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Show ! OUT1IIJI vi Clinical Neuro- ophthalmology 9( l!: 39- 42, 1989. Amyloid Ophthalmoplegia Ophthalmoparesis Secondary to Primary Systemic Amyloidosis Barrett Katz, M. D., Stanley Leja, M. D., Ronald B. Melles, M. D., and Gary A. Press, M. D. © 1989 Raven Press, Ltd., New York We report a patient with primary systemic amyloidosis and orbital involvement associated with ophthalmoparesis. We support this with the first demonstration of eye movement recordings and magnetic resonance imaging ( MRI) of such a patient. The patient presented with a restrictive ophthalmoparesis. Eye movement recordings documented slowed horizontal saccades. MRI of orbital structures suggests that all extraocular muscles were enlarged, with possible involvement of their tendinous insertions. Key Words: Amyloid ophthalmoplegia- Amyloidosis-- Magnetic resonance imaging. From the Departments of Ophthalmology ( B. K., S. L., R. B. M.), Neurosciences ( B. K.), and Radiology ( G. A. P.), University of California at San Diego, and the Veterans Administration Medical Center, La Jolla, CA. Address all correspondence and reprint requests to Dr. B. Katz at UCSD Eye Center M- 018, La Jolla, CA. 92093, U. S. A. 39 Amyloidosis is a disease of unknown etiology characterized by the accumulation of amyloid within different tissues. It has protean manifestations that include both ophthalmic and orbital signs. The classification of amyloidosis is a clinical one and is based upon the presence ( secondary) or absence ( primary) of concomitant systemic disease, whether or not there is a familial tendency, and the extent of involvement ( systemic versus focal). We report a patient with primary systemic amyloidosis and orbital involvement associated with ophthalmoparesis. We also demonstrate eye movement recordings and magnetic resonance imaging ( MRI) of such a patient. CASE REPORT A 48- year- old black woman had been followed with the diagnosis of primary systemic amyloidosis for 5 years. The patient initially sought medical attention with the complaint of an enlarged tongue. Her macroglossia proved to be due to amyloidosis that was demonstrated pathologically on biopsy. She ultimately required a tracheostomy for treatment of obstructive sleep apnea and a carpel tunnel release for entrapment neuropathy, both amyloid related. Initial examination revealed involvement of the breasts, soft tissue of the lower lip, mucosa of the vagina, and a single purpuric lesion of the left flank. The patient had hepatosplenomegaly, presumed secondary to amyloidosis. Chest radiograms showed borderline cardiac enlargement. Echocardiogram was notable for left ventricular wall size at the upper limits of normal and an enlarged right atrium and right ventricular cavity, consistent with amyloid cardiomyopathy. She was treated with furosemide, digoxin, and cy- 40 B. KATZ ET AL. 800 Degrees FIG. 2. Main sequence diagram of saccadic amplitude and duration. Ordinate is duration in milliseconds; abscissa is amplitude in degrees. Bracketed area encompasses ± 2 SO of normal. 20 30 20 10 o 10 150 Cf) " CJ ow 300 DISCUSSION Our patient had primary systemic amyloidosis, documented pathologically. She presented with the adult onset of horizontal diplopia felt clinically to be due to a restrictive ophthalmoparesis. Hori- 500 magnetic field. The patient had a head and orbital examination in axial and coronal planes. Tlweighted ( TR 1,000 msfTE 20 ms), proton densityweighted ( TR 2,500 msfTE 20 ms) and T2- weighte~ ( TR 2,500 msfTE 70 ms) pulse sequences were utilized. Each section was 5 mm in thickness, with a 2.5- mm gap between slices. A 256 x 256 matrix was utilized. Figure 3 demonstrates enlargement of the bellies of the extraocular muscles, with relative but not complete sparing of their tendinous insertions. No abnormalities of intracranial contents or cranial nerves were recognized; signal intensities of the extraocular muscles themselves and the orbital fat were normal on both Tl- weighted and T2- weighted images. Degrees FIG. 1. Main sequence diagram of saccadic amplitude and peak velocity. Ordina. te is v. elocity in degrees per second; abscissa is amplitude In degrees. Bracketed area encompasses ± 2 SO of normal. clic courses of Alkeran and prednisone every 8 weeks, with marked decrease in tongue size and clinical improvement. Her family history was. negative for amyloidosis, and she was hematologIcally normal, with no history of diseases known to re-sult in secondary amyloid. . At the age of 48, the patient presented. WIt~ a 3- week complaint of binocular horizontal dIplopIa. Ocular examination at that time revealed a best corrected vision of 6/ 6 in both eyes with normal color vision. Both orbits were full, with symmetric exophthalmometry ( 22 mm). There was in~ reased resistance to retropulsion bilaterally. Antenor segments, pupillary responses, and fund~ scopy w~ re within normal limits. There was no eVIdence of lId, corneal, or vitreal involvement. She had no chemosis, conjunctival infiltration, increased vascularity over the recti muscles, soft tissue fullness, or lid lag. There was minimally decreased ~ b~ uction of each eye, associated with an esodevIahon. Clinically, saccades were equally slowed in a~ l ~ eridians and truncated in the horizontal mendlan. Pursuits were normal, and optokinetic nystagmus was symmetrically elicited. Forced duction testing suggested a restrictive component to the ophthalmoparesis. Neurological examination was otherwise normal. MRI of orbital structures was obtained, and eye movements recorded. ThyrOid function tests ( T3- RIA, T4, T 3 uptake, TSH, free T 4 index, anti- thyroglobulin and anti- microsomal antibodies) were normal. Horizontal eye movement recordings were evaluated in our laboratory, as previously reported ( 1). Briefly, the system employs infrared illumination of each eye simultaneously by light- emitting diodes. A mirror transparent for visible light, yet reflective for infrared light projects the light reflected from each iris plane on to a linear array of 1,024 photo diodes. A video signal is generated from the output of the photo diodes. The addresses of the appropriate diodes are read by a microprocessor and the data made available for computer storage and analysis. This system allows for a linear range of 30°, spatial resolution of greater than 0.1°, temporal resolution of 4 ms, and the simultaneous recording of each eye. A main sequence diagram of saccadic velocity and amplitude is illustrated in Fig. 1. Figure 2 is a main sequence diagram of saccadic amplitude and duration. Both peak velocity and duration fall outside of the normal range (± 2 SD) as established in this laboratory. This was equally true for both abducting and adducting saccades. MRI was performed on a GE Signa scanner ( General Electric, Milwaukee) with a 1.5- T main I eli" .' IiclIru- lll" rthalmol. Vol. 9. No. 1. 1989 AMYLOID OPHTHALMOPLEGIA 41 FIG. 3. A: Axial T1- weighted section of MRI of orbital structures, demonstrating enlargement of medial and lateral rectus muscles in each eye, with some associated prominence of tendinous insertions. B: Coronal T1- weighted image through the retrobulbar portion of both orbits demonstrates variable enlargement of all rectus muscles ( r). Enlargement of the oblique muscles ( arrow) is also shown. The signal intensity of the extraocular muscles and orbital fat is normal in these images as well as on the proton- density and T2weighted images ( not shown). zontal ductions were limited, horizontal saccadic eye movements slowed. All ocular findings could be explained by amyloid infiltration of the extraocular muscles as a manifestation of primary systemic amyloidosis ( 2,3). Systemic amyloidosis can be secondary to pyogenic or granulomatous infection, arthritis, malignancy, or chronic inflammatory disease of the intestine; when it is not, it is considered primary. In both primary and secondary amyloidosis, muscles, skin, nerves, and blood vessels are commonly involved ( 4). Primary systemic amyloidosis shows a wide range of muscular involvement, affecting skeletal, cardiac, smooth, and extraocular fibers ( 5). In secondary amyloidosis, findings are typically more limited. Ophthalmoplegia has been reported in both the primary and secondary variants ( 3,6), and recently as the sole manifestation of amyloidosis ( 7). Primary and secondary amyloid can be localized or systemic. Amyloidosis involving the lid is suggestive of the primary systemic variant, whereas involvement of the conjunctiva and orbital content has been seen with both the primary and secondary forms. Corneal involvement is seen almost solely as a manifestation of hereditary localized amyloidosis, and involvement of the vitreous is generally a manifestation of another familial form of primary localized disease ( 8-- 11). Amyloid has the pathological appearance of a homogeneous, amorphous substance under light microscopy, but has the very distinctive characteristic of apple- green birefringence under polarized light. Amyloid stains positive with Congo red and periodic acid- Schiff ( PAS). Ultrastructural analysis, the most specific diagnostic method, demonstrates amyloid to consist of rigid, linear, nonbranching aggregated fibrils, 7.5- 10 nm wide and of indefinite length, with hollow cores ( 12). The amyloid fibrils are arranged in a B- pleated sheet formation, which produces the characteristic staining and optical features of amyloid deposits that replace and destroy normal tissues. Amyloid is deposited in all body tissues as a recognized aspect of the process of senescence. When amyloid deposition occurs in characteristic patterns and increased quantity, clinical amyloidosis results. Our patient has primary systemic amyloidosis based upon the lack of an underlying systemic disease, diffuse tissue involvement, and negative family history. She had a restrictive ophthalmoparesis with concomitant enlargement of her extraocular muscles. The characteristics of her MRI scan as well as the computed tomography ( CT) scan of another patient recently reported ( 7) suggest that the extraocular muscle involvement of amyloid may be somewhat different than the enlargement of muscles seen in thyroid orbitopathy. In amyloid orbitopathy, the tendinous insertions may show an increase in size not usually associated with thyroid disease. This observation requires further clinical and pathologic confirmation. Our patient's orbitopathy was accompanied by ~ lowed and prolonged saccades. Although the perIpheral nervous system is commonly affected in I C/ in Neuro- ophthalmol. Vol. 9. No. 1. 1989 42 B. KATZ ET AL. amyloidosis, the cranial nerves themselves are not. We interpret our findings to suggest that it is the infiltration of the extraocular muscles with amyloid that accounts for our patient's signs and symptoms. Namely, it is a peripheral ocular motor plant dynamic change that accounts for the ophthalmoparesis of amyloid. Acknowledgment: This work was supported in part by a grant from the Veterans Administration Medical Center ( B. K.). The authors wish to thank Dr. Bessie Floyd for allowing us to study this patient. REFERENCES 1. Katz B, Mueller K, Helmle H. Binocular eye movement recording with CCO arrays. Neuro- Ophthalmology 1987; 7: 8191. 2. Goebel HH, Friedman AH. Extraocular muscle involvement in idiopathic primary amyloidosis. Am J Ophthalmol 1971; 71: 1121- 7. 3. Raflo GT, Farrell TA, Sioussat RS. Complete ophthal- I ( fill Nellro · ophthalmol, Vol. 9, No. 1, 1989 moplegia secondary to amyloidosis. Am J Ophthalmol 1981; 92: 221-- 4. 4. Brownstein MH, Elliott R, Helwig EB. Ophthalmologic aspects of amyloidosis. Am JOphthalmol 1970; 69: 423- 30. 5. Kyle RA, Greipp PR. Amyloidosis ( AL): clinical and laboratory features in 229 cases. Mayo Clinic Proc 1983; 58: 66583. 6. Macoul KL, Winter FG. External ophthalmoplegia. Arch Ophthalmol 1968; 79: 182-- 4. 7. Holmstrom GE, Nyman KG. Primary orbital amyloidosis localized to an extraocular muscle. Br / Ophthalmol 1987; 71: 32- 3. 8. Schwartz MF, Green WR, Michels RG, Kincaid Me, Fogle J. An unusual case of ocular involvement in primary systemic nonfarniIial amyloidosis. OphthalmokJgy 1982; 89: 394-- 401. 9. Knowles JOM, } akobiec FA, Rosen M, Howard G. Amyloidosis of the orbit and adnexae. Surv Ophthalmol 1975; 19: 367- 84. 10. Rukavina JG, Block WO, Jackson LE, et aI. Primary systemic amyloidosis: a review and an experimental, genetic and clinical study of 29 cases with particular emphasis on the familial form. Medicine ( Baltimore) 1956; 34: 239-- 44. 11. Kaufman HE, Thomas LB. Vitreous opacities diagnostic of the familial primary amyloidosis. N Engl J Med 1959; 261: 1267- 71. 12. Glenner GG. Amyloid deposits and amyloidosis: the betafibriIoses. N Engl JMed 1980; 392: 1283- 92, 1333- 43. |
