Congenital color vision deficiency is a condition in which color discrimination ability differs from normal due to a congenital lack or functional abnormality of cone photopigments (L-cone, M-cone, S-cone). Because it is an innate way of seeing, the individual may not be aware of their color vision abnormality, especially in early childhood. Visual functions other than color vision are normal, and the condition does not progress (in the case of congenital red-green color vision deficiency and congenital blue-yellow color vision deficiency).
Congenital red-green color vision deficiency is the most common type, accounting for most cases encountered in daily clinical practice. It results from a lack of L-cone (red cone) or M-cone (green cone) photopigments, or from abnormal expression of the L and M genes on the X chromosome. Due to X-linked inheritance, it is significantly more common in males.
The former terms “color blindness” and “color weakness” are now avoided because they can lead to prejudice against affected individuals. The terms “color vision deficiency” or “color vision diversity” are recommended.
In anomalous trichromacy, which accounts for the majority of congenital red-green color vision deficiencies, individuals have three types of cones, but the sensitivity peak of one type is shifted. Therefore, they do not completely lack color vision. Red and green appear very similar, making them difficult to distinguish. Complete inability to discriminate colors occurs only in rod monochromacy (congenital achromatopsia), which is extremely rare.
Compared to normal color vision, the sensation of red and green is absent or very weak. In normal trichromats, red and green are perceived as very distinct colors, but in congenital red-green color vision deficiency, red and green appear very similar and are sometimes indistinguishable. Since this is the way they have always seen, individuals often do not notice the abnormality.
Specific difficulties in daily life include the following:
Severity is greater in dichromacy (severe) than in anomalous trichromacy (mild).
Visual acuity, visual field, and fundus are normal; it is detected only by color vision tests (pseudoisochromatic plates, Panel D-15, anomaloscope).
Type 1 Color Vision Deficiency (Protan)
It is caused by abnormality of L-cones.
Protanopia: L-cone deficiency (only M-cones and S-cones).
Protanomaly: Has M’-cones (incomplete M-cones) instead of L-cones.
Generally, dichromacy is more severe than anomalous trichromacy.
Deutan color vision deficiency
Caused by M-cone abnormality.
Deuteranopia: M-cone deficiency (only L-cones and S-cones).
Deuteranomaly: Has L’-cones (abnormal L-cones) instead of M-cones.
Most common among congenital red-green color vision deficiencies.
S-cone photopigment is deficient, making it difficult to distinguish blue from yellow. It is inherited in an autosomal dominant pattern with no sex difference. The frequency is estimated at 1 in 13,000 to 65,000 people. Visual functions other than color vision are normal, and the condition does not progress.
This is a condition where cones do not function and vision relies solely on rods. From early childhood, there is visual impairment with low vision around 0.1, photophobia (sensitivity to light), hemeralopia (poor vision in bright light), and nystagmus. Since cones are nonfunctional, color discrimination is absent, and vision improves in dim light. The prevalence is very rare, about 0.0025% to 0.0055%. There are complete and incomplete forms, with some residual cone function in the incomplete type.
This condition involves vision mediated only by S-cones and rods, and shows X-linked recessive inheritance. It is a rare disease with a frequency of less than 1 in 100,000 people. Similar to rod monochromacy, but some residual color discrimination may remain. Although it has been considered non-progressive, many cases develop progressive visual impairment and macular degeneration.
| Type | Frequency |
|---|---|
| Congenital red-green color blindness | Approximately 5% of males, 0.2% of females (Japanese) |
| Congenital tritanopia | 1 in 13,000 to 65,000 people |
| Rod monochromacy | Prevalence approximately 0.0025% to 0.0055% |
| S-cone monochromacy | Less than 1 in 100,000 |
| Type | Inheritance pattern | Causative gene | Notes |
|---|---|---|---|
| Congenital red-green color vision deficiency (type 1 and type 2) | X-linked recessive inheritance | L gene and M gene (on X chromosome) | More common in males; females are often carriers |
| Congenital blue-yellow color blindness (type 3) | Autosomal dominant inheritance | S gene (on chromosome 7) | No gender difference |
| Rod monochromacy | Autosomal recessive inheritance | CNGA3, CNGB3, GNAT2 | Very rare |
| S-cone monochromacy | X-linked recessive inheritance | LCR region abnormality or L/M missense mutation | Less than 1 in 100,000 people |
In X-linked recessive inheritance (congenital red-green color blindness, S-cone monochromacy), if the mother is a carrier, 50% of male children will be affected. Some carrier females may also show mild color vision abnormalities due to X-chromosome inactivation patterns. In autosomal recessive rod monochromacy, if both parents are carriers, there is a 25% chance of the child being affected.
The mechanisms of congenital red-green color blindness are broadly divided into the following two categories.
Congenital color vision deficiencies cannot be detected without color vision testing, as visual acuity, visual field, and fundus are normal.
Step 1: Screening — Pseudoisochromatic plates
The Ishihara color vision test (Ishihara plates) is the most widely used. It is recommended to combine two or more types of plates rather than just one. This detects the presence or absence of color vision deficiency.
Step 2: Severity assessment — Hue arrangement test
The Panel D-15 test (Farnsworth Panel D-15) is suitable. It evaluates the severity (strong, moderate, mild) of color vision deficiency and can roughly distinguish between type 1 and type 2.
Step 3: Definitive diagnosis and type classification — Anomaloscope
The Nagel anomaloscope is the standard. It determines the type by matching the mixture ratio of red (670 nm) and green (546 nm) to yellow (589 nm). It enables accurate type classification (type 1 vs type 2, dichromacy vs anomalous trichromacy) and is also used for the final determination of the presence or absence of color vision deficiency.
Some plates in the Standard Color Vision Test Part 2 (for acquired color vision deficiency) can detect this condition. Note that it is not detected by the standard Ishihara test.
Full-field ERG shows normal rod responses but markedly reduced cone responses. OCT is used to evaluate foveal structure.
Color vision testing in school health checkups has been recommended on a voluntary basis since a 2014 Ministry of Education, Culture, Sports, Science and Technology notification. Ideally, detailed type determination should be performed at an ophthalmology clinic around the fourth grade of elementary school (a physically and psychologically stable period). Understanding the exact type and degree before career choices helps the individual make appropriate career decisions.
There is no fundamental treatment for congenital red-green color blindness, congenital blue-yellow color blindness, or rod monochromacy. Glasses with color vision assist filters (color correction lenses) improve discrimination of some colors but do not restore normal color vision. They cannot be used during testing. For gene therapy at the research stage, see Section 7.
Since color vision deficiency is congenital, it must be kept in mind that even if the person misidentifies colors, it is never a “mistake” for them. The most important thing is to fully consider color vision deficiency in future educational and career choices, so that the person does not encounter difficulties due to it.
During school age, care must be taken not to make children feel inferior due to color vision deficiency. It is better to inform school teachers about the color vision deficiency. Sharing this information with the homeroom teacher can facilitate support such as consideration in color-coded blackboard writing, color graphs, and seating arrangements.
Information transmission that does not rely solely on color (combination of color + shape, pattern, and text labels) is important. The following accommodations are recommended in educational settings.
Because of X-linked recessive inheritance, the mother is often a carrier. Male children of carrier females have a 50% chance of developing the condition. Blue-yellow color blindness and rod monochromacy, which are autosomal, follow different inheritance patterns, so genetic counseling tailored to the type is recommended.
Color vision deficiency is an innate characteristic, and the individual does not need to feel inferior. Practical support includes informing the homeroom teacher and requesting consideration regarding the use of colors on the blackboard and teaching materials. Before career guidance in junior high and high school, having an ophthalmologist confirm the exact type and degree of the condition allows the individual to make confident career choices.
The human retina contains three types of cone cells.
The brain processes the signal ratios from the three types of cones to perceive color (Young-Helmholtz trichromatic theory). The L and M genes are arranged in tandem on the X chromosome, and the peculiarity of this arrangement provides a background for frequent mutations1).
The L and M genes share approximately 98% homology, making unequal crossing over during meiosis likely 1). Unequal crossing over results in deletion of the L or M gene, or generation of an L/M hybrid gene. When a hybrid gene is formed, the absorption spectrum of the cone photopigment shifts from its original position, leading to anomalous trichromacy. Complete deletion of the gene results in dichromacy.
The classification and molecular mechanisms of congenital red-green color vision deficiency are shown below 1).
| Classification | Cone status | Molecular mechanism |
|---|---|---|
| Normal trichromacy | L + M + S all normal | — |
| Type 1 dichromacy | L deficiency (M + S only) | Complete deletion of L gene |
| Type 2 dichromacy | M deficiency (L + S only) | Complete deletion of M gene |
| Type 1 trichromacy | L→M’ substitution (M’ + M + S) | L/M hybrid gene (shifted toward M) |
| Type 2 trichromacy | M→L’ substitution (L + L’ + S) | L/M hybrid gene (shifted toward L) |
Mutations in the S gene (on chromosome 7) cause deficiency of S-cone photopigment. It is an autosomal dominant trait, unrelated to the X chromosome, so there is no sex difference. Because it is dominant and requires only one mutated allele to manifest, if a parent is affected, the probability of transmission to a child is 50%.
The cause is an abnormality in the subunit composition of the cGMP-gated cation channel (CNG channel) in cones.
Loss of function of the CNG channel prevents cone photoresponse, leaving vision solely mediated by rods.
Deletion of the locus control region (LCR) prevents expression of both L and M genes, or missense mutations in L-cone and M-cone cause loss of function. Although it was considered non-progressive, many cases present with progressive visual impairment and macular degeneration.
Mancuso et al. reported successful restoration of red-green color vision in a squirrel monkey model by introducing the L-opsin gene using an AAV vector 2). This is a groundbreaking report demonstrating that new color vision channels can be acquired through gene transfer even in the mature mammalian nervous system. Human gene therapy for congenital red-green color blindness has not yet reached clinical trials due to safety and ethical issues.
For achromatopsia (rod monochromacy), clinical trials (Phase I/II) of gene therapy using AAV vectors targeting the CNGA3 and CNGB3 genes are ongoing 1).
Color vision assistive glasses (e.g., EnChroma) that filter specific wavelengths of light are commercially available and may improve discrimination of certain colors. However, they do not add new color channels and do not improve performance on color vision tests.
In 2003, revisions to the School Health and Safety Act enforcement regulations removed color vision testing from mandatory items in regular health checkups. Subsequently, cases were reported where individuals faced difficulties in career choices without being aware of their color vision deficiency. In 2014, a notice from the Ministry of Education, Culture, Sports, Science and Technology again recommended the implementation of color vision testing in schools (only for those who wish to participate) 3).
Gene therapy clinical trials for rod monochromacy (complete congenital color blindness) are ongoing, and future progress is expected. For congenital red-green color vision deficiency, color vision recovery has been reported in monkeys, but safety and ethical verification are necessary for human application, and the timing of practical use is undetermined.
