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Show Journal of Neuro- Ophthalmology 18( 4): 289- 291. 1998. €> 1998 I. ippincoll Williams & Wilkins, Philadelphia Proptosis With Acute Oculomotor and Abducens Nerve Palsies Daniel M. Jacobson, M. D. Objective: To determine whether orbital axial proptosis occurs in the affected eye of patients with acute oculomotor or abducens nerve palsy. Materials and Methods: In this prospective, cross- sectional survey, the Hertel instrument was used to measure the amount of axial protrusion in 26 consecutive patients with complete or severe acute oculomotor nerve palsy and 27 consecutive patients with complete or severe acute abducens nerve palsy. The Mann- Whitney test was used to compare the amount of relative proptosis of the affected eye in the patient groups with that of 40 control subjects. The absolute amount of the interocular difference in axial protrusion of the normal eyes was used to determine control values. The proportion of patients and control subjects with relative proptosis greater than 1 mm was compared using Fisher's exact test. Results: There was no significant difference in the degree of relative proptosis of the affected eye of patients with oculomotor nerve palsy or abducens nerve palsy as compared with the control eyes. Likewise, there was no significant difference in the proportion of patients with relative proptosis greater than 1 mm in either the oculomotor nerve palsy group or the abducens nerve palsy group as compared with the control group. Conclusions: Acute oculomotor or abducens nerve palsy does not produce any significant amount of orbital axial proptosis in the affected eye, at least as measured clinically using the Hertel instrument. Acute neurogenic ophthalmoplegia rarely causes relative proptosis greater than 1 mm. Key words: Proptosis- Orbit- Oculomotor nerve- Abducens nerve. Axial orbital proptosis is an important sign that may reflect an intraorbital lesion in a patient with ophthalmoplegia. However, one might expect that an acute injury producing neurogenic ophthalmoplegia from an ocular motor nerve palsy could also cause some degree of relative proptosis of the affected eye due to hypotonia of the denervated extraocular muscles. Historical and modern reference textbooks contain anecdotal observations of the association between acute ocular motor nerve palsy and proptosis. For example, Kestenbaum ( 1) stated that the eye becomes slightly exophthalmic if several Manuscript received December 9, 1997; accepted April 29, 1998. From the Departments of Neurology and Ophthalmology, Marsh-field Clinic, Marshfield, Wisconsin. Address correspondence to Daniel M. Jacobson, M. D., Neuro-ophthalmology ( 4F- 2), Marshfield Clinic, 1000 N. Oak Ave., Marsh-field, Wisconsin 54449. recti are paretic. Walsh ( 2) mentioned that in some cases of third nerve paralysis there is a definite degree of exophthalmos. Further, he indicated that he had observed as much as 3 mm of exophthalmos associated with such a process ( 2). Glaser ( 3), however, stated that there is little evidence to support the concept that oculomotor nerve paralysis causes detectable proptosis. 1 am not aware of any study that has formally evaluated whether proptosis occurs with ocular motor nerve palsies. The purpose of this investigation, therefore, was to determine whether axial orbital proptosis occurs in patients with acute oculomotor or abducens nerve palsies. METHODS The research proposal that this study was based on was reviewed by the expedited review process of the Institutional Review Board ( IRB) of the Marshfield Clinic and was determined to be exempt from IRB regulation. Oral consent was obtained from each participant. The degree of axial orbital protrusion was prospectively measured in two patient populations; the first group consisted of patients with complete or severe acute oculomotor and abducens nerve palsies, and the second group was a control group of healthy subjects. Acute was defined as a time interval of less than 2 weeks from onset of symptoms to evaluation. Severe ocular motor deficit was defined as an ophthalmoplegia that limited ocular ductions by at least 75% of normal, using a previously established standardized ophthalmoplegia grading scheme for oculomotor ( 4) and abducens ( 5) nerve palsies. The patients consisted of consecutive ambulatory individuals attending an outpatient, referral- based neuro-ophthalmology clinic. None of the patients had experienced orbital trauma or had other signs of orbital disease. The control subjects consisted of staff of the Marshfield Clinic who were selected solely on the basis of availability. None of the control subjects had symptoms of orbital disease or known disorders affecting the orbit. Proptosis was measured using the Hertel instrument ( Marco Products, Jacksonville, Florida) and a technique suggested by Rootman ( 6). While measuring protrusion of a subject's right eye, the examiner closed his left eye and asked the individual to look at his open right eye. Similarly, the subject was asked to look at the examiner's open left eye as he measured protrusion of their left eye. Measurements were determined at least twice for each 289 290 D. M. JACOBSON eye until a consistent and reproducible reading, estimated to the nearest 0.5 mm, was established. Relative proptosis of the affected eye in patients was defined as the axial measurement of the unaffected eye subtracted from the axial measurement of the affected eye. A positive value indicated that the affected eye protruded more than the unaffected eye. By convention, relative proptosis of the control subjects was determined by subtracting the axial measurement of the left eye from that of the right eye. A positive value indicated that the right eye protruded more than the left eye, whereas a negative value indicated that the left eye protruded more than the right eye. The assigned etiology of the ophthalmoplegia was determined retrospectively by reviewing the medical records of each of the patients after all had been enrolled. The specific category of injury of the affected ocular motor nerve was determined after considering the patient's history upon admittance, associated neurologic symptoms and medical conditions, results of laboratory and neuroimaging procedures if performed, and the natural history of the deficit. Exophthalmometry measurements were entered into a computerized database and statistical analysis system ( Graphpad Prism, San Diego, California). The Mann- Whitney test ( two- tailed) was used to compare whether the degree of relative proptosis differed between the groups of patients with complete and severe ophthalmoplegia. Then, the Mann- Whitney test was used to compare the degree of relative proptosis of the affected eye in patients with ocular motor nerve palsies with the absolute value of the interocu-lar difference in axial protrusion of the control subjects. Fisher's exact test ( two- tailed) was used to compare the proportion of patients with ocular motor nerve palsy who had relative proptosis of their affected eye greater than 1 mm with the proportion of control subjects with a similar degree of the absolute value of relative proptosis. RESULTS The study population included 26 patients with oculomotor nerve palsy and 27 patients with abducens nerve palsy. Their main demographic and clinical characteristics are summarized in Table 1. None of the patients with oculomotor nerve palsy had isolated deficits referable to the superior or inferior division. There was no significant difference in the degree of relative proptosis between the patients with oculomotor nerve palsy who had complete or severe ophthalmoplegia ( P = 0.72). Likewise, there was no significant difference in the degree of relative proptosis between the patients with abducens nerve palsy who had complete or severe ophthalmoplegia ( P = 0.26). Accordingly, patients with complete and severe ophthalmoplegia were combined for all subsequent analyses. The control subjects consisted of 40 healthy individuals, including 24 women and 16 men, ranging in age from 22 years to 78 years ( mean, 39 years). The amount of relative proptosis in this population ranged from - 1.0 mm to 1.5 mm ( median, 0 mm) ( Fig. 1). The average absolute value of relative proptosis was 0.38 mm ( standard deviation, 0.42 mm). The degree of relative proptosis of the affected eye in patients with oculomotor nerve palsy ranged from - 1.0 mm to 2.0 mm ( median, 0.5 mm), whereas the degree of relative proptosis of the affected eye in patients with abducens nerve palsy ranged from - 1.0 mm to 2.5 mm ( median, 0 mm) ( Fig. 2). There was no significant difference in the amount of relative proptosis of the affected eye in patients with oculomotor nerve palsy ( P = 0.71) or abducens nerve palsy ( P = 0.35) compared with the absolute value of relative proptosis in the control eyes. Only 4 of 26 ( 15%) patients with third nerve palsy and 3 of 27 ( 11%) patients with abducens nerve palsy had relative proptosis of their affected eye greater than 1 mm. Only 1 of 26 ( 4%) patients with third nerve palsy and 1 of 27 ( 4%) patients with abducens nerve palsy had relative proptosis of the affected eye of 2 mm or more. There was no significant difference in the proportion of patients with either oculomotor nerve ( P = 0.074) or abducens nerve ( P = 0.29) palsy who had relative proptosis greater than 1 mm in their affected eye as compared with the proportion of control subjects with an absolute value of relative proptosis greater than 1 mm. TABLE 1. Demographic and clinical features of 26 patients with acute oculomotor nerve palsy and 27 patients with acute abducens nerve palsy Age range ( mean), years No. women, men No. right, left eye affected Etiology, no. (%) Ischemia Compression Infiltration Brainstem stroke Undetermined Degree of opthhalmoplegia, no. (%) Complete Severe" Oculomotor Nerve Palsy 31- 86( 68) 11, 15 14, 12 24 ( 92) 1( 4) 1( 4) 0 0 13( 50) 13( 50) Abducens Nerve Palsy 40- 91 ( 70) 10, 17 15, 12 23 ( 85) 0 0 1 ( 4) 3( 11) 11( 41) 16( 59) ' Defined in the text as 75% limitation of ocular ductions. ./ Neiiro- Oplithalnwl, Vol. 18, No. 4, 1998 PROPTOSIS WITH THIRD AND SIXTH NERVE PALSY 291 - 1.0 - 0.5 0.0 0.5 1.0 1.5 2.0 2.5 Relative Proptosis, millimeters FIG. 1. Frequency distribution of the amount of relative proptosis measured in 40 control subjects. By convention, a positive value implies that the right eye was proptotic relative to the left eye. DISCUSSION The results of this study confirm that acute neurogenic ophthalmoplegia is not associated with a significant degree of axial orbital proptosis, as measured using the Hertel instrument. Proptosis greater than l mm is rare in that setting. The main conclusion of this study should be tempered by methodologic issues that may have introduced unintentional bias. For example, the measurements were made in an unblinded fashion. There was no practical way to employ a blinded examiner in this study for two reasons. First, the patient's ophthalmoplegia would have been obvious to the examiner as he was performing exophthalmometry measurements. Second, the measurements obtained by a blinded examiner may have correlated poorly with those obtained by the author. Musch and colleagues ( 7) demonstrated that Hertel exophthalmometry is subject to large interobserver variability. In this study, interocular measurements in patients and controls were performed by one examiner using a standardized technique, features that likely minimized methodologic variability. In an office setting, each physician uses an exophthalmometry instrument the same way with all patients. Therefore, the conclusions reached in this study are applicable for anyone who uses the Hertel instrument in a consistent manner. A control group was incorporated into this study mainly to ascertain the degree of interocular variability of axial protrusion that would be measured using this technique in the author's hands. Because the interocular difference of axial protrusion was the endpoint variable recorded in this study, there was no need to control age, gender, or other patient factors in the control population because these variables do not influence the interocular degree of axial protrusion ( 8). The ocular deviation present in many of the patients, ffll _! EHD Third \ U EL - 1.0 - 0.5 0.0 0.5 1.0 1.5 Relative Proptosis, millimeters FIG. 2. Frequency distribution of relative axial proptosis in 26 patients with acute third nerve palsy and 27 patients with acute sixth nerve palsy. By convention, a positive value implies that the affected eye was more proptotic than the unaffected eye. especially those with third nerve palsy, prevented them from fully shifting their gaze into the position requested. However, all patients were instructed to shift their gaze in the same manner so that this variable was minimized within each patient population. Although this inability to fully position some eyes into forward gaze might decrease the amount of protrusion measured in those patients, this should not detract from the conclusion of the study because, from a practical point of view, this is how proptosis is determined in clinical practice. The influence of this variable was likewise minimized in the current study by asking all patients and control subjects to fix upon a standard reference point. In conclusion, the results of this study confirm what seasoned clinicians likely already know- identification of 2 mm or more axial proptosis in an ophthalmoplegic eye is more consistent with a restrictive, not neurogenic, etiology. Until now, however, this clinical dictum was based upon anecdotal experience only and had not been substantiated by a formal investigation. REFERENCES 3 Kestenbaum A. Clinical Methods ofNeuro- ophlhalniologic Examination. 2nd ed. New York: Grunc and Stratum, I96l; 48l. Walsh FB. Clinical Nenro- ophthalmology. 2nd cd. Baltimore: Williams and Wilkins, 1957; 222. Glaser JS. Neuro- ophthalmology. 2nd ed. Philadelphia: J. B. Lip-pincott, 1990: 444. 4. Jaeobson DM, Broste SK. Early progression of ophthalmoplegia in patients with ischemic oculomotor nerve palsies. Arch Ophthalmol I995; l 13: 1535- 7. 5. Jaeobson DM. Progressive ophthalmoplegia with acute ischemic abducens nerve palsies. Am .1 Ophthalmol 1996; 122: 278- 9. 6. Rootman J. An approach to diagnosis of orbital disease. Can J Ophthalmol 1983; 18: 102- 7. 7. Musch DC, Frueh BR, Landis JR. The reliability of Hertel exophthalmometry. Observer variation between physician and lay readers. Ophthalmology 1985; 92: 1177- 80. 8. Migliori ME, Gladstone GJ. Determination of the normal range of exophthalmometric values for black and white adults. Am ./ Ophthalmol 1984; 98: 438- 42. ./ Neuro- OplillMlmol, Vol. 18. No. 4. I99H |
