Abstract
purpose. To resolve the discrepancy between nonrecordable full-field short
wavelength cone electroretinograms (S-cone ERGs) and the presence of
normal color vision in patients with the complete type of congenital
stationary night blindness (CSNB1).
methods. Conventional white-on-white (W-W) perimetry, blue-on-yellow (B-Y)
perimetry, and the Farnsworth–Munsell 100-hue test were performed in
five patients with CSNB1. Diagnosis of CSNB1 was made by clinical and
electrophysiological examinations. Twelve normal, age-matched control
subjects and an additional 7 normal, highly myopic subjects were
tested.
results. Color vision was normal in all the CSNB1 patients by the
Farnsworth–Munsell 100-hue test. B-Y perimetry demonstrated that blue
cone sensitivity in CSNB1 was normal in the fixation area, but the mean
sensitivities of the entire 60° field, the central 0°-to-15°, and
15°-to-30° ring were significantly decreased compared with the
normal and myopic subjects. The sensitivity difference between
15°-to-30° and 0°-to-15° in B-Y perimetry increased
significantly in CSNB1 compared with both normal and myopic control
subjects.
conclusions. Our perimetric results demonstrated that the S-cone function in CSNB1
is preserved only in the fovea and becomes abnormal toward the
peripheral retina. This accounts for the normal color vision that tests
mainly foveal function and the nonrecordable S-cone ERGs that arise
mainly from peripheral retina.
The Schubert–Bornschein type of congenital stationary
night blindness (CSNB)
1 shows an essentially normal fundus
and a negatively shaped, mixed rod–cone electroretinogram (ERG). The
amplitude of the a-wave is normal and larger than that of b-wave.
Careful analysis of the phenotype, strongly suggested that CSNB could
be divided into two clinical entities, the complete (CSNB1) and the
incomplete (CSNB2) types.
2 Recent genetic linkage analysis
has shown that these two types have different loci on the
X-chromosome
3 4 proving that they are distinct clinical
entities.
In CSNB1, the rod b-wave and scotopic threshold response (STR) are
absent, whereas the rod a-wave is normal, indicating a dysfunction of
the rod ON-bipolar cells.
5 Cone-driven ERGs recorded with
long-duration stimuli (long-flash photopic ERG) show an extremely
reduced b-wave (ON) with a large d-wave (OFF).
6 The shape
of these ERGs then resemble the ERGs of monkeys after an intravitreal
injection of 2-amino-4-phosphonobutyric acid, which blocks the ON
synapses on the bipolar cells selectively.
7 It has been
shown that the principal component of the short-wavelength–sensitive
cone (S-cone) ERG is cornea positive.
8 9 10 It thus
appears reasonable that S-cone ERG is nonrecordable in CSNB1 when
stimulated by full-field stimuli.
11 12 13 14 These results
strongly suggest that there is a selective dysfunction of the ON
(depolarizing) bipolar cells in both rod and cone visual pathways in
patients with CSNB1.
In spite of the nonrecordable full-field S-cone ERG, it has been
reported that the conventional psychophysical color vision tests are
essentially normal in CSNB1.
11 12 13 The reason for this
discrepancy remains unresolved. We hypothesized that this discrepancy
arises from the region of the retina tested. In conventional color
vision testing, the central retina is examined, and in the full-field
ERGs, the responses arise mainly from the peripheral retina. To test
this hypothesis, we tested the color vision by the Farnsworth–Munsell
100-hue test and performed blue-on-yellow (B-Y) perimetry in five
patients with CSNB1.
We evaluated conventional white-on-white (W-W) perimetry and
blue-on-yellow (B-Y) perimetry in five patients (age range, 14–21
years; mean, 17.6 years) with CSNB1. Their visual acuity ranged from
20/25 to 20/15. The distance spherical refractive error in the examined
eye ranged from −7.50 D to −11.00 D (mean, −9.75 D) and the maximum
power of the cylinder was −3.50 D. CSNB1 was diagnosed in patients by
determining the presence of typical clinical and electrophysiological
characteristics.
2
Conventional full-field ERGs were recorded after pupil dilatation with
0.5% tropicamide and 0.5% phenylephrine hydrochloride, and 30 minutes
of dark adaptation. The rod (scotopic) ERG was recorded with a blue
stimulus at an intensity of 5.2 × 10−3 cd/m2. The rod–cone mixed single flash (bright white) ERG
was recorded with a white stimulus at an intensity of 44.2
cd/m2. The cone and the 30-Hz flicker ERG were recorded
with a white stimulus intensity of 4 cd/m2 and 0.9
cd/m2, respectively.
The method for recording S-cone and long- and
middle-wavelength-sensitive cone (L-M cone) ERGs has been
described previously.
15 16 An LED contact lens electrode
was used. S-cone ERG was recorded with an LED of 450 nm (intensity, 3.3
log photopic trolands) under yellow background illumination (intensity,
4.8 log photopic trolands; Wratten No. 12, Eastman Kodak, Rochester,
NY) from a slide projector. We have shown that the ERGs elicited under
these conditions are S-cone mediated.
15 The LM cone ERG
was also recorded with an LED of 566 nm (stimulus intensity, 3.2 log
photopic trolands) under blue background illumination (intensity, 4.1
log photopic trolands; Wratten No.43; Eastman Kodak). The stimulus
frequency was 3 Hz with an ON-OFF ratio of 1.0.
The color vision test was performed using the Farnsworth–Munsell
100-hue test in all patients with CSNB1.
The normal age-matched control group was composed of 12 subjects (mean
age, 25.5 ± 5.1 years; range, 14–29 years). The distance
spherical refractive error in the tested eye ranged from −1.00 D to−
4.00 D (−1.35 ± 2.03, mean ± SD), and the maximum power
of the cylinder was −1.50 D. Visual acuity ranged from 20/20 to 20/10.
Because patients with CSNB1 are known to be highly myopic, additional
control subjects consisted of seven highly myopic subjects (mean age,
25.6 ± 4.8 years; range, 17–32 years). The distance spherical
refractive error in the tested eyes ranged from −6.00 D to −11.00 D
(−8.2 ± 1.75), and the maximum power of the cylinder was −3.00
D. Visual acuity ranged from 20/20 to 20/16.
All subjects met the inclusion criteria including normal intraocular
pressure (<20 mm Hg) and no history of glaucoma or diabetes,
congenital color vision defect, ocular surgery, or trauma. In addition,
none of the subjects had a family history of glaucoma or diabetes
mellitus. Slit lamp examination showed no opacity or yellowing of the
crystalline lens.
W-W perimetry and B-Y perimetry were performed using program 30-2 of a
Humphrey Field Analyzer (model 750; San Leandro, CA). The subjects’
pupils were fully dilated with 0.5% tropicamide. All testing was
performed with an appropriate near-add. The 30-2 program measures the
sensitivity at the fovea and at 76 equally spaced points, 6° apart,
which covered the central 27°. We used 75 points for analysis without
the two stimulus locations above and below the blind spot. W-W
perimetry was performed with a 10-cd/m2 white background
and a size III white stimulus, and B-Y perimetry was performed with a
100-cd/m2 yellow background and a size V blue (440 nm)
stimulus.
The statistics were calculated on a personal computer (StatView 4.02;
Abacus Concepts, Berkeley, CA). We divided the field into two
concentric areas; a central 0°-to-15° and a 15°-to-30° band,
and compared the mean thresholds of the fovea, the entire field, and
the 0°-to-15° and 15°-to-30° bands for both W-W and B-Y
perimetry in the three groups. A two-way analysis of variance was used
to test the significance of the difference of the sensitivity between
the three groups.
The research was conducted in accordance with institutional guidelines
and with the tenets of the World Medical Association Declaration of
Helsinki. After they received sufficient information, the subjects each
provided written, informed consent to participation in the study.