Differentiating between achromatopsia and cone dystrophy can be difficult, particularly in individuals with onset in early childhood; the best clinical discriminator is disease progression, which occurs in cone dystrophy and not typically in achromatopsia. In contrast with achromatopsia, dark-adapted rod thresholds are typically elevated by approximately 0.5 log unit in cone dystrophy [142].

CONCLUSIONS

A precise knowledge of the spectral sensitivity of the human rod and cone photoreceptors is central to our understanding and modeling of visual function in normals and individuals with color vision deficiencies. For the rods, spectral sensitivity and luminous efficiency are identical, and both are defined by the CIE 1951 V '(λ) function (see Chapter 15 on luminous efficiency functions). For the cones, the 2° and 10° cone fundamentals, and the associated lens and macular pigment and photopigment templates, of Stockman and Sharpe [2] and the photopic luminous efficiency functions of Sharpe et al. [143] provide a consistent set of standard functions with which to model human vision. These functions, and others, can be downloaded from http://www.cvrl.org.

ACKNOWLEDGMENT

This work was supported by the Wellcome Trust and Fight for Sight.

REFERENCES

1.Stockman A, Sharpe LT, Fach CC. The spectral sensitivity of the human short-wavelength cones. Vision Res 1999;39:2901–2927.

2.Stockman A, Sharpe LT. Spectral sensitivities of the middleand long-wavelength sensitive cones derived from measurements in observers of known genotype. Vision Res 2000;40:1711–1737.

3.Perlman I, Normann RA. Light adaptation and sensitivity controlling mechanisms in vertebrate photoreceptors. Prog Retin Eye Res 1998;17:523–563.

4.Pugh EN Jr, Nikonov S, Lamb TD. Molecular mechanisms of vertebrate photoreceptor light adaptation. Current Opin Neurobiol 1999;9:410–418.

5.Pugh EN Jr, Lamb TD. Phototransduction in vertebrate rods and cones: molecular mechanisms of amplification, recovery and light adaptation. In: Stavenga DG, de Grip WJ, Pugh EN, eds. Handbook of biological physics, Vol. 3, molecular mechanisms of visual transduction. Amsterdam: Elsevier; 2000:183–255.

6.Burns ME, Baylor DA. Activation, deactivation and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 2001;24:779–805.

7.Fain GL, Matthews HR, Cornwall MC, Koutalos Y. Adaptation in vertebrate photoreceptors. Physiol Rev 2001;80:117–151.

8.Arshavsky VY, Lamb TD, Pugh EN Jr. G proteins and phototransduction. Annu Rev Physiol 2002;64:153–187.

9.Kochendoerfer GG, Lin SW, Sakmar TP, Mathies RA. How color visual pigments are tuned. Trends Biochem Sci 1999;24:300–305.

10.Yokoyama S. Molecular evolution of vertebrate visual pigments. Prog Retin Eye Res 2000;19:385–419.

11.Deeb SS. The molecular basis of variation in human color vision. Clin Genet 2005;67:369– 377.

12.Stiles WS. The physical interpretation of the spectral sensitivity curve of the eye. In: Transactions of the optical convention of the Worshipful Company of Spectacle Makers. London: Spectacle Maker’s Company; 1948:97–107.

13.Mitchell DE, Rushton WAH. Visual pigments in dichromats. Vision Res 1971;11:1033–1043.

14.Stockman A. Colorimetry. In: Brown TG, Creath K, Kogelnik H, Kriss MA, Schmit J, Weber MJ, eds. The optics encyclopedia: basic foundations and practical applications. Berlin: Wiley-VCH; 2003:207–226.

15.Bongard MM, Smirnov MS. Determination of the eye spectral sensitivity curves from spectral mixture curves. Dokl Akad nauk SSSR 1954;102:1111–1114.

16.Stockman A, MacLeod DIA, Johnson NE. Spectral sensitivities of the human cones. J Opt Soc Am A 1993;10:2491–2521.

17.Young T. On the theory of light and colours. Philos Trans R Soc Lond 1802;92:20–71.

18.von Helmholtz HLF. On the theory of compound colours. Philosophical Magazine Series 4 1852;4:519–534.

19.Maxwell JC. Experiments on colours, as perceived by the eye, with remarks on colourblindness. Trans R Soc Edin 1855;21:275–298.

20.Rushton WAH. A foveal pigment in the deuteranope. J Physiol (Lond) 1965;176:24–37.

21.Dartnall HJ, Bowmaker JK, Mollon JD. Human visual pigments: microspectrophotometric results from the eyes of seven persons. Proc R Soc B 1983;B220(1218):115–130.

22.Schnapf JL, Kraft TW, Baylor DA. Spectral sensitivity of human cone photoreceptors. Nature 1987;325:439–441.

23.Kraft TW, Neitz J, Neitz M. Spectra of human L cones. Vision Res 1998;38:3663–3670.

24.Neitz M, Neitz J, Jacobs GH. Genetic basis of photopigment variations in human dichromats. Vision Res 1995;35:2095–2103.

25.Oprian DD, Asenjo AB, Lee N, Pelletier SL. Design, chemical synthesis, and expression of genes for the three human color vision pigments. Biochemistry 1991;30(48):11367–11372.

26.Merbs SL, Nathans J. Absorption spectra of human cone pigments. Nature 1992;356:431–432.

27.Merbs SL, Nathans J. Absorption spectra of the hybrid pigments responsible for anomalous color vision. Science 1992;258:464–466.

28.Asenjo AB, Rim J, Oprian DD. Molecular determinants of human red/green color discrimination. Neuron 1994;12:1131–1138.

29.König A, Dieterici C. Die Grundempfindungen und ihre Intensitäts-Vertheilung im Spectrum. Sitzungsberichte Akademie der Wissenschaften, Berlin 1886;1886:805–829.

30.Bouma PJ. Mathematical relationship between the colour vision system of trichromats and dichromats. Physica 1942;9:773–784.

31.Judd DB. Standard response functions for protanopic and deuteranopic vision. J Opt Soc Am 1945;35:199–221.

32.Judd DB. Standard response functions for protanopic and deuteranopic vision. J Opt Soc Am 1949;39:505.

33.Wyszecki G, Stiles WS. Color science: concepts and methods, quantitative data and formulae. New York: Wiley; 1967.

34.Vos JJ, Walraven PL. On the derivation of the foveal receptor primaries. Vision Res 1971;11:799–818.

35.Vos JJ. Colorimetric and photometric properties of a 2-deg fundamental observer. Color Res Appl 1978;3:125–128.

36.Estévez O. On the fundamental database of normal and dichromatic color vision. Doctoral dissertation, Amsterdam University; 1979.

37.Vos JJ, Estévez O, Walraven PL. Improved color fundamentals offer a new view on photometric additivity. Vision Res 1990;30:936–943.

38.Parsons JH. An introduction to colour vision. 2nd ed. Cambridge, UK: Cambridge University Press; 1924.

39.Boring EG. Sensation and perception in the history of psychology. New York: Appleton- Century-Crofts; 1942.

40.Le Grand Y. Light, colour and vision. 2nd ed. London: Chapman and Hall; 1968.

41.Stockman A, Sharpe LT. Cone spectral sensitivities and color matching. In: Gegenfurtner K, Sharpe LT, eds. Color vision: from genes to perception. Cambridge, UK: Cambridge University Press; 1999:53–87.

42.Smith VC, Pokorny J. Spectral sensitivity of the foveal cone photopigments between 400 and 500 nm. Vision Res 1975;15:161–171.

43.Maxwell JC. On the theory of compound colours and the relations of the colours of the spectrum. Philos Trans R Soc Lond 1860;150:57–84.

44.Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness SG. Molecular genetics of inherited variation in human color vision. Science 1986;232:203–210.

45.Nathans J, Thomas D, Hogness SG. Molecular genetics of human color vision: the genes encoding blue, green and red pigments. Science 1986;232:193–202.

46.Sharpe LT, Stockman A, Jägle H, et al. Red, green, and red-green hybrid photopigments in the human retina: correlations between deduced protein sequences and psychophysicallymeasured spectral sensitivities. J Neurosci 1998;18:10053–10069.

47.Blackwell HR, Blackwell OM. Blue mono-cone monochromacy: a new color vision defect. J Opt Soc Am 1957;47:338.

48.Blackwell HR, Blackwell OM. Rod and cone receptor mechanisms in typical and atypical congenital achromatopsia. Vision Res 1961;1:62–107.

49.Maxwell JC. On the theory of colours in relation to colour-blindness. A letter to Dr. G. Wilson. Trans R Scot Soc Arts 1856;4:394–400.

50.Stiles WS. The directional sensitivity of the retina and the spectral sensitivity of the rods and cones. Proc R Soc B 1939;B127:64–105.

51.Stiles WS. Mechanisms of colour vision. London: Academic; 1978.

52.Grützner P. Der normale Farbensinn und seine abweichungen. Ber Dtsch Ophthalmol Ges 1964;66:161–172.

53.Alpern A, Lee GB, Spivey BE. π1 cone monochromatism. Arch Ophthalmol 1965;74:334– 337.

54.Alpern M, Lee GB, Maaseidvaag F, Miller SS. Colour vision in blue-cone “monochromacy.” J Physiol (Lond) 1971;212:211–233.

55.Daw NW, Enoch JM. Contrast sensitivity, Westheimer function and Stiles-Crawford effect in a blue cone monochromat. Vision Res 1973;13:1669–1680.

56.Smith VC, Pokorny J, Delleman JW, Cozijnsen M, Houtman WA, Went LN. X-linked incomplete achromatopsia with more than one class of functional cones. Invest Ophthalmol Vis Sci 1983;24:451–457.

57.Hess RF, Mullen KT, Sharpe LT, Zrenner E. The photoreceptors in atypical achromatopsia. J Physiol (Lond) 1989;417:123–149.

58.Stiles WS, Burch JM. NPL colour-matching investigation: final report (1958). Opt Acta (Lond) 1959;6:1–26.

59.van Norren D, Vos JJ. Spectral transmission of the human ocular media. Vision Res 1974;14:1237–1244.

60.Crawford BH. The scotopic visibility function. Proc Phys Soc Lond 1949;B62:321–334.

61.Said FS, Weale RA. The variation with age of the spectral transmissivity of the living human crystalline lens. Gerontologia 1959;3:213–231.

62.Pokorny J, Smith VC, Lutze M. Aging of the human lens. Appl Optics 1988;26:1437–1440.

63.Xu J, Pokorny J, Smith VC. Optical density of the human lens. J Opt Soc Am A 1997;14:953–960.

64.Wald G. Human vision and the spectrum. Science 1945;101:653–658.

65.Bone RA, Sparrock JMB. Comparison of macular pigment densities in the human eye. Vision Res 1971;11:1057–1064.

66.Pease PL, Adams AJ, Nuccio E. Optical density of human macular pigment. Vision Res 1987;27:705–710.

67.Bone RA, Landrum JT, Fernandez L, Tarsis SL. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci 1988;29:843–849.

68.Bone RA, Landrum JT, Cains A. Optical density spectra of the macular pigment in vivo and in vitro. Vision Res 1992;32:105–110.

69.Terstiege H. Untersuchungen zum Persistenzund Koeffizientesatz. Die Farbe 1967;16:1–120.

70.Alpern M. Lack of uniformity in colour matching. J Physiol (Lond) 1979;288:85–105.

71.Miller SS. Psychophysical estimates of visual pigment densities in red-green dichromats. J Physiol (Lond) 1972;223:89–107.

72.King-Smith PE. The optical density of erythrolabe determined by retinal densitometry using the self-screening method. J Physiol (Lond) 1973;230:535–549.

73.King-Smith PE. The optical density of erythrolabe determined by a new method. J Physiol (Lond) 1973;230:551–560.

74.Smith VC, Pokorny J. Psychophysical estimates of optical density in human cones. Vision Res 1973;13:1199–1202.

75.Burns SA, Elsner AE. Color matching at high luminances: photopigment optical density and pupil entry. J Opt Soc Am A 1993;10:221–230.

76.Berendschot TTJM, van der Kraats J, van Norren D. Foveal cone mosaic and visual pigment density in dichromats. J Physiol (Lond) 1996;492:307–314.

77.König A. Über den menschlichen Sehpurpur und seine Bedeutung fur das Sehen. Acad Wiss Sitzungsber 1894;30:577–598.

78.Willmer EN. Further observations on the properties of the central fovea in colour-blind and normal subjects. J Physiol (Lond) 1950;110:422–446.

79.Thomson LC, Wright WD. The colour sensitivity of the retina with the central fovea of man. J Physiol (Lond) 1947;105:316–331.

80.Williams DR, MacLeod DIA, Hayhoe MM. Foveal tritanopia. Vision Res 1981;19: 1341–1356.

81.Hartridge H. The change from trichromatic to dichromatic vision in the human retina. Nature 1945;155:657–662.

82.McClellan JS, Marcos S, Prieto PM, Burns SA. Imperfect optics may be the eye’s defence against chromatic blur. Nature 2002;417:174–176.

83.Bedford RE, Wyszecki G. Wavelength discrimination for point sources. J Opt Soc Am 1958;48:129–135.

84.McCree KJ. Small-field tritanopia and the effects of voluntary fixation. Opt Acta (Lond) 1960;7:317–323.

85.Sharpe LT, Stockman A, Jägle H, Nathans J. Opsin genes, cone photopigments, color vision and colorblindness. In: Gegenfurtner K, Sharpe LT, eds. Color vision: from genes to perception. Cambridge, UK: Cambridge University Press; 1999:3–51.

86.Lakowski R. Theory and practice of colour vision testing. A review. Part I. Br J Indust Med Health 1969;26:173–189.

87.Lakowski R. Theory and practice of colour vision testing. A review. Part 2I. Br J Indust Med Health 1969;26:265–288.

88.Birch JB, Chisholm IA, Kinnear P, et al. Acquired color vision defects. In: Pokorny J, Smith VC, Verriest G, Pinckers AJLG, eds. Congenital and acquired color vision defects. New York: Grune and Stratton; 1979:243–348.

89.Birch JB. Diagnosis of defective colour vision. Oxford, UK: Oxford University Press; 1993.

90.Rayleigh L. Experiments on colour. Nature 1881;25:64–66.

91.von Helmholtz H. Handbuch der Physiologischen Optik. Hamburg: Voss; 1867.

92.Herschel JFW. Light. Encyclopedia Metropolitana, V. 1845:343.

93.Walls GL, Mathews RW. New means of studying color-blindness and normal foveal color vision. Univ Calif Pub Psychol 1952;7:1–172.

94.Walls GL, Heath GG. Neutral points in 138 protanopes and deuteranopes. J Opt Soc Am 1956;46:640–649.

95.Sloan LL, Habel A. Color signal systems for the red-green color blind. An experimental test of the three color signal system proposed by Judd. J Opt Soc Am Tech Dig 1955;45:592–598.

96.Massof RWB, J.E. Achromatic points in protanopes and deuteranopes. Vision Res 1976;16:53–57.

97.Hsia Y, Graham CH. Spectral luminosity curves for protanopic, deuteranopic, and normal subjects. Proc Natl Acad Sci U S A 1957;43:1011–1019.

98.Franceschetti A. Die Bedeutung der Einstellungsbreite am Anomaloskop für die Diagnose der einzelnen Typen der Farbsinnstörungen, nebst Bemerkungen über ihren Vererbungsmodus. Schweiz Med Wochenschr 1928;58:1273–9.

99.Stockman A, Sharpe LT, Merbs S, Nathans J. Spectral sensitivities of human cone visual pigments determined in vivo and in vitro. In: Palczewski K, ed. Vertebrate phototransduction and the visual cycle, part B methods in enzymology. Vol 316. New York: Academic Press; 2000:626–650.

100.Neitz J, Neitz M, Shevell SK. Trichromatic color vision with two spectrally distinct photopigments. Nat Neurosci 1999;2:884–888.

101.Fischer FP, Bouman MA, Doesschate TJ. A case of tritanopy. Doc Ophthalmol 1951;5– 6:73–87.

102.Wright WD. The characteristics of tritanopia. J Opt Soc Am 1952;42:509–521.

103.Walls GL. Notes on four tritanopes. Vision Res 1964;4:3–16.

104.Cole BL, Henry GH, Nathans J. Phenotypical variations of tritanopia. Vision Res 1965;6:301–313.

105.Kalmus H. Diagnosis and genetics of defective colour vision. Oxford, UK: Pergamon Press; 1965.

106.Engelking E. Die Tritanomalie, ein bisher unbekannter Typus anomaler Trichromasie. Graefes Arch Ophthalmol 1925;116:196–244.

107.Trendelenburg W. Ein Anomaloskop zur Untersuchung von Tritoformen der Farbenfehlsichtigkeit mit spektraler Blaugleichung. Klin Monatsbl Augenheilkd 1941;106:537–546.

108.Moreland JD, Kerr J. Optimization of a Rayleigh-type equation for the detection of tritanomaly. Vision Res 1979;19:1369–1375.

109.Moreland JD. Analysis of variance in anomaloscope equations. In: Verriest G, ed. Colour deficiencies VII, Documenta Ophthalmologica Proceedings Series, 39. The Hague: Dr. W. Junk; 1984:111–119.

110.Moreland JD, Roth A. Validation trials on an optimum blue-green equation. In: Verriest G, ed. Colour deficiencies VIII, Documenta Ophthalmologica Proceedings Series, 46. Dordrecht: Nijhoff-Junk; 1987:233–236.

111.Nathans J, Davenport CM, Maunenee IH, et al. Molecular genetics of human blue cone monochromacy. Science 1989;245:831–838.

112.Nathans J, Maumenee IH, Zrenner E, et al. Genetic heterogenity among blue-cone monochromats. Am J Hum Genet 1993;53:987–1000.

113.Alpern M, Lee GB, Spivey BE. π1-cone monochromatism. Arch Ophthal 1965;74:334–337.

114.Hess RF, Mullen KT, Zrenner E. Human photopic vision with only short wavelength cones: post-receptoral properties. J Physiol (Lond) 1989;417:150–169.

115.Green DG. Visual acuity in the blue cone monochromat. J Physiol (Lond) 1972;222:419–426.

116.Zrenner E, Magnussen S, Lorenz B. Blauzapfenmonochromasie: Diagnose, genetische Beratung und optische Hilfsmittel. Klin Monatsbl Augenheilkd 1988;193:510–517.

117.Reitner A, Sharpe LT, Zrenner E. Is colour vision possible with only rods and blue-sensitive cones? Nature 1991;352:798–800.

118.Sharpe LT, Stockman A, Jägle H, Knau H, Nathans J. L, M and L-M hybrid cone photopigments in man: deriving λmax from flicker photometric spectral sensitivities. Vision Res 1999;39:3513–3525.

119.Spivey BE. The X-linked recessive inheritance of atypical monochromatism. Arch Ophthalmol 1965;74:327–333.

120.François J, Verriest G, Matton-Van Leuven MT, de Rouck A, Manavian D. Atypical achromatopsia of sex-linked recessive inheritance. Am J Ophthalmol 1966;61:1101–1108.

121.Berson EL, Sandberg MA, Rosner B, Sullivan PL. Color plates to help identify patients with blue cone monochromatism. Am J Ophthalmol 1983;95:741–747.

122.Pitt FHG. The nature of normal trichromatic and dichromatic vision. Proc R Soc B 1944;B132:101–117.

123.Weale RA. Cone-monochromatism. J Physiol (Lond) 1953;121:548–569.

124.Weale RA. Photo-sensitive reactions in foveae of normal and cone-monochromatic observers. Opt Acta (Lond) 1959;6:158–174.

125.Fincham EF. Defects of the colour-sense mechanism as indicated by the accommodation reflex. J Physiol (Lond) 1953;121:570–580.

126.Crone RA. Combined forms of congenital color defects: a pedigree with atypical total color blindness. Br J Ophthalmol 1956;40:462.

127.Gibson IM. Visual mechanisms in a cone-monochromat. J Physiol Biochem 1962;161:10P– 11P.

128.Ikeda H, Ripps H. The electroretinogram of a cone monochromat. Arch Ophthalmol 1966;75:513–517.

129.Alpern ML. What is it that confines in a world without color? Invest Ophthalmol 1974;13:648–674.

130.Vajoczki L, Pease PL. Cone monochromacy: a case report. In: Cavonius CR, ed. Colour deficiencies XIII. Dordrecht: Kluwer Academic; 1997:283–290.

131.Kohl S, Varsanyi B, Antunes GA, et al. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet 2005;13:302–308.

132.Wissinger B, Gamer D, Jägle H, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet 2001;69:722–737.

133.Aligianis IA, Forshew T, Johnson S, et al. Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2). J Med Genet 2002;39(9):656–660.

134.Kohl S, Baumann B, Rosenberg T, et al. Mutations in the cone photoreceptor G-protein α- subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet 2002;71:422–425.

135.Pentao L, Lewis RA, Ledbetter DH, Patel PI, Lupski JR. Maternal uniparental isodisomy of chromosome 14: association with autosomal recessive rod monochromacy. Am J Hum Genet 1992;50:690–699.

136.Jägle H, Kohl S, Apfelstedt-Sylla E, Wissinger B, Sharpe LT. Manifestations of rod monochromacy. Color Res Appl 2001;26:S96S99.

137.Michaelides M, Aligianis IA, Ainsworth JR, et al. Progressive cone dystrophy associated with mutation in CNGB3. Invest Ophthalmol Vis Sci 2004;45:1975–1982.

138.Trankner D, Jägle H, Kohl S, et al. Molecular basis of an inherited form of incomplete achromatopsia. J Neurosci 2004;24:138–147.

139.Rosenberg T, Baumann B, Kohl S, Zrenner E, Jorgensen AL, Wissinger B. Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations. Invest Ophthalmol Vis Sci 2004;45:4256–4262.

140.François J. Heredity in ophthalmology. St. Louis: Mosby; 1961.

141.Sharpe LT, Nordby K. Total colour blindness: an introduction. In: Hess R, Sharpe LT, Nordby K, eds. Night vision: basic, clinical and applied aspects. Cambridge, UK: Cambridge University Press; 1990:253–289.

142.Berson EL, Gouras P, Gunkel RD. Progressive cone degeneration, dominantly inherited. Arch Ophthalmol 1968;80:77–83.

143.Sharpe LT, Stockman A, Jagla W, Jägle H. A luminous efficiency function, V*(λ), for daylight adaptation. J Vis 2005;5:948–968.

144.Viénot F, Brettel H, Ott L, Ben MBA, Mollon JD. What do colour-blind people see? Nature 1995;376(6536):127–128.

145.Brettel H, Viénot F, Mollon JD. Computerized simulation of color appearance for dichromats. J Opt Soc Am A 1997;14:2647–2655.