Color vision is an important element of human visual perception. Three types of cones in the retina (S-cones, M-cones, and L-cones) absorb light of different wavelengths, and color is perceived through comparative processing of these signals. Most mammals have dichromatic color vision, but primates acquired trichromatic color vision through duplication and divergence of the M-cone and L-cone genes on the X chromosome.
A condition in which color vision is abnormal is called color vision deficiency. It is broadly classified into congenital and acquired types.
Congenital color vision deficiency: Caused by genetic abnormalities in cone photopigments. It is binocular and non-progressive, and the sensation remains unchanged throughout life.
Acquired color vision deficiency: Refers to all color vision disorders caused by acquired conditions such as retinal diseases, optic nerve diseases, and cerebral lesions. Even if the primary disease is congenital, it is classified as acquired color vision deficiency.
The frequency of congenital red-green color vision deficiency varies by race: 6–8% in Caucasian males, about 5% in Japanese males, and about 0.2% in females. It is slightly lower in Black males at 2–4%. A meta-analysis across Africa reported a prevalence of 2.71%3). In Northern European males, it reaches up to 8%, making it one of the most common single-gene disorders worldwide4).
In Japan, color vision testing in elementary schools became optional in 2003, leading to an increase in cases where individuals grow up unaware of their color vision deficiency. Subsequently, a 2014 notification from the Ministry of Education, Culture, Sports, Science and Technology prompted schools to actively resume color vision testing and accommodations.
QHow common is congenital color vision deficiency?
A
It occurs in about 5% of Japanese males and about 0.2% of females. It is even more frequent in Caucasian males at 6–8%. Approximately 10% of females are estimated to be carriers.
The most notable feature of congenital color vision deficiency is the lack of awareness of color misperception. Since the sensation is innate, the individual is often unaware of color differences. Color misperception is more likely under the following conditions.
When the colored area is small
When saturation is low
When lighting is dim or during high-speed movement
When attention is distracted
In early childhood, colors are often mistaken, but with accumulated experience, the frequency of misidentification decreases as the child grows.
In acquired color vision deficiency, because the person has memory of normal color vision, they often notice the change in color perception. Visual acuity and visual field defects are often present, and these impairments usually cause greater difficulty in daily life than the color vision deficiency itself.
Complete color blindness (rod monochromacy) presents with the following symptoms:
Reduced visual acuity: 0.1 or less
Photophobia (glare): Marked in bright environments
Day blindness: Vision is actually better in dim light
Congenital nystagmus: Tends to decrease during near vision
As a color vision characteristic of congenital red-green color vision deficiency, dichromats experience confusion colors where different colors appear similar to normal color vision. The confusion color loci on the CIE chromaticity diagram are characteristic.
Protanopia: Neutral point near 495 nm. Relative luminosity is shifted toward short wavelengths, and red is perceived as a dark color.
Deuteranopia: Neutral point near 500 nm. Relative luminosity is close to normal color vision.
Tritanopia (congenital blue-yellow color blindness): The neutral point is around 570 nm. The confusion axis corresponds to the blue-yellow axis.
Clinical findings of acquired color vision deficiency include the following features.
It fluctuates in parallel with the exacerbation and remission of the underlying disease.
It may occur in only one eye, or there may be a difference in severity between the two eyes.
In the early stages of retinal or optic nerve disease, acquired blue-yellow color vision deficiency tends to appear.
In cerebral color vision deficiency, patients report that the visual field appears monochrome, or that colors become desaturated and grayish. It is often accompanied by prosopagnosia and topographic disorientation. Homonymous hemianopia (often upper quadrantanopia) is also present.
In achromatopsia, electroretinography (ERG) shows abnormal cone responses. The Panel D-15 test shows a scotopic axis. Specialized S-cone ERG is useful for differentiating between rod monochromacy and S-cone monochromacy.
QHow can achromatopsia be distinguished from red-green color blindness?
A
In achromatopsia, the cone electroretinogram is abnormal, accompanied by congenital nystagmus, photophobia, and marked visual acuity loss. In red-green color vision deficiency, visual acuity and visual fields are normal, and the electroretinogram is also normal.
Congenital red-green color vision deficiency: X-linked recessive inheritance. The L and M genes are located on the long arm of the X chromosome at Xq28. Unequal crossing over is prone to occur due to high gene homology (98%).
Congenital blue-yellow color vision deficiency: Autosomal dominant inheritance. The S cone opsin gene is located on chromosome 7 (7q22-qter). It is very rare, occurring in 1 in 13,000 to 65,000 people.
Achromatopsia (rod monochromacy): Autosomal recessive inheritance. Frequency is about 1 in 30,000. Six causative genes including CNGA3 and CNGB3 have been identified1).
According to Kollner’s rule (1912), retinal and macular lesions tend to cause blue-yellow color vision deficiency, while optic nerve lesions tend to cause red-green color vision deficiency. However, it is now recognized that both retinal and optic nerve diseases often initially present with acquired blue-yellow color vision deficiency.
Representative drug-induced color vision changes are shown below.
Sildenafil: Mildly inhibits phosphodiesterase 6, and accumulation of cGMP prevents hyperpolarization of cones. It causes transient cyanopsia, which resolves within hours to days after discontinuation.
Digoxin: Inhibits Na-K ATPase in retinal photoreceptors, causing xanthopsia.
QAre there any drugs that cause acquired color vision deficiency?
A
Sildenafil can cause transient blue vision, and digoxin can cause yellow vision. Both are due to pharmacological effects on retinal photoreceptors. Drugs with optic nerve toxicity can also cause acquired color vision deficiency.
Color vision tests are selected based on the purpose. For detecting congenital color vision deficiency, multiple pseudoisochromatic plates for screening are used in combination. An anomaloscope is required for definitive diagnosis.
These test plates utilize the color confusion theory and are the most common method for color vision screening.
Ishihara Color Vision Test: Excellent for detecting congenital red-green color vision deficiency. The international version uses 38 plates. Detection rate is high, but the accuracy of type classification using classification plates is low.
SPP Standard Color Vision Test Part 1: For congenital anomalies. Among the 10 detection plates, 8 or more correct answers indicate normal color vision. The classification accuracy is higher than that of the Ishihara test.
SPP Standard Color Vision Test Chart Part 2: For acquired color vision deficiencies. Focuses on detecting blue-yellow abnormalities. Test each eye separately.
The pseudoisochromatic plates are only for screening purposes; the type and degree of abnormality should not be determined solely by these plates.
This is a testing device based on Rayleigh matching, where a mixture of red (671 nm) and green (546 nm) light is matched to a yellow (589 nm) monochromatic light. It is the only instrument capable of definitive diagnosis of the type and degree of congenital color vision deficiency. It cannot be used to diagnose tritanopia because S cones are not involved.
Panel D-15: Arrange 15 color plates in order of hue. Suitable for assessing occupational aptitude. Test duration: 3–5 minutes.
Farnsworth-Munsell 100 Hue Test: Arrange 85 tiles. Evaluated by confusion angle, C-index, and S-index. Test duration: 15–20 minutes. The normal upper limit of total error score varies by age: around 50–90 for people in their 20s, and around 160 for those in their 50s.
Lantern test: Aptitude test for occupations involving signal light recognition. The JFC lantern uses three colors: red, green, and yellow.
Red desaturation test: A bedside test comparing the perception of red between the left and right eyes. Useful for evaluating optic neuropathy.
Cambridge Colour Test (CCT): A computerized pseudo-isochromatic test. It allows quantitative assessment of congenital and acquired color vision deficiencies and shows high sensitivity for early detection of acquired color vision defects2).
The characteristics of major color vision tests are summarized below.
Quantitative assessment of congenital and acquired
5–20 minutes
QCan a definitive diagnosis of color vision deficiency be made using only Ishihara plates?
A
Ishihara plates are a screening test with high detection rate for red-green color vision deficiency, but their accuracy in classifying types is low. An anomaloscope is required for definitive diagnosis. Additionally, Ishihara plates cannot detect blue-yellow color vision deficiency (tritanopia).
Currently, there is no curative treatment for congenital color vision deficiency. The mainstay of management is counseling and social support.
Counseling: Explain the characteristics of color misidentification with specific examples. Reassure children that there are generally no problems in daily life. For adolescents in their late teens, provide guidance to fully recognize color misidentification and take countermeasures.
Principles for avoiding color misidentification: The basic approach is not to distinguish by color. Use cues other than color, such as shape, position, and labels.
Career guidance: Difficulties may arise in occupations requiring subtle color discrimination. Provide advice after considering job content and restrictions.
For symptom management of achromatopsia, light-filtering lenses or tinted contact lenses are used to reduce photophobia. Red lenses have been reported to be useful for alleviating photophobia1). However, no improvement in color vision itself is achieved.
Since acquired color vision deficiency is a secondary change due to the underlying disease, treatment is directed at the underlying disease. Color vision testing is used as an indicator of the condition and disease activity.
6. Pathophysiology and Detailed Mechanism of Onset
The process of phototransduction in cones is as follows. Photons induce photoisomerization of 11-cis-retinal bound to opsin (a G protein-coupled receptor). Conversion to all-trans-retinal causes a conformational change in opsin, activating the G protein transducin. Activated transducin stimulates phosphodiesterase (PDE), which promotes the breakdown of cGMP. The decrease in cGMP concentration closes cGMP-gated cation channels, hyperpolarizing the photoreceptor cell1).
In the dark, a constant concentration of cGMP keeps the channels open, and the influx of cations (dark current) depolarizes the photoreceptor cell. Light stimulation stops this dark current and reduces the release of glutamate.
Color information is transmitted via retinal ganglion cells to the lateral geniculate nucleus (LGN).
L cone and M cone information: Transmitted via midget cells to the parvocellular layers of the LGN. Red-green opponency is encoded here.
S cone information: Transmitted via small bistratified cells to the koniocellular layers of the LGN. This reflects blue-yellow opponency.
After the LGN, information proceeds to the V1, V2, and V4 cortical areas of the occipital lobe. The V4 area contains many cells involved in color processing. Damage to the ventral occipital cortex can cause complete cerebral achromatopsia, while damage to the occipitotemporal lobe can cause hemiachromatopsia5).
The following principles are important in color perception:
Principle of univariance: A single photopigment cannot determine the wavelength of a photon. Color discrimination requires comparative input from different photoreceptors.
Color constancy: Humans can perceive the color of an object as constant even when lighting conditions change. The ratio of local photoreceptor activity is involved.
Mutations in CNGA3 and CNGB3 cause loss of function of the CNG channel, halting the entire cone phototransduction cascade. Cases with partial color vision retention have been reported with GNAT2 mutations 1).
Molecular mechanisms of red-green color vision deficiency
Both the L cone opsin gene (OPN1LW) and the M cone opsin gene (OPN1MW) are arranged in tandem on the X chromosome at Xq28. The two genes share more than 98% nucleotide sequence homology, and hybrid gene formation due to unequal crossing over occurs frequently. The differences in spectral absorption characteristics are mainly determined by amino acid residues at positions 277 and 285 of exon 5.
7. Latest Research and Future Prospects (Research Stage Reports)
All causative genes for achromatopsia have coding sequences of 2,600 base pairs or less, making them suitable for packaging into AAV vectors. Several phase I/II clinical trials targeting CNGA3 and CNGB3 are currently underway 1).
An overview of major clinical trials is shown below.
Trial ID
Target gene
Vector
Country
NCT02610582
CNGA3
rAAV8
Germany
NCT02935517
CNGA3
AAV2tYF
United States and Israel
NCT03001310
CNGB3
AAV8
United Kingdom
Fischer et al. (2020) reported the safety and functional improvement of subretinal injection of AAV8.CNGA3 in the NCT02610582 trial. Improvements in visual acuity, contrast sensitivity, and color vision were observed one year after treatment, and patient-reported outcomes also confirmed enhanced color discrimination ability1).
Michaelides et al. (2023) administered AAV8-hCARp.hCNGB3 to 11 adults and 12 children in the NCT03001310 trial. Safety was within acceptable range, and some subjects showed improvements in light sensitivity and vision-related quality of life1).
Mancuso et al. (2009) introduced a third opsin into adult red-green color vision-deficient primates and demonstrated the acquisition of trichromatic color vision. This result suggests that trichromatic color vision can be established even without an early developmental stage1).
However, it remains unproven whether gene therapy enables experimental animals to “perceive” new colors, and there are still challenges for clinical application in humans1).
Color-correcting glasses (e.g., Enchroma) use multi-notch filters to remove the overlap of red and green wavelengths, but CAD tests have not shown significant improvement in symptoms1). Development of tinted contact lenses (e.g., gold nanoparticle-containing hydrogels) is also underway, but all are still at the research stage.
In the future, technology to achieve artificial color vision by implanting electrodes into the retina, optic nerve, or visual cortex is being investigated 5). Currently, it is limited to reproducing low-resolution black-and-white vision, and controlled color vision reproduction has not been achieved.
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Costa MF, Henriques LD, Souza GS. An integrative review for clinical evaluation of color vision: The right test for the right disease. J Curr Ophthalmol. 2024;36:355-64.
Tilahun MM, Sema FD, Mengistie BA, Abdulkadir NH, Jara AG. Prevalence of color vision deficiency in Africa: Systematic review and meta-analysis. PLoS ONE. 2024;19(12):e0313819.
Almustanyir A. A global perspective of color vision deficiency: Awareness, diagnosis, and lived experiences. Healthcare. 2025;13:2031.
Zhang B, Zhang R, Zhao J, Yang J, Xu S. The mechanism of human color vision and potential implanted devices for artificial color vision. Front Neurosci. 2024;18:1428565.
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