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Citation: Tousignant, B.; Chatillon,
A.; Philibert, A.; Da Silva, J.; Fillion,
M.; Mergler, D. Visual Characteristics
of Adults with Long-Standing
History of Dietary Exposure to
Mercury in Grassy Narrows First
Nation, Canada. Int. J. Environ. Res.
Public Health 2023,20, 4827. https://
doi.org/10.3390/ijerph20064827
Academic Editor: Paul B. Tchounwou
Received: 31 January 2023
Revised: 23 February 2023
Accepted: 7 March 2023
Published: 9 March 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
International Journal of
Environmental Research
and Public Health
Article
Visual Characteristics of Adults with Long-Standing History
of Dietary Exposure to Mercury in Grassy Narrows First
Nation, Canada
Benoit Tousignant 1,2, * , Annie Chatillon 1, Aline Philibert 3, Judy Da Silva 4, Myriam Fillion 3,5
and Donna Mergler 3
1School of Optometry, Universitéde Montréal, 3744 Jean-Brillant, Montreal, QC H3T 1P1, Canada
2Department of Social and Preventive Medicine, School of Public Health, Universitéde Montréal,
7101 Avenue du Parc, Montreal, QC H3N 1X9, Canada
3Centre de Recherche Interdisciplinaire sur le Bien-être, la Santé, la Sociétéet L’environnement (Cinbiose),
Universitédu Québec àMontréal, C.P. 8888, Succ. Centre-Ville, Montréal, QC H3C 3P8, Canada
4Grassy Narrows First Nation, General Delivery, Grassy Narrows, ON P0X 1B0, Canada
5Département Science et Technologie, UniversitéTÉLUQ, 5800, Rue Saint-Denis, Bureau 1105,
Montréal, QC H2S 3L5, Canada
*Correspondence: benoit.tousignant@umontreal.ca
Abstract:
Since the 1960s, Grassy Narrows First Nation (Ontario, Canada) has been exposed to methyl
mercury (Hg) through fish consumption, resulting from industrial pollution of their territorial waters.
This cross-sectional study describes the visual characteristics of adults with documented Hg exposure
between 1970 and 1997. Oculo-visual examinations of 80 community members included visual acuity,
automated visual fields, optical coherence tomography [OCT], color vision and contrast sensitivity.
Median age was 57 years (IQR 51–63) and 55% of participants were women. Median visual acuity was
0.1 logMAR (Snellen 6/6.4; IQR 0–0.2). A total of 26% of participants presented a Visual Field Index
inferior to 62%, and qualitative losses assessment showed concentric constriction (18%), end-stage
concentric loss (18%), and complex defects (24%). On OCT, retinal nerve fiber layer scans showed
74% of participants within normal/green range. For color testing with the Hardy, Rand, and Rittler
test, 40% presented at least one type of color defect, and with the Lanthony D-15 test, median color
confusion index was 1.59 (IQR 1.33–1.96). Contrast sensitivity showed moderate loss for 83% of
participants. These findings demonstrate important loss of visual field, color vision, and contrast
sensitivity in older adults in a context of long-term exposure to Hg in Grassy Narrows First Nation.
Keywords:
methyl mercury; visual field; optical coherence tomography; color vision; contrast
sensitivity; Indigenous peoples
1. Introduction
For many Indigenous communities around the world, fish is an important component
of traditional food systems [
1
]; for some, fish is not only a nutritious food [
2
], but also the
heart of their culture and identity [
3
,
4
]. Colonization and dispossession have resulted in
land degradation and pollution, with profound impacts on Indigenous food
systems [5,6]
.
Mercury (Hg), from local and global sources, has polluted lakes, rivers, and oceans, bioac-
cumulating and biomagnifying through the aquatic food chain [
7
]. While the benefits of
fish consumption have been widely documented [
8
,
9
], coastal and riverside Indigenous
communities who rely on fish for sustenance are often at risk from the toxic effects of
methyl Hg exposure [
3
,
10
,
11
]. In Northern Ontario, Canada, the Asubpeeschoseewagong
Anishinabek (also known as Grassy Narrows First Nation) people have been exposed to
Hg for 60 years through fish consumption. Between 1962 and 1975, a chloralkali plant of a
pulp and paper mill discharged almost 10 tons of Hg into the fluvial lake system on their
traditional territories. In 1970, fish was a dietary mainstay [
12
] and blood Hg concentrations
Int. J. Environ. Res. Public Health 2023,20, 4827. https://doi.org/10.3390/ijerph20064827 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2023,20, 4827 2 of 14
were the highest in Canada [
13
]. Hg exposure decreased over time and stabilized in the
mid 1980s [
14
], paralleling the decline in fish Hg concentrations [
15
]. Fish Hg levels remain
high due primarily to the remobilization of inorganic Hg from riverbank erosion [16].
The visual system is a known target for methyl Hg toxicity from fish consumption.
Visual field constriction is a recognized cardinal feature of Minamata disease, a severe
neurological disorder first described following high exposure to methyl Hg in the Mina-
mata Bay [
17
–
22
]. Imaging studies have shown that such visual field constrictions were
associated with alterations in the striate cortex [
23
–
25
], corresponding to the retinotopic
mapping of the visual cortex [
26
]. Studies in communities with lower exposures have re-
vealed methyl Hg-related visual deficits in near visual contrast sensitivity [
27
,
28
] and near
visual acuity [
29
], as well as acquired color vision loss [
28
,
30
] and early onset age-related
cataracts [
31
]. Methyl Hg-related visual deficits are supported by imaging studies and
electrophysiological assessments [
23
,
25
,
32
]. Impaired visual processing through alterations
of visual evoked potentials (VEP) [
33
–
36
] has been associated with prenatal Hg exposure.
Animal studies provide evidence that methyl Hg acts not only on the central nervous
system, but also on the optic nerve and the retina [
37
–
40
]. Monkeys exposed to methyl Hg
pre- and postnatally showed later-life reduction of visual functions [41,42].
The objective of the present study is to provide a comprehensive portrait of the eye
and visual function characteristics in older adults of Grassy Narrows First Nation, with a
history of Hg exposure from freshwater fish consumption.
2. Materials and Methods
2.1. Study Design
This cross-sectional study is part of an ongoing community–university research part-
nership to better understand how the long-standing history of methyl Hg exposure has
been affecting current health and wellbeing in Grassy Narrows. Participants were selected
from the hair Hg biomarker database (1970–1997), previously described [14,43]. Inclusion
criteria were having at least four year-based Hg measurements and living in Grassy Nar-
rows community or the immediate region (n= 130). Of these, 89 (68.7%) participated in
the study. There was no difference in age or sex between participants (median: 57 years;
interquartile range: 51.8–63.3) and non-participants (median: 55 years; interquartile range:
51.0–61). Additional inclusion and exclusion criteria were specific to each test and are
detailed below.
2.2. Oculo–Visual Examination
A total of 81 participants (91% of total) underwent oculo–visual examinations, per-
formed by three therapeutic optometrists, following standard operating procedures. In June
and July 2021, assessments were carried out in a community school classroom, converted
into an examination room. The examinations included the following assessments:
Visual acuity. Distance visual acuity (DVA) was measured in logMAR using the Early
Treatment Diabetic Retinopathy Study (ETDRS) [
44
] computerized logarithmic letter chart,
with participants wearing habitual distance spectacle correction, if any. The measurements
were performed monocularly, then binocularly. Pinhole acuity was assessed whenever a
monocular measure was 0.3 logMAR or higher (6/12 Snellen equivalent or worse). Near
visual acuity (NVA) was measured with the near ETDRS logarithmic chart, first for each
eye individually, then with both eyes. Participants wore their habitual spectacle correction
used for near activities, when applicable.
Refraction. The HandyRef-K autorefractor (NIDEK CO., Ltd., Gamagori, Japan) was
used to measure participants’ refraction. This allowed us to optimize the reliability of other
tests, which required adequate near vision, such as color vision, contrast sensitivity, and
visual field testing, using appropriate trial lenses.
Optical coherence tomography (OCT). OCT measurements were carried out using the
Cirrus HD-OCT device (Carl Zeiss, Meditec Inc., Oberkochen, Germany). Two protocols
were performed for each eye, through undilated pupils. The first scan was centered on
Int. J. Environ. Res. Public Health 2023,20, 4827 3 of 14
the optic nerve head (ONH 200
×
200 protocol). The parameters selected for analysis
were retrieved from the Cirrus HD-OCT RNFL and ONH Analysis Report and include
the average RNFL thickness (aRNFL), the RNFL symmetry percentage, and the RNFL
thickness for each quadrant (superior, nasal, inferior, temporal). The second scan was
centered on the fovea (macular cube 512
×
128). The parameters selected for analysis were
the average ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness, the minimum
GCL + IPL thickness, and the average thickness of the GCL + IPL in the six sectors of the
elliptical annulus of the thickness map (superior, nasal-superior, nasal-inferior, inferior,
temporal–inferior, and temporal–superior), all provided in the Cirrus HD-OCT Ganglion
cell Analysis Report. When possible, scan acquisition was repeated in cases with weak
signal or acquisition errors (blinking, saccade, misalignment). For analysis, only scans
with signal strength of 6/10 or stronger were retained. Scans with persistent acquisition
errors, errors in segmentation algorithms, and obvious retinal or optic nerve concomitant
pathology visible on the OCT scans were also excluded from analysis.
Cataract grading. Because the presence of significant cataracts has the potential to
impact the results of the other variables measured, anterior segment eye examination was
performed with a portable slit lamp (PSL Classic portable slit lamp, Keeler Inc., Windsor,
UK), through undilated pupils. Cataracts were graded using the WHO cataract grading
system [
45
] for cortical, nuclear, and posterior subcapsular opacities. Considering the
results, the clinicians then graded the cataract in terms of visual impact according to clinical
judgement (no impact, mild impact, moderate impact, or severe impact) for each eye. Eyes
showing cataracts judged to have a severe visual impact were excluded from all analyses.
Color vision. Color vision function was evaluated using three distinct tests: the Hardy,
Rand, and Rittler (HRR) Standard Pseudoisochromatic Test, 4th edition (Good-Lite), the
Farnsworth D-15 saturated test, and the Lanthony D-15 desaturated test. The tests were
administered with True Daylight illuminator (Good-Lite Company, Elgin, IL, USA), with ha-
bitual corrective spectacles in place for participants of 39 years and less, and for participants
40 years and more whose near visual acuity was 6/15 or better. Those presenting a near
acuity of 6/18 or worse for at least one eye were provided with trial lenses corresponding
to the result of the autorefractor, plus 2.00D. The HRR test allows the identification of
the type of color defect on all three color axes, and the quantification of the color vision
defect as mild, medium, or strong [
46
]. It has shown to be superior to the Ishihara test for
detecting acquired color vision defects in patients presenting optic neuropathies [
47
]. It has
also been suggested as a more practical alternative to the Farnsworth–Munsell 100 Hue
test, with comparable ability to detect color vision defects [
48
]. The test was administered
monocularly according to guidelines provided by the manufacturer. As recommended,
for the second eye tested, the booklet was rotated upside down from initial position, to
reduce the potential memorization. Color vision was also tested binocularly using the
Farnsworth saturated D-15 to ensure understanding of the testing procedure. This was
followed by the Lanthony D-15 desaturated version, tested monocularly. Both the saturated
and desaturated versions of the D-15 required participants to place 15 caps in order of chro-
matic similarity. The Color Confusion Index (CCI), a ratio based on the sum of chromatic
differences between adjacent caps [
49
], was calculated. A CCI of 1 characterizes a normal
color vision; CCI increases as color vision decreases. Results above a threshold of 1.2 are
considered abnormal. Plotting tests results on circular D-15 diagrams allows qualitative
analysis of the type of color defect (normal, deutan, protan, tritan, tetartan). This test has
been widely used for the assessment of acquired color vision deficiency in exposure to
neurotoxic substances, including organic Hg [
28
,
30
,
50
]. Participants with results consistent
with congenital color vision defects on the saturated D-15 were excluded from the analysis.
Contrast sensitivity. Contrast sensitivity was measured with the Mars numerical con-
trast sensitivity test, according to instructions provided by manufacturer, under standard
lighting (The Mars Perceptix Corporation, Chappaqua, NY, USA). The Mars test uses charts
composed of 48 numbers varying in contrast. The contrast of each number, progressing
through the chart, decreases by a factor of 0.04 log units [
51
]. The test was administered
Int. J. Environ. Res. Public Health 2023,20, 4827 4 of 14
with habitual corrective spectacles, if any. Participants over 40 years old with a near acuity
of 6/18 or worse were given trial lenses based on autorefraction and age-appropriate
addition. For each eye, the test was performed at 40 cm, which is within the 40 cm to 59 cm
range recommended for testing medium spatial frequencies, as per the manufacturer’s
guidelines. The test was repeated monocularly for an exploratory appreciation of the
effects spatial frequency variation: once at 80 cm (low spatial frequencies), then 20 cm (high
spatial frequencies).
Visual field assessment. Visual field was assessed using the Humphrey Field Analyzer
3 (HFA, Carl Zeiss, Meditec Inc., Oberkochen, Germany). The HFA Central 30-2 perimetry
protocol assesses a grid of 76 points within the central 30
◦
of the visual field. It has been
used extensively in the study of neurological conditions, including toxic neuropathies [
52
].
The Central 30-2 Swedish Interactive Threshold Algorithm (SITA) Fast strategy protocol
was administered for each eye. Tests that did not meet the criteria of <15% false positives
and <20% fixation losses were repeated. When the criteria were not met after one repetition,
the tests were excluded from analysis. To characterize the different configurations of
visual field defects, a qualitative assessment of the pattern deviation plots results was
performed independently by two examiners (AC and BT); divergences were discussed
to reach consensus. The observed patterns were categorized as normal, mild scattered
defects, moderate concentric constriction, end-stage concentric constriction, central defects,
other localized scotomas, and complex defects (combination of scotomas not qualifying for
other categories).
2.3. Statistical Analyses
Prior to statistical analyses, all collected data were cleaned and categorized with
respect to normative data according to known cut-off values. Because the outcome mea-
surements from a person’s two eyes are usually positively correlated, the appropriate
statistical analysis requires accounting for the inter-eye correlation [
53
]. Within-group
inter-eye differences in outcomes were analyzed, using intraclass correlation coefficient
(ICC) and Bland–Altman plots to determine whether to use ‘one-eye’ analyses or ‘two-eye’
analyses [
54
]. ICC values were classified as excellent: values > 0.90; good: >0.75 and
≤
0.9;
moderate: ≥0.5 and ≤0.75; and poor: <0.5.
Inclusion criteria for statistical analyses included all participants who completed each
examination test. Another round of selection was performed for some tests that require
specific criteria (see description of tests above). Among the 81 participants, a total of 80
were eligible for analyses.
A series of descriptive statistics (measures of tendency and dispersion, classification
of data, and description) were conducted for each measurement, to provide a compre-
hensive portrait of eye and vision characteristics. Comparisons of score values between
sex and with age were analyzed using analysis of variance (ANOVA) (parametric test) or
Wilcoxon/Kruskal–Wallis test (rank sums; non-parametric test). When comparing classes
(categorical variables), the chi-squared tests (Pearson’s chi-squared test) was used. When
comparing contrast sensitivity for various testing distances, the mean difference between
two sets of observations was done.
2.4. Ethics and Informed Consent
This study was conducted in accordance with the Declaration of Helsinki as well as
the OCAP
®
Principles of Ownership, Control, Access, and Possession developed by the
First Nations Information Governance Centre [
55
]. The study protocol was approved by
Grassy Narrows First Nation Chief and Council. Ethics approval was obtained from the
Universitédu Québec àMontréal Research Ethics Board (certificate #3763_e_2020; 9 April
2020) and Manitoulin Anishinaabek Research Review Committee (certificate #2022-06;
26 May 2022). The manuscript was reviewed and approved by Grassy Narrows Chief and
Council. Informed consent was obtained from all participants involved in the study.
Int. J. Environ. Res. Public Health 2023,20, 4827 5 of 14
3. Results
The 80 participants included 44 (55%) women and 36 (45%) men. Median age was
57 years (IQR 51.3–63.8). ICC and Bland–Altman plots showed a good level of inter-eye
agreement (most variables < 0.75). Therefore, based on random selection, a total of 40 right
eyes (23 female, 17 male) and 40 left eyes (21 female, 19 male) were used for statistical analyses.
3.1. Visual Acuity
Table 1shows the characteristics of DVA and NVA. When including optimized pinhole
VA (n= 32) to account for uncorrected refractive error, median DVA was of 0.1 (Snellen
6/6.4; IQR 0–0.2). Binocular presenting NVA was 0.3 logMAR (6/12 Snellen; IQR 0.3–0.5).
There was no influence of age or sex on VA.
Table 1. Characteristics of visual acuity measurements.
NMedian logMAR
(IQR)
Distance visual acuity (presenting)
Crude monocular (without pinhole) 78 0.2 (0.1–0.27)
Optimized monocular (adjusted with pinhole for n= 32) 80 0.1 (0–0.2)
Binocular 80 0.1 (0–0.2)
Near visual acuity (presenting)
Binocular 80 0.3 (0.3–0.5)
Abbreviations: IQR, interquartile range; LogMAR, logarithm of minimum angle of resolution.
3.2. Automated Visual Field
Distribution of global indices for visual field are reported in Table 2. At least half of
participants presented abnormal values (P < 0.5%) for mean deviation (MD) and/or pattern
standard deviation (PSD) indices, consistent with the presence of overall field depression
or localized scotomas, respectively. One-fourth (25.7%) of participants presented a defect
using the 62% of VFI as a cut-off value for moderate visual field loss [56].
Table 2. Distribution of automated visual field indices and qualitative analyses of scotomas.
Visual Field Indices/Analyses N Median (IQR)/n(%)
Mean Deviation (MD) 68 −5.59 (−17.3; −2.36)
MD < −12 dB 68 21 (31%)
MD P < 0.5% 68 34 (50%)
Pattern Standard Deviation (PSD) 70 5 (2.27–7.81)
PSD P < 0.5% 70 37 (53.6%)
Visual Field Index VFI (%) 70 92 (63–98)
VFI > 81% 48 (64%)
VFI < 62% 18 (25.7%)
VFI < 15% 6 (8.57%)
Glaucoma Hemifield Test (GHT) 75
Within normal limits 17 (24%)
Borderline 5 (7%)
Outside normal limits 48 (69%)
Qualitative assessment (based on pattern deviation plot) 68
Normal 16 (23.5%)
Mild scattered defects 8 (17.8%)
Moderate concentric constriction 12 (17.6%)
End-stage concentric constriction 12 (17.6%)
Complex defects 15 (23.5%)
Central defects 1 (1.47%)
Other localized scotomas 3 (4.41%)
Scotomas (more than three contiguous points with P < 0.5%)
Total deviation plot 68 45 (66%)
Pattern deviation plot 54 27 (51%)
Abbreviations IQR: interquartile range.
Int. J. Environ. Res. Public Health 2023,20, 4827 6 of 14
No differences were observed with respect to sex for global indices in visual field
results. However, more older participants presented abnormal values for MD and more
were outside normal limits for GHT than the younger ones (Wilcoxon/Kruskal–Wallis
Tests [Rank Sums] 1-Way Test, chi-square Approximation,
χ2
= 8.11, p= 0.030 and
χ2
= 13.5,
p= 0.017, respectively).
Qualitative assessment of pattern deviation plots showed that three-quarters of par-
ticipants had a visual field with defects, the most common being concentric and complex
defects. An example of concentric peripheral loss of light sensitivity is shown in Figure 1in
the gray-scale plot, along with both mean deviation and pattern deviation plots.
The median number of scotomas in total deviation and in pattern deviation plots were
13 (n= 69, IQR: 1–61) and 5 (n= 54, IQR: 0–18), respectively. A total of 16 pattern deviation
plots (21.7%) were missing because of complete scotomas.
Figure 1. Printout of automated visual field testing showing concentric constriction.
Int. J. Environ. Res. Public Health 2023,20, 4827 7 of 14
3.3. Optical Coherence Tomography
Thickness of retinal layers, as measured by optic nerve and macular OCT scans, are
presented in Table 3. The average thicknesses of retinal nerve fiber layer (aRNFL) and
macula’s “average GCL + IPL” (ganglion cell layer added to inner plexiform layer) were
outside the normal ranges (green color code) for one-fourth of the participants (25.7% and
25.0%, respectively). The minimum GCL + IPL thickness was outside the normal range for
almost one-third of participants (29.4%).
Table 3.
Distribution of retinal layer thicknesses measured by optical coherence tomography (OCT).
OCT Scans N Median Thickness
µm (IQR)
Measurement in
Green/Normal Range
n(%)
Optic Disc Cube
Average RNFL thickness 70 86.5 (79–92) 52 (74.3%)
Thickness (by quadrant)
Superior 70 103 (94–114) 57 (81.4%)
Nasal 70 70.5 (62.8–77) 62 (88.5%)
Inferior 70 102 (103–125) 56 (80%)
Temporal 70 54 (46–61) 56 (80%)
Macular Cube
Average GCL + IPL thickness 68 78 (72–82) 51 (75%)
Minimum GCL + IPL thickness
68 74.5 (66.3–79) 48 (70.6%)
Thickness (by section)
Superior 68 78 (72.3–83.8) 52 (76.5%)
Superior nasal 68 79 (74.3–85.8) 56 (82.3%)
Inferior nasal 68 77 (72–83) 54 (79.4%)
Inferior 68 76 (70–81) 54 (79.4%)
Inferior temporal 68 78 (72–83) 55 (80.8%)
Superior temporal 68 77 (72–83) 54 (79.4%)
Abbreviations: RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layers.
No association was found between thicknesses in retinal or macular scans and sex.
However, in quadrants analyses, the superior, inferior, and average retinal layers thick-
nesses decreased with age. Older participants presented more abnormal ranges for superior
and inferior retinal layers (Wilcoxon/Kruskal–Wallis Tests (Rank Sums) 1-Way Test, chi-
square,
χ2
= 6.77, p= 0.033 and
χ2
= 8.85, p= 0.031, respectively) than younger ones. All
thicknesses in macula decreased with age, except for temporal quadrants. Upon qualitative
appreciation of the scans, there was no specific or localized pattern of thinning of retinal
layers (i.e., superior–inferior asymmetry, nerve fiber bundle loss) consistent with known
ocular pathologies.
3.4. Color Vision
Table 4shows that half of the participants had no defect on HRR color vision testing.
Blue–yellow and red–green color defects were observed for more than one-third of partici-
pants (37.1% and 37.7%, respectively). More women presented a blue–yellow defect than
did men (contingency table,
χ2
= 4.56, p= 0.033). One-third of participants had a defect
on both color ranges (32.5%). With increasing age, participants presented more defects
(Wilcoxon/Kruskal–Wallis Tests (Rank Sums) 1-Way Test, χ2= 10.9, p= 0.012).
Monocular desaturated D-15 color vision tests showed that 87% of participants pre-
sented a CCI value equal or greater than the abnormal threshold of 1.2. This proportion
was 55% for binocular saturated testing. CCI increased with age, for both saturated and
desaturated D-15 testing. Qualitative analysis of D-15 graphic plots (not shown here)
showed that most participants (n= 64, 88%) had complex color vision defects (three or more
error lines non-parallel to protan, deutan, tritan or tetartan lines). Sex was not significantly
associated with results on saturated and desaturated CCI.
Int. J. Environ. Res. Public Health 2023,20, 4827 8 of 14
Table 4. Distribution of color vision testing results.
Color Vision Test N n(%)/Median (IQR)
HRR testing (monocular)
B–Y defect 77 27 (37.1%)
R–G defect 77 29 (37.7%)
Color defect categories 77
B–Y normal and R–G normal 46 (49.7%)
B–Y normal and R–G defect 4 (5.20%)
B–Y defect and R–G normal 2 (2.60%)
B–Y defect and R–G defect 25 (32.5%)
D-15 testing
Saturated, CCI (binocular) 80 1.17 (1–1.46)
CCI > 1.2 44 (55%)
Desaturated, CCI (monocular) 77 1.59 (1.32–1.96)
CCI > 1.2 67 (87%)
Abbreviations: HRR, Hardy Rand and Rittler test; B–Y, blue–yellow; R–G, red–green; CCI, Color confusion index.
3.5. Cataracts
Slit lamp assessment of crystalline lenses showed low degrees (grade 0 or 1) of nuclear
sclerosis, cortical opacities, or posterior subcapsular cataracts. More than 89% of combined
lens opacities were judged as having either no or mild visual impact.
3.6. Contrast Sensitivity
Table 5shows that contrast sensitivity (CS) thresholds using the Mars chart was
abnormal for the great majority of participants (more than 80%) for all spatial frequencies.
CS was significantly higher in low (20 cm) and medium spatial frequencies (40 cm) when
compared with high (80 cm) spatial frequencies (paired sample t-test, t = 3.69, p< 0.001;
t = 3.12
,p= 0.003, respectively). There was no significant difference in CS between high
and medium spatial frequencies. With increasing age, more participants had severe loss of
CS for 80 cm (low spatial frequencies) (Wilcoxon/Kruskal–Wallis Tests [Rank Sums] 1-Way
Test, χ2= 10.7, p= 0.005).
Table 5. Distribution of Mars contrast sensitivity at various testing distances.
N Median (IQR)/n(%)
20 cm (high spatial frequencies) 76
log CS 1.48 (1.36–1.64)
Categories
Normal 8 (10.5%)
Moderate 65 (85.5%)
Severe 3 (3.95%)
40 cm (medium spatial frequencies) 76
log CS 1.48 (1.32–1.67)
Categories
Normal 10 (13.2%)
Moderate 63 (82.9%)
Severe 3 (3.9%)
80 cm (low spatial frequencies) 76
log CS 1.44 (1.29–1.56)
Categories
Normal 7 (9.2%)
Moderate 63 (82.9%)
Severe 6 (7.9%)
Abbreviations: CS, contrast sensitivity.
Int. J. Environ. Res. Public Health 2023,20, 4827 9 of 14
4. Discussion
This study is the first comprehensive description of eye and visual characteristics in a
First Nation population of older adults with a documented history of long-standing methyl
Hg exposure from fish consumption. Results show that there are abnormalities in visual
function of various degrees.
Automated visual field testing revealed that although two-thirds of participants had a
VFI of more than 81%, only one-fourth of participants presented normal pattern deviation
plots. More than half of participants showed either complex defects or moderate or end-
stage concentric visual field constrictions. Although many scotomas were more frequent in
participants 50 years and older, half of the younger participants (37–50 years) presented
moderate to severe visual field loss. These findings are consistent with previous studies,
where concentric constriction in visual field has been widely reported after methyl Hg
exposure from dietary intake [24,25,57–64].
In previous studies carried out in Grassy Narrows First Nation, visual field defects
were documented using Forster’s perimeter. Harada et al. reported 21.9% of 73 persons
examined had a “narrowed visual field” [
61
]. Takaoka et al. measured visual fields by
confrontation visual field test and reported 14% of 44 participants presented with “visual
constriction” [
65
]. In the present study, documentation of visual field using threshold
testing with an automated perimeter provided the means to better qualify and quantify
these visual losses.
Some of the underlying mechanisms of peripheral visual field defects in a context
of long-term methyl Hg toxicity have been described among patients with Minamata
disease. This condition, first described in Japan in the 1950s, following ingestion of marine
products contaminated with methyl Hg, is characterized by multiple neurological and
visual impairments, including visual field loss [
59
]. Following the classic retinotopic
mapping of the visual cortex [
26
], the central part of the visual field is represented in
the posterior part of the striate cortex, while the periphery corresponds to its anterior
part, along the calcarine fissure. Among Minamata patients, microscopic examination
showed neuropathological lesions including disintegration and loss of neurons in the
striate cortex [
66
]. Magnetic resonance imaging (MRI) scans showed dilatation of the
calcarine sulcus caused by atrophy of the visual cortex [
23
,
25
,
67
], and was correlated with
visual field losses [25].
The findings of the present study do not resemble the clinical picture of more common
conditions causing constricted visual field, such as glaucoma or retinitis pigmentosa. Those
diseases are not known to present in such prevalence and clustering pattern in any given
population. Glaucoma visual field loss is typically accompanied by specific retinal nerve
fiber loss along anatomical nerve fiber bundles corresponding to neural retinal rim loss [
68
],
none of which are obvious in these participants. Retinitis pigmentosa typically presents
with pronounced symptoms of nyctalopia and present in familial patterns due to genetic
transmission (autosomal dominant, autosomal recessive or X-linked) [69].
Although the current study took place 10 years after the last study looking at visual
field of individuals in Grassy Narrows [
61
], it is noteworthy that, in both studies, visual
field constriction was highly prevalent in individuals between 40 and 60 years old. While
this does not represent a formal longitudinal assessment, this could, nonetheless, suggest
that the effects of methyl Hg develop or endure over a long time period. While biomarkers
of Hg exposure have decreased over time in Grassy Narrows [
14
], Hg-induced impairments
of visual function might not recover following a reduction of exposure [70].
This study is one of the first to include retinal thickness data from OCT scans in the
context of methyl Hg exposure. Our results show that superior, lower, and average RNFL
thicknesses and most macular thicknesses (ganglion cell complex and inner plexiform
layer) are lower than the normal range. Quadrant and sectoral thicknesses show no
conspicuous areas of predilection for abnormal values, suggesting non-specific thinning.
Animal studies have shown retinal accumulation of inorganic Hg [
40
,
71
,
72
] and human
studies have reported slight generalized thinning of retinal layers following exposure to
Int. J. Environ. Res. Public Health 2023,20, 4827 10 of 14
inorganic Hg [
73
,
74
]. Our results could indicate that visual disturbances following exposure
to methyl Hg may be associated, at least in part, to a retinal mechanism. However, the
pathophysiology is likely multifactorial and distinct from other disease processes affecting
retinal structure and visual field loss, such as glaucoma, where a large loss proportion of
retinal fibers, visible on OCT, typically precedes visual field involvement [75].
An alternative hypothesis to the thinner retinal layers could be the involvement of
genetic factors. The distribution and thickness of retinal layers has been shown to differ
with respect to ethnicity [
76
,
77
]. The normative database included in the Cirrus HD-OCT
does not include the ethnic characteristics of the Anishinaabe or other First Nation peoples.
However, our results are unlikely affected only by potential ethnic variations in retinal
layer thickness. When compared to the seven population normative databases in those
studies, our sample’s aRNFL measurements were thinner than that of six other ethnicities
(signed-rank Wilcoxon tests, p< 0.0001) except for that of a population study conducted in
India (p= 0.32), which had the lowest thickness values of all [76,78].
Color vision testing with desaturated D-15 showed a high proportion of abnormal
results (87% of participants above or greater the normal CCI value of 1.2), no sex differences,
and a high proportion (88%) of complex patterns of defects. This is inconsistent with
congenital color vision loss [
79
] and points towards acquired color deficiency. This has
been reported with exposure to methyl Hg from fish consumption [
28
], which showed
mean CCI values ranging from 1.46 to 1.50 [
30
,
80
]. HRR color vision testing also revealed a
high proportion (39%) of color vision defects, most of them complex (combined red–green
and blue–yellow defects). Although this proportion is inferior to desaturated D-15 defects,
it is noteworthy that the HRR testing uses a shorter, forced-choice method compared to
the longer, more nuanced ranking task compared to the D-15. This may lead to more
specific and less sensitive results with HRR than with D-15, which may be more subject to
fatigue and lead to more frequent abnormal results. A number of studies have also shown
that persons exposed to methyl Hg may do well on tests using saturated colors such as
the Ishihara plates, but performance on desaturated tests is dose-related [
19
,
30
,
81
], and
persistent even following reduction of exposure [29].
In this study, contrast sensitivity (CS) was often reduced, with most participants
showing moderate to severe contrast loss in medium, low, and high spatial frequencies.
These findings are similar to those of previous studies carried out on methyl Hg toxicity
using sinusoidal grating tests [
27
,
28
,
82
,
83
]. Methyl Hg-related decrease in CS was first
observed with visual evoked potential testing in patients suffering from Minamata disease
in Japan [
27
]. Some authors suggested alteration of CS function could be connected
to methyl Hg accumulation in the retina [
39
,
71
,
72
], or as a result of alterations in the
visual cortex, where processing of contrast occurs [
19
,
84
–
86
]. Developmental exposure
and adulthood exposure to methyl Hg may produce different the patterns of spatial and
temporal vision defects [42].
Distance visual acuity (DVA) was in the normal range for most participants in this
study. The increase in acuity after pinhole suggested most loss on presenting DVA would
be due to uncorrected distance refractive error. These results were expected, as low DVA
is not a typical clinical feature of Hg exposure [
29
,
81
]. While near visual acuity (NVA)
presenting VA were low (0.3 logMAR binocular, 0.5 logMAR monocular), no refractive
nor pinhole compensations were performed at near, making it challenging to isolate the
influence of presbyopia from these results. One study [
29
] showed an association between
acceleration of the progression of presbyopia in individuals forty years and over and hair
Hg concentration.
Considering the nature of this community-based study, we had to make choices about
the type and quantity of assessments. Some examinations, such as VEPs or fundoscopy,
which could ideally complete a clinical picture in a typical health care setting, were not
collected. Rather, emphasis was put on the most known visual characteristics in relation
to dietary Hg exposure, notably visual field constriction. The introduction of OCT to
an observational study in this context was useful to describe retinal involvement, while
Int. J. Environ. Res. Public Health 2023,20, 4827 11 of 14
helping to distinguish visual losses, such as constricted visual field defects, from other
posterior segment conditions such as glaucoma.
5. Conclusions
Our findings clearly show that, in this First Nation community, there is a high preva-
lence of visual anomalies, such as peripheral visual field constriction, reduced retinal
thickness, defects in color vision, and reduced contrast sensitivity. Future studies will
examine the contribution of long-term Hg exposure from fish consumption and systemic
conditions to the visual deficits observed in adults of Grassy Narrows First Nation.
Author Contributions:
Conceptualization B.T., A.P., M.F., J.D.S. and D.M.; methodology B.T., A.P.,
M.F., J.D.S. and D.M.; formal Analysis A.P., B.T. and D.M.; investigation, B.T. and A.C.; resources,
M.F., A.P. and D.M.; data curation, A.P.; writing—original draft preparation, B.T., A.C., A.P. and
M.F.; writing—review and editing, A.P., M.F., J.D.S., A.C., B.T. and D.M.; project administration, M.F.
and D.M.; funding acquisition, M.F., A.P., D.M. and B.T. All authors have read and agreed to the
published version of the manuscript.
Funding:
This research was funded by the Canadian Institutes of Health Research, grant number
165879. The APC was funded by the Canadian Institutes of Health Research.
Institutional Review Board Statement:
This study was conducted in accordance with the Declaration
of Helsinki as well as the OCAP
®
Principles of Ownership, Control, Access, and Possession developed
by the First Nations Information Governance Centre [
55
]. The study protocol was approved by
Grassy Narrows First Nation Chief and Council. Ethics approval was obtained from the Université
du Québec àMontréal Research Ethics Board (certificate #3763_e_2020; 9 April 2020) and Manitoulin
Anishinaabek Research Review Committee (certificate #2022-06; 26 May 2022). The manuscript was
reviewed and approved by Grassy Narrows Chief and Council.
Informed Consent Statement:
Informed consent was obtained from all participants involved in
the study.
Data Availability Statement:
Restrictions apply to the availability of these data. Data were obtained
from and are the property of the Grassy Narrows First Nation, in keeping with the First Nations
principles of Ownership, Control, Access, and Possession (OCAP).
Acknowledgments:
We are grateful to the community of Grassy Narrows First Nation and to the
local study staff and students who made this study possible. We thank Mathieu Khoury for his
assistance in data collection, the Canadian Institutes of Health for financial support.
Conflicts of Interest: The authors declare no conflict of interest.
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