Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005
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eventually reaches normal threshold. Rod ERG response after the usual period of 30–40 min of dark-adaptation is reduced (Fig. 9.5). The EOG light-to-dark amplitude ratio is also correspondingly decreased. However, both the rod ERG response and the EOG light-to-dark ratio return to normal with prolonged dark adaptation in as short as 60 min or up to 180 min (51,55). Because scotopic ERG responses normalize after prolonged dark-adaptation, the clinician should alert the ERG laboratory if this disorder is suspected so that appropriately prolonged dark-adapted ERG will be performed. The photopic full-field ERG responses are normal or mildly reduced in fundus albipunctatus patients without macular dystrophy but are significantly reduced in those with macular dystrophy (54).
Figure 9.5 Standard full-field ERG responses from the patient with fundus albipunctatus of Fig. 9.4. Note the marked improved scotopic rod and combined rod–cone responses to near normal after prolonged dark adaptation of 150 min as compared to those after 30 min of dark adaptation.
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Oguchi Disease
Oguchi disease is a rare autosomal recessive disorder characterized by non-progressive impaired night vision and a yellowish discoloration appearance of the retina, which returns to normal after several hours of dark-adaptation (Mizuo– Nakamura phenomenon) (Fig. 9.6). Visual acuity, color vision, and visual fields are generally unaffected or near normal. The disorder was first reported by Oguchi (56) in Japan in 1907 but occurs also in other ethnic groups. Fuchs et al. (57) have shown that a homozygous 1-base pair deletion (1147delA) of codon 309 in the arrestin gene is a frequent cause of Oguchi disease. Subsequently, Yamamoto et al. (58) found homozygous as well as compound heterozygous mutations in the rhodopsin kinase gene in patients with Oguchi disease whose arrestin gene was normal. Rhodopsin kinase works with arrestin to deactivate rhodopsin after rhodopsin is stimulated by light. Abnormalities of arrestin or rhodopsin kinase produce marked delay in rod sensitivity recovery after light exposure. However, patients with arrestin homozygous 1-base pair deletion (1147delA) may have Oguchi disease or retinitis
Figure 9.6 Yellowish appearance of the retina in a patient with Oguchi disease. The color of the retina as well as the dark-adapted rod thresholds are restored after very prolonged dark adaptation. (From Ref. 96.) (Refer to the color insert.)
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pigmentosa indicating variable expressivity (59,60). In addition, a patient with Oguchi disease and sectoral retinitis pigmentosa has been described (61).
The diagnosis of Oguchi disease is based on the presence of Mizuo–Nakamura phenomenon and ERG findings (Fig. 9.7). Standard full-field ERG in Oguchi disease demonstrates a non-detectable scotopic rod response. Scotopic bright-flash combined rod–cone response shows a reduced a-wave and a severely reduced and prolonged negative b-wave (a-wave amplitude > b-wave amplitude) with correspondingly reduced oscillatory potentials (62). Photopic cone flash and flicker responses are generally normal but may occasionally be mildly reduced. With prolonged dark adaptation of 3–6 h, variable improvement of scotopic responses occurs (63). Dark adaptometry is abnormal although light sensitivity threshold improves with prolonged dark adaptation. Specialized ERG with photopic long-duration flash stimulus is normal, indicating normal ON and OFF responses (63). Likewise, the function of the three types of cones is normal by using
Figure 9.7 Full-field ERG responses of patients with Oguchi disease. Note the marked improved combined rod–cone responses after prolonged dark adaptation of 180–360 min as compared to those after 30 min of dark adaptation. (From Ref. 63 with permission from the Japanese Ophthalmological Society.)
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wavelength-specific (i.e., spectral) stimuli (64). Pattern ERG, pattern VEP, and multifocal ERG are normal (60). The EOG light-peak to dark-trough amplitude ratio in Oguchi disease is very reduced (63). Of note, previous findings of normal EOG and normal scotopic a-wave on the combined rod–cone response are contrary to the findings of more recent studies (65,66).
Fleck Retina of Kandori
Kandori et al. (67) described a disorder characterized by early onset non-progressive night vision impairment, relatively large yellow irregular shaped flecks in the peripheral retina, minimal dark adaptation abnormality, and normal visual fields. Although patients with this extremely rare condition may have impaired full-field ERG, EOG and VEP are usually normal, and dark adaptation is only minimally affected (67).
STATIONARY CONE DYSFUNCTION
DISORDERS
Hereditary Congenital Color Vision Deficiencies
A normal person requires all three primary colors, red, green, and blue, to match colors within the visible spectrum and is a normal trichromat. However, hereditary congenital color vision deficiency affects approximately 8% of males and 0.5% of females and are often X-linked recessive. Most affected persons are anomalous trichromats who uses abnormal proportions of the three primary colors to match colors in the light spectrum. Those individuals who need only two primary colors for matching colors are designated as dichromats. Persons with red-green deficiencies due to an abnormality of either red-sensitive or green-sensitive cones are said to have protan and deutan defects, respectively, and those with a blue-yellow deficiency due to an abnormality of the blue-sensitive cones have a tritan defect.
Congenital color deficiencies such as anomalous trichromatism are assessed most commonly using color plate tests such as the Ishihara and the Hardy–Rand–Rittler (HRR) tests
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where colored figures are seen by normal persons but missed by affected persons. Standard white-flash ERG responses are normal for dichromats and anomalous trichromats. However, specialized ERG recordings have demonstrated abnormalities of the early receptor potential (ERP) and responses to color stimuli. For example, in dichromats, the amplitudes of the R2 wave of the ERP is reduced (68). Abnormal ERG responses to color stimuli have also been found in dichromats and anomalous trichromats (69–71). Further, the x-wave which represents the initial scotopic cone response to red light is reduced in protanopes and protanomalous trichromats but not in deutanopes and deutanomalous trichromats.
Rod Monochromatism (Autosomal
Recessive Achromatopsia)
Rod monochromatism is an autosomal recessive congenital disorder characterized by severe or complete cone dysfunction. The condition is also commonly referred to as autosomal recessive achromatopsia, and affected persons are ‘‘monochromats’’ who perceive colors as shades of gray. Many patients with rod monochromatism harbor homozygous or heterozygous mutations of the CNGA3 gene encoding alpha-subunit of cone photoreceptor cGMP-gated channel on choromosome 2 (2q11) or the ACHM3 gene encoding beta-subunit of cone photoreceptor cGMP-gated channel on chromosome 8 (8q21) (72–74). Aside from poor color perception, other clinical features include decreased visual acuity, nystagmus, and light sensitivity. Visual acuity is variable and ranges from 20=40 to 20=400 due to cone dysfunction and the development of early-onset sensory nystagmus. Retinal appearance is usually normal or minimally abnormal with mild non-specific pigmentary changes. ‘‘Complete’’ and ‘‘incomplete’’ forms of rod monochromatism have been designated on the basis of the severity of clinical and ERG findings as well as colormatching tests (Fig. 9.8) (75). Complete rod monochromats have severe disease with markedly impaired visual acuity and non-detectable full-field ERG cone responses while incomplete rod monochromats have better visual acuity and
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Figure 9.8 Examples of standard full-field ERG responses in rod monochromatism. The photopic cone flash and 30-Hz flicker responses are non-detectable in ‘‘complete’’ rod monochromats and severely reduced in ‘‘incomplete’’ rod monochromats. Similar genotypes are found in complete and incomplete rod monochromats, and members from the same family may have complete or incomplete form of the disease. The ERG responses of rod monochromatism are similar to cone dystrophy and X-linked blue cone monochromatism. These conditions may be differentiated by clinical features and hereditary pattern as well as by specialized ERG and psychophysical testing.
detectable but severely reduced full-field ERG cone responses. However, complete and incomplete forms of rod monochromatism are usually results of variable expressivity. Similar genetic mutations are found in complete and incomplete rod monochromats, and affected members of the same family may have complete or incomplete form of the disease (74).
The diagnosis of rod monochromatism is based on a combination of clinical findings, full-field ERG responses, and genetic analysis. Full-field ERG is a key diagnostic test in rod monochromatism with ERG responses similar to those of cone dystrophy. However, in contrast to cone dystrophy,
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symptoms of rod monochromatism typically occur in the first years of life with nystagmus. In general, the following is noted on standard full-field ERG in rod monochromatism: (1) scotopic rod flash response—normal or mildly reduced, (2) scotopic combined rod–cone bright-flash response—reduced a-wave and b-wave with variable prolongation, (3) oscillatory poten- tials—reduced, and (4) photopic cone flash and flicker responses—non-detectable in ‘‘complete" rod monochromat and severely reduced in ‘‘incomplete’’ rod monochromat. Of interest, ‘‘complete’’ rod monochromats and blue cone monochromats have similar standard full-field ERG responses but can be differentiated on the basis of hereditary pattern, genetic testing, specialized color testing, and specialized ERG testing (see below).
Blue Cone Monochromatism (X-Linked
Incomplete Achromatopsia)
Blue cone monochromatism is a rare X-linked recessive disorder characterized by the absence of functional longwavelength (L) ‘‘red’’ sensitive cone photoreceptors and medium-wavelength (M) ‘‘green’’ sensitive cone photoreceptors. The function of the short-wavelength (S) ‘‘blue’’ sensitive cone photoreceptors is preserved. Blue cone monochromatism is caused by alterations of the genes encoding the photosensitive pigments of the L- and M-cones, which are arranged in a tandem array with a locus control region on the X chromosome (76,77). Genotypes among persons with blue cone monochromacy or related variants of the disorder are extremely heterogeneous and diverse (78–81). The gene encoding the ‘‘blue’’ photosensitive pigment of the S-cones located on chromosome 7 remains unaffected.
Affected males with blue cone monochromatism have decreased visual acuity of generally 20=80 or worse, myopia, impaired color vision, and congenital nystagmus. These clinical features are similar to those of autosomal recessive rod monochromatism. However, blue cone monochromats of some families with progressive bilateral macular atrophy have been described (76,78,82,83).
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Aside from genetic analysis, the differentiation between X-linked blue cone monochromatism and autosomal recessive rod monochromatism is made on the basis of hereditary pattern, specialized color testing, spectral sensitivity testing, or specialized ERG testing. Because the S-cones contribute minimally to the standard full-field ERG, standard white-flash responses of blue cone monochromats and rod monochromats are similar and demonstrate normal or near normal scotopic rod response, reduced scotopic bright-flash rod–cone flash response, and markedly reduced or non-detectable photopic cone response (78). Further, in those blue monochromats with progressive bilateral macular atrophy, the full-field ERG responses and clinical findings would be similar to those with cone dystrophy. However, S-cone full-field ERG response is detectable in blue cone monochromats by using yellow background and blue flash stimulus (84).
In 1983, Berson et al. (85) developed a color test to distinguish patients with blue cone monochromatism from those with rod monochromatism. The test consists of two instructional and four test plates. Each test plate has three identical blue-green arrows and one purple-blue arrow. The test plates differ from one another with respect to the chromaticity of the purple-yellow arrow. Patients with blue cone monochromatis can easily identify the purple-blue arrows on all four test plates but none of the rod monochromats could identify the purple-blue arrows on the test plates. However, the Berson color test may not necessarily differentiate patients with blue cone monochromatism from those with cone dystrophy (86). In terms of more commonly available color tests, blue cone monochromats are much more likely to correctly identify the blue-yellow plates in the HRR color plate test and are unlikely to make any errors along the tritan axis on the Farnsworth D15 panel hue discrimination test (87).
Using spectral sensitivity measurements under lightadapted conditions, blue cone monochromats show a peak sensitivity near light wavelength 440 nm while rod monochromats demonstrate a peak sensitivity near 504 nm (88–90). Spectral sensitivity measurements are made by determining the brightness threshold for light stimuli of
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various wavelengths. Spectral sensitivity may be obtained through subjective responses of the patient or by ERG so that the minimal luminance of a color stimulus of a specific wavelength that would elicit a response is determined (91).
Female carriers of blue cone monochromatism are generally asymptomatic but may have mild nystagmus and color vision abnormalities (92). The most common full-field ERG finding is a reduced and prolonged 30-Hz flicker cone response although impaired cone flash and scotopic brightflash rod-cone response may also occur (93,94).
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