| OCR Text |
Show Journal of Clinical Neuro-ophthalmology 13(4): 258-261, 1993. Botulinum Toxin Type A in Upper Lid Retraction of Graves' Ophthalmopathy Roberto Ebner, M.D. © 1993 Raven Press, Ltd., I'Jew York Botulinum toxin type A (BTTA) was injected in the upper lid of 6 patients to reduce palpebral retraction due to Graves' ophthalmopathy. Five unilateral and one bilateral (all female) cases constitute the present series. Injection of 2.5 to 7.5 units of BTTA in the affected lids produced ptosis of 2 to 3 mm in 5 patients. A bilateral case showed a positive but insufficient response by the third injection. An acceptable position of the affected eyelids was maintained for 1 to 8 months. The drugeffect period varied in every patient, regardless of the dose injected, amount of retraction, or endocrine status (hyper, hypo, or euthyroidism) at the moment of treatment. In 5 of 6 patients BTTA provided acceptable upper lid position without cosmetic discomfort. The early results obtained encouraged the use of botulinum toxin in this entity. Key Words: Dysthyroidism-Lid retraction-Ptosis. From the Neuro-ophthalmology Unit, British Hospital of Buenos Aires, Buenos Aires, Argentina This material was presented in part at the lNOS (International Neuro-ophthalmology Symposium) June 28-July 3, Williamsburg, Virginia, U.S.A. This paper has no financial support. The author states that he has no proprietary interest in the development or marketing of this or any other competing drug. Address correspondence and reprint requests to Dr. Roberto Ebner, Cnel. Oiaz 2277/5*"0", (1425) Buenos Aires, Argentina. 258 Botulinum toxin type A (BITA) is one of the most potent neurotoxins known. Acting at the motor end plate (neuromuscular junction), blocking acetylcholine release, BTTA produces temporary muscle weakening. This principle was used in ophthalmology during the last decade in the treatment of strabismus, sixth nerve palsy, nystagmus, dysthyroid ophthalmoplegia, blepharospasm, and other disorders (1-6). Treatment of upper lid retraction due to Graves' ophthalmopathy was suggested in 1973 by Scott and colleagues (7), who later reported the results obtained in 3 patients (from a series of 8) with dysthyroidism and lid retraction treated with BITA (4). Good results were observed in two cases and temporary benefits in the third. There were no further papers on this subject. Protective ptosis was also produced with BTTA injection to aid the healing process of corneal diseases (8). This report provides data of 6 patients having endocrine ophthalmopathy where lid retraction was treated with BTTA in the attempt to normalize lid position. MATERIAL AND METHODS Six patients (all female) having present or past evidence of dysthyroidism were selected for treatment of lid retraction with BTTA injection, despite the presence of exophthalmos and/or ophthalmoparesis. The clinical profiles of these patients are summarized in Table 1. Vnilaterallid retraction was present in 5 cases, and one case was bilateral. The degree of retraction is expressed in millimeters measured from the corneal limbus (12 hr) to the free palpebral border. Cases I, 2, 3, and 5 were euthyroid at the time of injection while patients 4 and 6 were receiving treatment for hyperthyroidism. Each vial of BTTA, containing 100 V, was pre- BTTA IN GRAVES' OPHTHALMOPATHY TABLE 1. 259 Lid Patient! retraction Units of Follow-up Endocrine Lid position Case age Eye (mm) BTIA (weeks) Complications status (3rd week after BTIA) 1 BO/42 LE 3 5 &2.5 38 Ptosis Euthyroid OU equal 2 MO/38 LE 2.5 2.5 x 2 12 Euthyroid OU equal 3 FU38 RE 3.5 2.5 x 2 8 Euthyroid Retraction 0.5 mm 4 HC/23 OU 4 2.5 x 3 12 Hyperthyroid Retraction 1 mm RE, 2.5 mm LE 5 HE/51 RE 2 2.5 x 3 16 Ptosis Euthyroid OU equal 6 MM/36 RE 3 5 10 Ptosis Hyperthyroid Retraction 1 mm pared with 2 ml of saline solution. The concentration obtained was 5 U/O.l ml. The site of injection in the upper lid was at the superior tarsal border (pars cartilaginosa) at a point slightly lateral to its center (Fig. 1). The injection was subcutaneous, aiming at levator palpebrae muscle fibers from the point of entrance. By diffusion, the drug will also reach the superior fascicles of the Muller muscle. In every attempt, 2.5 to 5 units of toxin was delivered. Patients were injected 1, 2, or more times. The delay between injections was usually 7 days. Patients were seen weekly in the first month, then every other week until the third month, when they were seen monthly. All patients accepted in this series to be treated with BITA had full knowledge of possible side effects (edema/pain at the site of injection, tearing, annoying ptosis, or diplopia). No patient was pregnant or evidenced myasthenic disorders. None of the 6 patients was willing to undergo surgical procedures to correct lid position. RESULTS Five patients developed a reduction in the amount of lid retraction after I, 2, or 3 injections of BITA, providing a good palpebral position (Figs. 2 and 3). In case 4 the response was mild with a remaining retraction of 1 mm on the right eye and I FIG. 1. Site of injection. The scheme is offered for a right eye. See text. 2.5 mm on the left, even though the patient felt comfortable with the results obtained (Fig. 4). Effects of the therapy lasted from 8 to 32 weeks. Daily variations were observed by patients at the time the toxin lost its effect, the lids being better positioned in the first hours of the day and retracting in the evening. Side effects observed were complete undesirable ptosis in Case 1 and mild ptosis (the lid covering the upper third of the corneal surface) in Cases 5 and 6. Excessive ptosis vanished by the second week in all three cases (Fig. 5). All cases are detailed in Table 1. DISCUSSION The use of BITA in order to produce weakness in the levator palpebrae muscle provided good results in 5 cases of lid retraction due to Graves' ophthalmopathy. Four cases required 2 or 3 injections to reach normal lid position. In Scott's series (4), two cases required several BITA injections to obtain the desired results. In all cases, when the drug's effect disappeared, the recurring lid retraction was 1-2 mm less than FIG. 2. Case 1: (A) Retraction on the left eye before treatment. (B) 32 weeks after botulinum injection. I Clin Neuro-oplttlUllmol. Vol. 13. No.4. 1993 260 R. EBNER (A) (B) .' (C), 1. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 1980;87:1044-7. 2. Helveston EM, Pogrebniac AE. Treatment of acquired nystagmus with botulinum A toxin. Am JOphthalmol1988; 106:584-6. 3. Scott AB, Kraft SP. Botulinum toxin injection in the management of lateral rectus paresis. Ophthalmology 1985;92: 677-83. 4. Scott AB. Injection treatment of endocrine orbital myopathy. Doc OphthalmoI1984;58:141-5. 5. Frueh BR, Felt DP, Wojno TH, Museh DC. Treatment of REFERENCES duced by BTTA persist for at least 3 years. The longest follow-up provided in our series is 38 weeks in Case 1. No relationship was observed between the initial amount of retraction, the doses received by each patient, and the duration of muscular weakening. The longer-lasting effects tended to be seen in euthyroid patients. BTTA proved to be safe and useful to weaken retracted lids in Graves' disease and had minor side effects. Larger series and longer follow-ups matching these preliminary results will more precisely determine the main site of injection, the mean effective dose, the mean effective time, and the best endocrine status for initiating therapy. FIG. 5. Case 5: (A) Before and (B) after 5 days of botulinum. (C) The ptosis disappeared by the 2nd week. FIG. 3. Case 3: (A) Before and (B) after 4 weeks of botulinum. {A) the measurement before treatment. Some patients did not need further injections. BTTA, acting by its chemical neuromuscular blockage, produced lid position modifications, but why some pati:nts needed just one injection while others reqUired two or more injections, and why every vanishing result led to a better lid position is not clearly understood. Borodic and Ferrante (9), in their article on repeated BTTA injections and muscle changes, pointed out that permanent dysmorphic alterations in the preterminal axon or ultrastructural changes of muscle fiber are possible. These authors also mention that in a muscle subjected to repeated BITA injections, long-term chronic irreversible changes may occur, such as permanent neurogenic muscle atrophy with resulting fibrosis and muscular scarring, even though, in the short term, diffuse atrophy appears to be reversible. Those changes could partially explain our results. Holds and colleagues (10) noted that changes in- FIG. 4. Case 4: (A) Before and (B) after 3rd injection. JGin Neuro-ophthalmol, Vol. 13. No.4, 1993 BTTA IN GRAVES' OPHTHALMOPATHY 261 blefarospasm with botulinum toxin: a preliminary report. Arch OphthalmoI1984;102:1464-8. 6. Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injections as a treatment for blefarospasm. Arch Ophthalmol 1985;103:347-50. 7. Scott AB, Rosenbaum A, Collins CL. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol 1973;12: 924-7. 8. Kirkness CM, Adams GGW, Dally PN, Lee JP. Botulinum toxin A induced protective ptosis in corneal disease. Ophthalmology 1988;95:473-80. 9. Borodic GE, Ferrante R. Effects of repeated botulinum toxin injections on orbicularis oculi muscle. / Clin NeuroophthalmoI1992; 12:121-7. 10. Holds JB, Alderson K, Fogg SG, Anderson RL. Motor nerve sprouting in human orbicularis muscle after botulinum A injection. Invest Ophthalmol Vis Sci 1990;31:964-7. ] elin Neuro-ophthalmol, Vol. 13, No.4, 1993 |
