IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Terasaki, H.
Right arrow Articles by Kondo, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Terasaki, H.
Right arrow Articles by Kondo, M.
(Investigative Ophthalmology and Visual Science. 1999;40:2761-2764.)
© 1999 by The Association for Research in Vision and Ophthalmology, Inc.

Blue-on-Yellow Perimetry in the Complete Type of Congenital Stationary Night Blindness

Hiroko Terasaki, Yozo Miyake, Ryoji Nomura, Masayuki Horiguchi, Satoshi Suzuki and Mineo Kondo

From the Department of Ophthalmology, Nagoya University School of Medicine, Japan.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
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.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
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-chromosome3 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.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
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 x 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.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The conventional full-field rod and cone ERGs of a normal subject, a representative highly myopic normal subject, and a representative subject with CSNB1 are shown in Figure 1 A. The patients showed a nondetectable rod (scotopic) ERG with relatively good cone (photopic and 30-Hz flicker) ERGs. A mixed cone–rod single flash ERG showed a negative-type ERG with nonrecordable oscillatory potentials.2 These are the characteristics of the ERGs of a patient with CSNB1.



View larger version (9K):
[in this window]
[in a new window]
  		Figure 1. (A) Full-field ERGs in a normal subject, a highly myopic normal subject, and a representative patient with complete CSNB. (B) S-cone and L-M cone ERGs in a normal subject, a highly myopic normal subject, and a representative patient with complete CSNB.

 
Figure 1B shows representative S-cone and L-M cone ERGs from a normal subject, a highly myopic subject, and a subject with a representative case of CSNB1. In CSNB1, the S-cone ERGs were not recordable with short-wavelength stimuli, whereas the L-M-cone ERG showed a larger a-wave, extremely small b-wave, and a large off-wave (d).6 14

Color vision defects were not detectable in any patients with the Farnsworth–Munsell 100-hue test. The total error scores of the seven normal myopes were 20 to 61 (mean score, 41) and those of the five eyes with CSNB1 ranged from 8 to 92 (mean score, 38). The upper limit of normal reported in the same age range was 100 errors.17

Figure 2 shows the gray scale of W-W and B-Y perimetry in five patients with CSNB1. B-Y perimetry in all cases demonstrated a decrease in sensitivity as the testing areas became more eccentric.



View larger version (44K):
[in this window]
[in a new window]
  		Figure 2. Gray-scale displays of W-W perimetry and B-W perimetry in five CSNB1 patients and a representative highly myopic normal subject. B-Y perimetry in all CSNB1 patients demonstrated a similar progressive decrease of sensitivity with increasing eccentricity.

 
In W-W perimetry, the foveal sensitivity was significantly decreased in CSNB1 compared with that in the normal and the highly myopic groups. In B-Y perimetry, in contrast, there was no significant difference in foveal sensitivity among the three groups. The mean group sensitivity for the entire testing field and the mean sensitivity of the central 0°-to-15° and 15°-to-30° bands in both W-W perimetry and B-Y perimetry were significantly decreased in the patients with CSNB1 compared with those in the normal and myopic groups.

To examine the loss in B-Y sensitivity with eccentricity, we compared the ratio of the sensitivities in the 0°-to-15°and 15°-to-30° bands obtained by W-W and B-Y perimetry. The reduction of B-Y sensitivity in CSNB1 with eccentricity was more prominent compared with that in both the normal and the myopic subjects. Although the reduction of W-W sensitivity with eccentricity was also significantly different between CSNB1 and normal subjects, there was no significant difference between CSNB1 and the myopic subjects (Table 1) .


View this table:
[in this window]
[in a new window]
  		Table 1. Mean Sensitivity of Different Areas in W-W and B-Y Perimetry in CSNB1

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
All the patients in the present study were classified as having the complete type CSNB (CSNB1) because of the negatively shaped, mixed rod and cone ERGs with a normal a-wave with relatively well preserved cone ERG. Besides the findings of rod visual functions, the long-flash photopic ERGs revealed a hyperpolarizing pattern, suggesting a defect of the synapse to the depolarizing (ON) bipolar cells in both rod and cone visual pathways.7

There is some evidence that there is a predominance of S-cone ON units at the ganglion cell level, and the defect in CSNB1 may thus have a more profound effect on the S-cone system.18 Indeed, our patients with CSNB1 showed nondetectable S-cone ERG when stimulated with full-field stimuli, which agrees well with earlier reports.11 12 In spite of the nonrecordable S-cone ERG, the conventional color vision tests were essentially normal, which has been reported by other investigators.11 12 MacKay et al.11 believed that the S-cone ERGs depended on the presence of normal rod function and were therefore not essential for normal color vision. Kamiyama et al.12 reported the absence of S-cone ERGs with normal color vision evaluated by the Farnsworth Panel D-15 test in CSNB1. They compared the S-cone ERGs with a few conventional color vision tests but none of these studies examined the sensitivity of the short-wave–sensitive cones in the peripheral retina.

In addition to conventional color vision tests, we assessed the short-wavelength pathway using B-Y automated perimetry. This technique uses a high-luminance yellow background to adapt selectively the green and the red pathways and suppresses rod activity simultaneously. This particular combination of wavelength and luminance of the stimulus and background isolates the short-wavelength system optimally.19 20 With the use of this technique, the S-cone sensitivities were topographically measured over 60° of the central field. The effect of lens absorption should be considered in the assessment of blue sensitivity; however, the foveal S-cone sensitivity showed no significant difference among three groups, which provided evidence against a lens-absorption effect.

We found that the S-cone sensitivity in CSNB1 was preserved normally only in the fovea but then decreased abnormally in the entire measured peripheral field. Because CSNB1 is usually associated with high myopia, as in our present patients, it was essential to take into consideration the S-cone sensitivity of highly myopic eyes, because blue sensitivity has been reported to decrease more significantly with an increase of refractive error.21 This significant depression of blue sensitivity in the peripheral retina in CSNB1 was also supported, even when compared with highly myopic subjects without CSNB1 as control subjects.

Considering the hill of vision, retinal sensitivity decreases with eccentricity from the fovea even in normal subjects according to the results of W-W perimetry (radial effect).22 We calculated the ratio of a central 0°-to-15° sensitivity to 15-to-30° sensitivity for both W-W and B-Y perimetry. The radial effect in B-Y sensitivity was greater in CSNB1 than in the normal and the highly myopic normal control subjects. In W-W perimetry, the radial effect in CSNB1 was more significant compared with normal subjects, but not when compared with the highly myopic normal subjects.

Milam et al.13 touched briefly on the results of B-Y perimetry in two patients with CSNB in their analysis of cutaneous melanoma–associated retinopathy (MAR). They reported that foveal blue sensitivity was reduced by 10 dB in MAR but was completely normal in CSNB. They did not perform conventional color vision tests in the CSNB patients, but it is very interesting that their patients with MAR showed the nonrecordable S-cone ERG with similar pattern of B-Y perimetry. Other studies have reported that there are several pathophysiological similarities between CSNB1 and MAR.23 24 In both disorders, the ON synapse to the bipolar cells in both the rod and cone visual pathways can be exclusively affected. The present results strongly suggest that the topographic abnormalities of the S-cone function in the retina have a similar pattern in both disorders.

Our results indicate that the S-cone function in CSNB1 was preserved only in the fovea and became abnormal toward the peripheral retina. This may explain the discrepancy between normal conventional color vision tests and nonrecordable S-cone ERGs in CSNB1, because the color vision tests are mainly related to the central retinal function, whereas the full-field ERG reflects the activity mainly in the peripheral retina.


   Footnotes
 
Supported by Grants-in-Aid 04454440 and 09671791 from the Ministry of Education, Science, and Culture, Japan.

Submitted for publication December 23, 1998; revised May 25, 1999; accepted June 24, 1999.

Commercial relationships policy: N.

Corresponding author: Hiroko Terasaki, MD, Department of Ophthalmology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-0065, Japan. E-mail: terasaki{at}med.nagoya-u.ac.jp


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Schubert, G, Bornschein, H. (1952) Beitrag zur Analyse des Menschlichen Electroretinogram Ophthalmologica 123,396-413[Medline][Order article via Infotrieve]
  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[Abstract/Free Full Text]
  3. Bergen, AA, ten Brinkv, JB, Riemslag, F, et al (1996) Conclusive evidence for a distinct congenital stationary night blindness locus in Xp21.1 J Med Genet 33,869-872[Abstract/Free Full Text]
  4. Hardcastle, AJ, David–Gray, ZK, Jay, M, Bird, AC, Bhattacharya, SS (1997) Localization of CSNBX(CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp Invest Ophthalmol Vis Sci 38,2750-2755[Abstract/Free Full Text]
  5. 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[Abstract/Free Full Text]
  6. Miyake, Y, Yagasaki, K, Horiguchi, M, Kawase, Y. (1987) On- and off- responses in photopic electroretinogram in complete and incomplete types of congenital stationary night blindness Jpn J Ophthalmol 31,81-87[Medline][Order article via Infotrieve]
  7. Sieving, PA (1993) Photopic ON & OFF-pathway abnormalities in retinal dystrophies Trans Am Opt Soc 91,701-773
  8. Norren, DV, Padmos, P. (1973) Human and macaque blue cones studied with electroretinography Vision Res 13,1241-1254[Medline][Order article via Infotrieve]
  9. Miyake, Y, Yagasaki, K, Ichikawa, H. (1985) Differential diagnosis of congenital tritanopia and dominantly inherited juvenile optic atrophy Arch Ophthalmol 103,1496-1501[Abstract/Free Full Text]
  10. Yokoyama, M. (1979) Blue sensation in eye disease Jpn J Clin Ophthalmol 33,111-125
  11. MacKay, CJ, Saeki, M, Gouras, P, Roy, M. (1995) Congenital and acquired nyctalopia eliminate the S-cone ERG without disturbing color vision [ARVO Abstract] Invest Ophthalmol Vis Sci 36(4),S925
  12. Kamiyama, M, Yamamoto, S, Nitta, K, Hayasaka, S. (1996) Undetectable S cone electroretinogram b-wave in complete congenital stationary night blindness Br J Ophthalmol 80,637-639[Abstract/Free Full Text]
  13. Milam, AH, Assri, JC, Jacobson, SG, Lubinski, WP, Feun, LG, Alexander, LR (1993) Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy Invest Ophthalmol Vis Sci 34,91-100[Abstract/Free Full Text]
  14. Miyake, Y, Horiguchi, M, Suzuki, S, Kondo, M, Tanikawa, A. (1997) Complete and incomplete types of congenital stationary night blindness (CSNB) as a model of "off-retina" and "on-retina." Lavail, MM Hollyfield, JG Anderson, RE eds. Degenerative Retinal Diseases ,31-41 Plenum Press New York.
  15. Horiguchi, M, Miyake, Y, Kondo, M, Suzuki, S, Tanikawa, A, Koo, HM (1995) Blue light-emitting diode built-in contact lens electrode can record human S-cone electroretinogram Invest Ophthalmol Vis Sci 36,1730-1732[Abstract/Free Full Text]
  16. Suzuki, S, Horiguchi, M, Tanikawa, A, Miyake, Y, Kondo, M. (1998) Effect of age on short-wavelength sensitive cone electroretinogram and long- and middle-wavelength sensitive cone electroretinogram Jpn J Ophthalmol 42,424-430[Medline][Order article via Infotrieve]
  17. Verriest, G. (1963) Further studies on acquired deficiency of color discrimination J Opt Soc Am 53,185-195[Medline][Order article via Infotrieve]
  18. Kolb, H, Lipets, LE (1991) The anatomical basis for colour vision in the vertebrate retina Gouras, P eds. The perception of colour ,128-145 Macmillan London.
  19. Wald, G. (1964) The receptors of human color vision Science 145,1007-1017[Free Full Text]
  20. Felius, J, de Jong, LA, van den Berg, TJ, Greve, EL. (1995) Functional characteristics of blue-on-yellow perimetric thresholds in glaucoma 36 ,1665-1674
  21. Kawabata, H, Fujimoto, N, Adachi–Usami, E. (1997) Sensitivity loss of short wavelength sensitive cones in myopic eyes by blue-on-yellow perimetry Jpn J Ophthalmol Soc 101,648-655
  22. Katz, J, Sommer, A. (1986) A symmetry and variation in the normal hill of vision Arch Ophthalmol 104,65-68[Abstract/Free Full Text]
  23. Berson, EL, Lessell, S. (1988) Paraneoplastic night blindness with malignant melanoma Am J Ophthalmol 106,307-311[Medline][Order article via Infotrieve]
  24. Alexander, KR, Fishman, GA, Peachey, NS, Marchese, AL, Tso, MOM (1992) "On" response defect in paraneoplastic night blindness with cutaneous malignant melanoma Invest Ophthalmol Vis Sci 33,477-483[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Neurophysiol.Home page
N. W. Khan, M. Kondo, K. T. Hiriyanna, J. A. Jamison, R. A. Bush, and P. A. Sieving
Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness
J Neurophysiol, January 1, 2005; 93(1): 481 - 492.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
L E Allen, I Zito, K Bradshaw, R J Patel, A C Bird, F Fitzke, J R Yates, D Trump, A J Hardcastle, and A T Moore
Genotype-phenotype correlation in British families with X linked congenital stationary night blindness
Br J Ophthalmol, November 1, 2003; 87(11): 1413 - 1420.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Nakamura, S. Ito, H. Terasaki, and Y. Miyake
Novel CACNA1F Mutations in Japanese Patients with Incomplete Congenital Stationary Night Blindness
Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1610 - 1616.
[Abstract] [Full Text]

Home page
 Br J OphthalmolHome page
M Hayashi and S Yamamoto
Changes of cone electroretinograms to colour flash stimuli after successful retinal detachment surgery
Br J Ophthalmol, April 1, 2001; 85(4): 410 - 413.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Terasaki, H.
Right arrow Articles by Kondo, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Terasaki, H.
Right arrow Articles by Kondo, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS