J. A. Barth, Leipzig
Exp. Clin. Endocrino!. Vol. 97, No. 2/3, 1991, pp. 231-234
Medizinische Klinik Innenstadt, Ludwig-Maximilians-Universität
(Direktor: Prof. Dr. P. C. Scriba), München/Germany
Why Do We Need the Ophthalmologist?
With 1 Figure
In the diagnostic scheme (Fig. 1) of Jacobson and Gorman (1984) only a small section of the circumference depicts the endocrinological methods to evaluate eye signs and symptoms before and during treatment of endocrine orbitopathy. The more conclusive informations have to be derived from the ophthalmological investigations. Since Werner (1977) has established his classical classification and graduation of endocrine orbitopathy, orbital echography (Holt et al., 1985; Ossoinig, 1989), computerized imaging (Holt et al., 1985; Markl et al., 1986; Ullerich et al., 1983; UnsOld et al., 1981) and magnetic resonance tomography (Marki et al., 1990) have been used to visualize intraorbital pathological characteristics of the syndrome. By these methods typical but not strictly pathognomonic changes can be documented and in part be measured, e.g. muscle thickness. But reproducibility of these informations depends on a standardizaExamination of extraocular muscle movement
CT scan
Ultrasound
Visual acuity and color perception
Clinical evaluation Serum
14 -T3 T.S.l.
Fundoscopy +
TRH
Perimetry
13
Ultrasound
suppression
Visual evoked responses Unilateral
Bilateral
Exophthalmometry Fig. 1
Diagnostic procedures in endocrine orbitopathy (Jacobson and Gorman, 1984).
Downloaded by: University of Pittsburgh. Copyrighted material.
C. R. PIcKA1UT
232
Exp. Clin. Endocrinol. 97 (1991) 2/3
tion of performance and evaluation. For this purpose cooperation of radiologists and ophthalmologists is demanded (Unsöld et al., 1981). The synopsis of the functional ophthalmological findings and the morphological alterations of orbital structures allows today a more precise definition of the individual clinical symptoms (see contribution of Boergen and Pickardt, 1990). Thus, it can be anticipated that the highly subjective indices (Bartalena et al., 1983; Donaldson et al., 1973; Kriss et al., 1989; Olivotto et al., 1985; van Ouwerkerk et al., 1985; Prummel et al., 1989) for severity and activity of endocrine orbitopathy can be given up in the future. Using more objective parameters we can hope to clarify wether there is an influence of thyroid function (for review see Pickardt, 1989; Gwinup et al., 1982) and treatment of hyperfunction (Bartalena et al., 1989) on development of eye symptoms or not. Moreover, a benefit
radiotherapy is not predictable for the individual patient using the conventional activity indices. Therefore, we have to make new efforts to find an answer for at least some of the open questions concerning natural history and the response to various therapeutical regimes of the endocrine orbitopathy. As far as radiotherapy is concerned, this treatment has no disadvantages when performed properly and most authors agree that the signs of involvement of periocular tissues respond by some degree in most cases (Bartalena et al., 198,3; Donaldson et al., 1973; Hartemann et al., 1986; Heinze et al., 1974; Hurbli et al., 1985; Olivotto et al., 1985; van Ouwerkerk et al., 1985; Sautter-Bihi and Heinze, 1989; Tengetal, 1980; Uhlenbrock et al., 1984). The response rate of proptosis is approximately 30% (for review see SautterBihi and Heinze, 1989; Uhlenbrock et al., 1984). The response rate of muscle function impairment is questionable, surgical corrections are mentioned, e.g. for 40% of patients after radiation (Kriss et al., 1989). Kriss et al. (1989) stated that proptosis and eye muscle involvement only rarely resolve completely. In approximately 40% of patients functional eye muscle disturbances do not respond to radiotherapy regardless the severity. The response rate seems to be higher when radiotherapy is combined with glucocorticosteroid treatment (Bartalena et al., 1983; van Ouwerkerk et al., 1985). The question of optimal time of treatment (Bartalen et al., 1983; Donaldson et al., 1973; Hartemann et al., 1986; Hurbli et al., 1985; Olivotto et al., 1985; van Ouwerkerk et al., 1985) and optimal radiation dosage (Donaldson et al., 1973; Heinze et al., 1974; Kriss et al., 1989; Sautter-Bihl and Heinze, 1989; Uhlenbrock et al., 1984) are unanswered until today. To find the answer we need precise, comparable and reproducible criteria.
Glucocorticosteroids are used for systemic immunosuppression (for review see McConahey, 1984; Nagayama et al., 1987) but there are no standardized guidelines con-
cerning dosage and duration. It seems sure that treatment with 1-1.5 mg prednisone equivalents per kg body weight and day can avoid sightloss. But with respect to the dosage and time dependency of the response of proptosis and muscle function impairment convincing studies are lacking and resistent forms of endocrine orbitopathy can not be yet
identified. But because of the well known side effects of longterm treatment with glucocorticosteroids the relation of risk and benefit has to be investigated with more objective parameters. The same is true for azathioprin and cyclophosphamide (Bigos et al., 1979; Burrow et al., 1970; Wall et al., 1979). Cyclosporin A has been used repeatedly (Borel and Ryffel, 1985; Brabant et al., 1984; Howlett et al., 1984; Kahaly et al., 1986; Karlsson et al., 1985; McGregor et al., 1985;
Downloaded by: University of Pittsburgh. Copyrighted material.
of treatment of eye signs and symptoms by systemic immunosuppression and/or
C. R. PIcnT, Cooperation of Thyrodologist and Ophthalmologist
233
Mihatsch et al., 1988; Utech et al., 1985; Weetman et al., 1983; Witte et al., 1985). Due to
the different diagnostic criteria the results can not be compared. In a study of a small population of patients with active orbitopathy of a highly resistent course we could not detect a systematic amelioration of proptosis or a decrease of muscle thickness (Witte et al., 1985). There was expectedly no change in antibody titers. Improvement of soft tissue involvement did not exceed that induced by glucocorticosteroids. Kahaly et al. (1986) and
Utech et al. (1985) reported better results but both proposed the combination of cyclosporin A and glucocorticosteroids. Prummel et al., (1989) demonstrated in a prospective study that glucocorticosteroids were more effective than cyclosporin A but the because of the serious side effects of cyclosporin A, which are much less predictable than those of glucocorticosteroids, cyclosporin A should be used only for study purposes. To find a more conclusive answer to all these questions, we need the cooperation with the ophthalmologist who can provide us with more objective data to follow the evolution of endocrine ophthalmopathy with and without treatment.
References BARTALENE, L., et al.: Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: Comparison with systemic corticosteroids alone. J. Clin. Endocrino!. Metabl. 56
(1983) 1139-1144. BARTALENA, L., et al.: Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N. Eng!. J. Med. 321 (1989) 1349-1352. BOERGEN, K. P.; PICKARDT, C. R.: Classification of symptoms in endocrine orbitopathy. (1990) Manuscript in preparation. Bioos, S. T., et al.: Cyclophosphamide in the managemePt of advanced Graves' ophthalmopathy. Ann. Intern. Med. 90 (1979) 921-923. BOREL, J. E; RYFFEL, B.: The mechanism of action of ciclosporin: A continuing puzzle. In: Ciclosporin in Autoimmune Diseases. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp.
24-32. B1sA1qT, G., et al.: Ciclosporing in infiltrative eye disease. Lancet 1(1984) 515-516. BuRRow, G. M., et al.: Immunsuppressive therapy for the eye changes of Graves' disease. J. Clin. Endocrino!. Metab. 31 (1970) 307-3 11. DONALDSON, S. S., et al.: Supervoltage orbital radiotherapy for Graves' ophthalmopathy. J. Clin. Endocrinol. Metab. 37 (1973) 276-284. GWINUP, G., et al.: Effect on exophthalmos of various methods of treatment of Graves' disease. J. Amer. Med. Ass. 247 (1982) 2135-2138. HARTEMANN, P., et al.: Le traitement des ophthalmopathies thyroidiennes par la radiotherapie orbitaire externe. Ann. d' Endocrinol. 47 (1986) 389-394. HEINZE, G., et al.: Strahlentherapie der endokrinen Ophthalmopathie mit 18 MeV Bremsstrahlung. Strahlentherapie 148 (1974) 226-234. HOLT, J. E., et al.: Extraocular muscle size comparison using standardized A-scan echography and computerized tomography scan measurements. Ophthalmopathy 92 (1985) 1351. HOWLET, T. A., et al.: Deterioration of severe ophthalmopathy during cyclosporin treatment. Lancet 11(1984)1101. HURBLI, T., et al.: Radiation therapy for thyroid eye diseases. Amer. J. Ophthalmol. 99 (1985)
633-637. JACABsON, D. H.; Goai N, C. A.: Endocrine ophthalmopathy: Current ideas concerning etiology, pathogenesis and treatment. Endocrine Reviews 5 (1984) 200-220. y, G., et al.: Ciclosporin and prednisone in treatment of Graves' ophthalmopathy: A conK trolled randomized and prospective study. Europ. J. Clin. Invest. 16 (1986) 415-422.
Downloaded by: University of Pittsburgh. Copyrighted material.
combination of both drugs in the nonresponder groups lead to a better result. But
Exp. Clin. Endocrinol. 97 (1991) 2/3
234
KARLSSON, F. A., et al.: A pilot study of ciclosporin in endocrine ophthalmopathy. In: Ciclosporin in Autoimmune Disease. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp. 242-246.
KRISS, J. P., et al.: Supervoltage orbital radiotherapy for progressive' Graves' ophthalmopathy: Results of a twenty-year-experience. Acta Endocrinol. (Kbh.) 121 (1989) 154-159, (Suppi. 2). MARKL, A., et al.: Computertomographie bei endokriner Orbitopathie: Auswirkungen
unterschiedlicher Gantry-Kippung und Patientenlagerung auf die Messung der Augen-
muskeldicken und Möglichkeiten der Korrektur. Digit. Bilddiagn. 6 (1986) 81-85. MARKL, A., et al.: Magnetic resonance imaging in Graves' ophthalmopathy: Comparison with computed tomography. Submitted for publication in "Radiology". MCCONAHEY, W. M.:
In: The Eye and Orbit in Thyroid Disease. Eds. GORMAN, C. A.;
WALLER, R. R.; DYER, J. A., New York: Raven Press 1984, pp. 317-324.
diseases. Klin. Wschr. 66 (1988) 43-47. NAGAYAMA, Y.,
et al.:
Tleatment of Graves' ophthalmopathy with high-dose intravenous
methylprednisolone pulse therapy. Acta Endocrinol. (Kbh) 116 (1987) 513. OLIVOTT0, I. A., et al.: Supervoltage radiotherapy for Graves' ophthalmopathy: CCABC technique and results. mt. J. Radiation Oncology 11 (1985) 2085-2090. OssolNlci, K. C.: The role of standardized ophthalmic echography in the management of Graves' ophthalmopathy. In: Graves' Ophthalmopathy, Developments in Ophthalmopathy. Eds. PICKARDT, C. R.; BOERGEN, K. P., Basel: Karger 1989, pp. 28-37. OUWERKERK vAN, B. M., et al.: Radiotherapy of severe ophthalmic Graves' disease. J. Endocrinol.
Invest. 8 (1985) 241-247. PALESTINE, A. G., et al.: Renal histopathologic alterations in patients treated with cyclosporin for uveitis. New. Engl. J. Med. 314 (1986) 1293-1298. PICKARDT, C. R.: Konservative Therapie der endokrinen Ophthalmopathie, eine Übersicht uber die
neuere Literatur. Akt. Endokrinol. Stoffw. 10 Sonderheft (1989) 169-173. PRUMMEL, M. F., et
al.: Prednisone and Cyclosporine in the treatment of severe Graves'
ophthalmopathy. N. Engl. J. Med. 321 (1989) 1353-1359. SAUTTER-BIHL, M.-L.; HEINZE, H. G.: Strahlentherapie der endokrinen Ophthalmopathie. In: Graves' Ophthalmopathy, Developments in Ophthalmopathy. Eds. PICKARUr, C. R.; BOERGEN, K. P., Basel: Karger 1989, 139-154 and Dtsch. Med. Wschr. 114 (1989) 1214-1220. ThNG, C. S., et al.: An evaluation of supervoltage orbital irradiation for Graves' Ophthalmopathy. Clin. Endocrinol. 13 (1980) 545-55 1. UHLENBROCK, D., et al.: Strahientherapie der endokrinen Ophthalmopathy - Auswertung von 56 Fällen. Strahlentherapie 160 (1984) 485-491. ULLERICH, K., et
al.: Die Bedeutung der Computertomographie für die Diagnose und
Therapiebeurteilung der endokrinen Orbitopathie. Akt. Endokrinol. Stoffw. 4 (1983) 30-41. UNSOLD, R., et al.: Zur Diagnose orbitaler Muskelerkrankungen. Klinische Anwendung von Computer-Rekonstruktionen, Klin. Mbl. Augenheilkd. 178 (1981) 436-438.
UTECH, C., et al.: Tteatment of severe Graves' ophthalmopathy with cyclosporin A. Acta Endocrinol. 110 (1985) 4689-4694. WALL, J. R., et al.: Thyroid antibodies and other immunological abnormalities in patients with Graves' ophthalmopathy: Effect of treatment with cyclophosphamide. Clin. Endocrinol. (Oxf.) 10 (1979) 79-91. WEETMAN, A. P., et al.: Cyclosporin improves Graves' ophthalmopathy. Lancet 11(1983)486-489.
WERNER, S. C.: Modification of the classification of the eye changes in Graves' diseae. Am J. Ophthalmol. 83 (1977) 725-727. WITTE, A., et al.: Treatment of Graves' ophthalmopathy with cyclosporin A. Klin. Wschr. 63(1985)
1000 1004. Author's address: Dr. C. R. PICKARDT, Med Klinik Innenstadt, Ludwig-Maximilians-Universität München, Ziemsenstr. 1, W-8000 München 2, Germany
Downloaded by: University of Pittsburgh. Copyrighted material.
MCGREGOR, A. M., et al.: Ciclosporin in the management of Graves' ophthalmopathy. In: Ciclosporin in Autoimmune Diseases. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp. 229-234. MIHATSCH, M. J., et al.: Cyclosporin-associated nephropathy in patients with autoimmune
Exp. Clin. Endocrino!. Vol. 97, No. 2/3, 1991, pp. 231-234
Medizinische Klinik Innenstadt, Ludwig-Maximilians-Universität
(Direktor: Prof. Dr. P. C. Scriba), München/Germany
Why Do We Need the Ophthalmologist?
With 1 Figure
In the diagnostic scheme (Fig. 1) of Jacobson and Gorman (1984) only a small section of the circumference depicts the endocrinological methods to evaluate eye signs and symptoms before and during treatment of endocrine orbitopathy. The more conclusive informations have to be derived from the ophthalmological investigations. Since Werner (1977) has established his classical classification and graduation of endocrine orbitopathy, orbital echography (Holt et al., 1985; Ossoinig, 1989), computerized imaging (Holt et al., 1985; Markl et al., 1986; Ullerich et al., 1983; UnsOld et al., 1981) and magnetic resonance tomography (Marki et al., 1990) have been used to visualize intraorbital pathological characteristics of the syndrome. By these methods typical but not strictly pathognomonic changes can be documented and in part be measured, e.g. muscle thickness. But reproducibility of these informations depends on a standardizaExamination of extraocular muscle movement
CT scan
Ultrasound
Visual acuity and color perception
Clinical evaluation Serum
14 -T3 T.S.l.
Fundoscopy +
TRH
Perimetry
13
Ultrasound
suppression
Visual evoked responses Unilateral
Bilateral
Exophthalmometry Fig. 1
Diagnostic procedures in endocrine orbitopathy (Jacobson and Gorman, 1984).
Downloaded by: University of Pittsburgh. Copyrighted material.
C. R. PIcKA1UT
232
Exp. Clin. Endocrinol. 97 (1991) 2/3
tion of performance and evaluation. For this purpose cooperation of radiologists and ophthalmologists is demanded (Unsöld et al., 1981). The synopsis of the functional ophthalmological findings and the morphological alterations of orbital structures allows today a more precise definition of the individual clinical symptoms (see contribution of Boergen and Pickardt, 1990). Thus, it can be anticipated that the highly subjective indices (Bartalena et al., 1983; Donaldson et al., 1973; Kriss et al., 1989; Olivotto et al., 1985; van Ouwerkerk et al., 1985; Prummel et al., 1989) for severity and activity of endocrine orbitopathy can be given up in the future. Using more objective parameters we can hope to clarify wether there is an influence of thyroid function (for review see Pickardt, 1989; Gwinup et al., 1982) and treatment of hyperfunction (Bartalena et al., 1989) on development of eye symptoms or not. Moreover, a benefit
radiotherapy is not predictable for the individual patient using the conventional activity indices. Therefore, we have to make new efforts to find an answer for at least some of the open questions concerning natural history and the response to various therapeutical regimes of the endocrine orbitopathy. As far as radiotherapy is concerned, this treatment has no disadvantages when performed properly and most authors agree that the signs of involvement of periocular tissues respond by some degree in most cases (Bartalena et al., 198,3; Donaldson et al., 1973; Hartemann et al., 1986; Heinze et al., 1974; Hurbli et al., 1985; Olivotto et al., 1985; van Ouwerkerk et al., 1985; Sautter-Bihi and Heinze, 1989; Tengetal, 1980; Uhlenbrock et al., 1984). The response rate of proptosis is approximately 30% (for review see SautterBihi and Heinze, 1989; Uhlenbrock et al., 1984). The response rate of muscle function impairment is questionable, surgical corrections are mentioned, e.g. for 40% of patients after radiation (Kriss et al., 1989). Kriss et al. (1989) stated that proptosis and eye muscle involvement only rarely resolve completely. In approximately 40% of patients functional eye muscle disturbances do not respond to radiotherapy regardless the severity. The response rate seems to be higher when radiotherapy is combined with glucocorticosteroid treatment (Bartalena et al., 1983; van Ouwerkerk et al., 1985). The question of optimal time of treatment (Bartalen et al., 1983; Donaldson et al., 1973; Hartemann et al., 1986; Hurbli et al., 1985; Olivotto et al., 1985; van Ouwerkerk et al., 1985) and optimal radiation dosage (Donaldson et al., 1973; Heinze et al., 1974; Kriss et al., 1989; Sautter-Bihl and Heinze, 1989; Uhlenbrock et al., 1984) are unanswered until today. To find the answer we need precise, comparable and reproducible criteria.
Glucocorticosteroids are used for systemic immunosuppression (for review see McConahey, 1984; Nagayama et al., 1987) but there are no standardized guidelines con-
cerning dosage and duration. It seems sure that treatment with 1-1.5 mg prednisone equivalents per kg body weight and day can avoid sightloss. But with respect to the dosage and time dependency of the response of proptosis and muscle function impairment convincing studies are lacking and resistent forms of endocrine orbitopathy can not be yet
identified. But because of the well known side effects of longterm treatment with glucocorticosteroids the relation of risk and benefit has to be investigated with more objective parameters. The same is true for azathioprin and cyclophosphamide (Bigos et al., 1979; Burrow et al., 1970; Wall et al., 1979). Cyclosporin A has been used repeatedly (Borel and Ryffel, 1985; Brabant et al., 1984; Howlett et al., 1984; Kahaly et al., 1986; Karlsson et al., 1985; McGregor et al., 1985;
Downloaded by: University of Pittsburgh. Copyrighted material.
of treatment of eye signs and symptoms by systemic immunosuppression and/or
C. R. PIcnT, Cooperation of Thyrodologist and Ophthalmologist
233
Mihatsch et al., 1988; Utech et al., 1985; Weetman et al., 1983; Witte et al., 1985). Due to
the different diagnostic criteria the results can not be compared. In a study of a small population of patients with active orbitopathy of a highly resistent course we could not detect a systematic amelioration of proptosis or a decrease of muscle thickness (Witte et al., 1985). There was expectedly no change in antibody titers. Improvement of soft tissue involvement did not exceed that induced by glucocorticosteroids. Kahaly et al. (1986) and
Utech et al. (1985) reported better results but both proposed the combination of cyclosporin A and glucocorticosteroids. Prummel et al., (1989) demonstrated in a prospective study that glucocorticosteroids were more effective than cyclosporin A but the because of the serious side effects of cyclosporin A, which are much less predictable than those of glucocorticosteroids, cyclosporin A should be used only for study purposes. To find a more conclusive answer to all these questions, we need the cooperation with the ophthalmologist who can provide us with more objective data to follow the evolution of endocrine ophthalmopathy with and without treatment.
References BARTALENE, L., et al.: Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: Comparison with systemic corticosteroids alone. J. Clin. Endocrino!. Metabl. 56
(1983) 1139-1144. BARTALENA, L., et al.: Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N. Eng!. J. Med. 321 (1989) 1349-1352. BOERGEN, K. P.; PICKARDT, C. R.: Classification of symptoms in endocrine orbitopathy. (1990) Manuscript in preparation. Bioos, S. T., et al.: Cyclophosphamide in the managemePt of advanced Graves' ophthalmopathy. Ann. Intern. Med. 90 (1979) 921-923. BOREL, J. E; RYFFEL, B.: The mechanism of action of ciclosporin: A continuing puzzle. In: Ciclosporin in Autoimmune Diseases. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp.
24-32. B1sA1qT, G., et al.: Ciclosporing in infiltrative eye disease. Lancet 1(1984) 515-516. BuRRow, G. M., et al.: Immunsuppressive therapy for the eye changes of Graves' disease. J. Clin. Endocrino!. Metab. 31 (1970) 307-3 11. DONALDSON, S. S., et al.: Supervoltage orbital radiotherapy for Graves' ophthalmopathy. J. Clin. Endocrinol. Metab. 37 (1973) 276-284. GWINUP, G., et al.: Effect on exophthalmos of various methods of treatment of Graves' disease. J. Amer. Med. Ass. 247 (1982) 2135-2138. HARTEMANN, P., et al.: Le traitement des ophthalmopathies thyroidiennes par la radiotherapie orbitaire externe. Ann. d' Endocrinol. 47 (1986) 389-394. HEINZE, G., et al.: Strahlentherapie der endokrinen Ophthalmopathie mit 18 MeV Bremsstrahlung. Strahlentherapie 148 (1974) 226-234. HOLT, J. E., et al.: Extraocular muscle size comparison using standardized A-scan echography and computerized tomography scan measurements. Ophthalmopathy 92 (1985) 1351. HOWLET, T. A., et al.: Deterioration of severe ophthalmopathy during cyclosporin treatment. Lancet 11(1984)1101. HURBLI, T., et al.: Radiation therapy for thyroid eye diseases. Amer. J. Ophthalmol. 99 (1985)
633-637. JACABsON, D. H.; Goai N, C. A.: Endocrine ophthalmopathy: Current ideas concerning etiology, pathogenesis and treatment. Endocrine Reviews 5 (1984) 200-220. y, G., et al.: Ciclosporin and prednisone in treatment of Graves' ophthalmopathy: A conK trolled randomized and prospective study. Europ. J. Clin. Invest. 16 (1986) 415-422.
Downloaded by: University of Pittsburgh. Copyrighted material.
combination of both drugs in the nonresponder groups lead to a better result. But
Exp. Clin. Endocrinol. 97 (1991) 2/3
234
KARLSSON, F. A., et al.: A pilot study of ciclosporin in endocrine ophthalmopathy. In: Ciclosporin in Autoimmune Disease. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp. 242-246.
KRISS, J. P., et al.: Supervoltage orbital radiotherapy for progressive' Graves' ophthalmopathy: Results of a twenty-year-experience. Acta Endocrinol. (Kbh.) 121 (1989) 154-159, (Suppi. 2). MARKL, A., et al.: Computertomographie bei endokriner Orbitopathie: Auswirkungen
unterschiedlicher Gantry-Kippung und Patientenlagerung auf die Messung der Augen-
muskeldicken und Möglichkeiten der Korrektur. Digit. Bilddiagn. 6 (1986) 81-85. MARKL, A., et al.: Magnetic resonance imaging in Graves' ophthalmopathy: Comparison with computed tomography. Submitted for publication in "Radiology". MCCONAHEY, W. M.:
In: The Eye and Orbit in Thyroid Disease. Eds. GORMAN, C. A.;
WALLER, R. R.; DYER, J. A., New York: Raven Press 1984, pp. 317-324.
diseases. Klin. Wschr. 66 (1988) 43-47. NAGAYAMA, Y.,
et al.:
Tleatment of Graves' ophthalmopathy with high-dose intravenous
methylprednisolone pulse therapy. Acta Endocrinol. (Kbh) 116 (1987) 513. OLIVOTT0, I. A., et al.: Supervoltage radiotherapy for Graves' ophthalmopathy: CCABC technique and results. mt. J. Radiation Oncology 11 (1985) 2085-2090. OssolNlci, K. C.: The role of standardized ophthalmic echography in the management of Graves' ophthalmopathy. In: Graves' Ophthalmopathy, Developments in Ophthalmopathy. Eds. PICKARDT, C. R.; BOERGEN, K. P., Basel: Karger 1989, pp. 28-37. OUWERKERK vAN, B. M., et al.: Radiotherapy of severe ophthalmic Graves' disease. J. Endocrinol.
Invest. 8 (1985) 241-247. PALESTINE, A. G., et al.: Renal histopathologic alterations in patients treated with cyclosporin for uveitis. New. Engl. J. Med. 314 (1986) 1293-1298. PICKARDT, C. R.: Konservative Therapie der endokrinen Ophthalmopathie, eine Übersicht uber die
neuere Literatur. Akt. Endokrinol. Stoffw. 10 Sonderheft (1989) 169-173. PRUMMEL, M. F., et
al.: Prednisone and Cyclosporine in the treatment of severe Graves'
ophthalmopathy. N. Engl. J. Med. 321 (1989) 1353-1359. SAUTTER-BIHL, M.-L.; HEINZE, H. G.: Strahlentherapie der endokrinen Ophthalmopathie. In: Graves' Ophthalmopathy, Developments in Ophthalmopathy. Eds. PICKARUr, C. R.; BOERGEN, K. P., Basel: Karger 1989, 139-154 and Dtsch. Med. Wschr. 114 (1989) 1214-1220. ThNG, C. S., et al.: An evaluation of supervoltage orbital irradiation for Graves' Ophthalmopathy. Clin. Endocrinol. 13 (1980) 545-55 1. UHLENBROCK, D., et al.: Strahientherapie der endokrinen Ophthalmopathy - Auswertung von 56 Fällen. Strahlentherapie 160 (1984) 485-491. ULLERICH, K., et
al.: Die Bedeutung der Computertomographie für die Diagnose und
Therapiebeurteilung der endokrinen Orbitopathie. Akt. Endokrinol. Stoffw. 4 (1983) 30-41. UNSOLD, R., et al.: Zur Diagnose orbitaler Muskelerkrankungen. Klinische Anwendung von Computer-Rekonstruktionen, Klin. Mbl. Augenheilkd. 178 (1981) 436-438.
UTECH, C., et al.: Tteatment of severe Graves' ophthalmopathy with cyclosporin A. Acta Endocrinol. 110 (1985) 4689-4694. WALL, J. R., et al.: Thyroid antibodies and other immunological abnormalities in patients with Graves' ophthalmopathy: Effect of treatment with cyclophosphamide. Clin. Endocrinol. (Oxf.) 10 (1979) 79-91. WEETMAN, A. P., et al.: Cyclosporin improves Graves' ophthalmopathy. Lancet 11(1983)486-489.
WERNER, S. C.: Modification of the classification of the eye changes in Graves' diseae. Am J. Ophthalmol. 83 (1977) 725-727. WITTE, A., et al.: Treatment of Graves' ophthalmopathy with cyclosporin A. Klin. Wschr. 63(1985)
1000 1004. Author's address: Dr. C. R. PICKARDT, Med Klinik Innenstadt, Ludwig-Maximilians-Universität München, Ziemsenstr. 1, W-8000 München 2, Germany
Downloaded by: University of Pittsburgh. Copyrighted material.
MCGREGOR, A. M., et al.: Ciclosporin in the management of Graves' ophthalmopathy. In: Ciclosporin in Autoimmune Diseases. Ed. SCHINDLER, R., Berlin: Springer-Verlag 1985, pp. 229-234. MIHATSCH, M. J., et al.: Cyclosporin-associated nephropathy in patients with autoimmune
