- Email: [email protected]
Association of Thyroid Disease With Retinitis Pigmentosa and Gyrate Atrophy
5. Levine EA, Ronan SG, Shirali SS, Das Gupta TK. Malignant melanoma in a child with oculocutaneous albinism. J Surg Oncol 1992;51:138-142.
Association of Thyroid Disease With Retinitis Pigmentosa and Gyrate Atrophy Scott M. Whitcup, MD, Fumino Iwata, MD, Marvin J. Podgor, PhD, David Valle, MD, Puspha K. Sran, MD, and Muriel I. Kaiser-Kupfer, MD PURPOSE: To compare the prevalence of thyroid disease in patients with retinitis pigmentosa, in patients with gyrate atrophy of the choroid and retina, and in patients with no history of ocular disease. METHOD: Forty-four patients with retinitis pig mentosa, 34 patients with gyrate atrophy, and 30 normal control patients with no ocular disease were evaluated in a case-control study for the presence of thyroid disease. RESULTS: Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa and seven of 34 patients with gyrate atrophy but in only one of 30 control patients. Compared with control pa tients, the odds ratio for the occurrence of thyroid disease was 6.2 for patients with retinitis pigmen tosa and 12.7 for patients with gyrate atrophy. CONCLUSION: These data suggest an increased occurrence of thyroid disease in patients with retinitis pigmentosa and gyrate atrophy.
A
N ASSOCIATION BETWEEN THYROID DISEASE AND
noninfectious ocular inflammatory disease has been reported,1 and some patients with retinal degen erations may have secondary immunologie disease.2 We therefore evaluated the occurrence of thyroid
Accepted for publication July 9, 1996. The National Eye Institute, National Institutes of Health (S.M.W., EL, M.J.P., P.K.S., M.I.K.-K.), and the Howard Hughes Medical Institute Laboratory of Genetics, The Johns Hopkins University School of Medicine (D.V.). Inquiries to Scott M. Whitcup, MD, National Eye Institute, 10 Center Dr, Bldg 10, Rm ION 202, Bethesda, MD 20892-1858; fax: (301) 496-7295.
VOL.122, N o . 6
disease in patients with two forms of retinal degenera tion: gyrate atrophy and retinitis pigmentosa. We performed a case-control study of 44 patients with retinitis pigmentosa, 34 patients with gyrate atrophy, and 30 control patients. Patients with retini tis pigmentosa and gyrate atrophy were enrolled in natural history protocols at the National Eye Institute of the National Institutes of Health (NIH), Bethesda, Maryland. Control patients with no history of eye disease or thyroid disease and no ocular disease on ophthalmologic examination were obtained as part of an NIH research protocol on normal visual function. Appropriate informed consent was obtained for all patients. Evaluation of all participants included a detailed family history, medical history, physical examination, ocular examination including slit-lamp biomicroscopy and dilated ophthalmoscopy, and thyroid function tests including a serum thyroid-stimulating hormone (TSH) level, free thyroxine level, and antithyroid and antimicrosomal antibodies. Thyroid disease was diag nosed when a patient had a history of thyroid disease that required treatment or had current symptoms of hyperthyroidism or hypothyroidism supported by ab normal thyroid function tests. We compared the Occurrence of clinical thyroid disease in two groups at a time by computing age-adjusted (grouped into the categories younger than 20 years, 20 to 49 years, and 50 years or older) and gender-adjusted odds ratios, exact two-sided P values, and mid-P corrected 95% confidence intervals on the odds ratios. The mean ± SD age was 38 ± 13 years for patients with retinitis pigmentosa (range, 15 to 63 years), 28 ± 18 years for patients with gyrate atrophy (range, 5 to 65 years), and 35 ± 14 years for control patients (range, 22 to 68 years). Twenty-four (55%) of the retinitis pigmentosa patients, 17 (50%) of those with gyrate atrophy, and 19 (63%) of the normal volun teers were women. Clinical data, including the results of the thyroid function tests for the patients diagnosed with thyroid disease, are listed in Table 1. All patients diagnosed with thyroid disease in this study had a history of symptoms suggestive of the disease as well as docu mented abnormal thyroid function tests. All but two of the patients, one with gyrate atrophy and one a normal volunteer, had received treatment for thyroid disease. Thirteen of the 14 patients diagnosed with
BRIEF REPORTS
903
Table 1. Clinical Data From Patients Diagnosed With Thyroid Disease Thyroid-Stimulating
Patient No., Age (yrs), Gender
Ocular Diagnosis
Thyroid Diagnosis
Treatment
1,34, M 2, 50, F 3, 51, F 4, 36, F 5,21, M 6, 61, F 7, 60, F 8, 23, M 9, 29, F 10, 39, F 11,62, M
Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Retinitis pigmentosa Retinitis pigmentosa Retinitis pigmentosa Retinitis pigmentosa
Hashimoto's thyroiditis Hashimoto's thyroiditis Hyperthyroid/hypothyroid Thyroiditis Hypothyroid Hashimoto's thyroiditis Hashimoto's thyroiditis Hypothyroid Hyperthyroid Hypothyroid Hyperthyroid/hypothyroid
12, 35, F 13,39, F 14, 24, F
Retinitis pigmentosa Retinitis pigmentosa Normal
Hypothyroid Hypothyroid Hashimoto's thyroiditis
Levothyroxine Levothyroxine Levothyroxine None Levothyroxine Levothyroxine Levothyroxine Levothyroxine Radioactive iodine Levothyroxine Radioactive iodine/ levothyroxine Levothyroxine Levothyroxine None
Hormone* (μΐυ/ml)
Antithyroid Antibody'
Antimicrosmal Antibody»
14.4 77.1 85.5 4.3 8.5 43.8 11.6 9.3 <0.1 157.2 77.6
1:1,280 <1:10 <1:10 1:320 <1:10 <1:10 <1:10 <1:10 <1:10 <1:10 <1:10
1:6,400 1:1,600 <1:100 1:6,400 <1:100 1:400 1:800 <1:100 1:1,600 <1:100 <1:100
<1:10 <1:10 1:320
<1:100 <1:100 1:1,600
7.8 <0.1 6.3
"The normal range for thyroid-stimulating hormone is 0.42 to 4:4 μΐυ/ml. The normal range for antithyroid antibody is <1:10. ♦The normal range for àntimicrosomal antibody is < 1:100.
thyroid disease had at least one documented abnor mal TSH level. One patient with gyrate atrophy had a normal TSH level but had symptomatic hypothyroid' ism and an elevated antithyroid antibody level of 1:6,400. Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa (13.6%), seven of 34 pa tients with gyrate atrophy (20.6%), and one of 30 normal control patients (3.3%) (Table 2). The esti mated odds for thyroid disease in patients with gyrate atrophy was almost 13 times that of the normal volunteers. The estimated odds for thyroid disease in patients with retinitis pigmentosa was approximately six times that of the normal volunteers. In this study, the estimated odds ratio approximates the relative risk for thyroid disease in these patients. The mean age of patients with gyrate atrophy and thyroid disease (45 years) was significantly higher than that in gyrate atrophy patients without thyroid disease (24 years; P = .008). However, there was no statistically signifi cant difference in the mean age of patients with retinitis pigmentosa with or without thyroid disease (38 years for both). Although abnormal thyroid function tests and overt thyroid disease are common in the general 904
Table 2. Comparison of Thyroid Disease in Patients With Retinitis Pigmentosa (RP) and Gyrate Atrophy (GA) and Normal Volunteers
Comparison
Odds Ratio
95% Confidence Interval
P Value
GA vs normals RP vs normals GA vs RP
12.7 6.2 4.0
1.3,360 0.8, 150 1.0, 17
.02 .11 .04
population, prevalence is higher in older persons and in women. Six percent of women and 2.5% of men over the age of 60 years have serum TSH levels greater than twice the upper limit of normal.3 Overall, clinically important hypothyroidism occurs in 1.5% to 2% of women and 0.2% of men.4 A high preva lence of thyroid disease in patients with gyrate atrophy and retinitis pigmentosa is especially striking considering the demographics of this patient popula tion: the mean age of gyrate atrophy patients with thyroid disease was 45 years and that of retinitis pigmentosa patients with thyroid disease was 38 years. In addition, two of the seven gyrate atrophy patients and two of the six retinitis pigmentosa patients with thyroid disease were men. Only one of the normal
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER
1996
volunteers was diagnosed with thyroid disease, which matches expectations from population estimates.3,4 In addition to the six patients with retinitis pigmentosa and the seven patients with gyrate atrophy diagnosed with definite thyroid disease, another four patients with retinitis pigmentosa and three patients with gyrate atrophy had abnormal thyroid function tests but were asymptomatic and, according to the strin gent diagnostic criteria for this study, were not considered to have thyroid disease. If these patients had been classified as having thyroid disease, the calculated odds ratios for thyroid disease in patients with gyrate atrophy and retinitis pigmentosa would have been even higher. REFERENCES 1. Boskovich SA, Lowder CY, Meisler DM, Gutman FA. System ic diseases associated with intermediate uveitis. Cleve Clin J Med 1993;60:460-465. 2. Thirkill CE, Roth AM, Takemoto DJ, Tyler NK, Keltner JL Antibody indications of secondary and superimposed retinal hypersensitivity in retinitis pigmentosa. Am J Ophthalmol 1991;112:132-137. 3. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid: thyroid deficiency in the Framingham Study. Arch Intern Med 1985;145:1386-1388. 4. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol (Oxf) 1977;7:481-493.
In Vivo Detection of Perineural Circular Arterial Anastomosis (Circle of Zinn-Haller) in a Patient With Large Peripapillary Chorioretinal Atrophy
raphy with a scanning laser ophthalmoscope in the same patient. RESULTS: In the area of peripapillary atrophy, a circumferential vascular loop consistent with a portion of the circle of Zinn-Haller could be detected by the two imaging methods. CONCLUSION: The circle of Zinn-Haller can be visualized in vivo because of the peripapillary atrophy.
T
Ki Ho Park, MD, Goji Tornita, MD, PhD, Eiji Onda, MD, Yoshiaki Kitazawa, MD, PhD, and George A. Cioffi, MD PURPOSE: In vivo visualization of perineural circular arterial anastomosis (circle of ZinnHaller) has been considered impossible because of the arterial circle's location in the sclera. We investigated whether the circle of Zinn-Haller could be detected in a glaucoma patient who had a large area of temporal peripapillary chorioretinal atrophy. METHODS: We performed both scanning laser Doppler flowmetry and indocyanine green angiogVOL.122, No. 6
Figure 1. Photograph of the right optic nerve head shows a thinned neuroretinal rim at the temporal superior disk sector and a large peripapillary atrophy at the temporal side of the disk.
HE EXISTENCE OF A PERINEURAL CIRCULAR ARTERIal anastomosis (circle of Zinn-Haller) has been controversial.1,2 Onda and associates,3 using a microvascular corrosion casting technique, found a com plete or partial circle of Zinn-Haller located at the scierai level 200 to 300 μπι posterior to the suprachoroidal space. Detection of the circle of Zinn-Haller in
Accepted for publication June 21, 1996. Department of Ophthalmology, School of Medicine, Oifu University (O.T., E.O., Y.K.); Department of Ophthalmology, College of Medicine, Seoul National University (K.H.P.); and Devers Eye Institute, Legacy Portland Hospital (G.A.C.). Inquiries to Yoshiaki Kitazawa, MD, PhD, Professor and Chairman, Department of Ophthalmology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan; fax: 81-58-265-9012; e-mail: [email protected]
BRIEF REPORTS
905
Association of Thyroid Disease With Retinitis Pigmentosa and Gyrate Atrophy Scott M. Whitcup, MD, Fumino Iwata, MD, Marvin J. Podgor, PhD, David Valle, MD, Puspha K. Sran, MD, and Muriel I. Kaiser-Kupfer, MD PURPOSE: To compare the prevalence of thyroid disease in patients with retinitis pigmentosa, in patients with gyrate atrophy of the choroid and retina, and in patients with no history of ocular disease. METHOD: Forty-four patients with retinitis pig mentosa, 34 patients with gyrate atrophy, and 30 normal control patients with no ocular disease were evaluated in a case-control study for the presence of thyroid disease. RESULTS: Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa and seven of 34 patients with gyrate atrophy but in only one of 30 control patients. Compared with control pa tients, the odds ratio for the occurrence of thyroid disease was 6.2 for patients with retinitis pigmen tosa and 12.7 for patients with gyrate atrophy. CONCLUSION: These data suggest an increased occurrence of thyroid disease in patients with retinitis pigmentosa and gyrate atrophy.
A
N ASSOCIATION BETWEEN THYROID DISEASE AND
noninfectious ocular inflammatory disease has been reported,1 and some patients with retinal degen erations may have secondary immunologie disease.2 We therefore evaluated the occurrence of thyroid
Accepted for publication July 9, 1996. The National Eye Institute, National Institutes of Health (S.M.W., EL, M.J.P., P.K.S., M.I.K.-K.), and the Howard Hughes Medical Institute Laboratory of Genetics, The Johns Hopkins University School of Medicine (D.V.). Inquiries to Scott M. Whitcup, MD, National Eye Institute, 10 Center Dr, Bldg 10, Rm ION 202, Bethesda, MD 20892-1858; fax: (301) 496-7295.
VOL.122, N o . 6
disease in patients with two forms of retinal degenera tion: gyrate atrophy and retinitis pigmentosa. We performed a case-control study of 44 patients with retinitis pigmentosa, 34 patients with gyrate atrophy, and 30 control patients. Patients with retini tis pigmentosa and gyrate atrophy were enrolled in natural history protocols at the National Eye Institute of the National Institutes of Health (NIH), Bethesda, Maryland. Control patients with no history of eye disease or thyroid disease and no ocular disease on ophthalmologic examination were obtained as part of an NIH research protocol on normal visual function. Appropriate informed consent was obtained for all patients. Evaluation of all participants included a detailed family history, medical history, physical examination, ocular examination including slit-lamp biomicroscopy and dilated ophthalmoscopy, and thyroid function tests including a serum thyroid-stimulating hormone (TSH) level, free thyroxine level, and antithyroid and antimicrosomal antibodies. Thyroid disease was diag nosed when a patient had a history of thyroid disease that required treatment or had current symptoms of hyperthyroidism or hypothyroidism supported by ab normal thyroid function tests. We compared the Occurrence of clinical thyroid disease in two groups at a time by computing age-adjusted (grouped into the categories younger than 20 years, 20 to 49 years, and 50 years or older) and gender-adjusted odds ratios, exact two-sided P values, and mid-P corrected 95% confidence intervals on the odds ratios. The mean ± SD age was 38 ± 13 years for patients with retinitis pigmentosa (range, 15 to 63 years), 28 ± 18 years for patients with gyrate atrophy (range, 5 to 65 years), and 35 ± 14 years for control patients (range, 22 to 68 years). Twenty-four (55%) of the retinitis pigmentosa patients, 17 (50%) of those with gyrate atrophy, and 19 (63%) of the normal volun teers were women. Clinical data, including the results of the thyroid function tests for the patients diagnosed with thyroid disease, are listed in Table 1. All patients diagnosed with thyroid disease in this study had a history of symptoms suggestive of the disease as well as docu mented abnormal thyroid function tests. All but two of the patients, one with gyrate atrophy and one a normal volunteer, had received treatment for thyroid disease. Thirteen of the 14 patients diagnosed with
BRIEF REPORTS
903
Table 1. Clinical Data From Patients Diagnosed With Thyroid Disease Thyroid-Stimulating
Patient No., Age (yrs), Gender
Ocular Diagnosis
Thyroid Diagnosis
Treatment
1,34, M 2, 50, F 3, 51, F 4, 36, F 5,21, M 6, 61, F 7, 60, F 8, 23, M 9, 29, F 10, 39, F 11,62, M
Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Gyrate atrophy Retinitis pigmentosa Retinitis pigmentosa Retinitis pigmentosa Retinitis pigmentosa
Hashimoto's thyroiditis Hashimoto's thyroiditis Hyperthyroid/hypothyroid Thyroiditis Hypothyroid Hashimoto's thyroiditis Hashimoto's thyroiditis Hypothyroid Hyperthyroid Hypothyroid Hyperthyroid/hypothyroid
12, 35, F 13,39, F 14, 24, F
Retinitis pigmentosa Retinitis pigmentosa Normal
Hypothyroid Hypothyroid Hashimoto's thyroiditis
Levothyroxine Levothyroxine Levothyroxine None Levothyroxine Levothyroxine Levothyroxine Levothyroxine Radioactive iodine Levothyroxine Radioactive iodine/ levothyroxine Levothyroxine Levothyroxine None
Hormone* (μΐυ/ml)
Antithyroid Antibody'
Antimicrosmal Antibody»
14.4 77.1 85.5 4.3 8.5 43.8 11.6 9.3 <0.1 157.2 77.6
1:1,280 <1:10 <1:10 1:320 <1:10 <1:10 <1:10 <1:10 <1:10 <1:10 <1:10
1:6,400 1:1,600 <1:100 1:6,400 <1:100 1:400 1:800 <1:100 1:1,600 <1:100 <1:100
<1:10 <1:10 1:320
<1:100 <1:100 1:1,600
7.8 <0.1 6.3
"The normal range for thyroid-stimulating hormone is 0.42 to 4:4 μΐυ/ml. The normal range for antithyroid antibody is <1:10. ♦The normal range for àntimicrosomal antibody is < 1:100.
thyroid disease had at least one documented abnor mal TSH level. One patient with gyrate atrophy had a normal TSH level but had symptomatic hypothyroid' ism and an elevated antithyroid antibody level of 1:6,400. Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa (13.6%), seven of 34 pa tients with gyrate atrophy (20.6%), and one of 30 normal control patients (3.3%) (Table 2). The esti mated odds for thyroid disease in patients with gyrate atrophy was almost 13 times that of the normal volunteers. The estimated odds for thyroid disease in patients with retinitis pigmentosa was approximately six times that of the normal volunteers. In this study, the estimated odds ratio approximates the relative risk for thyroid disease in these patients. The mean age of patients with gyrate atrophy and thyroid disease (45 years) was significantly higher than that in gyrate atrophy patients without thyroid disease (24 years; P = .008). However, there was no statistically signifi cant difference in the mean age of patients with retinitis pigmentosa with or without thyroid disease (38 years for both). Although abnormal thyroid function tests and overt thyroid disease are common in the general 904
Table 2. Comparison of Thyroid Disease in Patients With Retinitis Pigmentosa (RP) and Gyrate Atrophy (GA) and Normal Volunteers
Comparison
Odds Ratio
95% Confidence Interval
P Value
GA vs normals RP vs normals GA vs RP
12.7 6.2 4.0
1.3,360 0.8, 150 1.0, 17
.02 .11 .04
population, prevalence is higher in older persons and in women. Six percent of women and 2.5% of men over the age of 60 years have serum TSH levels greater than twice the upper limit of normal.3 Overall, clinically important hypothyroidism occurs in 1.5% to 2% of women and 0.2% of men.4 A high preva lence of thyroid disease in patients with gyrate atrophy and retinitis pigmentosa is especially striking considering the demographics of this patient popula tion: the mean age of gyrate atrophy patients with thyroid disease was 45 years and that of retinitis pigmentosa patients with thyroid disease was 38 years. In addition, two of the seven gyrate atrophy patients and two of the six retinitis pigmentosa patients with thyroid disease were men. Only one of the normal
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER
1996
volunteers was diagnosed with thyroid disease, which matches expectations from population estimates.3,4 In addition to the six patients with retinitis pigmentosa and the seven patients with gyrate atrophy diagnosed with definite thyroid disease, another four patients with retinitis pigmentosa and three patients with gyrate atrophy had abnormal thyroid function tests but were asymptomatic and, according to the strin gent diagnostic criteria for this study, were not considered to have thyroid disease. If these patients had been classified as having thyroid disease, the calculated odds ratios for thyroid disease in patients with gyrate atrophy and retinitis pigmentosa would have been even higher. REFERENCES 1. Boskovich SA, Lowder CY, Meisler DM, Gutman FA. System ic diseases associated with intermediate uveitis. Cleve Clin J Med 1993;60:460-465. 2. Thirkill CE, Roth AM, Takemoto DJ, Tyler NK, Keltner JL Antibody indications of secondary and superimposed retinal hypersensitivity in retinitis pigmentosa. Am J Ophthalmol 1991;112:132-137. 3. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid: thyroid deficiency in the Framingham Study. Arch Intern Med 1985;145:1386-1388. 4. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol (Oxf) 1977;7:481-493.
In Vivo Detection of Perineural Circular Arterial Anastomosis (Circle of Zinn-Haller) in a Patient With Large Peripapillary Chorioretinal Atrophy
raphy with a scanning laser ophthalmoscope in the same patient. RESULTS: In the area of peripapillary atrophy, a circumferential vascular loop consistent with a portion of the circle of Zinn-Haller could be detected by the two imaging methods. CONCLUSION: The circle of Zinn-Haller can be visualized in vivo because of the peripapillary atrophy.
T
Ki Ho Park, MD, Goji Tornita, MD, PhD, Eiji Onda, MD, Yoshiaki Kitazawa, MD, PhD, and George A. Cioffi, MD PURPOSE: In vivo visualization of perineural circular arterial anastomosis (circle of ZinnHaller) has been considered impossible because of the arterial circle's location in the sclera. We investigated whether the circle of Zinn-Haller could be detected in a glaucoma patient who had a large area of temporal peripapillary chorioretinal atrophy. METHODS: We performed both scanning laser Doppler flowmetry and indocyanine green angiogVOL.122, No. 6
Figure 1. Photograph of the right optic nerve head shows a thinned neuroretinal rim at the temporal superior disk sector and a large peripapillary atrophy at the temporal side of the disk.
HE EXISTENCE OF A PERINEURAL CIRCULAR ARTERIal anastomosis (circle of Zinn-Haller) has been controversial.1,2 Onda and associates,3 using a microvascular corrosion casting technique, found a com plete or partial circle of Zinn-Haller located at the scierai level 200 to 300 μπι posterior to the suprachoroidal space. Detection of the circle of Zinn-Haller in
Accepted for publication June 21, 1996. Department of Ophthalmology, School of Medicine, Oifu University (O.T., E.O., Y.K.); Department of Ophthalmology, College of Medicine, Seoul National University (K.H.P.); and Devers Eye Institute, Legacy Portland Hospital (G.A.C.). Inquiries to Yoshiaki Kitazawa, MD, PhD, Professor and Chairman, Department of Ophthalmology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan; fax: 81-58-265-9012; e-mail: [email protected]
BRIEF REPORTS
905