Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005

retinal diseases should be ruled out. Furthermore, the possibility of exposure to toxins, such as chloroquine [17] or digoxin [18], which can cause cone dysfunction, could be ruled out

because she had no history of taking such drugs. Because of her acute and severe clinical course, other factors such as inflammation should be considered.

References

1.Sloan LL, Brown DJ (1962) Progressive retinal degeneration with selective involvement of the cone mechanism. Am J Ophthalmol 54:629–636

2.Miyake Y (2000) Phenotypes of cone dysfunction syndrome. Folia Ophthalmol Jpn 51:725–733

3.Berson EL, Gouras P, Gunkel RD (1968) Progressive cone-rod degeneration. Arch Ophthalmol 80:68–76

4.Ohba N (1974) Progressive cone dystrophy: four cases of unusual form. Jpn J Ophthalmol 18:50–69

5.Miyake Y, Horiguchi M, Tomita N, Kondo M, Tanikawa A, Tekahashi H, et al. (1996) Occult macular dystrophy. Am J Ophthalmol 122:644–653

6.Miyake Y, Goto S, Ota I, Ichikawa H (1984) Vitreous fluorophotometry in patients with cone-rod dystrophy. Br J Ophthalmol 68:489–493

7.Nakazawa M, Kikawa E, Chida Y, Tamai M (1994) Asn244His mutation of the peripherine/RDS gene causing autosomal dominant cone-rod degeneration. Hum Mol Genet 3:1195–1196

8.Freund CL, Gregory-Evans CY, Furukawa T, Papaioannou M, Looser J, Ploder L, et al. (1997) Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell 91:543–553

9.Perrault I, Rozet JM, Gerber S, Kelsell RE, Souied E, Cabot A, et al. (1998) A retGC-1 mutation in autosomal dominant cone-rod dystrophy. Am J Hum Genet 63:651–654

10.Payne AM, Downes SM, Bessant DA, Taylor R, Holder, GE, Warren MF, et al. (1998) A mutation in guanylate cyclase activator 1A (GUCA1A) in an

autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. Hum Mol Genet 7:273–277

11.Cremers FP, van de Pol DJ, van Driel M, den Hollander AI, van Haren FJ, Knoers NV, et al. (1998) Autosomal recessive retinitis pigmentosa and conerod dystrophy caused by slice site mutations in the Stargardt’s disease gene ABCR. Hum Mol Genet 7:355–362

12.Demirci FY, Rigatti BW, Wen G, Radak AL, Mah TS, Baic CL, et al. (2002) X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15. Am J Hum Genet 70:1049–1053

13.Ito S, Nakamura M, Ohnishi Y, Miyake Y (2004) Autosomal dominant cone-rod dystrophy with R838H and R838C mutations in the GUCY2D gene in Japanese patients. Jpn J Ophthalmol 48:228–235

14.Pinkers A, Deutman AF (1977) Peripheral cone disease. Ophthalmologica 54:629–636

15.Kondo M, Miyake Y, Kondo N, Ueno S, Takakuwa H, Terasaki H (2004) Peripheral cone dystrophy: a variant of cone dystrophy with predominant dysfunction in the peripheral cone system. Ophthalmology 111:732–739

16.Nomura R, Kondo M, Tanikawa A, Yamamoto N, Terasaki H, Miyake Y (2001) Unilateral cone dysfunction with bull’s eye maculopathy. Ophthalmology 108:49–53

17.Krill AE, Deutman FA, Fishman M (1973) The cone degenerations (review). Doc Ophthalmol 35:1–80

18.Weleber RG, Shults WT (1981) Digoxin retinal toxicity: clinical and electrophysiological evaluation of a cone dysfunction syndrome. Arch Ophthalmol 99:1568–1572

Congenital rod monochromacy is an autosomal recessively inherited disorder characterized in the complete form by complete absence or severely depressed color vision, reduced visual acuity, nystagmus, and photophobia [1]. There is also an incomplete form of this disorder, where color vision and/or visual acuity are only mildly affected and nystagmus and photophobia may be absent [2]. In both forms, the fundus and fluorescein angiograms are normal, and the most characteristic feature in terms of the diagnosis is the selective reduction or absence of the photopic component of the full-field ERGs [2]. The ERG findings provide key diagnostic information, particularly in the incomplete form when visual acuity is relatively good [2]. The condition is stationary.

Histological examination of eyes with complete monochromatism has shown 5%–10% reduction in the normal number of extrafoveal cones and abnormal structure of the foveal cones [3]. Molecular genetic studies have shown that mutations in the CNGB3 gene encoding the b-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia [4].

A representative case of rod monochromacy [2] was seen in a 13-year-old girl (case 1) who

is the sister of an 18-year-old young man (case 2). During a 10-year follow-up of the siblings, their visual functions did not deteriorate, and their fundi remained normal (Fig. 2.108). In case 1, the visual acuity was 0.1 OD and 0.4 OS, and color vision tests showed a mild acquired red-green deficiency. She had nystagmus but did not complain of photophobia. Her older brother (case 2) also had decreased visual acuity in the beginning, but his vision gradually improved to 1.0 with normal color vision in both eyes. Despite such differences in the visual functions in this sibling, his full-field ERGs were essentially identical to his sister’s ERGs, showing selective absence of the photopic components (Fig. 2.109). The full-field ERGs indicated that both siblings had congenital stationary cone dysfunction.

The question arose as to why case 2 had normal visual acuity and normal color vision despite the undetectable full-field cone ERGs. Rod–cone (two-color) perimetry showed that the brother indeed had widespread dysfunction of the cones with normal rod function. However, the cone function was preserved in only a small portion in the foveola, which provided normal visual acuity and color vision.

References

1.Goodman G, Ripps H, Siegel IM (1963) Cone dysfunction syndrome. Arch Ophthalmol 70:214–231

2.Miyake Y (2000) Phenotypes of cone dysfunction syndrome. Folia Ophthalmol Jpn 51:725–733

3.Falls HF, Wolter JR, Alpern M (1965) Typical total monochromacy; a histological and psychophysical study. Arch Ophthalmol 74:610–616

Fig. 2.108. Fundus photographs and fluorescein angiograms for two siblings with rod monochromacy. (From Miyake [2])

Fig. 2.109. Full-field ERGs recorded from two siblings with rod monochromacy whose fundus photographs are shown in Fig. 2.107. (From Miyake [2])

4.Kohl S, Baumann B, Broghammer M, Jagle H,

Sieving P, Kellner U, et al. (2000) Mutations in the CNGB3 gene encoding the b-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet 9:2107–2116

Blue cone monochromacy, a rare color vision disorder, was first described by Blackwell in 1957 [1]. It shares many characteristics with rod monochromacy. Blue cone monochromats differ from rod monochromats in their inheritance pattern; blue cone monochromats have an X-linked recessive pattern, whereas rod monochromats have an autosomal recessive inheritance. The molecular genetic study indicated that mutations exist in the red and green opsin in blue cone monochromats [2].

A pedigree of a Japanese family with blue cone monochromacy with three affected members and one female carrier is shown in Fig. 2.110 [3]. The fundus of one of these patients is shown in Fig. 2.111, which is essentially normal, although in the late stage some

atrophic changes may develop in the macula. The visual acuity is approximately 0.2–0.3, which is slightly better than that of the complete form of rod monochromacy. Unlike rod monochromats, the blue cone function is selectively preserved. The results of the Farnsworth dichotomous Panel D-15 test shows several crossing lines perpendicular to the tritan axis (Fig. 2.112).

Examination with a Nagel anomaloscope yielded results similar to those seen with complete rod monochromatism, although most of the values are below those measured in a group of patients with complete rod monochromatism. The spectral sensitivity curve determined by increment thresholds of 1° steps showed a narrow curve with a peak around 440nm (Fig. 2.113).

The full-field ERGs recorded from members of this family were nearly normal for the rod ERGs, with absence of the photopic ERG in the three affected members (Fig. 2.114). Although the blue cone ERG is present in blue cone monochromats (Fig. 2.115), the amplitude of the blue cone ERG is too small to be detected in

the full-field cone ERGs, and the implicit time is too long to follow 30-Hz flicker stimuli.

The diagnosis of this disorder is based on the presence of severely affected color vision with preserved blue function, nearly unrecordable photopic ERGs,and a family pedigree compatible with an X-linked inheritance pattern.

References

1.Blackwell HR, Blackwell OM (1957) “Blue monocone monochromacy”: a new color vision defect. J Opt Soc Am 47:338

2.Nathans J, Davenport CM, Maumenee IH, Lewis RA, Hijtmancik JF, Litt M, et al. (1989) Molecular

Fig. 2.115. Full-field ERGs elicited by photopically matched red and blue stimuli recorded from a normal subject, a rod monochromat, and two blue cone monochromats (cases 1 and 3). The patient with rod monochromacy shows absent red and blue responses, but the patients with blue cone monochromacy show small responses elicited by only the blue stimulus. The ERGs are characterized by an absent a-wave and a small b-wave with delayed implicit time. These are the properties of blue (S)-cone ERGs

genetics of human blue cone monochromacy. Science 245:831–838

3.Terasaki H, Miyake Y (1992) Japanese family with blue cone monochromatism. Jpn J Ophthalmol 36: 132–141

Congenital tritanopia is a rare disease with an autosomal dominant inheritance pattern [1]. It is characterized by tritanopic color vision defects, a normal fundus, and normal visual acuity (Fig. 2.116). Both rod and cone components of standard full-field ERGs are normal.

Congenital tritanopia and dominantly inherited juvenile optic atrophy (DIJOA) have

several clinical characteristics in common. In addition to having a dominant hereditary pattern, patients with DIJOA may also have tritanopic color vision defects [2]. However, these patients may have slightly to moderately reduced visual acuity, visual field defects, and temporal pallor of the optic disk (Fig. 2.117). The severity of these abnormalities varies even

within the same family. Thus, in patients with minimal alterations, the changes in the visual acuity and visual field may be so subtle that a definitive diagnosis cannot be made unless other, more obviously affected family members are examined.

It had been hypothesized that the two diseases may be the same clinical entity [3, 4]. However, as shown in Fig. 2.118, the blue (S) cone ERG is unrecordable in patients with congenital tritanopia but is within the normal range in those with DIJOA [5]. These findings supported the argument that congenital tritanopia and DIJOA are not the same disease. The abnormal S-cone ERG in patients with congenital tritanopia indicates a retinal origin of

the tritan defect, most likely in the blue cone itself. On the other hand, the normal blue cone ERG in patients with DIJOA indicates that the tritan defect is caused by disturbances of the visual pathway proximal to the layer of origin of the ERG, most likely in the optic nerve.

This hypothesis has been proven to be conclusively correct by molecular genetic analyses. In 1992 we detected two point mutations in the gene encoding the blue-sensitive opsin, each leading to an amino acid substitution [6]. These findings showed that these mutations cause tritanopia (Fig. 2.119). On the other hand,Votruba et al. detected the genetic mutation (OPA1) locus to be within a 2 CM interval of chromosome 3q in patients with DIJOA [7].