MACULAR DEGENERATION IN A JAPANESE PATIENT WITH ACERULOPLASMINEMIA Toshitaka Itabashi, MD, Yuko Wada, MD, Asako Tada, MD, Marie Sukegawa, MD, Eiko Imai, MD, Hajime Sato, MD, Toshiaki Abe, MD, Kohji Nishida, MD
Purpose: To characterize the clinical features of a Japanese patient with macular degeneration in aceruloplasminemia. Methods: The clinical features were evaluated by visual acuity measurements, fluorescein angiography, electroretinography, and kinetic visual field testing. Results: We observed a Japanese patient with macular degeneration in aceruloplasminemia. This patient also had diabetes mellitus and neurodegeneration. Ocular examination showed macular degeneration, which included yellow deposits around the macula area and no foveal reflex. Conclusion: It has been reported that Japanese patients with aceruloplasminemia have atrophy of the retinal pigment epithelium in the midperipheral area and yellowish discoloration of the fundus. However, the retinal findings and results of fluorescein angiography in our case were very similar to those for a white patient. We suggest that retinal degenerations in Japanese patients with aceruloplasminemia have clinical variability. We believe that impairment of iron metabolism caused by iron overload in the retina led to retinal degeneration in this case. RETINAL CASES & BRIEF REPORTS 1:264 –266, 2007
From the Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.
The ocular findings for patients with aceruloplasminemia are variable (e.g., multiple subretinal yellow lesions, retinal pigment epithelium atrophy, dark choroid, yellowish discoloration of the fundus, and macular degeneration).3,4 To date, the ocular findings have been reported only for two patients with aceruloplasminemia, one white3 and one Japanese.4 We describe a Japanese patient with aceruloplasminemia whose ocular findings were similar to those reported for the white patient. These findings indicate that the ocular signs of aceruloplasminemia are not ethnically based.
Aceruloplasminemia is a rare autosomal recessive disorder characterized by retinal degeneration, dementia, and diabetes mellitus.1,2 In 1987, it was reported that mutations in the ceruloplasmin gene cause aceruloplasminemia,2 suggesting that mutations of the ceruloplasmin gene can lead to iron overload in the retina, brain, and pancreas. Iron overload is most likely the cause of degeneration in each of these tissues, leading to maculopathy, dementia, and diabetes.
Case Report Supported in part by a grant from the Research Committee on Chorioretinal Degenerations and Optic Atrophy, the Ministry of Health, Labor and Welfare of the Japanese Government (to T.I.), Tokyo, Japan, and a Grant-In-Aid for Scientific Research from the Ministry of Education, Science, and Culture of the Japanese Government (17591817 to Y.W.), Tokyo, Japan. Reprint requests: Toshitaka Itabashi, MD, Department of Ophthalmology, Tohoku University School of Medicine, 1-1, Seiryomachi, Aoba-ku, Sendai 980-8574, Japan; e-mail: [email protected]. tohoku.ac.jp
A 56-year-old woman first visited our clinic at 52 years of age because she had been diagnosed with diabetes mellitus. Visual acuity was corrected to 1.2 in both eyes, and she did not have visual symptoms. Slit-lamp biomicroscopic examination disclosed normal appearing cornea, anterior chamber, iris, lens, and vitreous bilaterally. Fundus examination showed that the optic disks and retinal vessels were normal but that the retinal pigment epithelium had a mottled appearance in both eyes.
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Fig. 1. Fundus photographs and fluorescein angiograms of our patient. Top, Fundus photographs of the patient at 56 years of age showing yellow deposits around the macula area and no foveal reflex in the left eye. Bottom left, Early-phase (22 seconds) fluorescein angiogram of the left eye did not show the bright hyperfluorescent spot, which was observed in the late frame. Bottom right, Late-phase fluorescein angiogram of the left eye showing granular hyperfluorescence around the macula area corresponding to retinal pigment epithelium atrophy and a bright hyperfluorescent spot.
She first noted decreased visual acuity in her left eye at 55 years of age. Visual acuity was corrected to 1.0 in both eyes. Fundus examination showed yellow deposits around the macula area and no foveal reflex was present bilaterally (Fig. 1). Fluorescein angiography demonstrated granular hyperfluorescence around the macula areas corresponding to retinal pigment epithelium atrophy in both eyes (Fig. 1). In addition, a bright hyperfluorescent spot was observed in the upper area of the macula in the left eye, which was not observed on the early frame of fluorescein angiography (Fig. 1). Kinetic visual field tests showed a paracentral scotoma in the left eye and normal visual field in the right eye (Fig. 2). Cone electroretinograms were decreased bilaterally. The a-waves of the photopic electroretinograms were within the normal range, and the b-waves were reduced to 79% of the normal mean for both eyes (normal mean, 87.7–132.9 V). The scotopic b
waves and both a and b waves of the bright flash electroretinogram were within normal limits for both eyes (Fig. 2).
Discussion It is well known that patients with aceruloplasminemia develop retinal degeneration. The two previous cases showed that the retinal findings for the white and Japanese patients were very different. The previously described white patient had predominant retinal pigment epithelium atrophy in the macula area and multiple subretinal yellowish lesions.3 On the other hand, the previously described Japanese patient had retinal pigment
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Fig. 2. Visual fields and electroretinograms for our patient. Top, Results of Goldmann kinetic visual fields tests of the patient at 54 years of age showing a paracentral scotoma in the left eye. Bottom, Electroretinograms showing a bwave reduction to 79% of the normal mean for both eyes. The scotopic b waves, both a and b waves of the bright flash electroretinogram, and the a waves of the photopic electroretinogram were within the normal range for both eyes.
epithelium atrophy in the midperipheral area and yellowish discoloration of the fundus.4 Dunaief et al3 suggested that the clinical variation in these two groups might be caused by the degree of ocular pigmentations, light exposure, diabetic control, lipid profile, and kind of mutations in the hemochromatosis gene. In our case, the retinal findings and results of fluorescein angiography were very similar to those for the white patient with aceruloplasminemia, except for the bright hyperfluorescent spot around the macula. The bright hyperfluorescent spot spread with time and was not detected in the early frame, which indicates that it might have been choroidal neovascularization. These findings suggest that the clinical features were most likely not based on ethnicity. Although the role of iron in the retina is not completely known, it is generally believed that the impairment of iron metabolism caused by iron overload in the retina leads to
retinal degeneration. Findings of additional molecular genetic analyses will augment our understanding of the clinical variability of aceruloplasminemia. Key words: aceruloplasminemia, hereditary ceruloplasmin deficiency, macular degeneration, retinal degeneration. References 1. 2.
3.
4.
Harris ZL. Aceruloplasminemia. J Neurol Sci 2003;207:108– 109. Miyajima H, Nishimura Y, Mizoguchi K, et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration. Neurology 1987;37:761–767. Dunaief JL, Richa C, Franks EP, et al. Macular degeneration in a patient with aceruloplasminemia, a disease associated with retinal iron overload. Ophthalmology 2005;112:1062–1065. Yamaguchi K, Takahashi S, Kawanami T, et al. Retinal degeneration in hereditary ceruloplasmin deficiency. Ophthalmologica 1998;212:11–14.
Purpose: To characterize the clinical features of a Japanese patient with macular degeneration in aceruloplasminemia. Methods: The clinical features were evaluated by visual acuity measurements, fluorescein angiography, electroretinography, and kinetic visual field testing. Results: We observed a Japanese patient with macular degeneration in aceruloplasminemia. This patient also had diabetes mellitus and neurodegeneration. Ocular examination showed macular degeneration, which included yellow deposits around the macula area and no foveal reflex. Conclusion: It has been reported that Japanese patients with aceruloplasminemia have atrophy of the retinal pigment epithelium in the midperipheral area and yellowish discoloration of the fundus. However, the retinal findings and results of fluorescein angiography in our case were very similar to those for a white patient. We suggest that retinal degenerations in Japanese patients with aceruloplasminemia have clinical variability. We believe that impairment of iron metabolism caused by iron overload in the retina led to retinal degeneration in this case. RETINAL CASES & BRIEF REPORTS 1:264 –266, 2007
From the Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.
The ocular findings for patients with aceruloplasminemia are variable (e.g., multiple subretinal yellow lesions, retinal pigment epithelium atrophy, dark choroid, yellowish discoloration of the fundus, and macular degeneration).3,4 To date, the ocular findings have been reported only for two patients with aceruloplasminemia, one white3 and one Japanese.4 We describe a Japanese patient with aceruloplasminemia whose ocular findings were similar to those reported for the white patient. These findings indicate that the ocular signs of aceruloplasminemia are not ethnically based.
Aceruloplasminemia is a rare autosomal recessive disorder characterized by retinal degeneration, dementia, and diabetes mellitus.1,2 In 1987, it was reported that mutations in the ceruloplasmin gene cause aceruloplasminemia,2 suggesting that mutations of the ceruloplasmin gene can lead to iron overload in the retina, brain, and pancreas. Iron overload is most likely the cause of degeneration in each of these tissues, leading to maculopathy, dementia, and diabetes.
Case Report Supported in part by a grant from the Research Committee on Chorioretinal Degenerations and Optic Atrophy, the Ministry of Health, Labor and Welfare of the Japanese Government (to T.I.), Tokyo, Japan, and a Grant-In-Aid for Scientific Research from the Ministry of Education, Science, and Culture of the Japanese Government (17591817 to Y.W.), Tokyo, Japan. Reprint requests: Toshitaka Itabashi, MD, Department of Ophthalmology, Tohoku University School of Medicine, 1-1, Seiryomachi, Aoba-ku, Sendai 980-8574, Japan; e-mail: [email protected]. tohoku.ac.jp
A 56-year-old woman first visited our clinic at 52 years of age because she had been diagnosed with diabetes mellitus. Visual acuity was corrected to 1.2 in both eyes, and she did not have visual symptoms. Slit-lamp biomicroscopic examination disclosed normal appearing cornea, anterior chamber, iris, lens, and vitreous bilaterally. Fundus examination showed that the optic disks and retinal vessels were normal but that the retinal pigment epithelium had a mottled appearance in both eyes.
264
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Fig. 1. Fundus photographs and fluorescein angiograms of our patient. Top, Fundus photographs of the patient at 56 years of age showing yellow deposits around the macula area and no foveal reflex in the left eye. Bottom left, Early-phase (22 seconds) fluorescein angiogram of the left eye did not show the bright hyperfluorescent spot, which was observed in the late frame. Bottom right, Late-phase fluorescein angiogram of the left eye showing granular hyperfluorescence around the macula area corresponding to retinal pigment epithelium atrophy and a bright hyperfluorescent spot.
She first noted decreased visual acuity in her left eye at 55 years of age. Visual acuity was corrected to 1.0 in both eyes. Fundus examination showed yellow deposits around the macula area and no foveal reflex was present bilaterally (Fig. 1). Fluorescein angiography demonstrated granular hyperfluorescence around the macula areas corresponding to retinal pigment epithelium atrophy in both eyes (Fig. 1). In addition, a bright hyperfluorescent spot was observed in the upper area of the macula in the left eye, which was not observed on the early frame of fluorescein angiography (Fig. 1). Kinetic visual field tests showed a paracentral scotoma in the left eye and normal visual field in the right eye (Fig. 2). Cone electroretinograms were decreased bilaterally. The a-waves of the photopic electroretinograms were within the normal range, and the b-waves were reduced to 79% of the normal mean for both eyes (normal mean, 87.7–132.9 V). The scotopic b
waves and both a and b waves of the bright flash electroretinogram were within normal limits for both eyes (Fig. 2).
Discussion It is well known that patients with aceruloplasminemia develop retinal degeneration. The two previous cases showed that the retinal findings for the white and Japanese patients were very different. The previously described white patient had predominant retinal pigment epithelium atrophy in the macula area and multiple subretinal yellowish lesions.3 On the other hand, the previously described Japanese patient had retinal pigment
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Fig. 2. Visual fields and electroretinograms for our patient. Top, Results of Goldmann kinetic visual fields tests of the patient at 54 years of age showing a paracentral scotoma in the left eye. Bottom, Electroretinograms showing a bwave reduction to 79% of the normal mean for both eyes. The scotopic b waves, both a and b waves of the bright flash electroretinogram, and the a waves of the photopic electroretinogram were within the normal range for both eyes.
epithelium atrophy in the midperipheral area and yellowish discoloration of the fundus.4 Dunaief et al3 suggested that the clinical variation in these two groups might be caused by the degree of ocular pigmentations, light exposure, diabetic control, lipid profile, and kind of mutations in the hemochromatosis gene. In our case, the retinal findings and results of fluorescein angiography were very similar to those for the white patient with aceruloplasminemia, except for the bright hyperfluorescent spot around the macula. The bright hyperfluorescent spot spread with time and was not detected in the early frame, which indicates that it might have been choroidal neovascularization. These findings suggest that the clinical features were most likely not based on ethnicity. Although the role of iron in the retina is not completely known, it is generally believed that the impairment of iron metabolism caused by iron overload in the retina leads to
retinal degeneration. Findings of additional molecular genetic analyses will augment our understanding of the clinical variability of aceruloplasminemia. Key words: aceruloplasminemia, hereditary ceruloplasmin deficiency, macular degeneration, retinal degeneration. References 1. 2.
3.
4.
Harris ZL. Aceruloplasminemia. J Neurol Sci 2003;207:108– 109. Miyajima H, Nishimura Y, Mizoguchi K, et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration. Neurology 1987;37:761–767. Dunaief JL, Richa C, Franks EP, et al. Macular degeneration in a patient with aceruloplasminemia, a disease associated with retinal iron overload. Ophthalmology 2005;112:1062–1065. Yamaguchi K, Takahashi S, Kawanami T, et al. Retinal degeneration in hereditary ceruloplasmin deficiency. Ophthalmologica 1998;212:11–14.
