Chromatopsia is a condition in which the entire visual field appears tinted with a specific hue, similar to looking through a color filter. It belongs to a category of acquired color vision disorders and is distinguished from dyschromatopsia (reduced color discrimination) and achromatopsia (complete loss of color vision).
The following five types of chromatopsia are known:
Xanthopsia and cyanopsia are relatively common and have been reported in association with many drugs and diseases. Erythropsia is also seen to some extent, but chloropsia and ianthinopsia are rare. Drug-induced causes are considered the most common cause of chromatopsia1).
Chromatopsia is a condition in which the color of the environment appears enhanced, whereas color vision deficiency is a condition in which the ability to distinguish colors is reduced or absent. In chromatopsia, specific colors appear tinted, whereas in color vision deficiency, it becomes difficult to distinguish colors. Both can be considered color vision disorders with opposite directions.
The main symptom of chromatopsia is that the entire field of vision appears to have a specific tint.
The timing of subjective symptom onset varies depending on the cause. In drug-induced cases, symptoms often appear within days to weeks after starting administration, and there are reports of onset the day after starting oral tranexamic acid (TXA) 2).
Ophthalmologic findings vary greatly depending on the cause.
Based on the site of origin, chromatopsia is classified into three groups: central (cerebral), optical, and retinal.
Central
Drug-induced: The most common cause. Many drugs are involved, including digitalis, PDE5 inhibitors, and TXA.
Cerebrovascular disorders: Damage to the lingual gyrus and fusiform gyrus of the occipital lobe causes cerebral color vision deficiency.
Psychiatric disorders: May appear with Charles Bonnet syndrome or Alice in Wonderland syndrome.
Psychogenic: Common in girls around age 10. Shows atypical test results with no reproducibility.
Optical
Post-cataract surgery: Removal of the lens increases transmission of short-wavelength light, causing blue vision or red vision.
Jaundice: Increased blood bilirubin causes yellow vision.
After fluorescein angiography: May cause transient yellow vision.
Corneal opacity: Causes color changes due to light scattering and absorption.
Retinal
Retinal hemorrhage: Caused by iron-mediated oxidative damage to cone cells due to heme accumulation 1). Often presents as erythropsia.
Macular edema: Causes dysfunction of cone cells.
Central serous chorioretinopathy: Reported as a cause of chloropsia.
Representative drugs that cause chromatopsia are shown below.
Typical examples include digitalis preparations (yellow vision), PDE5 inhibitors such as sildenafil (blue vision), tranexamic acid, diuretics (e.g., hydrochlorothiazide), and the anthelmintic santonin. For details, see the “Causes and Risk Factors” section.
In the diagnosis of chromatopsia, screening for causative drugs is important first.
Since drug-induced causes are most common, taking a medication history is the first step in diagnosis. In ophthalmologic examination, color vision testing and cone electroretinography are useful for diagnosing digitalis toxicity, and fundus examination and OCT are used to search for retinal causes.
Since chromatopsia is a result of an underlying disease, treatment is based on removing the cause.
| Cause | Treatment policy |
|---|---|
| Digitalis poisoning | Immediately discontinue or adjust concentration |
| PDE5 inhibitors | If mild, observe course |
| TXA | Discontinue and switch to alternative drug |
| Retinal hemorrhage | Treat underlying disease |
| Cerebral | Treat cerebrovascular disorder |
The prognosis for drug-induced chromatopsia is generally good. With digitalis, symptoms often disappear within days to weeks after discontinuation, but there are reports that color vision abnormalities did not improve. With TXA, recovery was rapid after discontinuation 2). When associated with retinal hemorrhage or cerebrovascular disease, it depends on the prognosis of the underlying disease.
In drug-induced cases, recovery often occurs after discontinuing or adjusting the dose of the causative drug. With digitalis, improvement is often seen within days to weeks. However, if the cause is retinal hemorrhage or cerebrovascular disease, it depends on the outcome of the underlying disease.
The human retina contains three types of cones: L-cones (long wavelength), M-cones (medium wavelength), and S-cones (short wavelength), which receive red, green, and blue light, respectively. This is called trichromacy 1).
Signals from cones are processed as color opponency. Three opponent channels—blue/yellow, red/green, and black/white—are formed, where activation of one suppresses the other 1). Retinal ganglion cells respond in this color-opponent manner.
Digitalis inhibits Na⁺-K⁺ ATPase, which impairs the dark current of retinal photoreceptors. The Na⁺-K⁺ ATPase of cone cells is more sensitive to digitalis than that of rods, and due to differences in cell body size, cone function is selectively impaired. This results in a clinical picture of cone dysfunction syndrome. The effect is highly concentration-dependent.
PDE5 inhibitors such as sildenafil cross-inhibit cone-specific phosphodiesterase (PDE6). PDE6 is an enzyme that regulates intracellular cGMP concentration and controls photoresponse characteristics 1). This inhibition alters the photoresponse of cones, resulting in cyanopsia. PDE5 is also present in choroidal and retinal vessels, which may additionally affect hemodynamics.
In retinal hemorrhage, iron ions are released into the surrounding retina as hemoglobin is deoxygenated. S-cones are more vulnerable to iron-mediated oxidative stress than M-cones and L-cones, and selective damage to S-cones may cause erythropsia 1).
The parafoveal area of the macula has a high density of S-cones, and hemorrhage in this region increases the risk of S-cone damage 1). Additionally, the blue-yellow opponent pathway differs morphologically and molecularly from the red-green opponent pathway, and it has been suggested that it may have unique vulnerability to diseases and drugs 1).
The lingual gyrus and fusiform gyrus (V4 and V8 areas) in the ventromedial occipital lobe are important regions for color perception. Damage to these areas causes cerebral achromatopsia, where colors disappear and the world appears gray or black and white. Unilateral lesions may cause only half of the visual field to appear black and white.
On the other hand, cerebral dyschromatopsia is thought to arise through a phantom-limb-like mechanism, as in Charles Bonnet syndrome, where the visual cortex attempts to “fill in” areas deprived of sensation.
Iron ions from retinal hemorrhage cause oxidative stress on surrounding cone cells. S-cones, which sense blue, are more vulnerable to iron oxidation than other cones. When S-cones are selectively damaged, the blue-yellow opponent pathway is impaired, leading to a shift in color perception toward red (erythropsia) 1).
Vaphiades et al. (2021) reported a case of erythropsia associated with macular dehemoglobinized intraretinal hemorrhage in the right eye of a 65-year-old woman1). OCT revealed hyperreflective lesions in the inner retina, suggesting possible involvement of the outer layers. The authors proposed that among the midget ganglion cells, which constitute about 90% of the macular region, the blue-yellow opponent pathway may have inherent vulnerability distinct from the red-green opponent pathway. Vulnerability due to histological characteristics of S-cones and high S-cone density in the parafovea may also contribute to the mechanism.
Kiser et al. (2021) reported a case of a 7-year-old girl with factor VII deficiency who developed chromatopsia the day after starting oral TXA (10 mg/kg three times daily)2). Symptoms resolved after discontinuation following a total of four doses (total 2,600 mg). Ophthalmic examination revealed no abnormalities. This is the first pediatric case of chromatopsia associated with oral TXA. A pharmacological effect of TXA on cone cells is suspected, but the detailed mechanism remains unknown.
