Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005
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2.10 Complete and Incomplete Types of CSNB 113
References
1.Schubert G,Bornscein H (1952) Beitrag zur Analyse des menshlichen Electroretinograms. Ophthalmologica 123:396–412
2.Miyake Y, Yagasaki K, Horiguchi M, Kawase Y, Kanda T (1986) Congenital stationary night blindness with negative electroretinogram: a new classification. Arch Ophthalmol 104:1013–1020
3.Boycott KM, Pearce WG, Musarella MA, Weleber RG, Maybaum LA, Birch DG, et al. (1998) Evidence for genetic heterogeneity in X-linked congenital stationary night blindness. Am J Hum Genet 62: 865–875
4.Bech-Hansen NT, Naylor MJ, Maybaum TA, Sparkes RL, Koop B, Birch DG, et al. (2000) Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nat Genet 26:319–323
5.Pusch CM, Neitz C, Brandau O, Pesch K, Achatz H, Feil S, et al. (2000) The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nat Genet 26:324–327
6.Strom TM, Nyakatura G, Apfelstedt-Sylla E, Hellebrand H, Lorenz B, Weber BH, et al. (1998) An L- type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nat Genet 19:260–263
7.Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce
WG, Koop B, Fishman GA, et al. (1998) Loss- of-function mutations in a calcium-channel a1- subunit gene in Xp 11.23 cause incomplete X-linked congenital stationary night blindness. Nat Genet 19:264–267
8.Miyake Y, Yagasaki K, Horiguchi M, Kawase Y (1987) Onand off-responses in photopic electroretinogram in complete and incomplete types of congenital stationary night blindness. Jpn J Ophthalmol 31:81–57
9.Sieving PA (1993) Photopic onand off-pathway abnormalities in retinal dystrophies. Trans Am Ophthalmol Soc 91:701–773
10.Miyake Y (2002) Establishment of the concept of new clinical entities: complete and incomplete form of congenital stationary night blindness. Acta Soc Ophthalmol Jpn 106:737–756
11.Nakamura M, Ito S, Terasaki H, Miyake Y (2001) Novel CACNA1F mutations in Japanese patients with incomplete congenital stationary night blindness. Invest Ophthalmol Vis Sci 42:1610– 1616
12.Weleber RG, Pillers DM, Powell BR, Hanna CE, Magenis RE, Buist NRM (1989) Åaland Island eye disease (Forsius-Eriksson syndrome) associated with contiguous deletion syndrome at Xp 21. Arch Ophthalmol 107:170–179
13.Miyake Y, Horiguchi M, Ota I, Shiroyama N (1987) Characteristic ERG flicker anomaly in incomplete congenital stationary night blindness. Invest Ophthalmol Vis Sci 28:1816–1823
14.Miyake Y, Horiguchi M, Terasaki H, Kondo M (1994) Scotopic threshold response in complete and incomplete types of congenital stationary night blindness. Invest Ophthalmol Vis Sci 35:3770–3775
15.Slaughter HM, Miller RF (1981) 2-Amino-4-phos- phonobutyric acid: a new pharmacological tool for retina research. Science 211:182–185
16.Slaughter HM, Miller RF (1983) An excitatory amino acid antagonist blocks cone input to signconserving second-order retinal neurons. Science 219:1230–1232
17.Kolb H, Lipets LE (1991) The anatomical basis for color vision in the vertebrate retina. In: Gouras P (ed) The perception of colour. Macmillan, London, pp 128–145
18.Kamiyama M, Yamamoto S, Nitta K, Hayasaka S (1996) S-cone electroretinogram b-wave in complete congenital stationary night blindness. Br J Ophthalmol 80:637–639
19.Miyake Y, Horiguchi M, Suzuki S, Kondo M, Tanikawa A (1997) Complete and incomplete type congenital stationary night blindness as a model of “on-retina” and “off-retina.” In: LaVail MM, Hollyfield JG, Anderson RE (eds) Degenerative retinal diseases. Plenum, New York, pp 31–41
20.Terasaki H, Miyake Y, Nomura R, Horiguchi M, Suzuki S, Kondo M (1999) Blue-on-yellow perimetry in the complete type of congenital stationary night blindness. Invest Ophthalmol Vis Sci 40:2761– 2764
21.Kondo M, Miyake Y, Kondo N, Tanikawa A, Suzuki S, Horiguchi M, et al. (2001) Multifocal ERG findings in complete type congenital stationary night blindness. Invest Ophthalmol Vis Sci 42:1342–1348
22.Miyake Y, Kawase Y (1984) Reduced amplitude of oscillatory potentials in female carriers of X-linked recessive congenital stationary night blindness. Am J Ophthalmol 98:208–225
23.Miyake Y (1991) Carrier state of congenital stationary night blindness. In: Heckenlively JR (ed) Principle and practice of clinical electrophysiology of vision. Mosby-Year Book, St. Louis, pp 711–712
24.Miyake Y, Kawase K, Kanda T (1986) Study on congenital stationary night blindness. Jpn Rev Clin Ophthalmol 80:288–293
25.Nakamura M, Ito S, Terasaki H, Miyake Y (2002) Incomplete congenital stationary night blindness associated with symmetrical retinal atrophy. Am J Ophthalmol 134:463–465
26.Nakamura M, Ito S, Piao CH, Terasaki H, Miyake Y (2003) Retinal and optic disc atrophy associated with a CACNA1F mutation in a Japanese family. Arch Ophthalmol 121:1028–1033
1142 Hereditary Retinal and Allied Diseases
2.11 Fundus Albipunctatus
Fundus albipunctatus is a type of congenital stationary night blindness with an autosomal recessive inheritance pattern [1]. The fundus of these patients has a characteristic appearance: a large number of discrete, small, round or elliptical, yellowish white lesions at the level of the RPE (Fig. 2.82). The most characteristic property of their visual function is a delay in dark adaptation, which can be detected by the psychophysically determined dark-adaptation curve [2] (Fig. 2.83) and by ERGs (Fig. 2.84) [2] and EOGs [3]
(Fig. 2.85). It requires 2–3h to attain the final dark-adapted threshold, the maximum scotopic ERG responses, and the normal EOG light rise. The cone-mediated ERGs are essentially normal (Fig. 2.83), and the visual acuity and visual fields are within normal limits.
In 1992 we found that fundus albipunctatus patients may also have widespread cone dysfunction [4]. Such patients often have bull’s-eye maculopathy (Fig. 2.86) with progressively decreased of visual acuity and color vision. The
Fig. 2.82. Fundus of a patient with typical fundus albipunctatus
Fig. 2.83. Dark-adaptation curve obtained from a normal control, and from patients with fundus albipunctatus and Oguchi’s disease
2.11 Fundus Albipunctatus 115
Fig. 2.85. Light rise of the EOG in a patient with fundus albipunctatus after various periods of pre-dark adaptation. Note the marked increase in the light rise after an increase in the duration of dark adaptation up of 60 min. DA, dark adaptation; LA, light adaptation. (From Miyake et al. [3])
Fig. 2.84. Full-field ERGs recorded from a normal subject and from a patient with fundus albipunctatus after 30 min (middle) and 3 h (right) of dark adaptation (DA)
Fig. 2.86. Fundus of a patient with fundus flavimaculatus associated with bull’s-eye maculopathy. (From Miyake et al. [4])
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full-field ERGs recorded from three patients are shown in Fig. 2.87. As with typical fundus albipunctatus, all patients had delayed recovery of the rod ERGs, and the maximum ERG responses were obtained only after prolonged dark adaptation. The maximum amplitude of the b-wave in some patients was smaller than normal (case 2), indicating that rod function even after prolonged dark adaptation does not completely return to normal levels. Unlike the typical fundus albipunctatus, all patients have a marked reduction of cone-mediated ERGs. The progressive decrease in visual function, widespread dysfunction of the cone system, and bull’s-eye maculopathy suggest an association of fundus albipunctatus with cone dystrophy.
An example of the changes in the fundus during a long follow-up period in a patient with fundus albipunctatus associated with cone dystrophy is also shown (case 3) in Fig. 2.87. This patient was first examined by us in 1981 at the age of 40 years, when he reported that he had had night blindness from a young age. His visual acuity was 1.2 in both eyes, and his fundus had the typical fundus albipunctatus pattern, with normal-appearing macula in both eyes (Fig. 2.88). His rod ERG was undetectable, and a negative-type mixed rod–cone ERG was recorded after 30min of dark adaptation (Fig. 2.87,case 3). The amplitude in the ERGs became normal when recorded after 3h of dark adaptation. However, unlike typical fundus albipunctatus, his cone-mediated ERGs were nearly absent, suggesting an association with cone dystrophy. At the initial examination, it was difficult to imagine that the disease in this patient was associated with cone dystrophy because his fundus appeared similar to that of typical fundus albipunctatus with a normalappearing macula, and his visual acuity was 1.2. What was intriguing was that his full-field
cone-mediated ERGs were undetectable.This patient has been followed for more than 20 years, and bull’s-eye maculopathy began to appear in 1992 (Fig. 2.88). He was found to have homozygous mutations in the RDH5 gene.
In many of our patients with fundus albipunctatus, the cone-mediated ERGs are extremely abnormal or essentially absent when they are associated with cone dystrophy. When we first reported such patients, it was still unclear whether their disorder represented an advanced stage of fundus albipunctatus, a distinct disease entity, or a chance combination of two diseases. In 1999, the 11-cis retinol dehydrogenase gene, RDH5, was identified as the mutated gene in patients with typical fundus albipunctatus [5].
We have analyzed the genetic makeup of many patients with fundus albipunctatus and cone or macular dystrophy and found that all of them had homozygous or compound heterozygous mutations in the RDH5 gene [6]. Because some mutations were detected in both groups, and because there was a progressive decrease in visual functions in patients with cone dystrophy, it was concluded that mutations of the RDH5 gene can cause progressive cone dystrophy as well as congenital stationary night blindness.After analyzing our large series of patients, we concluded that approximately one-third of the patients with this disorder have associated cone dystrophy or macular dystrophy, and the disease process in such patients is progressive. This points to the important fact that fundus albipunctatus is not always stationary, and that about one-third of the patients have a progressive disease that is associated with diffuse cone dystrophy. We have thus changed the disease concept of fundus albipunctatus, which had been believed to be a subtype of CSNB.
2.11 Fundus Albipunctatus 117
Fig. 2.87. Full-field |
ERGs |
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recorded |
from |
three |
representative patients with fundus albipunctatus associated with cone dystrophy. In each case, the upper tracings are the responses recorded after 30 min of dark adaptation, and the lower traces are the responses recorded after prolonged dark adaptation. All patients have a marked decrease of the cone-medi- ated ERGs. After a long period of dark adaptation, the rod ERGs increased to within the normal limits in cases 1 and 3 but were still smaller than the normal limits in case 2. (From Miyake et al. [4])
Fig. 2.88. Appearance of the fundus in a patient with fundus albipunctatus associated with cone dystrophy. The photographs were taken in 1981 (top) and 2002 (bottom)
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References
1.Carr RE, Margolis S, Siegel IM,Weale RE (1976) Fluorescein angiography and vitamin A and oxalate levels in fundus albipunctatus. Am J Ophthalmol 82:549–558
2.Carr RE, Ripps H, Siegel IM, Weale RE (1966) Rhodopsin and the elecrical activity of the retina in congenital nightblindness. Invest Ophthalmol Vis Sci 5:497–505
3.Miyake Y, Watanabe I, Asano T, Sakai T (1974) Further studies on EOG in retinitis punctata albescens (effects of change of dark adaptation on EOG). Folia Ophthalmol Jpn 25:518–527
4.Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K (1992) Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 76:375– 379
5.Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP (1999) Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 22:188–191
6.Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y (2000) A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 41:3925–3932
2.12 Oguchi’s Disease 119
2.12Oguchi’s Disease
Oguchi’s disease, first reported by Oguchi in 1907 [1], is an unusual form of congenital stationary night blindness. It is characterized by a peculiar grayish white discoloration of the fundus (Fig. 2.89). In 1913 Mizuo found that this unusual fundus coloration disappeared after a long period of dark adaptation [2]. This change in fundus coloration is now called the Mizuo phenomenon (Fig. 2.89).
Mutations in the arrestin gene [3] or the rhodopsin kinase gene [4] cause the recessive form of Oguchi’s disease.Arrestin and rhodopsin kinase act in sequence on reactive rhodopsin to stop the phototransduction cascade. Most patients who have been reported with mutations in the arrestin gene are Japanese [5].
Visual acuity, visual field, and color vision are normal in patients with Oguchi’s disease. Rod function is absent both subjectively and electroretinographically after 30min of dark adaptation, but the subjective rod function may reappear after 2–3h of dark adaptation [6] (Fig. 2.83).
Full-field ERGs recorded after 30min of dark adaptation from seven patients with Oguchi’s disease [7] are shown in Fig. 2.90. The rod ERGs are absent, and the cone-mediated ERGs are essentially normal. The mixed rod–cone ERG (Fig. 2.91) has a negative
configuration with relatively well-preserved OPs. For comparison, the mixed rod–cone ERG of a patient with complete CSNB is also shown. The a-wave amplitude in Oguichi patients is reduced compared to that of normal controls and patients with complete CSNB. After 3h of dark adaptation, the amplitudes of the a-wave and b-wave of the mixed rod–cone ERGs are larger, but they are still not normal.
Consistent findings in the mixed rod–cone ERGs recorded after 30min of dark adaptation in patients with Oguchi’s disease are (1) negative ERGs with reduced a-waves; (2) nearly absent b-waves; (3) relatively well-preserved OPs; and (4) essentially normal cone-mediated ERGs (Fig. 2.91).
The pathogenic defect in the cone visual pathway in Oguchi’s disease is different from that of complete CSNB and incomplete CSNB. Unlike complete and incomplete CSNB, the amplitude and waveform of the photopic ERGs elicited by long-duration stimuli are normal, indicating that the on and off systems of the cone visual pathway are functioning normally (Fig. 2.92). The focal macular ERGs are also normal (Fig. 2.93). The EOG ratio in Oguchi’s disease is lower than normal in most Japanese patients [7].
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Fig. 2.89. Fundus of a patient with Oguchi’s disease while lightadapted (top) and after a long period of dark-adaptation (bottom), demonstrating the Mizuo phenomenon
Fig. 2.90. Full-field ERGs recorded from a normal control and seven patients with Oguchi’s disease. (From Miyake et al. [7], with permission)
2.12 Oguchi’s Disease 121
Fig. 2.91. Full-field mixed rod–cone ERGs recorded from a normal control, a patient with complete CSNB, and seven patients with Oguchi’s disease. ERGs were recorded after 30 min (middle) and after 3 h (right) of dark adaptation. (From Miyake et al. [7], with permission)
Fig. 2.92. Full-field photopic ERGs elicited by long-duration stimuli and recorded from a normal subject, a patient with Oguchi’s disease, and a patient with complete CSNB. (From Miyake et al. [7])
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Fig. 2.93. Focal macular ERGs elicited by three differently sized spots from a patient with Oguchi’s disease and recorded with two different time constants (T.C.). All components are within the normal range, indicating that the macula was functioning normally
References
1.Oguchi C (1907) Uber eine Abart von Hemeralopie. Acta Soc Ophthalmol Jpn 11:123–134
2.Mizuo G (1913) On a new discovery in the dark adaptation of Oguchi’s disease. Acta Soc Ophthalmol Jpn 17:1854–1859
3.Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A (1995) A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet 10:360–362
4.Yamamoto S, Sippel KC, Berson EL, Dryja TP (1997) Defects in the rhodopsin kinase gene in patients
with the Oguchi form of stationary night blindness. Nat Genet 15:175–178
5.Nakamura M, Yamamoto S, Okada M, Ito S, Tano Y, Miyake Y (2004) Novel mutations in the arrestin gene and associated clinical features in Japanese patients with Oguchi’s disease. Ophthalmology 111:1410–1414
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7.Miyake Y, Horiguchi M, Suzuki S, Kondo M, Tanikawa A (1996) Electrophysiological findings in patients with Oguchi’s disease. Jpn J Ophthalmol 40:511–519