Eiko Ando

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (32)125.47 Total impact

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    ABSTRACT: Background: to investigate the vitreous opacity in patients with familial amyloidotic polyneuropathy (FAP) in two major endemic areas, Japan and Sweden. Methods: we obtained clinical data for 90 patients with vitreous opacity that was associated with FAP amyloidogenic transthyretin (ATTR) Val30Met; 18 Japanese patients and 72 Swedish patients. We reviewed medical records at Kumamoto University Hospital in Japan and Umeå University Hospital in Sweden. We evaluated the characteristics of the patients, systemic and ocular histories, clinical findings and treatment. RESULTS: swedish patients were significantly older at the onset of vitreous opacity (mean age 67.8 years) than were Japanese patients (47.6 years). A similar age difference was found for the onset of polyneuropathy. In addition, Swedish patients without polyneuropathy were significantly older (74.1 years) at the onset of vitreous opacity than those with polyneuropathy (64.6 years). A significant difference in the occurrence of vitreous opacity as the only manifestation of FAP was seen for Swedish patients (35%) compared with Japanese patients (6%). CONCLUSIONS: swedish FAP ATTR Val30Met patients appeared to develop vitreous opacity later and more frequently compared with Japanese patients.
    No preview · Article · Sep 2010 · Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis
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    ABSTRACT: To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients. Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities-the most common ocular manifestation of FAP-in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis. Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not. Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.
    No preview · Article · Feb 2010 · Archives of ophthalmology
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    ABSTRACT: Patients with familial amyloidotic polyneuropathy (FAP TTR Met 30) manifest clinical jindings, such as auto-nomic dysfunction, sensori-motor polyneuropathy, and visceral organ impairment with the progression of the disease. to clarih the clinical features of each patient and to determine the accurate clinical stages of FAt patients were given clinical scores and divided into 4 different groups by their clinical symptoms. Radar charts of the scores revealed that the shapes of the plotted scores between 2 different time examinations were similar until the bedridden stage of FAc suggesting that the clinical type of FAP had been determined at the onset of the disease and did not change as the disease progressed Retrospective stu4 revealed that most of the patients were near death when the total score became about 70. This evaluating method for FAP TTR Met30 may be useful in systematically evaluating the heterogeneity and the stage of each FAP patient, and also in elucidating the effect of therapies on the patients.
    No preview · Article · Jul 2009 · Amyloid
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    M Wakita · T Kawaji · E Ando · T Koga · M Inatani · H Tanihara · Y Ando

    Full-text · Article · May 2006 · British Journal of Ophthalmology
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    ABSTRACT: To report the clinicopathological findings for a unique ocular amyloid angiopathy in patients with familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin Y114C. Three case reports. Retrospective review of clinicopathological findings, course, and treatment of the 3 patients. Visual acuity, intraocular pressure, fundus photography, fluorescein angiography (FA), indocyanine green angiography, and histopathological analysis. In the 32-year-old patient, in the early stage of FAP, indocyanine green angiography demonstrated multiple sites of hyperfluorescence, with staining along major choroidal veins. Retinal vessels appeared normal clinically and on FA. In the 48-year-old patient, who had late-stage FAP, examination of the fundus revealed pinpoint white amyloid opacities over the retinal surface, sheathing of retinal vessels, and scattered retinal hemorrhages. Fluorescein angiography showed vascular closure, focal staining, and microaneurysms. Indocyanine green angiography revealed multiple sites of hyperfluorescence, with staining along retinal and choroidal vessels. Examination during follow-up revealed that these vascular changes continued to progress. Histopathological study of an eye obtained at autopsy from the 49-year-old patient revealed marked intravascular and extravascular amyloid deposition. Severe and progressive amyloid angiopathy causing visual disturbance was seen in patients with FAP caused by amyloidogenic transthyretin Y114C.
    No preview · Article · Jan 2006 · Ophthalmology
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    ABSTRACT: Ocular symptoms of transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) suggest that ciliary pigment epithelium (CPE) may synthesize TTR and its TTR may lead to amyloid formation in addition to TTR from vessels and retinal pigment epithelium (RPE). To clarify sites of TTR synthesis in ocular tissues, we performed in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) for qualitative detection of TTR mRNA. In addition, we quantified levels of TTR mRNA expression by means of real-time quantitative RT-PCR. Furthermore, although TTR is an anti-acute phase protein in serum level, no reports on changes in TTR expression in ocular tissues during acute inflammation exist. To investigate changes in TTR expression in ocular tissues during inflammation, we induced uveitis by endotoxin challenge in rabbits and used real-time quantitative RT-PCR to examine changes in TTR mRNA expression in ocular tissues. In situ hybridization and RT-PCR qualitatively demonstrated TTR mRNA not only in RPE but also in CPE. Real-time quantitative RT-PCR showed that the level of TTR mRNA expression in the CPE was about one-third of that in the RPE. TTR mRNA expression in ocular tissues decreased as the degree of inflammation increased. These results suggest that TTR synthesized in the CPE may lead to ocular manifestations, especially glaucoma, in FAP. TTR mRNA also acts as an anti-acute phase reactant in ocular tissues.
    No preview · Article · Oct 2005 · Experimental Eye Research
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    ABSTRACT: We describe a case of vitreous amyloidosis without systemic symptoms in familial amyloidotic polyneuropathy (FAP) associated with Val30Met transthyretin mutation. A healthy 74-year-old woman noticed left blurred vision and floaters in 1992. Severe vitreous opacities were identified in the left eye. The patient displayed no systemic symptoms, and Congo red staining of the biopsy samples of the stomach and duodenum revealed no amyloid deposition. A diagnosis of FAP was confirmed following genetic investigation. Vitrectomy and cataract surgery was performed with intraocular lens implantation in April 1998. Histopathological examination of the vitreous material revealed amyloid fibrils. Intraocular pressure (IOP) gradually elevated and cupping of the optic disc enlarged. Trabeculectomy was performed in February 2000, but postoperative IOP was again elevated and a needling procedure was performed in March 2000. No postoperative recurrence of vitreous opacity has been reported and IOP has remained well controlled. In the present case, ocular manifestations were the only symptoms of FAP and systemic symptoms have not developed, after more than 12 years. FAP should be suspected as the cause in cases of vitreous opacities in patients from areas with endemic foci of FAP.
    No preview · Article · Jan 2005 · Amyloid
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    ABSTRACT: Liver transplantation has served as a treatment for patients with familial amyloidotic polyneuropathy (FAP) because variant transthyretin (TTR), the pathogenic protein of FAP, is predominantly produced by the liver. However, the effect on amyloid formation of TTR that is synthesised by the retina and the choroid plexus remains to be elucidated in FAP patients with liver transplants. To investigate changes in ocular tissues and the central nervous system (CNS) of FAP patients after liver transplantation. Clinical study. Graduate School of Medical Sciences, Kumamoto University, Japan. Transplantation of livers from cadaveric or living donors. Preoperative measures and postoperative (16-108 months) follow-up of clinical data, including routine ophthalmologic, neurologic, and laboratory evaluations. In 22 patients with FAP related to the amyloidogenic TTR (ATTR) Val30Met and 3 patients with FAP ATTR Tyr114Cys, after liver transplantation, 3 patients began to show evidence of de novo glaucoma, and 1 had vitreous opacity that was caused by the variant TTR. Another three patients showed new amyloid deposits in the pupillary margin, which could lead to glaucoma and vitreous opacity. As for changes in the CNS and levels of total protein and TTR in cerebrospinal fluid (CSF), after liver transplantation, two FAP ATTR Tyr114Cys patients exhibited de novo amyloid deposition in the leptomeninges, and total protein and TTR levels in CSF were significantly increased. Oculoleptomeningeal involvement in FAP was not prevented by liver transplantation because variant TTR produced by the retina and the choroid plexus forms amyloid fibrils in situ.
    No preview · Article · Mar 2004 · Transplantation
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    ABSTRACT: To elucidate the clinical features and surgical outcomes of the treatment of secondary glaucoma associated with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). Retrospective case study. Forty-nine Japanese patients with FAP. For all patients, measurement of best-corrected visual acuity, intraocular pressure, and visual fields as well as slitlamp and ocular fundus examinations were conducted and compared. In addition, the exact mutation of the amyloidogenic TTR variants was analyzed for all 49 patients with FAP. The TTR mutations included amyloidogenic TTR (ATTR) Val30Met in 41 patients, ATTR Tyr114Cys in 6, ATTR Ser50Ile in 1, and a compound heterozygous mutation of ATTR Val30Met + Arg104His in 1. The onset of secondary glaucoma was defined as elevation of intraocular pressure and glaucomatous changes in visual field defects. Secondary glaucoma was detected in 12 (24%) of the 49 patients. The incidence of secondary glaucoma in patients with the Val30Met mutation (17%) was lower than for the other FAP genotypes (P =.02 using the chi(2) test). Of 20 glaucomatous eyes, amyloid deposition on the pupil and anterior surface of the lens was found in 18 eyes. Amyloid deposition was found prior to glaucoma in 11 eyes and at the first visit to our clinic in another 7 eyes. In the 11 eyes in which the onset of glaucoma occurred following amyloid deposition along the pupil, the mean +/- SD period between the onsets of pupillary amyloid deposition and glaucoma was 2.55 +/- 1.43 years (range, 0.2-4.0 years). Further statistical analyses revealed significant relationships between the onset of secondary glaucoma and both amyloid deposition (P<.001) and vitreous opacity (P<.001). Surgical treatment was required in 15 (75%) of the 20 glaucomatous eyes. In 9 (81%) of the 11 eyes that underwent trabeculectomy, the intraocular pressure was well controlled at or lower than 20 mm Hg during the follow-up period. In the eyes that underwent combined trabeculotomy and sinusotomy (2 eyes), nonpenetrating trabeculectomy (1 eye), or a cyclodestructive procedure (1 eye), the intraocular pressure was poorly controlled. Glaucoma is not a rare condition in patients with FAP, especially because liver transplantation now enables patients with FAP to live longer. Careful observation of amyloid deposition along the pupil allows the prediction of glaucoma onset.
    No preview · Article · Mar 2003 · Archives of Ophthalmology
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    ABSTRACT: To report the prevalence of vitreous opacities and the outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy (FAP). Observational case series. In 37 patients with FAP and the ATTR Val30 Met mutation, vitreous opacities were present in 14 eyes of 9 patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in five eyes of three patients. In six patients with the ATTR Tyr114Cys mutation, vitreous opacities were present in both eyes of all six patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in nine eyes of six patients. The mean follow-up period after vitreous surgery was 20.9 +/- 16.8 months (range, 3 to 52 months). The prevalence of vitreous opacities is much higher in patients with ATTR Tyr114Cys (100%) than in those with ATTR Val30 Met (24%). The mean age at the onset of vitreous opacities was significantly lower in the patients with ATTR Tyr114Cys (37.0 +/- 5.3 years) than in the nine patients with ATTR Val30 Met (52.8 +/- 9.1 years; P <.005). Visual acuity improved in all 14 eyes after vitreous surgery; however, final visual acuity decreased in one eye owing to the occurrence of a central retinal vein occlusion. Vitreous opacities mildly increased in two eyes. Our data suggest that the ATTR Val30 Met and ATTR Tyr114Cys mutations induce different clinical features of vitreous opacities. Vitreous surgery combined with phacoemulsification and implantation of an intraocular lens is a safe and useful treatment. Careful long-term follow-up should be performed.
    No preview · Article · Feb 2003 · American Journal of Ophthalmology
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    ABSTRACT: To determine the origin of transthyretin (TTR) in the aqueous humor of patients with familial amyloidotic polyneuropathy (FAP), we measured TTR levels and analyzed the TTR forms in the aqueous humor of three FAP patients (one patient; liver transplanted, and two patients; non-transplanted). The total TTR levels were almost the same as reported previously in non-transplanted patients and slightly increased in a transplanted patient. Analyses with mass spectrometry in the two non-transplanted FAP ATTR V30M patients revealed that both wild type and variant TTR forms were detected in their aqueous humor samples. Moreover, variant TTR forms could be detected in the aqueous humor of the transplanted patient while the liver produced no variant TTR. These results suggest that variant TTR in aqueous humor may be derived from retina where TTR was produced. In conclusion, TTR metabolism may occur in its own ocular cycle and variant TTR produced by the retina may play an important role in amyloid formation in the ocular tissues of FAP patients.
    No preview · Article · Jan 2003 · Amyloid
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    ABSTRACT: Type I (transthyretin Met30) familial amyloid polyneuropathy (FAP TTR Met30) occurs in 2 endemic foci in Japan. We have also reported late-onset Japanese cases unrelated to an endemic focus and showing distinctive clinicopathologic features. To compare clinical and geographic features of FAP TTR Met30 between patients with onset before and after 50 years of age. Clinical information was obtained through a nationwide survey by the Study Group for Hereditary Neuropathy in Japan. Families with early-onset disease in this study numbered 82, and those with late onset, 59. In families with late onset, neuropathy showed male preponderance, low penetrance, little relationship to endemic foci, sensorimotor symptoms beginning distally in the lower extremities with disturbance of both superficial and deep sensation, and relatively mild autonomic symptoms. Families with early onset showed higher penetrance, concentration in endemic foci, predominant loss of superficial sensation, severe autonomic dysfunction, and atrioventricular nodal block requiring pacemaker implantation. This study confirmed differences in clinical and geographic features between early- and late-onset FAP TTR Met30. Late-onset cases may be more prevalent and widespread than previously believed.
    No preview · Article · Dec 2002 · JAMA Neurology
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    ABSTRACT: It is known that the severity of ocular symptoms does not always correlate with the systemic symptoms in patients with familial amyloidotic polyneuropathy (FAP ATTR V30M). The ocular tissues may have their own TTR metabolic system. The aim of this study is to clarify the distribution of amyloid deposition in the ocular tissues and to investigate the relationship between ocular symptoms and histopathological changes. We analyzed histopathologically 9 autopsied eyes taken from 3 Japanese and 6 Swedish patients with FAP ATTR V30M. Localization of amyloid deposition varied among the different cases, but there were some tendencies in the distribution. The degree of amyloid deposition in the ocular tissues was not always correlated with the duration of the disease. The frequency of amyloid deposition in the conjunctiva, iris, trabecular meshwork and vitreous body were 88.9%, 44.4%, 11.1% and 11.1% respectively in the 9 patients. These frequencies in the histopathological changes correlated with the frequencies in the clinical ocular manifestations as previously reported.
    No preview · Article · Oct 2002 · Amyloid
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    ABSTRACT: Twenty-nine-year-old twin brothers having the amyloidogenic transthyretin (ATTR) Val30Met gene developed the clinical symptoms of familial amyloidotic polyneuropathy (FAP) in 1995. The twins had the same educational background and lived in the same district. FAP manifestations were similar in both cases, although electromyographic examinations revealed sensorimotor polyneuropathy in No. 1 and sensory polyneuropathy in No. 2. DNA analysis revealed that they were monozygotic twins. In addition to environmental factors, genetic factors may play an important role in determining the onset of FAP.
    No preview · Article · Jul 2000 · Amyloid
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    ABSTRACT: Twenty-nine-year-old twin brothers having the amyloidogenic transthyretin (ATTR) VaBOMet gene developed the clinical symptoms of familial amyloidotic polyneuropathy (FAP) in 1995. The twins had the same educational background and lived in the same district. FAP manifestations were similar in both cases, although electromyographic examinations revealed sensorimotor polyneuropathy in No. 1 and sensory polyneuropathy in No. 2. DNA analysis revealed that they were monozygotic twins. In addition to environmental factors, genetic factors may play an important role in determining the onset of FAP.
    No preview · Article · Jun 2000 · Amyloid
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    ABSTRACT: Since 1990, liver transplantation for familial amyloidotic polyneuropathy (FAP) has been carried out world-wide, and the outcome of the procedure seems to be promising. FAP is inherited systemic disease caused by mutated transthyretin. The most common cause is the valine to methionine substitution at position 30 (Met30). We have developed a scoring system for FAP Met30 that takes into account a variety of clinical symptoms of the disease. Six patients with FAP Met30 underwent extensive examinations according to our scoring system before and after transplantation. All patients survived the procedure and are alive after transplantation. Improvements of sensory and autonomic disturbances were observed during the initial 12 months after the procedure only, thereafter the patients' status remained unchanged. Following transplantation, no improvement of motor function and visceral organ damage were observed, but the modified body mass index improved in four of six patients after the operation. These results suggest that liver transplantation of FAP patients stops the progress of the disease, and that minor improvements are noted in several patients after the procedure. However, transplantation should be performed early after the onset of the disease in order to preserve the patients' functional status.
    No preview · Article · Jan 2000 · Journal of the Neurological Sciences
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    ABSTRACT: A 64-year-old Japanese male suffering from very slowly progressive amyloidosis was studied by immunohistopathologic, mass spectrometric, and molecular genetic methods. After confirming the immunoreactivity of transthyretin (TTR) in the amyloid deposits using an anti-TTR polyclonal antibody, matrix-assisted laser desorption ionization/time-of-flight-mass spectrometry (MALDI/TOF-MS) was employed to look for the presence of variant TTR(s) in the serum. Two variant forms of TTR, one with a molecular weight 32 Da greater and another with a molecular weight 19 Da less than that of normal TTR encoded by the two respective alleles, were detected in this patient. Direct sequence analysis confirmed the presence of a double substitution: one at codon 30 from GTG (Val) to ATG (Met) and the other at codon 104 from CGC (Arg) to CAC (His) in the two alleles. MALDI/TOF-MS of the parents of the proband revealed that his father was a heterozygote of ATTR Arg104His and his mother was a heterozygote of ATTR Val30Met. The total TTR and retinol binding protein (RBP) concentrations in the serum samples of the proband were very high compared with those of FAP ATTR Val30Met patients and control subjects. We report here a new compound heterozygote in the TTR gene with familial amyloidotic polyneuropathy (FAP).
    No preview · Article · Nov 1999 · Biochemical and Biophysical Research Communications
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    ABSTRACT: We performed biochemical and immunological examinations of heterozygotic carriers of the transthyretin (TTR) mutant Y114C associated with familial amyloidotic polyneuropathy (FAP). The total serum TTR levels in Y114C TTR carriers were extremely low when analyzed by single radial immunodiffusion (SRID), whereas by indirect enzyme-linked immunosorbent assay (ELISA) procedure, their total TTR concentrations were increased. Recombinant homozygotic Y114C TTR showed no immunoreactivity towards a TTR antibody when analyzed by SRID, whereas by the ELISA procedure presented the same degree of reactivity as that of normal TTR or isolated serum heterozygotic Y114C TTR. These results indicate that immunodifusion based techniques cannot properly determine TTR serum levels in Y114C carriers. Analyses of serum TTR of the Y114C TTR carriers by electrospray ionization mass spectrometry (ESI-MS) with the orifice corn voltage at 60 V revealed a small peak of the free Y114C TTR in addition to large TTR peaks of normal TTR. The levels of the free mutant TTR increased with the orifice corn voltage at 90 V. In contrast, increase in orifice voltage from 60 to 90 V produced a reduction in the level of normal TTR. The results suggest a different pattern of association between monomers in Y114C relative to normal TTR.
    No preview · Article · Sep 1999 · Biochemical and Biophysical Research Communications
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    ABSTRACT: The aim of the present study was to analyze the forms of wild type and mutated monomeric transthyretin (Val30Met) in the amyloid fibrils of patients with familial amyloidotic polyneuropathy by electrospray ionization mass spectrometry (ESI-MS). The solubility of amyloid fibrils from the vitrectomized samples was examined to determine the appropriate solution for ESI-MS. ESI-MS analysis revealed that heterozygotic Val30Met amyloid fibrils contained 14.6 +/- 7.5% normal TTR. In all samples, 3 different types of variant ATTR could be identified: Full length ATTR, and -57, and -157 (or 156) Da from ATTR Val30Met were found. The two peaks showing -57, and -157 (or 156) Da from ATTR Val30Met corresponded to the -Gly, and -Gly-Pro sequences of ATTR Val30Met from the N-terminal. The results illustrate the heterogeneity of ATTR amyloid deposits and this method may be very useful for analyzing amyloid fibrils in ATTR related amyloidosis.
    No preview · Article · Jul 1999 · Amyloid
  • M. Okuyama · H. Ideta · Y. Ando · E. Ando · A. Negi
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    ABSTRACT: A 61 year-old male visited to Ideta Eye Hospital 13 years ago with a complaint of floaters in his right eye. His corrected visual acuity was (0.6) in his right eye and (1.0) in his left eye, and several opacities were visible in the vitreous of his right eye. Two years later the patient returned complaining of further decrease in vision in the right eye. On fundus examination, vitreous opacities with a glass-wool appearance were seen posterior to the equator in the right eye and vision was (0.03) in this eye. Pars plana vitrectomy was performed on the right eye and visual acuity improved to 1.0. However, 5 years later intraocular pressure in the patient's right eye rose to 72 mm Hg. Medical treatments were ineffective and 5 consecutive glaucoma filtering operations were performed. By 11 years after his first visit, the patient's visual acuity had decreased to (0.06) in the right eye and to (0.7) in the left eye, and fundus examination of the patient's left eye revealed vitreous opacities with a glass-wool appearance. Familial amyloidotic polyneuropathy (FAP) was suspected and the patient was referred to the Department of Internal Medicine. Amyloidotic polyneuropathy was verified by rectal biopsy and genetic evaluation of the patient and family revealed presence of the ATTR Met 30 gene, confirming the diagnosis of FAP.
    No preview · Article · Jan 1999 · Folia Japonica de Ophthalmologica Clinica

Publication Stats

730 Citations
125.47 Total Impact Points


  • 1990-2010
    • Kumamoto University
      • • Department of Ophthalmology
      • • Graduate School of Medical Sciences
      • • School of Medicine
      • • Department of Medical Biochemistry
      Kumamoto, Kumamoto, Japan
  • 2002-2003
    • Kumamoto Kinoh Hospital
      Kumamoto, Kumamoto Prefecture, Japan
  • 1996-1999
    • Umeå University
      • • Department of Medical Biochemistry and Biophysics
      • • Department of Public Health and Clinical Medicine
      Umeå, Vaesterbotten, Sweden