Recent studies have revealed that the major component of deposited amyloid in familial amyloidotic polyneuropathy (FAP) types I (1) and II (2) is variant transthyretin (TTR). Since both normal and variant TTR are predominantly synthesized by the liver(3, 4), liver transplantation for FAP patients is now considered to be promising therapy (4, 5). In fact, after liver transplantation, variant TTR levels in the serum decreased to below 1% of pretransplant levels, and clinical features were improved or at least not deteriorated after liver transplantation (4). However, TTR is also synthesized by the choroid plexus and the retinal pigment epithelium of the eye (6), and the role of TTR synthesized by these tissues is not well known.
We had a 41-year-old female FAP patient who underwent orthotopic liver transplantation about 4 years after the onset of the disease. Quantitative clinical examinations of this patient were performed between the time before and 6 and 12 months after liver transplantation. Six months after the operation, orthostatic hypotension, gastrointestinal dysfunction, bladder dysfunction, and decreased sweating were significantly improved. Subjective and objective peripheral sensory impairment was also partially improved. She started to live a normal daily life 7 months after the operation. In contrast, serial ophthalmologic examinations revealed that, although no amyloid deposition was recognized in the eye before and 6 months after the operation, 12 months after the liver transplantation some significant deposits were observed by slitlamp examination in the pupillary margin and the surface of the lens of her left eye. This change may have occurred after liver transplantation because repeated serial ocular examinations had been performed before the operation. Because this patient showed no other ocular and systemic diseases except for FAP in addition to the appearance of this deposit, we considered this deposit to be an amyloid deposition. There was a decrease in the patient's secretion of tears, but this was unchanged compared with the data before and 6 months after the operation.
Despite a small amount of total protein level in the aqueous humor, the ratio of TTR to total protein was extremely high compared with that in the serum (percentage of TTR in the aqueous humor: 7-8%, in the serum: 0.04-5% of the total protein level) (7). TTR recognized in the aqueous humor may be the product of TTR synthesized by the eye, but not by the liver. There have been some reports of progressive vitreous amyloid after liver transplantation (8). There is a possibility that a secondry effect of clinical or subclinical preexisting amyloid deposits may have contributed to the ocular change in this patient; however, the information obtained from our findings and results from other reports support the hypothesis that amyloid fibrils in the eye may be derived from another source of variant TTR than the liver.
There is no doubt that liver transplantation is still the only way to save the life of FAP patients; however, ocular amyloidosis is one of the most important findings in FAP, and no therapy for ocular symptoms causes blindness in patients. Thus, precise and long-term follow-up for ocular amyloidosis before and after liver transplantation is needed.
First Department of Internal Medicine, and Departments of Ophthalmology and Neurology; Kumamoto University School of Medicine; Kumamoto 860, Japan
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