Erythropsia and Chromatopsia: Case Study and Brief Review

ABSTRACT

A 65-year-old woman presented with erythropsia (red-tinged vision) in the right eye from a subfoveal macula dehaemoglobinised intraretinal haemorrhage. Erythropsia is a type of chromatopsia, a condition in which objects appear to be abnormally coloured or tinged with colour. This manuscript provides a brief review of colour vision abnormalities including chromatopsia, and additionally we discuss dyschromatopsia and achromatopsia defined as deficiency and absence of colour vision respectively, both of which may be congenital or acquired. We theorise that the mechanism of the chromatopsia may be selective damage of ganglion cells involved in colour opponency.

Introduction

Colour vision disturbances are very common in ophthalmology. This manuscript provides a brief review of colour vision abnormalities including chromatopsia, dyschromatopsia and achromatopsia.

Case report

A 65-year-old diabetic and hypertensive woman with a history of rheumatoid arthritis presented for evaluation of erythropsia in the right eye (OD) for 2 weeks. Her primary care physician obtained computerised tomography angiography (CTA) of the head and neck one week prior, which was normal. The source images were reviewed and there was no evidence of a stroke. Her medications included etanercept, methotrexate, buspirone, zolpidem, carvedilol, buspirone, topiramate, hydroxychloroquine, gabapentin and insulin lispro. The examination showed a normal mental status, blood pressure and heart rate. The acuity was 20/70 OD and 20/20 in the left eye (OS). Confrontation fields were normal in both eyes (OU) and colour vision was deficient in one plate OD and normal OS using eight Ishihara pseudoisochromatic plates. Her pupils were of normal size and reactivity, without a relative afferent pupillary defect. Her ocular motility and anterior segments were normal. She had early cataracts OU and otherwise a normal anterior segment examination. The vitreous was clear OU. Fundus examination showed normal optic nerves OU but there was a yellow elevated lesion with dark edges approximately one disk diameter across in the right subfoveal macula representing dehaemoglobinised intraretinal haemorrhage (Figure 1). The retinae was otherwise normal OU. Optical coherence tomography (OCT) showed an area of dense hyperreflectivity intraretinally OD (Figure 2).

Figure 1.

Fundus photograph of the right eye showing a yellow elevated lesion with dark edges approximately one disc diameter across

Figure 2.

Optical coherence tomography of the right macula showing an area of dense hyperreflectivity in the subfoveal superficial retina representing a dehaemoglobinised intraretinal haemorrhage

Discussion

To understand this case it is important to highlight that normal human colour vision is trichromatic, which means that any colour can be matched by a mixture of three judiciously selected primary colours¹ and thus the normal human retina contains three types of cones: a cone that absorbs long wavelengths of light (L cones); a cone that absorbs medium wavelength of lights (M cones); and a cone that absorbs short wavelengths of light (S cones). This is called trichromacy. Cone photoreceptors are linked to form three opposing colour pairs of blue/yellow, red/green, and black/white. Activation of one member of the pair inhibits activity in the other. This is called colour opponency. The absence of one type of cone would result in dichromacy, or the presence of only two types of cones. Monochromacy is the presence of only one type of cone. Both monochromacy and dichromacy are almost always the result of genetic abnormalities. There are several types of dichromacy. Protanopia is the absence of L cones, which results in the inability to see red. Deuteranopia is the absence of M cones, which results in the inability to see green. Tritanopia is the absence of S cones, which results in the inability to see blue. Anomalous trichromacy, or a relative weakness of one type of cone, will also result in dyschromatopsia or “colour weakness”. Similar to dichromacy, an anomalous trichromacy can be described as protanomaly (red vision weakness), deuteranomaly (green vision weakness), or tritanomaly (or blue vision weakness).¹ These photoreceptor changes may not only result in dyschromatopsia, but also an absence of hue perception, which is called achromatopsia, both of which may be congenital and acquired (Table 1).

Table 1.

Definitions of various terms defined as related to colour vision perception

MonochromacyHas only one type of cone	Dichromacy Has only two types of cones			Anomalous Trichromacy Has all three types of cones, but one is weaker than the rest
Achromatopia Total colour blindness (black and white vision)	Protanopia Red vision blindness	Deuteranopia Green vision blindness	Tritanopia Blue vision blindness	Protanomaly Red vision weakness	Deuteranomaly Green vision weakness	Tritanomaly Blue vision weakness

Congenital dyschromatopsia occurs in approximately 8.0%–8.7% in men and approximately 1% in women.² It arises from disorders in the genes coding, expressing or involved in the operation of cone photopigments.² It is bilateral, symmetrical and generally affects the entire visual field. Rod monochromatism causing achromatopsia is a congenital cone photoreceptor disorder affecting about 1 in 30,000 individuals. These patients have normal rod function but no detectable cone function; therefore, everything they see is in shades of grey (total colour blindness). Patients usually present in infancy with nystagmus and photophobia.³ Although congenital dyschromatopsia usually affects individual cones and thereby a single subsystem of colour vision, such characteristics are not frequently encountered in acquired dyschromatopsia.⁴

Acquired dyschromatopsia, by contrast, may demonstrate progression or regression, may affect one eye or both eyes asymmetrically, affect only a portion of the visual field and can be very symptomatic to the patient.⁵ It occurs in patients with ocular or visual pathway disease. It is common in demyelinating optic neuritis, glaucoma and juvenile macular degeneration² in addition to a variety of other disorders including age related macular degeneration, congenital stationary night blindness, retinitis pigmentosa, retinal vascular occlusion, central serous retinopathy, myopic degeneration, chorioretinitis, diabetic and hypertensive retinopathy, papilloedema, methyl alcohol poisoning, dominant hereditary optic atrophy, Leber’s hereditary optic neuropathy, central serous retinopathy, Stargardt’s and Best’s disease and lesions of the chiasm and posterior visual pathways.¹ Dyschromatopsia in optic neuropathy is generally associated with mild visual acuity loss where dyschromatopsia associated with a maculopathy is generally associated with more severe visual acuity loss.⁶

Cerebral achromatopsia is a rare central nervous system disorder where the colour is completely drained from an object. It arises from impaired cortical processing rather than from damage to the retina or optic nerves.^6,7 These patients see the world as “drained of colour,” “dirty,” or in shades of black and white. It can involve the entire visual field or just one hemifield, and loss of colour vision may be partial (dyschromatopsia) or complete. These patients typically have a lesion affecting the lingual and/or fusiform gyri on the inferior occipital surface and most cases involve bilateral lesions, but unilateral lesions (often associated with hemiachromatopsia) occur as well.⁷

Chromatopsia is defined as the perceived increase in environmental hue, much the opposite of dyschromatopsia or achromatopsia.³ It may result from changes to normal photoreceptor cell distribution, their ability to communicate with post-synaptic neurons, or changes to the post-synaptic neurons themselves. The most common causes of acquired chromatopsia are drug effects. There are hundreds of drugs that may induce chromatopsia.^8,9 The more familiar ones to clinicians include xanthopsia or yellow hue, commonly caused by digoxin, in therapeutic levels, which may also cause disturbance of colour discrimination more specifically tritanopia (blue-yellow colour blindness) and non-specific loss of colour discrimination.¹⁰ Cyanopsia, or a bluish tinge is commonly due to the inhibition of cone phosphodiesterase (PDE), a group of enzymes whose prominent function is regulating cyclic guanosine monophosphate levels and therefore rod and cone light response properties.¹¹ Because of the presence of PDE5 in choroidal and retinal vessels, these medications increase choroidal blood flow and cause vasodilation of the retinal vasculature.¹² Other than drug effects, chromatopsia also occurs after cataract extraction, retinal diseases, and medical illnesses like jaundice.¹³

In regard to our patient, retinal haemorrhage, if left untreated, may result in photoreceptor cell toxicity. As a haemorrhage is de-haemoglobinised, iron ions are released into the surrounding retina. Cones are known to be more sensitive than rods to iron-mediated oxidative damage.¹⁴ However, iron toxicity often mentioned in the context of haemorrhage is a late event in its course and thus may not apply to this patient. It is also difficult to determine how severely the photoreceptor inner and outer segments were affected. On OCT, the haemorrhage was located in the inner retina, shadowing externally to the outer nuclear layer (Figure 2) and raising the possibility of direct damage to inner retinal cells. Normally, retinal ganglion cells respond in an opponent fashion to activation of different cone classes (colour opponency) requiring a firing rate above baseline to activate one cone class and decrease their firing rate below baseline to activate a different cone class.¹⁵ The ganglion cell layer in this part of the macula, which was affected by the haemorrhage in this case, contains ~90% midget ganglion cells. The majority are red-green opponent with no chromatic selectivity. Because in the human retina there is ample reserve of these cells one might not necessarily see chromatopsia if only a percentage were damaged. However, the blue-yellow opponent pathway is chromatically, morphologically, and presumably molecularly distinct from the red-green opponent cells.¹⁶ Thus, this pathway could have unique vulnerabilities to disease, systemically delivered drugs, or haemorrhage as in our patient, resulting in erythropsia. Some studies suggest that histological differences in the structure of S-cones may cause them to be more vulnerable than the M-cones and L-cones to damage.¹⁷ There is also evidence that the parafoveal retina, where our patient’s haemorrhage was located, contains a greater density of S-cones than the rest of the retina.^18,19 However, given the complexity of colour perception, it seems unlikely that erythropsia would result in the selective damage of one population of cones.

We do not believe drugs were implicated in our patient’s chromatopsia because the chromatopsia was unilateral (OD) and not bilateral as is generally the case with a drug-induced chromatopsia. We did, however review her medications for drug effects. They were as follows. Hydroxychloroquine that the patient was taking for rheumatoid arthritis, if toxic, causes dyschromatopsia in the form of a preferential impairment of tritan discrimination (cannot distinguish blue and yellow colours), not erythropsia.²⁰ The topiramate taken by the patient for migraine is more commonly associated with palinopsia or the persistence or recurrence of visual images after the initial stimulus has been removed and is believed to be caused by failure to suppress after images.^21,22 Gabapentin, zolpidem and buspirone have been associated with visual hallucinations.^23,24 Additionally, our patient did not have cataract extraction (which may post-operatively cause erythropsia)²⁵ nor any evidence of a homonymous visual field defect on examination or a lesion in the posterior visual pathways on neuroimaging, which may be implicated in dyschromatopsia or achromatopsia but typically not chromatopsia.⁷

This manuscript serves as reminder that colour vision abnormalities come in many forms and that a comprehensive ophthalmological examination is vital in patients presenting with colour vision disturbances. Our case highlights the fact that that erythropsia can not only stem from a vitreous haemorrhage for apparent reasons (not our patient), but may stem from a retinal haemorrhage as in our patient, even in the dehaemoglobinised state. This may be possible not because the patient is seeing red blood cells in the vitreous, but due to selective damage of neurons involved in colour opponency.

Funding Statement

This work was supported in part by an unrestricted grant from the Research to Prevent Blindness, Inc. N.Y., N.Y.