Inherited Color Vision Deficiency: A Literature Review

Ziske Maritska1, Biana Lisa2, Aisyah Azani2, Azillah Syukria Novitri2, Anggita Patra Ali2
1. Department of Medical Biology, Faculty of Medicine, Universitas Sriwijaya, Palembang, South Sumatera,
Indonesia
2. Department of Opthalmology, Faculty of Medicine, Universitas Sriwijaya – Mohammad Hoesin Hospital,
Palembang, South Sumatera, Indonesia

ABSTRACT
Inherited color vision deficiency, also known as color blindness, is an interesting topic in the
field of literature. Numerous studies have been conducted to understand the experiences of
individuals with inherited color vision deficiency and their perception of the world. CVD can
be further classified into several different categories, with red-green color vision
abnormalities being the most prevalent and blue-yellow color vision defects being less
common. While these CVDs interfere with color perception, they have no negative effects on
vision clarity. If the X chromosome or chromosomes 7, 2, 8, or 10 are involved, CVD may be
an X-linked recessive trait, an autosomal dominant trait, or, very infrequently, an autosomal
recessive trait. There are some genes that involved in the role of color vision deficiency
development. Several tests, including the Color Plates Test, the Anomaloscope Test, and the
Hue Test, are used to identify CVD in an individual and to determine the severity of the
condition. This knowledge contributes to the development of strategies, interventions, and
additional devices that can improve the quality of life for individuals with color blindness.
Keyword: Inherited color vision deficiency, color blindness, genetic perspective.

INTRODUCTION
One of the chief characteristic features of humans is that they have three different channels of
vision for conveying color information related with three different cone cells. However, when
there is an error in the development of one or more types of retinal cone cells that receive
color in light and transmit that information to the optic nerve, CVD occurs. 1 People with
color vision deficiency (CVD) is unable to perceive colors due to the retinal cones' inability
to distinguish between different wavelength stimuli. 2 Red-green color blindness is the most
prevalent type of color vision impairment. People who are affected frequently struggle to
distinguish between distinct hues of yellow, red, and green. Defects in blue-yellow color
vision are uncommon. In addition to drugs, chemical exposure, and aging, color vision issues
can also be caused by these.3
There were 2.85% of the students in the study region in Nigeria who had color vision
deficiencies. Males had a higher rate of CVD (4.29% vs. 1.58%) than females did. A very
low level of CVD status awareness among students was discovered. 4 One of study in
Wolkite, Southern Ethiopia reported 4.1% of people had color vision deficiencies overall,
3.6% of whom were male and 0.6% were female. Most of the subjects who were colorblind
were unaware of their condition.5
Generally, people with CVD may have a variety of difficulties in their daily lives and at
school. Troublesome subjects perform less well in their work than their classmates who are
color-normal. It is crucial that all medical professionals with CVD understand their illness.6

TYPES OF COLOR VISION DEFICIENCY

Due to the damage to the color receiving neurons, people with color vision deficit (or so-
called color blindness) are unable to see the colorful environment. The injured neurons are
unable to differentiate certain hues, whether as a result of hereditary issues or chemical
injuries. Protanomaly (red weak), deuteranomaly (green weak), and tritanomaly (blue weak)
are a few typical kinds of color vision deficiencies.7
On the basis of three light-sensitive pigments, humans can see color. It is shown in three
dimensions and has three colors. The power present at each wavelength determines the color
stimulus. The retina has three kinds of cone photo-pigment neuronal cells, L-, M-, and S-
cones, which accounts for normal trichromacy. Each of these receptor types is stimulated to
varying degrees by a variety of light wavelengths. For instance, yellowish green light
significantly stimulates L and M cones but only slightly S cones. Red light activates L-cones
more than M-cones, and rarely any S-cones.7,8

Typ
Range Peak Wavelength
e
S 400–500 nm 420–440 nm
M 450–630 nm 534–555 nm
L 500–700 nm 564–580 nm
Table 1. The response of cone cells in the human eye to light wavelength. 7

The color processing is done in two steps. First, the cone stimulus is recombined to generate
two color opponents and luminance. Second, an adaptive signal regulation method operates
within the operational range and stabilizes the object's illumination variations. When
sensitive pigments are destroyed or lose their effectiveness, humans can only see a portion of
the visible spectrum compared to those with normal vision.7
Color vision loss is caused mostly by two sources: inherited as a result of cone opsin
mutations that change the amount or function of the distinct cone types expressed in the
retina, or acquired as a result of secondary disruption of cone function and structure.7,9
Color vision deficiencies are divided into three categories. There are three types:
monochromacy, dichromacy, and anomalous trichromacy. Trichromats are people who have
normal color vision. Monochromats are colorblind in general and may have one cone route in
addition to the rod pathway. Dichromats lack a cone photopigment, hence they only have two
cone channels. Anomalous trichromats have all three cone photopigments, but one of them is
abnormal, with a displaced peak sensitivity.7
Dichromasy and anomalous trichromasy can be classified according to the affected cone
photopigment. Three terms that are used also used to describe CVD are protan, deutan, and
tritan. A protanope lacks the L-cone photopigment and is unable to distinguish between
reddish and greenish colours because the red-green opponent mechanism cannot be built.
Because a deuteranope lacks M-cone photopigment, the reddish and greenish colours are
indistinguishable. Mutations in the human long-wavelength (L) or middle-wavelength (M)
cone opsin genes are located on the X-chromosome at Xq28 (genetic designation OPN1LW
and OPN1MW). People with tritanopia lack the S-cone photopigment and so cannot
distinguish between yellowish and bluish colours. Mutations in the human short-wavelength
(S) cone opsin genes are located on an autosome on chromosome 7 at 7q32 (genetic name
OPN1SW).7,9

Male (%
Type Female (%)
)
Protanopia 1.0 0.02
Deuteranopia 1.1 0.01
Trianopia 0.002 0.001
 Male (%
Type Female (%)
)
Protanomaly 1.0 0.02
Deuteranomaly 4.9 0.38
Tritanomaly ∼0 ∼0
Total 8.002 0.44
Table 2. Approximate percentage occurrences of various types of color vision deficiency. 7

Deutan (red-green) CVD has an autosomal dominant inheritance pattern, whereas tritan CVD
has a sex-linked recessive inheritance pattern. The genetics of CVDs are especially
significant in the clinic because patients frequently want to know why they have a CVD and
if they will carry their CVD to their offspring. Since so few examples of congenital hereditary
tritanopia had been documented, it was formerly believed that it did not exist. It is crucial to
distinguish between acquired and congenital tritan abnormalities since tritan-like CVDs are
linked to illness.7
Achromatopsia (ACHM), often referred to as rod monochromatism or complete color
blindness, is a retinal condition that damages the cones of the retina, the kind of
photoreceptors that are responsible for sharp daytime vision. Pathogenic mutations in one of
the six cone photoreceptor-expressed genes are the root cause of ACHM. Cone
photoreceptors suffer a functional loss and slowly degenerate as a result of these alterations.
Unlike color blindness, in which mutations and rearrangements in the genes encoding the
various cone photopigments affect only spectral sensitivity but not the main photoreceptor
function, ACHM has grave consequences for all aspects of daylight vision mediated by the
cone photoreceptors. Patients with ACHM have poor visual acuity, photophobia, and
nystagmus and are not able to distinguish colors which first appears at birth or in the early
years of infancy.10,11

GENETIC PERCEPTION

Abnormal color vision typically subdivides into congenital and acquired forms. The
congenital disorders of color vision occur due to defects in genes encoding cone opsins,
genes that encode the expression of cone opsins, and genes for proteins involved in
phototransduction (such as PDE and CNG channel subunits). Such defects have a wide range
of possible outcomes and may feature different rates of progression, retinal degeneration, and
loss of visual acuity. Guanylate cyclase deficiencies can lead to Leber congenital amaurosis
and severe vision loss early in life. In contrast, rod dystrophies leading to retinitis pigmentosa
may cause late color vision abnormalities as degenerating rods affect cone structure and
function. Additional causes of color vision defects include fundus albipunctatus and Stargardt
disease. Acquired color vision deficiency, or dyschromatopsia, can occur due to any injury or
disruption to visual pathways.12
The term "anomalous trichromats" refers to both protomaly and deuteramaly. This is due to
the fact that while all three types of cones are still present in both types of color blindness
(thus the name trichromats), one of the three cones in each type is mutant or defective (hence
the word anomalous). The longwavelength, red photopsin gene is mutated in protanomaly,
leading to the anomalies seen in those who have the condition. Furthermore, as was indicated
in the part before, there is only one OPN1LW gene, and it is situated at position 28 (Xq28) on
the long arm of the X chromosome. Protanomaly is a sex-linked illness due to this location on
the X chromosome, which also explains why males experience the condition more frequently
than females. Similar to deuteranomaly and protanomaly, tritanomaly is a mutation or defect
in a cone rather than the absence of a particular type of cone. In tritanomaly, the blue
photopsin cone encoded by the OPN1SW gene malfunctions, causing people to view the
world around them in a variety of pink and turquoise hues instead of orange, yellow, red,
blue, green, and violet.13
The development of green-red hybrid genes or the loss of the green pigment gene(s) cause
deuteranopia. Similar to protans, the Ser180Ala polymorphism affects how well the normal
and hybrid pigments are separated in the spectrum and, thus, how severe the color vision
deficiency is. Tritanopia has been linked to the following chromosome 7 gene mutations in
the blue pigment gene: Ser214Pro, Gly79Arg, and Pro264Ser.14

COLOR VISION DEFICIENCY DETECTION

Color Plates Test

There are multiple types of pseudoisochromatic color plate test.1 The Ishihara color plates test
is one of the most popular tests for color blindness. This exam asks the subject to recognize
any numbers or forms contained in a pattern made up of a number of plates with colored dots.
Conditions or numerals can be seen by people with normal color vision, but color blind
people may have trouble seeing them.15
Your opthalmologist will ask you to perform this test by focusing on a circle with a variety of
colorful dots and a dot-based object, such as a letter, number, or wavy line. You might have a
specific form of color vision impairment if the shape disappears into the backdrop and you
are unable to notice it. Different color plates can be used to test for different types of color
vision deficiencies.16 The Ishihara color plates test to detects red-green deficiency.17
Dvorine American Optical Hardy-Rand-Rittler, Tokyo Medical College, and City University
Test are additional color plate variations in addition to the Ishihara test. Different types of
color blindness are detected using these screens. For instance, the Hardy-Rand-Rittler can
detect blue-yellow and red-green color vision issues while the Ishihara test only looks for red-
green blindness.15

Anomaloscope test
An optical device called an anomaloscope has two separate colored fields and control knobs.
Your doctor will instruct you to examine the anomaloscope and compare the hue and
brightness of the lights in the two fields. The knobs will be used to change the colors.15
The gold standard for accurate CVD diagnosis has been regarded as color matching
performed using an anomaloscope. Red-green Rayleigh matching and blue-green Moreland
matching experiments are made possible using an anomaloscope, in which the observer
modifies the mixed light side of the bipartite field to correspond to the light on the reference
side.18
Hue Test
In a hue test, colored blocks will be present. Your eye doctor will want you to arrange them
in the sequence of the rainbow, starting with red and ending with purple. You may experience
a specific type of color vision impairment if you find it difficult to organize them properly.
Eye doctors routinely perform this test to those whose jobs require them to have
exceptionally accurate color vision, such as graphic designers.19
The test consists of displaying 9 pairs of lights that are vertically arranged. combinations of
red, green, and/or yellow colors. Identify the colors (some of which are the same) going up
and down.Only two seconds are spent displaying the colors.You can simply click the next
button if you are unable to distinguish the colors.20
By asking participants to arrange 85 caps according to color, the Farnsworth-Munsell 100 hue
test (FM100) offers a rather thorough assessment of participants' color discrimination abilities
for Protan, Deutan, and Tritan, although the activity is very time-consuming, as is the
examination of FM100 error scores. Although D-15, a condensed version of FM100,
addresses these problems, it can be difficult to evaluate the error scores from either test.
Additionally, CVD patients can use brightness cues to complete the arranging job and raise
test results.21
In certain professions and with children in school, having a diagnosis might help people
recognize when they might need to seek help to prevent making mistakes or being
misunderstood. The suitability of a person with a color vision impairment for a particular job
can also be determined using more complex testing. For instance, a Lantern test is used to
determine who is unfit for employment that require the ability to reliably detect the colors of
lights for safety purposes, such as railway driving, the maritime and aviation industries, or
other occupations. 22
Cambridge Colour Test
The Cambridge Colour Test offers a quick way to test people for color vision deficits, but it
may also be used to look more closely at how hereditary or acquired diseases affect people's
ability to distinguish between colors. It enables the researcher to track the disease's
development or remission quantitatively over time. Numerous medications have an adverse
effect on color vision, and the pharmacologist will find that the test is ideal for tracking the
short- or long-term progression of such side-effects. By exploring chromatic sensitivity along
the lines of color confusion, the test identifies discrimination ellipses in color-deficient
people. Ellipses are typically oriented and expanded when measured in people with even
somewhat abnormal color vision (see references).23 With the aid of computer-based testing,
efforts have been undertaken to enhance the performance of conventional color vision exams.
The Cambridge Color Test (CCT) takes the pseudoisochromatic pattern from the printed tests
mentioned above and uses forced-choice adaptive techniques with a colored Landolt C
orientation-identification stimulus embedded in static luminance noise.24

GENE THERAPY AND DEVICES FOR COLOR BLINDNESS

Gene therapy is a promising avenue of treatment for many congenital retinal dystrophies.
Many genetic disorders present in non-human animals that are analogous to conditions seen
in humans. Translational therapies for gene replacement, typically mediated by recombinant
adeno-associated virus (rAAV), have been successful in treating multiple congenital defects
affecting color vision. RPE65 genetic defects, which affect the ability of the retinal pigment
epithelium to recycle retinyl esters and can cause Leber congenital amaurosis, was
successfully treated with gene therapy in dog models. The treatment has since been extended
to humans, yielding the first FDA-approved gene therapy treatment for inherited retinal
dystrophy. Other promising treatments include gene therapy for CNGB3 congenital
achromatopsia, countering the absence of a CNG channel subunit in cones, which has been
successful in dogs, and gene therapy for red-green color blindness in squirrel monkeys.25
A possible new treatment option for color vision problems is gene therapy. The three most
common achromatopsia genes, CNGB3, CNGA3, and GNAT2, have been the subject of
numerous experimental research in animal models, as well as a limited number of phase I/II
clinical trials. The genes for L-opsin and M-opsin have also been targeted. By using ERGs
and visually triggered behavior, they all demonstrated a sustained improvement in cone cell
functionality. Additionally, it has been shown that intravitreal injections rather than subretinal
ones may be a safer way to deliver the genes used in the therapy. Few studies have found a
strong link between early intervention and improved results. The research that has been done
so far in genetic ophthalmology is considered to be very promising. 26 Cone density does
appear to decrease with aging, according to some data. 27 However, additional study and effort
are required before gene therapy is introduced as a recognized and secure kind of treatment.26
More improvements in contact lens technology led to new prototypes for color-blind patients.
Unfortunately, there haven't been many clinical assessments and no interventional phase
studies to evaluate effectiveness and results for color vision.28
Patients with CVD use tinted lenses and spectacles so they can discern between
indistinguishable colors. Tinted lenses and glasses enable color blind people to discriminate
between colors that had previously looked to be the same, despite the fact that they do not
simulate normal color vision. For people who are color blind, Enchroma spectacles and
ChromaGen lenses are the most popular and efficient options.29 For the correction of
deuteranomaly color blindness, a PDMS-based lens with plasmonic and biocompatible
properties has been developed and tested.30
CONCLUSION
The literature findings above suggested that color vision deficiencies are a group of visual
impairments that are characterized by faulty color discrimination. CVD can caused by
inherited gene mutation or acquired. They include achromatopsia, yellow-blue color
blindness, and red-green color blindness. The deficits are brought on by changes in the genes
encoding for different retinal cone components. Several genetic mutation could contribute to
affect the color vision deficiency. There is no therapy to cure color blindness for human in
recent years, but the patient is expected to be able to adapt to that condition to conduct
everyday life with or without additional devices.
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8.

Attachment
1. Name : Biana Lisa
NIM : 04032782327005
Institution : Department of Opthalmology, Faculty of Medicine, Sriwijaya
University-Mohammad Hoesin Hospital, Palembang, Indonesia
Signature :

2. Name : Aisyah Azani

NIM : 04032782327006
Institution : Department of Opthalmology, Faculty of Medicine, Sriwijaya
University-Mohammad Hoesin Hospital, Palembang, Indonesia
Signature :

3. Name : Azillah Syukria Novitri

NIM : 04032782327007
Institution : Department of Opthalmology, Faculty of Medicine, Sriwijaya
University-Mohammad Hoesin Hospital, Palembang, Indonesia
Signature :

4. Name : Anggita Patra Ali

NIM : 04032782327008
Institution : Department of Opthalmology, Faculty of Medicine, Sriwijaya
University-Mohammad Hoesin Hospital, Palembang, Indonesia
Signature :