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Show !ounuJl of CliniCilI Neuro-ophthalmology IJ(l): 67-71, 1993. © 1993 Raven Press, Ltd., New York A Comparative Study of Tear Secretion in Blepharospasm and Hemifacial Spasm Patients Treated with Botulinum Toxin Jane Price, D.O.B.A. and Justin Q'Day, F.R.A.C.O. In the neuro-ophthalmology clinic at St. Vincent's Hospital, Melbourne, 57 patients with blepharospasm and 50 patients with hemifacial spasm were treated with botulinum toxin. Schinner tear tests were conducted on all the patients prior to each treatment and at 1 week following treatment where possible. The results were compared with a control group of 107 patients selected by age and sex. The blepharospasm patients were found to have a significantly lower tear secretion than that of the control group, using the Mann-Whitney test (median = 3.5 mm, compared with median-l1.0 mm, p < .0001). This did not improve following treatment. The patients with hemifacial spasm did not have significantly different tear secretion from that of the control group (t = 1.0, p> .05). To investigate whether there was any relationship between the symptoms and the result of the Schinner test, a survey was also conducted on the patients with blepharospasm and hemifacial spasm regarding symptoms, frequency, and type of drops/ointment used. Key Words: Dry eye-Schirmer Tear Test-Botulinum toxin-Blepharospasm-Hemifacial spasm. From the Neuro-ophthalmology Department, St. Vincent's Hospital, Melbourne, Australia. Address correspondence and reprint requests to Dr. Justin O'Day, 55 Victoria Pde, Fitzroy 3065, Australia. 67 Botulinum toxin is an effective treatment for blepharospasm and hemifacial spasm (1-4). When injected locally, it causes progressive muscular paralysis by interfering with the release of acetylcholine at the neuromuscular junction (5-7). A number of blepharospasm patients prior to or after treatment with botulinum toxin developed irritable eyes. There appeared to be a decrease in tear secretion in some patients, and therefore we decided to investigate the relationship between tear secretion, before and after botulinum treatment, in patients with blepharospasm and hemifacial spasm. In order to keep a clear, optically high-quality cornea, there needs to be a fine interplay between the production of the tear film, the dynamics of lid closure, and the removal of the tears by the forces of the lacrimal pump (8-11). It was considered likely, based on the knowledge of the formation, distribution, and removal of tears, that there would be an abnormality in tear function associated with abnormal lid function. The levator palpebrae superioris and the orbicularis oculi are two reciprocally acting skeletal muscles that work to control movement of the upper eyelid. The smooth muscle, Mueller's muscle, also plays an additional role in raising the eyelid. Patients with blepharospasm and hemifacial spasm have been found to have slow blinks in both the opening and the closing of the eyelids and this does not improve following treatment with botulinum toxin (12). The normal tear film evaporates quickly (tear breakup time 15-30 seconds (13,14), and therefore the blink reflex plays an important role in preventing dry spots from developing on the cornea and probably has a function in improving reflex tear secretion. This flow is thought to decrease during sleep, under topical anaesthesia and under general anaesthesia (15,16). 68 J. PRICE AND J. O'DAY 60 55 N 50 U 45 MB 40 E R 35 0 30 F 25 E 20 Y E 15 S 10 5 0 0 5 10 15 20 25 30 35 SCHIRMER MEASUREMENT (MM) 40 FIG. 1. Schirmer test results for 107 control patients (214 eyes). Several methods of measuring tear secretion have been described previously (17-21) and it is the aim of this study to investigate tear production in patients with blepharospasm and hemifacial spasm using the Schirmer tear test and to correlate any symptoms they may have with the Schirmer test measurements. MATERIALS AND METHODS At St. Vincent's Hospital, Melbourne, 107 patients, 57 with blepharospasm and 50 with hemifacial spasm, were treated with botulinum toxin. A total of 429 treatments were given with a mean follow-up of 16.5 months (range 0.6-32.8). A control group consisting of 107 patients selected by age, sex, and informed consent had their tear secretion measured using the Schirmer tear test. These patients were selected from a general ophthalmic practice and were not excluded or included because of their ocular condition unless it was physically impossible to conduct the test (e.g., the presence of a lid lesion, sutures, etc.). The Schirmer test was performed according to the directions provided. That is, the test was performed before any topical medication was given and without local anaesthetic. The rounded tips were bent at right angles and were placed in the lower fornix of the eye. The patients sat with their eyes closed for 5 minutes. The test was performed by the same person each time. Similarly, all the blepharospasm patients and hemifacial spasm patients had their tear production tested with the Schirmer test strips prior to each botulinum treatment and at 1 week following the initial treatment when possible; however, since some patients were country, interstate, or elderly, not all of them had the Schirmer test performed at 1 week post-treatment. For the majority of patients (1021107), a survey was also conducted to establish what symptoms NU MB E R FIG. 2. Schirmer test result for 54 (108 0 eyes) blepharospasm patients. F EYE S 50,----------------------., 45 40K\\\\~ 35 30 25 20 15 10 51\\\\\,\\\\\ o I Clin Neuro-ophtholmol, Vol. 13, No.1. 1993 o 5 10 15 20 25 30 35 SCHIRMER MEASUREMENT (MM) 40 COMPARATIVE TEAR SECRETION 69 were complained of and the frequency and type of drops or ointment that were used and whether they provided any relief. All data from the Schirmer test measurements and the dry eye survey were entered onto a data base and analysed using the Minitab statistical program in consultation with Melbourne University Statistical Consulting Centre. RESULTS The mean age of the patients who received botulinum toxin was 63.0 ± 12.1 years, and the mean age of the control group was 64.4 ± 10.4 years. This was not significantly different using the twosample t test (t = 0.9, P> .05). The ratio of females to males in the control group was 2.0:1, in the blepharospasm group was 2.3:1, and in the hemifacial spasm group was 2.7:1. There was no significant difference in the Schirmer test results for females and males in any of the groups. The mean Schirmer result for the control group was 13.4 ± 10.0 mm compared with 7.9 ± 8.9 mm for the blepharospasm group (see Figs. 1 and 2). When compared statistically, there was a significant difference between the blepharospasm group and the control group using the Mann-Whitney test (median = 3.5 mm compared with median = 11.0, P < .0001). There was no significant difference between the hemifacial spasm group (mean = 12.2 mm, SO = 10.0) and the control group (t = 1.0, P > .05). When the Schirmer readings were compared for the affected and unaffected eyes in the hemifacial spasm patients, there was no significant difference in the measurements. The mean Schirmer measurement for the affected eye was 12.2 ± 9.6 mm and for the unaffected eye was 12.2 ± 10.6 mm (t = 0.01, P > .05). The results of the Schirmer test were divided ) 10mm 31llll FIG. 3. Schirmer results for the blepharospasm group (54 patients). )·10mm 63% FIG. 4. Schirmer results for the control group (107 patients). into three separate groups: 0 to <5 mm, 5 to <10 mm, and those who had a Schirmer measurement of ~1O mm. Using the chi-square test, there were significantly more patients with a measurement of <5 mm in the blepharospasm group (56%) than in the control group (21 %) (X2 = 20.1, P < .0001). However, there was no significant difference between the control group and the hemifacial spasm group (26%) (X2 = 0.6, P > .05) (see Figs. 3-6). The Schirmer measurements for the blepharospasm patients did not improve following treatment with botulinum toxin. The pre-treatment measurement was 7.9 ± 8.8 mm compared with the post-treatment measurement of 9.2 ± 7.0 mm, p > .05. The t test on the difference between the pre- and post-treatment Schirmer measurements was not significant (t = 1.4, P > .05). The Schirmer results for 22 blepharospasm patients (44 eyes) who had 5 or more consecutive Schirmer tests were compared to investigate the reliability or variability of the Schirmer test. The mean and standard deviation for each eye was calculated and plotted. This showed that the variabil- )- 10mm 48% FIG. 5. Schirmer test result for the hemifacial spasm group (50 patients). I Gill Neuro-ophlhalmol. Vol. 13. No. 1. 1993 70 J. PRICE AND J. O'DAY SCHIRMER MEASUREMENT (MM) 161---------=-....:.-....:..:..:..:~---------- 14 13.4 12 10 8 6 4 2 0 CONTROLS HEMIFACIAL SPASM BLEPHAROSPASM PATIENT GROUP • MEAN (MM) ~ MEDIAN (MM) FIG. 6. Summary of the Schirmer test results. ity appeared to be related to the magnitude of the measurement, that is, the larger the average Schirmer measurement, the larger the variability. The average standard deviation for the 44 eyes that had repeated measurements was ±3.5 mm. However, when the measurements were divided into 3 groups, the standard deviation increased with the larger measurements. Therefore, with an average Schirmer measurement over 5 or more consecutive tests you could expect a standard deviation of ±2.18 mm if the average measurement was <5 mm and as much as ±7.23 mm if the average measurement over the 5 or more tests was greater than 10 mm (see Table 1). Of the 56% of blepharospasm patients with a Schirmer's measurement of less than 5 mm, 50% complained of dry eye, 40% felt they had no symptoms, 7% did not complete a form, and 3% complained of watery eyes (see Fig. 7). In the 30 blepharospasm patients who had dry eyes, 11 of them used tear substitutes on a regular basis; 82% of those using drops complained of dry eye, and the remaining 18% had no symptoms or complained of a watery eye. Several types of tear substitutes were used in varying amounts to provide relief of symptoms. TABLE 1. The average standard deviation for Schirmer measurements with repeated testing Group (average reading for each eye after repeated testing) oto <5 mm 5to <10 mm ~10 mm Average SO for each eye after repeated testing ±2.18 mm ±5.18 mm ±7.23 mm No. 30 8 6 DISCUSSION Diminished tear secretion was found in patients with blepharospasm. It is not known whether the reduction in tear secretion is one of a number of factors that may play a part in the causation of blepharospasm. Unfortunately, treatment with botulinum toxin did not improve tear function, nor did the use of tear substitutes cause the blepharospasm to diminish. The lack of improvement in tear secretion with effective treatment for the blepharospasm would suggest that either this is an underlying condition that persists or the defective tear secretion is related to the defective lid closure. Although the botulinum improves the blepharospasm, it does not improve the physiology of the blink reflex to increase tear secretion back to normal. Furthermore, if the reduced tear secretion was due to the abnormal lid closure, one might expect that with the DRY EYE 50.. ~~~~~~~WATERY EYE 3.. NOT RECORDED 7.. NORMAL 40.. FIG.. 7. Symptoms for blepharospasm patients with a Schirmer result of 0 - <5 mm (30 patients). I elin Neuro-ophthalnwl. Vol. 13, No. 1. 1993 COMPARATIVE TEAR SECRETION 71 hemifacial spasm patients there would be reduced tear secretion in the affected eye, and this was not the case. As we were unable to demonstrate any improvement in the blepharospasm with the use of artificial tears, we concluded that these patients with reduced tear secretion, who are asymptomatic, probably do not need tear substitutes, as this may result in a low compliance rate. CONCLUSION The blepharospasm patients were found to have dry eyes when compared with the hemifacial spasm patients and the control group. This did not improve when the blepharospasm was treated with botulinum toxin and may indicate that the dry eyes could be a predisposing factor, along with others, to developing blepharospasm rather than as a result of the abnormal lid closure. The investigation of symptoms also shows that not all patients who demonstrate dry eyes on the Schirmer test necessarily complain of dry eyes. The variability of the Schirmer test with repeated testing appeared to be related to the average size of the measurement. The larger the measurement, the larger variation you could expect with a repeated measurement. REFERENCES 1. Scott}, Kennedy R. et al. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985;103: 347-50. 2. Price}. O'Day J. Botulinum toxin for the treatment of blepharospasm and hemifacial spasm. Aust Orth J1991;27:69-76. 3. 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