 90 PD). The patient samples of these 2 conditions had a wide range of ages. We assessed this by dividing the cases into 3 different age-groups. Interestingly, for DRS-I cases, 59% were between ages 2 and 18 years, while 71% of the 6NP cases were older than 18 years. Only 2 6NP cases (3%) were in the age-group of #2 years. This supports the finding that congenital 6NP is extremely rare (6). There are limitations to our study. We realize that secondary medial rectus fibrosis can develop in long- TABLE 2. Mean near and distance measurements (6SD) of DRS-I and 6NP patients within the 3 abduction deficit categories: mild (22.5 to 0), intermediate (23), and severe (23.5 to 25) Abduction Deficit DRS-I 6NP P Value for Near P Value n Near Distance n Near Distance for Distance 22.5 to 0 8 4.63 6 7.31 8.88 6 12.14 28 19.04 6 13.20 28.00 6 14.77 0.0063 0.0059 23 10 2.90 6 5.22 1.60 6 3.20 10 23.40 6 19.77 30.70 6 16.87 0.0024 0.0012 25 to 23.5 51 10.04 6 9.45 12.25 6 11.07 24 38.38 6 19.21 48.63 6 18.09 ,0.0001 ,0.0001 Batra et al: J Neuro-Ophthalmol 2011; 31: 117-120 119 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. standing DRS-I or 6NP, creating a secondary restrictive component that can alter the abduction deficit or eye po-sition in primary gaze. Unfortunately, we did not have data on forced ductions in every case and could not analyze this potential effect. Also, it is difficult to compare abduction deficits in DRS-I cases, which are relatively stable but can change with fibrosis, to 6NP cases, which may have a more variable range of presentation and continue to change based on etiology. However, we noticed a greater degree of ab-duction deficit in DRS-I than in 6NP cases and felt that it is important to look at the abduction deficit between the 2 groups to see if a trend or difference exists when com-paring it to primary position measurements. We attempted to minimize the variations within either group by analyzing the measurements at initial presentation and omitting re-solving or long-standing paresis. Unfortunately, it is not possible to estimate the degree of abduction deficit based on just primary position meas-urements for 6NP. Even though a general progression in esotropia was seen as the abduction deficit increased, there was a wide range of esotropia measurements for each degree of abduction deficit (0 to25). However, as seen on Table 3, if a patient has an abduction deficit of 22.5 or less, it is 7.43 times more likely that this is due to 6NP than DRS-I. When clinical signs such as globe retraction, lid fissure changes and an upshoot or downshoot, are difficult to detect in patients with an abduction deficit, it is important to obtain primary position strabismus measurements both at distance and near. By looking at the magnitude of primary position esotropia, comparing this esotropia measurement with the severity of abduction deficit, and also looking at the distance-near disparity of the measurements, one can obtain important information that will aid in differentiating DRS-I from 6NP. In addition, the age of the patient was also a distinguishing factor with those less than 18 years more likely to have DRS-I and older than 18 years to have 6NP. When measuring young children, most clinicians can get a near measurement either by Krimsky or Hirschberg method. Therefore, we found ORs by looking at near measurements and abduction deficit (Table 4). We used the reference group 14,near ET#90 and 25.0#abduction deficit#23.5. If a patient has a 25 to 23.5 abduction deficit and near ET #14 PD, the relative odds of this being 6NP is 0.078 times (P = 0.0002). If a patient has a 22.5 to 0 abduction deficit and near ET .14 PD, the relative odds of this being 6NP is 12.852 times (P = 0.0185). ACKNOWLEDGMENT The authors thank Yoojin Lee, MS, MPH, Statistical As-sociate at Tufts Medical Center, for help with statistical analysis. REFERENCES 1. Shauly Y, Weissman A, Meyer E. Ocular and systemic characteristics of Duane syndrome. J Pediatr Ophthalmol Strabismus. 1993;30:178-183. 2. Raab E. Clinical features of Duane's syndrome. J Pediatr Ophthalmol Strabismus. 1986;2:64-68. 3. Engle EC, Andrews C, Law K, Demer JL. Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus. Invest Ophthalmol Vis Sci. 2007;48:189-193. 4. Aroichane M, Repka M. Outcome of sixth nerve palsy or paresis in young children. J Pediatr Ophthalmol Strabismus. 1995;3:152-156. 5. Wagner R, Caputo A, Guo S, Santiago A. Guidelines for diagnosing Duane's retraction syndrome in infants and young children. Ophthalmic Hyperguide. Section: Pediatric Ophthalmology. Available at: http://www.ophthalmic. hyperguides.com/tutorials/pediatric/duanes_retraction/ tutorial.asp. Accessed March 1, 2008 6. Caputo AR, Wagner RS, Guo R. Infantile abduction deficit: Duane's retraction syndrome or abducens palsy? A study of 24 cases. Binocul Vis Strabismus Q. 1996; 11:213-218. TABLE 4. Association between abduction deficit categories with near esotropia measurements and the likelihood of having 6NP Category Odds Ratio 95% Confidence Limits 0#near ET#14 and 22.5#abduction deficit#0 1.592 0.523-4.849 0#near ET#14 and 23.5,abduction deficit,22.5 0.286 0.067-1.219 0#near ET#14 and 25.0#abduction deficit#23.5 0.078 0.02-0.297 14,near ET#90 and 22.5#abduction deficit#0 12.852 1.543-107.024 14,Near ET#90 and 23.5,abduction deficit,22.5 6 0.673-53.495 Reference group: 14,near ET#90 and 25.0#abduction defi-cit# 23.5. TABLE 3. Association between abduction deficit categories and the likelihood of having 6NP Effect Odds Ratio 95% Confidence Limits Abduction deficit group 22.5 ; 0 vs 25 ; 23.5 7.437 2.954-18.727 Abduction deficit group 23 vs 25 ; 23.5 2.125 0.780-5.787 120 Batra et al: J Neuro-Ophthalmol 2011; 31: 117-120 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
