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Clinical science
1
Department of
Ophthalmology, King Khaled
Eye Specialist Hospital, Riyadh,
Saudi Arabia
2
Department of Diagnostic
Imaging, King Khaled Eye
Specialist Hospital, Riyadh,
Saudi Arabia
3
Department of Research, King
Khaled Eye Specialist Hospital,
Riyadh, Saudi Arabia
4
Department of
Ophthalmology, College of
Medicine, King Saud
University, Riyadh,
Saudi Arabia
Correspondence to
Dr Alberto Galvez-Ruiz,
Department of Ophthalmology,
King Khaled Eye Specialist
Hospital, Riyadh 11462,
Saudi Arabia;
algarui@yahoo.com
Received 5 November 2014
Revised 12 January 2015
Accepted 22 February 2015
Published Online First
16 March 2015
To cite: Galvez-Ruiz A,
Elkhamary SM, Asghar N,
et al. Br J Ophthalmol
2015;99:1220–1223.
1220
Cupping of the optic disk after methanol poisoning
Alberto Galvez-Ruiz,1 Sahar M Elkhamary,2 Nasira Asghar,3 Thomas M Bosley4
ABSTRACT
Purpose To assess the frequency and significance of
optic disk cupping after methanol poisoning.
Methods We retrospectively reviewed the medical
records of 50 consecutive patients with methanol
poisoning, including visual acuity, pupillary reaction, and
optic disk features such as the presence and degree of
cupping. All patients were examined in the chronic
phase after optic nerve damage.
Results Optic disk cupping ≥0.8 c/d was present in at
least one eye of 22 of these 50 patients (43/100 eyes).
Severity of cupping was statistically symmetric in the two
eyes, and increasing severity of cupping was correlated
with worse visual acuity ( p=0.007) and increasing visual
field loss. Degree of cupping was significantly correlated
with increasing patient age but not with putaminal
necrosis.
Conclusions Optic disk cupping after methanol
poisoning may be more common than previously
recognised. Cupping in this setting may reflect toxicity of
methanol metabolites to axons and glial cells in the
prelaminar, laminar and retrolaminar regions, and seems
to be important as a marker for worse optic nerve
damage.
INTRODUCTION
Methanol is a clear, colourless alcohol that is com-
monly used in industry as a component of products
such as antifreeze, windshield-wiper fluid and
model aeroplane fuel.1 2 In Saudi Arabia, it can be
found as the solvent in some brands of perfume
and cologne. Ingestion of methanol may be acci-
dental,3 or due to a suicide attempt,4 but the most
serious exposure typically occurs when it is
ingested mistakenly as a substitute for ethanol.2 5
Methanol intoxication may produce permanent
loss of vision in as many as one-quarter of surviving
patients2 6 7 because of injury to the optic nerve8 9
and the retina10 through a mechanism probably
involving impairment of mitochondrial function.11
The presence of a central scotoma is common,12 13
but other visual field defects can occur as well.8
The optic nerve in acute intoxication has a hyper-
aemic appearance, often with oedema of the peri-
papillary retina, particularly along the arcades.8 14
The optic nerve gradually becomes pale over
30–60 days after ingestion, developing atrophy in
virtually all seriously affected patients.6–9
A chronic optic disk appearance grossly similar
to the cupping found in glaucoma has been
reported in a few patients exposed to metha-
nol.12 13 15 Similar optic atrophy with cupping
outside of the setting of glaucoma has been
reported in patients with arteritic ischaemic optic
neuropathy (ION),16 and much less commonly in
non-arteritic ION17–19 and other types of optic
nerve damage.20 The cause of cupping in artertic
Galvez-Ruiz A, et al. Br J Ophthalmol 2015;99:1220–1223. doi:10.1136/bjophthalmol-2014-306354
ION may be ischaemia of all cell types in the prela-
minar, laminar and retrolaminar regions of the
optic nerve head,16 but the aetiology of the rare
cupping that occurs in certain other non-
glaucomatous optic neuropathies is not well under-
stood. The current study evaluated 50 consecutive
patients with chronic optic atrophy secondary to
methanol poisoning for the presence of optic disk
cupping.
MATERIALS AND METHODS
This is a retrospective case series of 50 consecutive
patients seen at the King Khaled Eye Specialist
Hospital, or the King Saud University hospitals
since September 2008 who admitted to drinking
unbranded alcohol, perfume, or cologne within
days before losing vision in both eyes, and who
received a complete neuro-ophthalmologic assess-
ment (by AG-R or TMB) during a stable clinical
phase more than 1 month after exposure. Medical
records, ophthalmologic testing, and neuroimaging
were reviewed. None of the patients were exam-
ined during the acute phase of intoxication, but
some had provided medical records and fundus
photos from the time of initial evaluation else-
where. A number of patients reported being treated
with bicarbonate and folate, but none received
ethanol or fomepizole.6 7 21 22 Patients were
excluded from the study if documentation was
inadequate for diagnosis or evaluation, if the
patient had known glaucoma, or if intraocular pres-
sure was more than 21 mm Hg in either eye.
Clinical characteristics were evaluated, including
age, gender, visual acuity, visual fields, pupillary
reaction and fundus features, with special attention
to the presence or absence of optic nerve cupping.
Goldmann perimetry was performed based on patient
vision. Cup-to-disc ratios were taken from chart
records or assessed from fundus photography. Criteria
for defining cupping were left to the clinical judgment
of the examiner (AG-R or TMB). Optical coherence
tomography (OCT) was not generally performed
because of poor fixation. Statistical analysis was per-
formed using Statistical Package for the Social Sciences
(SPSS V.14.0.0, SPSS Inc). Where necessary, Snellen
visual acuity was converted to the logarithm of the
minimum angle of resolution for statistical comparison.
This study was carried out after the approval of
the Human Ethics Committee/Institutional Review
Board at the King Khaled Eye Specialist Hospital
and the Research Committee of the Ophthalmology
Department at King Saud University, Riyadh.
RESULTS
All 50 patients reported acute or subacute, painless,
bilateral visual loss a month or more before evalu-
ation. All were male and young to middle aged
(mean age 38.1 years; range 17–64 years). All
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Clinical science

eventually admitted to drinking unbranded alcohol a day or two cupping resembling advanced glaucomatous cupping (figure 2).
before visual loss and hospitalisation. Some admitted to drinking The presence of optic disk cupping after methanol intoxication
alcohol, cologne, or perfume only when family members were has been described in previous reports, generally in cases of iso-
not present. A number were able to provide medical records lated patients.12 13 23 This series of 50 patients with visual loss
from their initial evaluation, and some had fundus photos from after methanol exposure implies that this phenomenon is likely
that time. more common than previously thought, affecting more than
Table 1 details clinical observations relevant to severe optic 40% of individuals with permanent visual loss after methanol
disk cupping in these patients. Every patient had visual loss and exposure. Cupping was variable between patients, with more
some degree of optic atrophy bilaterally (figure 1A, B), but some severe cupping statistically associated with worse visual acuity.
also had optic disk cupping on one or both sides (figure 1C, D). Generally, cupping was relatively symmetric in the two eyes of
Cupping greater than 0.8 cup-to-disk ratio (c/d) was present in at an individual patient, and increased with advancing age of the
least one eye of 22 patients (43/100 eyes). The degree of docu- patient at the time of injury. Cupping was not statistically asso-
mented cupping in both eyes was significantly correlated with ciated with putaminal necrosis or other neurologic signs and
visual acuity (Spearman’s correlation 0.278, p=0.007). The symptoms.
degree of documented cupping in one eye was significantly corre-
lated with cupping in the contralateral eye of the same patient
(Spearman’s correlation 0.983, p<0.001). The degree of cupping
was significantly correlated with increasing age (Spearman’s cor-
relation 0.279, p=0.05). In order to know if the variables follow
either a non-normal or a normal distribution, we used the
Shapiro-Wilk test.
Comparison of early and late fundus photographs in two
patients documented progressive cupping after initial methanol
exposure (figure 2).
MRI was obtained for 30 of these patients, and documented
putaminal necrosis in 13 patients. Degree of optic disk cupping
was not significantly different in patients with and without puta-
minal necrosis (Mann-Whitney U test=52, p=0.145).

DISCUSSION
This study evaluated the presence of optic disk cupping in 50
consecutive patients with visual loss due to methanol intoxica-
tion seen at two major ophthalmologic centres in the Middle
East. All 50 patients had optic atrophy (figure 1), and 22
patients (44%) had prominent optic nerve cupping (cup-to-disc
ratio >0.8) in at least one eye. Two patients provided the oppor-
tunity to observe the progression of optic disk cupping by com-
paring fundus photographs taken approximately 1 week after
methanol exposure with photographs taken approximately
1 month later (figure 2).
One major characteristic of methanol poisoning is progressive
bilateral visual loss beginning hours to days after exposure, and
resulting in optic atrophy within 30–60 days. In some patients
reported here, progressive optic atrophy included progressive

Table 1 Optic disk cupping in methanol intoxication

Cupping ≥0.8 c/d Cupping <0.8 c/d p≤

Patients affected (at least one 22 28

eye with cupping ≥0.8)
Eyes affected (cupping ≥0.8) 43 57
Mean age±SD 41.14±11.94 38±7.46 0.575*
(minimum–maximum values) (29.2–53.08) (30.54–45.46)
Sex 22 male : 0 female 28 male : 0 female
Mean visual acuity (range) LP CF 0.008†
(20/25—NLP) 20/30-NLP
Putaminal necrosis 6 7 0.302‡
Figure 1 Optic disk appearance after methanol intoxication. Fundus
*Mann-Whitney U test comparison between age in both groups (Cupping ≥0.8 c/d vs
Cupping <0.8 c/d).
photographs showing examples of the appearance of the optic disk in
†Mann-Whitney U test comparison between logarithm of the minimum angle of four patients, labelled A, B, C and D. For each patient, the right optic
resolution (logMAR) visual acuity and degree of cupping in both eyes. disk is shown on the left side, and the left optic disk is shown on the
‡Pearson χ2 comparing degree of cupping in both eyes of patients with (13 patients) right side. (A and B) Patients with optic atrophy without cupping.
and without (12 patients) putaminal necrosis on neuroimaging.c/d, cup-to-disc ratio;
NLP, no light perception.
(C and D) Patients with prominent cupping when photographed more
than 1 month after methanol exposure.
Galvez-Ruiz A, et al. Br J Ophthalmol 2015;99:1220–1223. doi:10.1136/bjophthalmol-2014-306354 1221
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Clinical science
Figure 2 Progressive cupping after methanol intoxication. Fundus
photography of two patients with progressive cupping after methanol
poisoning documented by sequential fundus photography. The right
optic disk is shown on the left side, and the left disk is shown on the
right side. (A) Fundus photographs taken in a patient at 7 days after
methanol exposure showing cup-to-disk ratio estimated as 0.5 in both
eyes. (B) Similar photographs taken 1 month after exposure in the same
patient as A showing cup-to-disk ratio estimated as 0.9 in both eyes.
(C) Fundus photographs taken at 10 days after methanol exposure in a
different patient showing no cupping in the right eye and a cup-to-disk
ratio estimated as 0.2 in the left eye. (D) Similar photographs taken
6 weeks after exposure in the same patient as C showing cup-to-disk
ratio estimated as 0.8 in both eyes.
Cupping of the optic nerve head likely has somewhat differ-
ent mechanisms in different optic neuropathic processes. In the
setting of glaucomatous cupping, gradual remodelling of the
perilaminar extracellular matrix probably occurs over time.
Optic nerve head astrocytes and cells of the lamina cribrosa
itself may be involved, with posterior migration of the laminar
insertion into the scleral canal resulting in progressive glau-
comatous cupping.24 25 Of course, optic nerve damage leading
to cupping in glaucoma occurs over years with preservation of
the neuroretinal rim until later stages of the disease.26
1222 Galvez-Ruiz A, et al. Br J Ophthalmol 2015;99:1220–1223. doi:10.1136/bjophthalmol-2014-306354
Other types of optic neuropathies result in cupping less fre-
quently and less consistently. Perhaps the most common of these
alternative causes of non-glaucomatous cupping is arteritic
anterior ION (AION),25 in which cupping may be present in
over 90% of eyes.17 Cupping in arteritic AION may be caused
by profound ischaemia in the perilaminar region causing sub-
stantial loss of both axons and glia in the prelaminar area
together with retrolaminal fibrosis leading to backward bowing
of the lamina.25 The frequency of cupping in non-arteritic
AION is much less,17 possibly because of less profound ischae-
mia.16 Cupping has also been rarely reported in other optic
neuropathic processes.20 The reason for occasional cupping
under these circumstances is not clear because optic nerve
cupping usually does not occur in these settings despite exten-
sive loss of optic nerve axons.19
It is possible that the cupping observed in some patients after
methanol poisoning may be caused by acute, severe toxicity to
axons in the perilaminar region of the optic nerve, as well as
injury to prelaminar astrocytic glial cells and retrolaminar oligo-
dendrocytes caused by mitochondrial dysfunction. This injury
may result in substantial loss of axons and other cells in the
perilaminar region comparable to that of arteritic AION leading
to cupping, because axonal loss in the optic nerve head is not
anatomically replaced by sufficient glial activation in some
patients. Atrophy without cupping may occur because axonal
loss may be compensated by astrocytic glial proliferation in
patients with less severe poisoning or in those who received
timely treatment.
There are several limitations to this study. All the patients
reported here sought an ophthalmologic evaluation because of
chronic visual loss after methanol exposure, and there may well
be patients not evaluated who had milder visual loss after
methanol exposure with or without some cupping and pallor of
the disk. Patients were not assessed by the authors during the
acute phase after poisoning, so it is possible that pre-existing
cupping of the optic disc may have been present in some
patients; however, none of these patients had a history of glau-
coma. Fundus photography was not stereoscopic, and the optic
nerve and nerve fibre layer were not assessed using OCT
because patients generally had poor vision with little or no
fixation.
In summary, more than 40% of patients in this series with
visual loss after methanol exposure developed optic disk
cupping, possibly due to axonal loss in the optic nerve head not
compensated by sufficient glial activation. These patients, gener-
ally, had somewhat worse visual loss, and were somewhat older
than patients with methanol-induced visual loss who did not
experience cupping. Optic disk cupping in methanol patients
had a similar appearance to the cupping that occurs in condi-
tions such as glaucoma and arteritic anterior ION. This phe-
nomenon may be more common than previously realised in the
setting of methanol intoxication.
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics Committee/Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
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Galvez-Ruiz A, et al. Br J Ophthalmol 2015;99:1220–1223. doi:10.1136/bjophthalmol-2014-306354 1223

 Downloaded from http://bjo.bmj.com/ on November 15, 2015 - Published by group.bmj.com

Cupping of the optic disk after methanol

poisoning
Alberto Galvez-Ruiz, Sahar M Elkhamary, Nasira Asghar and Thomas M
Bosley

Br J Ophthalmol 2015 99: 1220-1223 originally published online March

16, 2015
doi: 10.1136/bjophthalmol-2014-306354

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