Purpose: The aim of this study was to compare the efficacy of the Farnsworth D-15 hue test in detecting early ethambutol
toxicity compared to the Ishihara pseudoisochromatic plates.
Methods: This retrospective study was conducted at the Department of Ophthalmology, Caritas Medical Centre in
Hong Kong from January 2012 to April 2013. Medical records for consecutive patients with tuberculosis referred for suspected
ethambutol-induced toxic optic neuropathy were reviewed. All consenting subjects underwent both the Ishihara pseudoisochromatic
plates and the Farnsworth D-15 hue test. Those with pre-existing optic neuropathies, poor visual acuity, significant
cataract, known congenital colour vision defects, retinopathies, and those on other systemic medications with potential
ocular toxicity side effects were excluded. The qualitative results for the 2 screenings tests were compared.
Results: During the study period, 65 eligible subjects, with tuberculosis, prescribed with ethambutol, were recruited.
On Ishihara pseudoisochromatic plates testing, all (100%) of the subjects had normal results. On Farnsworth D-15 hue testing,
23.1% (15/65) had abnormal results: 12.3% (8/65) had a tritan (blue-yellow) defect and 10.8% (7/65) had non-specific
colour defects not conferring to a single colour deficiency.
Conclusion: The Farnsworth D-15 hue test appears to be more sensitive than the Ishihara pseudoisochromatic plates
in detecting colour defects as an initial subjective screening tool for suspected ethambutol-related optic neuropathy.
Ethambutol; Farnsworth D-15 hue test; Ishihara pseudoisochromatic plates; Tuberculosis
Tuberculosis remains an important infectious disease in
Hong Kong Special Administrative Region, China. Although
the incidence is on a decreasing trend, from 97.9 cases per
100000 people in 2002 to 69.6 in 2012, the incidence is still
higher than in Europe and America, where the incidence was
42 and 28 cases per 100,000 people respectively.
Ethambutol is one of the most commonly prescribed antituberculosis
medications in Hong Kong. The drug has been
well associated with ocular toxicity manifesting as optic
neuropathy since its first use in the 1960's[3,4]. Ethambutolinduced
optic neuropathy is duration and dose dependent,
although rare cases of idiosyncratic reaction presenting days
after the commencement of a standard dose have been reported [5,6]. Symptoms of toxicity does not usually occur until
1.5 months after the initiation of therapy. The reported
incidence of toxicity is 18% in those with a daily dose > 35
mg/kg, 5-6% in those with 25 mg/kg, and approximately 1%
with a daily dose of 15 mg/kg for 2 months or more[4,8,9]. In
Hong Kong, the standard daily dose is15 mg/kg for the treatment
of pulmonary tuberculosis. At this dosage, toxic optic
neuropathy is uncommon.
Signs and symptoms of ethambutol-induced optic neuropathy
can be subtle or even subclinical in the early stage. Colour
vision abnormality (dyschromatopisa) is one of the first
detectable signs. Blue-yellow (tritan) defects occur earlier
on whilst red-green (protan) defects develop later on in the
course of the toxicity[10-12]. As the visual impairment
caused by ethambutol toxicity may not be completely reversible,[
13-15] early detection and prompt cessation of the
drug is essential to avoid significant permanent visual impairment.
Ishihara pseudoisochromatic plates are commonly used for
the screening of colour vision defects in patients with suspected
ethambutol toxicity due to the wide availability, ease of
use of the plates and the traditional belief that acquired optic
neuropathies generally cause protan defects. As Ishihara pseudoisochromatic
plates are mainly designed to detect protan
colour defects, it may not be the most ideal assessment tool for
ethambutol toxicity that manifest with a tritan colour defect.
The Farnsworth D-15 hue test is a simplification of the Farnsworth-
Munsell 100 hue test with fewer coloured caps to rearrange
and hence requires less testing time. The Farnsworth
D-15 hue test is conducted under natural day light and subjects
are asked arrange a series of coloured caps based on the
ability to appreciate similarities in colour shades (Figure 1).
The results are compared to the reference sequence in order
to categorize the different types of colour defects into protan,
deutran, or tritan16 (Figure 2).
The aim of this study was to compare the efficacy of the Farnsworth
D-15 hue test in detecting early ethambutol toxicity
compared to the Ishihara pseudoisochromatic plates.
This retrospective study was conducted at the Department of
Ophthalmology, Caritas Medical Centre in Hong Kong Special
Administrative Region, China from January 2012 to April
2013. Medical records of consecutive patients with tuberculosis
who were referred to our unit for suspected ethambutol toxicity
(usually presenting with visual blurring) were reviewed.
All consenting subjects underwent both the Ishihara pseudoisochromatic
plates and the Farnsworth D-15 hue test. The exclusion
criteria included: subjects with pre-existing optic neuropathies
(glaucoma, optic nerve compression, ischemic optic
neuropathy, or optic neuritis); poor visual acuity inhibiting the
appreciation of the first Ishihara test page; significant cataract
(especially the nuclear sclerosis type that could affect color vision);
known congenital colour vision defects; retinopathies;
and those who were on other systemic medications with the
potential for optic neuropathy toxicities including digitalis and
The Ishihara pseudoisochromatic plates test was performed as
follows: the first 17 plates were presented to the patient at a
distance of 75cm; subjects that were unable to read at least 9
of the 17 plates in either eye were labeled as "optic neuropathy
The Farnsworth D-15 hue test was done by a single orthoptist.
All 15 colored caps were randomly set on a table. Subjects were
asked to select a colored cap that most closely resembled the
shade of the reference cap. Subjects then continued to arrange
the rest of the colored caps in sequence of resembling shades.
The investigator scored the test by referencing the sequence of
numbers on the back of each cap and plotted the sequence onto
a score sheet. If the sequence was correct from 1 through 15, a
circle was formed on the score sheet. If the sequence deviated
from the reference, cross-lines were formed suggesting either
a protan, deutran, or tritan defect (Figure 2). The test
was completed within a time frame of 2 minutes. Test results
were interpreted by 2 investigators in addition to the testing
orthoptist. Those who had cross-lines on the score sheet were also labeled as "optic neuropathy suspects".
All optic neuropathy suspects were arranged with additional
tests including Humphrey Visual Field and Optical Coherence
Tomograph (OCT) for the retinal nerve fibre layer thickness
for definitive confirmation of toxic optic neuropathies. Whilst
waiting for these investigations, physicians were also informed
of the possibility of ethambutol toxicity and where appropriate,
ethambutol was stopped after consideration of the risks
During the study period, 71 subjects, all with tuberculosis infection
prescribed with ethambutol, were referred to our unit
for suspected ethambutol toxicity. Six were excluded from this
study (2 had glaucoma, 2 had poor vision from cataract, 1 had
epiretinal membranes over both maculas, and 1 had congenital
colour vision deficiency).
Sixty-five subjects were eligible for the study. On Ishihara
pseudoisochromatic plates testing, all (100%) of the subjects
had normal results. On Farnsworth D-15 hue testing, 23.1%
(15/65) were labeled as optic neuropathy suspects; of which,
12.3% (8/65) had a tritan defects whilst 10.8% (7/65) had nonspecific
colour defects not conferring to a single colour defect.
The physicians were notified of the abnormal Farnsworth
D-15 hue test results whilst the subjected waited for objective
Tuberculosis is a relevant infectious disease in our locality
and suspected toxicities with ethambutol is not uncommonly
encountered. Currently, patients with suspected ethambutol
toxicity are referred to ophthalmology units for screening.
Prior to the arrangement of more definitive objective assessments
for toxic optic neuropathy like visual field or OCT, subjective
tests are use to test for dyschromatopsia since tritan
defects are one of the first signs of acquired toxic optic neuropathy[
10-12]. The Ishihara pseudoisochromatic plates
are one of the most commonly used screening tools but as we
have demonstrated, the detection rate of dyschromatopisa in
65 with suspected ethambutol toxicity was zero. However, on
the same population, the Farnsworth D-15 hue test detected
dyschromatopisa in 23.1% of subjects, of which 12.3% were
confirmed to have tritan defects compatible with toxic optic
neuropathy. We postulate that the suboptimal detection rate in
the Ishihara pseudoisochromatic plates is primarily due to the
fact that the plates are designed to detect for protan anomalies
that usually manifest in more advanced toxic optic neuropathy[
10-12]. It is important however, to note that the decision
to stop ethambutol should not solely rely on the results of
a single subjective, but rather a mutli-disciplinary consideration
of symptoms, subjective and objective tests, and liaison
with physicians on the risks and benefits of stopping treatment.
However, it is imperative to keep in mind that detection
from objective investigations like visual field or OCT may be
limited in the early stages of toxicity, thus, in real clinical
practice, clinicians are often faced with the clinical decision to
determine the likelihood of toxicity based on subjective colour
vision testing and in such cases, Farnsworth D-15 hue test seems superior to the Ishihara pseudoisochromatic plates.
Our study had its limitations. Firstly, all subjects presented to
our unit for the first time for the screening of ethambutol ocular
toxicity and no baseline colour vision tests were available.
Secondly, all patients were also concomitantly on isoniazid
as combination therapy for tuberculosis which can also potentially
cause optic neuropathy although reports on the frequency
of isoniazid toxicity are lacking in the literature and
likely to be less frequent than ethambutol. Thirdly, both
tests were highly subjective, based on the intelligence and
comprehensibility of subjects but as the aim of this study was
to compare between these 2 subjective assessments, both tests
were subjected to the same confounding factor. Fourthly, it is
our understanding than many of the 15 subjects with abnormal
Farnsworth D-15 hue test results had their ethambutol
immediately stopped by the physicians in order to minimize
the risk of toxicity hence many of them did not have their objective
tests completed. Lastly, we only included subjects with
suspected ethambutol toxicity, future studies including normal
subjects as controls would help to eliminate all bias.
The Farnsworth D-15 hue test appears to be more sensitive
than the Ishihara pseudoisochromatic plates in detecting colour
defects as an initial assessment for ethambutol-related optic