David L. Epstein, MD, MMM
Primary familial amyloidosis is a generalized systemic disease that may involve the eyes in a number of ways. Bilateral, often severe, open-angle glaucoma may develop in the third, fourth, or fifth decade of life, with progressive accumulation of amyloid vitreous opacities. These vitreous opacities may increase to the extent that vision is seriously impaired and the fundus cannot be seen. The opacities can also develop in the absence of glaucoma. Glaucoma in cases reported by Legrand et al,1 Limon et al,2 and Tsukahara and Matsuo3 has been described as similar to pigmentary glaucoma or to open-angle glaucoma associated with exfoliation, in that there was pigment on the back of the cornea, a heavy accumulation of pigment in the trabecular meshwork, and abnormal transillumination of the iris. In all cases, there were amyloid vitreous opacities. Deposition of amyloid fibrils in the trabecular meshwork has been described by Tsukahara and Matsuo3 and Segawa4 from electron microscopy of trabeculectomy biopsy specimens. Amyloid in this location may have an important role in the obstruction of aqueous outflow.
In a case of familial amyloidosis reported by Plane et al,5 clinically, there was pigment in the angle and powdery material assumed to be amyloid in the vitreous and on the front surface of the lens, yet no glaucoma.
In a series of 70 patients older than 40 years of age with lattice corneal dystrophy as a manifestation of amyloid disease, Meretoja6 diagnosed open-angle glaucoma in 23% but noted no vitreous changes.
In another report,7 17% of patients with vitreous amyloidosis (requiring vitrectomy) also required filtration surgery. There is a strong hereditary tendency in familial amyloidosis, and in any family in which there is hereditary glaucoma with pigment dissemination or vitreous opacities, all members of the family should be examined for amyloidosis and open-angle glaucoma. Similarly, evidence of amyloidosis and open-angle glaucoma should be looked for in patients with lattice corneal dystrophy.8
Our experience with primary familial amyloidosis and glaucoma included the following 2 cases.
A 55-year-old woman had a strong family history of glaucoma (ie, mother, uncle, and brother). Her brother became blind from glaucoma and was said to have a great cloud of vitreous opacities. When he died, extensive amyloidosis was found at autopsy. She herself had been under treatment for glaucoma for several months, using 4% pilocarpine every 2 hours, epinephrine twice a day, eserine ointment at bedtime, and acetazolamide 250 mg 3 times daily. Despite this treatment, intraocular pressure (IOP) was right and left 52 mm Hg. Vision was right and left 6/9. The angles were wide open with ciliary band visible for 360 degrees. There was light brown pigment on the corneoscleral meshwork throughout, but the band was not as dark or broad as in pigmentary glaucoma. The right disc was almost totally cupped. In the right eye, the lower field was limited on the perimeter, absent entirely on the tangent screen. In the left eye, the cup was wide but within physiologic limits, and the field was full.
A trephining was done on the right eye. Acetazolamide was discontinued postoperatively, and within 2 days the IOP in the left eye was 70 mm Hg despite intensive local medication. A trephining was done on the left eye. For several months, IOP ranged from 12 to 15 mm Hg in both eyes, and there appeared to be good functioning blebs, but opacities began to appear in the vitreous. These opacities were not blood and did not resemble exudative opacities. These gradually increased until the fundi could not be seen. Nine months after operation, IOP was right 24 mm Hg, left 32 mm Hg, and the bleb in each eye, though unchanged in height and extent, now had a whitish opaque appearance. Only at the borders did the blebs appear thin and succulent. At first, IOP could be lowered substantially by digital pressure from below. This was done regularly by the patient. She was given pilocarpine 4% and epinephrine. Two years after the operations, IOP was right and left 27 mm Hg on pilocarpine and epinephrine, and it could not be lowered by digital pressure. An operation was done on both eyes, and a thin flap was dissected to the limbus; the whitish tissue was excised, exposing the scleral opening. (The appearance of this whitened but still elevated bleb tissue was so different from the appearance of an ordinary scarred bleb that we assume it was infiltrated by amyloid, but unfortunately histologic studies were not performed on this tissue.)
During the following 9 months, IOP was 12 to 20 mm Hg and could always be lowered by digital pressure. However, within 2 years, there was gradual failure of filtration, and under the care of Richard J. Simmons, MD, the following procedures were done in succession: cyclocryotherapy in the right eye, combined cataract extraction and cyclodialysis on both eyes, another cyclodialysis on both eyes, and then another cyclocryotherapy on both eyes.
After the cataract extraction and cyclodialysis, vision was only counting fingers at a few feet in the better left eye due to vitreous opacities. Later, a vitrectomy was done on the left eye by Robert J. Brockhurst, MD, with restoration of good vision in this eye. Examination of the material removed by vitrectomy established that it contained amyloid. When last seen, IOP was right 22 mm Hg and left 11 mm Hg; corrected vision, left 6/12.
A man aged 57 years, uncle of the patient in the preceding case, was first seen in 1944, with vision right faint hand motions, left counting fingers at 16 feet. IOP was right 90 mm Hg and left 58 mm Hg. The anterior chambers were of good depth. In both eyes, there were deep corneal opacities near the limbus nasally and temporally and some near the pupil, but there were no vessels in the cornea. There were also many vitreous opacities, but the fundi could be seen. The right disc was totally cupped and atrophic; the left was similarly cupped, but the nasal rim was intact. The left eye on the perimeter showed loss of slightly more than the lower nasal quadrant; on the tangent screen, there was a double Bjerrum scotoma isolating a small central island. With intensive miotic therapy, IOP in the left eye fell to 38 mm Hg. A filtering operation was done on this eye. During the next 7 months, IOP was usually in the mid- to low 20s but could always be softened by digital pressure, which the patient did regularly. Then, IOP rose to 35 mm Hg, and a cyclodialysis was done. During the following 7 years, IOP was generally 13 to 17 mm Hg. The vitreous opacity gradually increased so that, at the last visit in 1952, fundus details could not be seen. Last vision recorded was 6/60.
The family history of amyloidosis proven in 2 members of this family and the gradual increase in vitreous opacity make it probable that the patient in Case 49-2 also suffered from amyloid disease. The good control of the glaucoma for more than 7 years after filtering operation and cyclodialysis is unusual in this disease. Our experience with these patients confirms the observation of others that intraocular amyloidosis is a very serious disorder.
A relationship between ocular amyloidosis and pseudoexfoliation syndrome has been described by Meretoja and Tarkkanen,9 on the basis of histologic evidence, suggesting that the pseudoexfoliation syndrome may be a form of amyloid disease. However, clinically, we have not noted vitreous opacities to be associated with pseudoexfoliation and glaucoma.
A recent report has implicated histopathologically the deposition of a cytoskeletal-modulating protein (gelsolin) product in ocular tissues in the Finnish familial form of systemic amyloidosis (Meretoja’s syndrome).10 The authors suggest that the amyloid deposits in the optic nerve might cause an increase in susceptibility of the optic nerve to cupping.
1. Legrand J, Guenel J, Dubigeon M. Glaucome et opacification du vitre par amylose. Bull Soc Ophthalmol Fr. 1986;68:13-20.
2. Limon S, Rousselie F, Joseph E. A propos d’une observation familiale d’amylose vitréenne héréditaire associée à un glaucoma. Arch Ophthalmol (Paris). 1973;33:525-528.
3. Tsukahara S, Matsuo T. Secondary glaucoma accompanied with primary familial amyloidosis. Ophthalmologica. 1977;175:250-262.
4. Segawa K. The fine structure of the iridocorneal angle tissue in glaucomatous eyes (5). Glaucoma secondary to primary familial amyloidosis. Jpn J Clin Ophthalmol. 1976;30:1375-1380.
5. Plane C, Maupetit J, Colnet G, et al. Manifestations oculaires de l’amy-lose Portugaise de Corino de Andrade. Bull Soc Ophthalmol Fr. 1977;77:123-125.
6. Meretoja J. Comparative histological and clinical findings in eyes with lattice corneal dystrophy of two different types. Ophthalmologica. 1972;165:15-37.
7. Doft BH, Machemer R, Skinner M, et al. Pars plana vitrectomy for vitreous amyloidosis. Ophthalmology. 1987;94:607-611.
8. Starck T, Kenyon KR, Hanninen LA, et al. Clinical and histopathologic studies of two families with lattice corneal dystrophy and familial systemic amyloidosis (Meretoja syndrome). Ophthalmology. 1991;98:1197-1206.
9. Meretoja J, Tarkkanen A. Occurrence of amyloid in eyes with exfoliation. Ophthalmic Res. 1977;9:80-91.
10. Kivela T, Tarkkanen A, Frangione B, et al. Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja’s syndrome. Invest Ophthalmol Vis Sci. 1994;35:3759-3769.