The Human Brain and its Perception of Color
A Study in Understanding Color Deficient Patients

By Mikaela C. Krueger, ABOM

INTRODUCTION

As someone drawn toward all things visual, I appreciate the subtle variances in color. Color is a big part of my life, from the way one views art to the infinite ways color develops a mood or enlivens the spirit within everyday life. Beyond this, our society functions on color as related to safety or procedure, and this too, affects one's ease of movement through—and comprehension of—the world we live in. I never thought to question the ability versus the inability to see color or the stress of color deficiency.

Two years ago, a small girl walked into my office with her mother. I was shocked to hear that she was completely color blind. I sat and listened to their story, witnessing the anxiety of a woman who felt helpless and unable to assist her little girl and a child who would learn differently from others and be presented with struggles related to a lack of seeing color as the majority of others do. As an optician, I wanted to combat an obstacle and learn as much as I could about this difficult issue.

This course presents an opportunity to do just that—to dive into the subject profoundly. It is my hope that my research and cumulative work will help to inform other eyecare professionals to empower their patients who struggle with color issues to seek ways to recognize this deficiency early and discover how to work with it. It is our job to educate others about such an obstacle, as they trust and rely on those of us committed to the field of optics.

COLOR PERCEPTION

Color perception is the process of the mechanics of the eye receiving light through the eye and on to the retina. Our color receptors—cone cells— translate this information through the optic nerve and on to the brain for interpretation. At our most cone-saturated point, the central fovea, we have over 200,000 cone cells in each square millimeter. We have three cone receptors: short, medium and long (oftentimes misinterpreted as red, green and blue) that work together to develop a perception of the overall visible color spectrum. These cone receptor cells over-lap and mix to send all the colors of the visible spectrum to the brain for interpretation. Of the whole electromagnetic spectrum, visible light entails a small section, 390 to 780 nanometers. This would be regarded as normal color vision.

HISTORY OF COLOR VISION DEFICIENCY

Color vision deficiency (CVD), color blindness, Daltonism or more accurately, anomalous tri-chromacy, are all terms used to describe a person with an inability to distinguish the color spectrum clearly or correctly. Humans have studied this topic for over 200 years, searching for answers to such anomalies.

In 1794, Mr. John Dalton questioned his own color deficiency, deuteranopia, as compared to his brother's broader color perception. He noticed that he incorrectly identified colors that his brother had no challenge perceiving. This self-study was the first known writing in regards to CVD. Dalton postulated that his vitreous humor was possibly tinted blue, selectively filtering longer wavelengths. After his death, Dalton requested his eyes be dis-sected and examined to prove his hypothesis. This early explanation was incorrect (his vitreous was clear), but it also shows a fascination with different ways we perceive color.

GENETICS

CVD patients have a loss of normal color perception due to two major physiological changes: congenital or acquired. Ninety-nine percent of CVD patients suffer from red/green color blindness or congenital CVD. Congenital CVD is acquired by a defect on the X chromosome; this makes the likelihood far greater in men, due to the fact that they have only one X chromosome. Females have two X chromosomes and therefore would require both to have the defect to inherit the genetic form of CVD. If a female has con-genital CVD, her sons will inherit it because both of her X chromosomes are affected.

According to The National Eye Institute, genetic-related CVD can be present at birth, begin in childhood, or not appear until adulthood. CVD is recessive, and its severity can range from mild to severe. The rate of CVD is roughly 8 percent in males and 0.5 percent in females, which equates to ~12.8 million men and ~0.8 million women in the United States alone.

It is important to note that the entire visible spectrum is affected by CVD. These individuals will experience a skewed color perception over their entire color field because our primary colors mix to create the full color spectrum. This can have tremendous implications for normal life, personal safety and work requirements. (See Table 1.)

TABLE 1: HOW GENES ARE INHERITED Genes are bundled together on structures called chromosomes. One copy of each chromosome is passed by a parent at conception through egg and sperm cells. The X and Y chromosomes, known as sex chromosomes, determine whether a person is born female (XX) or male (XY) and also carry other traits not related to gender. In X-linked inheritance, the mother carries the mutated gene on one of her X chromosomes and will pass on the mutated gene to 50 percent of her children. Because females have two X chromosomes, the effect of a mutation on one X chromosome is offset by the normal gene on the other X chromosome. In this case, the mother will not have the disease, but she can pass on the mutated gene and so is called a carrier. If a mother is a carrier of an X-linked disease (and the father is not affected), there is: A 1 in 2 chance that a son will have the disease. A 1 in 2 chance that a daughter will be a carrier of the disease. No chance that a daughter will have the disease. In autosomal recessive inheritance, it takes two copies of the mutant gene to give rise to the disease. An individual who has one copy of a recessive gene mutation is known as a carrier. When two carriers have a child, there is a: 1 in 4 chance of having a child with the disease. 1 in 2 chance of having a child who is a carrier. 1 in 4 chance of having a child who neither has the disease nor is a carrier. In autosomal dominant inheritance, it takes just one copy of the mutant gene to bring about the disease. When an affected parent with one dominant gene mutation has a child, there is a 1 in 2 chance that a child will inherit the disease. The National Eye Institute (nei.nih.gov/health/color_blindness/facts_about)

RED GREEN CVD

There are four main sub forms of red/green CVD: protanopia, protanomaly, deuteranopia and deuteranomaly. (See Tables 2 and 3.) Protanopia and protanomaly refer to the red photoreceptor and are far more rare than deuteranopia. They each compose only 1 percent of the population of males. Deuteranopia (~1.5 percent) and deuteranomaly (~5 percent) refer to the green photoreceptor and are the most common. Deutans compose 6 percent of the male population, which is the primary population of CVD. These forms account for the largest population and most common forms of CVD.

CVD patients with either form of Protanopia or deuteranopia experience the world in colors lacking a mixture of red or green. Depending on the severity of their impairment, red and green are hard to differentiate and can appear brown, and often other colors like violet are impacted due to the lack of color mixing in the brain.

EFFECTS OF CVD

A study published by researchers for visual neuroscience questioned whether congenital CVD significantly affects the judgment of surface colors in the real world. They found that deuteranomalous trichromats' ability to judge surface colors in natural scenes under different daylight conditions was similar to normal trichromats, but protanomalous trichromats seemed to be at a marked disadvantage. They also stated that the most common form of CVD, deuteranomalous trichromacy, had the least impact on surface color judgments in natural scenes.

BLUE/YELLOW CVD

Blue/yellow CVD is acquired or is an autosomal recessive trait that can occur in successive generations. The two autosomal types are very rare: tritanomaly and tritanopia. (See Table 3.) This rare disease affects the blue photoreceptor and is an autosomal recessive disorder not carried on either the X or Y chromosomes, but instead on chromosome 7. Tritan disorders affect males and females equally, but less than 1 in 10,000 people are affected. As with the other forms of CVD, these two varieties affect the entire color spectrum. The perceived landscape can take on varying hues of gray, red and pink tones.

It is interesting to note that these individuals may also suffer from a disruption in their circadian rhythm; scientists have postulated a link between blue light and sleep disorders. The inability to perceive blue light is an interesting possibility in sleep cycle disruption.

DISEASES AND CVD

Acquired CVD along the blue-yellow or S wavelength can be caused by a variety of illness, injury or exposures and can occur at any age. Typically the causes of this form of CVD are unlikely to be bilateral, and patients often have a milder form of Tritan symptoms.

Cataracts are one cause of acquired CVD symptoms. They can cause a mild or moderate limiting function due to the thickening and yellowing effect on the intraocular lens that naturally filters blue light. Cataracts make it harder to distinguish color with a lack of illumination or with color desaturation. Patients may sense their world as "brighter" and "more vivid" post IOL. Their color perception is compromised or limited due to the filter of their discolored intraocular lens.

Many chronic diseases of the eye dealing with the macula, such as glaucoma, AMD and reti-nopathy will cause color perception issues that worsen over time. Various commonly prescribed medications, chemicals, drugs and herbal compounds can cause ocular CVD side effects. Chronic alcoholism, Alzheimer's, Parkinson's, multiple sclerosis and sickle cell anemia, as well as commonly used drugs that treat heart problems, high blood pressure, infections and psychological problems are being studied as possible causes of acquired CVD. To date, there are over 100 medications likely to cause these side effects. (See Table 5.)

TABLE 2 PROTANOMALY: In males with protanomaly, the red cone photopigment is abnormal. Red, orange and yellow appear greener, and colors are not as bright. This condition can be mild, moderate or severe and can interfere with daily living. Protanomaly is an X-linked disorder estimated to affect 1 percent of males. PROTANOPIA: In males with protanopia, there are no working red cone cells. Red appears as black. Certain shades of orange, yellow and green all appear as yellow. Protanopia is an X-linked disorder that is estimated to affect 1 percent of males. For protanopes and protanomals, a very common everyday problem is distinguishing between blues, purples and deep pink. The National Eye Institute (nei.nih.gov/health/color_blindness/facts_about)	TABLE 5: AQUIRED CVD Acquired CVD may occur at any age due to eye disease or lesions elsewhere in the visual pathways or processes. Due to greater incidence of eye disease as the population ages, acquired defects are more likely. Acquired defects occur monocularly at first and differ in this respect from congenital CVD. Some of the major causes of acquired CVD are listed below. DISEASE Diabetes Cataract Macular degeneration Glaucoma Retinitis pigmentosa SUBSTANCE TOXICITY Antibiotics Antidepressants Various other prescribed and non-prescribed medications Dietary supplements Chemical solvents TRAUMA Eye or head injury NEUROLOGICAL (optic nerve damage) Retinopathy Optic neuritis Neuropathy Lesions Ganglion cell Richmond Products' "Color Vision Deficiency, a Concise Tutorial for Optometry and Ophthalmology"
TABLE 3 DEUTERANOMALY: In males with deuteranomaly, the green cone photo pigment is abnormal. Yellow and green appear browner (depending on severity), and it is difficult to tell violet from blue. This condition is mild and doesn't interfere with daily living. Deuteranomaly is the most common form of color blindness and is an X-linked disorder affecting 5 percent of males. DEUTERANOPIA: In males with deuteranopia, there are no working green cone cells. They tend to see reds as brownish-yellow and greens as beige. Deuteranopia is an X-linked disorder that affects about 1 percent of males. The National Eye Institute (nei.nih.gov/health/color_blindness/facts_about)
TABLE 4 TRITANOMALY: People with tritanomaly have functionally limited blue cone cells. Blue appears greener, and it can be difficult to tell yellow and red from pink. Tritanomaly is extremely rare. It is an autosomal dominant disorder affecting males and females equally. TRITANOPIA: People with tritanopia, also known as blue-yellow color blindness, lack blue cone cells. Blue appears green, and yellow appears violet or light gray. Tritanopia is an extremely rare autosomal recessive disorder affecting males and females equally. The National Eye Institute (nei.nih.gov/health/color_blindness/facts_about)

SEVERE CVD

TABLE 6 CONE MONOCHROMACY: This rare form of color blindness results from a failure of two of the three cone cell photo-pigments to work. There is red cone monochromacy, green cone monochromacy and blue cone monochromacy. People with cone monochromacy have trouble distinguishing colors because the brain needs to compare the signals from different types of cones in order to see color. When only one type of cone works, this comparison isn't possible. People with blue cone monochromacy may also have reduced visual acuity, nearsightedness and uncontrollable eye movements, a condition known as nystagmus. Cone monochromacy is an autosomal recessive disorder. ROD MONOCHROMACY OR ACHROMATOPSIA: This type of monochromacy is rare and is the most severe form of color blindness. It is present at birth. None of the cone cells have functional photopigments. Lacking all cone vision, people with rod monochromacy see the world in black, white and gray. And since rods respond to dim light, people with rod monochromacy tend to be photophobic—very uncomfortable in bright environments. They also experience nystagmus. Rod monochromacy is an autosomal recessive disorder. The National Eye Institute (nei.nih.gov/health/color_blindness/facts_about)

The most severe forms of CVD are rod and cone monochromacy. (See Table 6.) The lack of multiple cone receptors makes it impossible for the brain to mix and create the tremendous volume of hues normal trichromats appreciate. These monochromacy types differ from each other due to their relation to the rod or cone cells of the retina.

Cone monochromacy affects the cone cells, and the effect on color perception is reflected by a lack of color mixing. This occurs because only one set of cone receptor cells is functioning, and the brain is unable to correctly distinguish between colors. The brain needs more than one color to mix to produce the color spectrum.

Rod monochromacy affects both the rod and cone cells. These individuals lack the ability to see any color at all since no cone receptors are functioning. This is Achromatopsia or total color blindness. Patients with this form typically experience reduced acuity, photophobia and nystagmus.

Monochromatic and dichromatic patients lack the ability to see many of the hues across the spectrum, as they have just one or two primaries to produce their color vision mixing. This limits the expanse of normal trichromacy. Those who are anomalous trichromats experience a similar lack of contrast, but not to the degree of "di" or "mono" chromates because they have all three mixing receptors.

REALITY AT HOME

The child whom I referenced in the introduction has achromatopsia. (See Table 6.) She has 20/450, photopic acuity and 20/200 scotopic acuity. She is extremely photophobic, has a nystagmus and suffers from many other related health issues. She is unable to play in the sun or be exposed to direct sunshine. Her life is nearly nocturnal. We have outfitted her with specific lenses and specialized frames that limit her exposure to sunlight both indoors and out. She requires a deep amber tint for functioning indoors. She is learning Braille.

LIVING WITH CVD

Most CVD patients have genetic-related loss from birth, but there is often no sign of color vision impairment. CVD patients become aware of their deficiency when they are corrected in conversation or when things become difficult to distinguish due to very close colors or hues. It is possible that a CVD person distinguishes by shape only because it is difficult for them to "see" the difference in color. For example, it can be difficult to distinguish a red fire hydrant in a field of green grass; or red berries on a bush may look green for a deuteranope. Distinguishing a blue flower from a purple specimen may also be difficult. CVD patients may learn colors by memorizing objects by their "color name," or contrasting colors near to the object to visually compare a color.

CVD patients learn to cope with their impairment as best they can. This can include a labeling system, organizing clothing by color and memorizing traffic signs and signals. CVD patients experience life differently from trichromats (and from each other) due to the variation in severity and type of CVD. Some of these effects cause inconveniences, but others can be dangerous. One known issue related to CVD is "reaction time." In general, reaction times are slower as the CVD patient is trying to find the shape or other stimuli that they can associate an object with. Driving cars and dealing with signal lights, road signs, as well as daily tasks such as matching clothing, ripeness of fruits and complete cooking of foods can be stressful.

VISUAL AWARENESS

Hue, illumination or brightness, and color saturation of an object can combine to increase the ability of a CVD patient (depending on severity) to experience color more fully. Color saturation has a noticeable effect on perception. The more unsaturated a color, the more difficult it is to distinguish. Therefore, higher contrast and saturation can aid in color distinction. Greater illumination also benefits those with CVD to perceive smaller changes in hues. It is very difficult for these patients to identify a color without other references, and the shape may be the main clue to an object, not necessarily the color.

Routine eye exams during childhood can diagnose children early so that parents and teachers are aware that substantial amounts of information may be missed or misinterpreted. This can be empowering to the parents and the child, and teach teachers the need to seek ways to assist in a new learning process and build the child's self-esteem.

TESTING

There are five main systems for testing specific color vision perception. Optometrists often employ the Ishihara color test, which specifically tests for red/green color loss. This test uses a series of colored circles containing a group of dots in various patterns, often numbers which are readily seen by normal trichromats. This form of testing is considered obsolete due to the lack of tritan plates, which are becoming a necessity due to the higher likeli-hood of tritan defects from acquired CVD.

The 4th addition HRR Pseudo Isochromatic plates now feature protan, deutan and tritan plates. They are touted as a replacement for the Ishihara plates in both thoroughness and efficiency of testing. These plates, in method, are similar to the Ishihara plates.

The newer Cambridge test uses the same concept as the Ishihara color test, but is displayed on a computer monitor in which a series of "C" shapes change orientation. The orientation is readily recognized by trichromats, but difficult or impossible to perceive for CVD patients.

A more detailed analysis, which can also determine the severity of the color deficiency, can be found using the Farnsworth-Munsell 100 hue test. This test can accurately measure the patient's ability to differentiate subtle changes in hue and determines the severity of CVD. Four rows of colors are arranged in subtle hue changes and viewed under simulated daylight conditions. This is a rigorous test, and often, those with normal trichromacy can struggle with its parameters.

The anomaloscope is a set of visible lights in which a viewer matches the bottom light to the top sample light. This test allows the viewer to mix colors to match the sample light, in both color and brightness.

VISUAL AIDS

TABLE 7
TYPES OF COLOR VISION DEFICIENCY	MALES	FEMALES
Overall Anomalous trichromacy Protanomaly Deutanomaly Tritanomaly Dichromacy Protanopia Deuteranopia Tritanopia* Monochromacy Rod monochromacy Cone monochromacy Atypical monochromacy	~8% 1% 5% Rare 1% 1.5% 0.008% Rare Rare Very rare	~0.5% 0.01% 0.4% Rare 0.01% 0.01% 0.008% Rare Rare Very rare
Prevalence of congenital color deficiencies (webvision.med.utah.edu/book/part-viii-gabac-receptors/color-perception)

Visual aids can improve the ability to differentiate colors. Depending on the level and type of impairment, lenses such as EnChroma can be worn, amplifying saturation and con-trast of color. EnChroma are new lenses that incorporate a patent pending filter. They are available in three densities—two forms of sunglasses and a lighter filter indoor version. EnChroma lenses amplify the perception of all three primary colors (red, green and blue) simultaneously and block where the cones' sensitivities overlap. The result is a "boost" to the chromatic saturation of colors.

Red contacts (X-CHROM) can be placed on the non-dominant eye to increase one's ability to distinguish between colors. This will allow the eyes to perceive colors differently and heighten some perception, but it will also cause perception issues with other parts of the spectrum due to the skewed message the brain is receiving as a result of the tinted lenses. These are not suitable for driving at night because of the dim lighting conditions.

RESEARCH AND APPROVAL

Although there are no cures for color blindness, there are gene therapies that are being explored as a future solution. These genetic treatments are currently not in human trials. Researchers are injecting human red photo pigment cells into the retinas of adult male squirrel monkeys. The monkeys, born without the necessary photoreceptors, are able to see trichromaticaly after the gene therapy. This proves that the brain has red "detection" in place. Clinical treatment has restored red/green sensitivity and normal trichromacy to these specimens.

These researchers are also embarking on the tremendous challenge to cure rod monochromacy. Researchers using an animal model of rod monochromacy are combining gene therapy and delivery with the addition of neurotropic factors to help nerve cells grow. These gene therapies are the most promising possibility for a cure of CVD and offer hope to others experiencing cone loss from macular degeneration and other forms of color loss.

It is important to note that the FDA has guidelines for describing visual aids for CVD patients. These guidelines are there to protect against misleading or excessive claims that were prevalent before the passing of the cosmetic act of 1976.

CONCLUSION

It must be our goal as eyecare professionals to improve the lives and conditions of patients within our level of expertise. The knowledge of those leading the research to advance solutions for color deficient individuals is crucial for this significant population. We can no longer be satisfied with providing patients with basic care, but become more aware of diversity within the condition, embracing new technologies and genetic possibilities.

We have the ability to make an immeasurable impact on many lives, if we catch CVD early and pinpoint the degree of deficiency. I often think of that little girl and mother in my hometown who deal with this situation on a daily basis. Children are resilient and often adapt quickly to change and circumstance when structure is put into place and support is there. I have a good feeling about this moment in time in regard to CVD and that family.

As we push forward into more research and timely comprehension of color deficiency, I hope to watch that brave, versatile girl grow to adulthood with confidence and an ability to overcome the odds. I like to think of her mother worrying not about her daughter's eyes, but more about what she will wear to prom or where she will go to college. CVD exists, but does not have to prevent a high standard of living for these patients. Life can be easier for our patients, as we help them make informed decisions that can advance their well-being.