sharma2012

1040-5488/12/8902-0178/0 VOL. 89, NO. 2, PP. 178–182
OPTOMETRY AND VISION SCIENCE
Copyright © 2012 American Academy of Optometry
ORIGINAL ARTICLE
Methanol Poisoning: Ocular and
Neurological Manifestations
Ranjana Sharma*, Sanjay Marasini†, Ananda Kumar Sharma*, Jeevan Kumar Shrestha‡,
and Bhagvat Prasad Nepal‡
ABSTRACT
Purpose. The purpose of this study was to examine the effectiveness of ethanol and high-dose intravenous steroid for
preserving vision in acute methanol poisoning.
Methods. Eight cases of acute methanol poisoning presented to the emergency department. Detailed physical examination including neurological assessment was performed. Detailed ocular examinations were performed including visually
evoked potential and electroretinography in indicated cases. All patients had visual symptoms. Pupillary abnormality was
observed in all. Edema of the optic disc and nerve fiber layer were common fundus findings. The majority of cases were
treated with methylprednisolone intravenously. Ethanol was given intravenously in four cases who presented within 48 h.
Hemodialysis was performed in two cases having neurological manifestations and metabolic acidosis. Sodium bicarbonate was given to four patients. Folinic acid and multivitamins were also given to all the patients based on neurological
advice.
Results. Most of the patients showed a good response to the treatment. In 87.5% of the cases, improvements in visual
acuity of at least two lines were noted in follow-up visits.
Conclusions. Early presentation with prompt treatment has a significant role in preserving and improving visual acuity.
Ethanol and high-dose intravenous methylprednisolone can be an alternative treatment with better visual outcome where
fomepizole is unavailable.
(Optom Vis Sci 2012;89:178–182)
Key Words: fomepizole, methanol poisoning, ocular toxicity, pupillary abnormality
M
ethyl alcohol is a colorless and odorless liquid, which is
highly toxic. The pathological effects of methanol intoxication are attributed to the accumulation of the
toxic metabolites formaldehyde and formic acid.1 They are toxic to
the central nervous system, gastrointestinal tract, and the eyes causing metabolic acidosis and cellular dysfunction.2 After methanol
intoxication, symptoms that have been described are blurred vision, double vision, photophobia, and changes in color perception.3 There may be constricted visual fields and occasionally a
total loss of vision. Characteristic visual dysfunctions include pupillary dilation and loss of pupillary reflex.4,5 The ophthalmic diagnostic clues may include hyperemia of the optic disc, optic disc
*MD
†
BOptom
‡
FRCS
Department of Ophthalmology, Kathmandu University Hospital, Dhulikhel
Hospital, Dhulikhel, Nepal (RS, SM, BPN), and BP Koirala Lions Center for
Ophthalmic Studies, Institute of Medicine, Tribhuwan University, Maharajgunj,
Nepal (AKS, JKS).
edema, or disc pallor.6 The aim of this study was to examine the
effectiveness of ethanol and high-dose intravenous steroid for preservation and restoration of visual acuity when fomipizole is not
available as the treatment.
MATERIALS AND METHODS
The alcohol consumed by patients involved in this outbreak was
manufactured illegally and transferred into mineral water bottles in
the districts surrounding of Kathmandu. The alcohol was then sold
in remote villages in Sindhupalchowk, Ramechhap, Dolakha, and
Sindhuli districts where the outbreak occurred in July 2008. It
claimed 31 lives. Eight of the victims presented to the emergency
department of the hospital. Altered sensoria were observed in all
cases during presentation at the hospital. Informed consent was
taken for examination and publication of the report. The case
series was studied prospectively and follow-up examinations were
performed at the time of discharge, on seventh day after discharge,
after 1 month, 3 months, and 1 year later.
Optometry and Vision Science, Vol. 89, No. 2, February 2012
Methanol Poisoning: Ocular and Neurological Manifestations—Sharma et al.
Detailed histories about the amount of alcohol intake, local
brand name, onset of visual symptoms, progression of vision loss,
and associated neurological and gastrointestinal symptoms were
taken. The diagnosis of methanol poisoning was based on the
history, clinical presentation, ocular evaluation, elevated anion and
osmolar gaps, the presence of methanol in the blood, and the
absence of other toxins in a toxicology screen.
Detailed ocular evaluation consisted of measurement of the presenting visual acuity, assessment of the pupillary size and reaction,
anterior segment evaluation, and fundus evaluation under full mydriasis with binocular indirect ophthalmoscopy. Extraocular motility was assessed in six cardinal positions of gaze. Visually evoked
potential and electroretinography (ERG) were performed in selected cases with normal looking fundi and abnormal pupillary
reactions.
Non-enhanced computerized tomography (CT) scan of the
brain was conducted in all patients, and it was repeated in some
with neurological manifestations. Conventional brain magnetic
resolution imaging with a 1.5-T Gyroscan Interna scanner was also
performed during follow-up visits on patients who had had no
improvement in vision.
Seven patients were treated with pulse methylprednisolone 500
mg in 200 ml of ringer lactate administered intravenously over 2 h
twice a day for 3 days followed by oral prednisolone 1 mg/kg for 11
days. One patient who presented on the seventh day after methanol consumption was treated with oral steroid 1 mg/kg for 10 days
which was then tapered over 2 weeks. Ethanol was given intravenously in four patients who presented within 48 h. Hemodialysis
was performed in two patients having additional neurological
179
manifestations and metabolic acidosis. Sodium bicarbonate was
given to four patients having bicarbonate concentrations ⬍15
mEq/L. Folinic acid and multivitamins were added to the treatment of all the patients based on neurological consultation.
Patients were discharged once they were neurologically stable.
They were followed up regularly in the neuro-ophthalmology
clinic. This special clinic is run jointly by a neuro-ophthalmologist
and a neurologist. The follow-up examination consisted of visual
acuity measurement, pupillary assessment, and detailed fundus
examination. No undesirable side effects of the treatment were
observed.
RESULTS
There were eight cases (seven male and one female). The mean
age was 48.75 (range, 45 to 60 years). The patient characteristics
on the day of presentation, delay from methanol ingestion to onset
of symptoms, systemic manifestations, assessments performed, and
the treatment given are presented in Table 1.
Six patients gave a history of intake of local brand “sofi” found to
be contaminated with methanol; however, two cases could not
name the brand consumed. The patients presented with a range of
vision from severe impairment to complete blindness. The degree
of visual impairment at presentation is shown in Table 2.
Bilateral ocular involvement was noted in 67% of the cases. In
all the cases, the pupil was involved. Pupil diameter was 3 to 4 mm
with a sluggish reaction in 12 eyes (75%). Five eyes (31.25%) had
relative afferent pupillary defect. Four eyes (25%) had pupil sizes of
5 to 6 mm, and pupils were fixed to both the direct and consensual
TABLE 1.
Summary of the investigation and the treatment
Time of
presentation
Onset of
symptoms
(within)
Other
manifestations
Case
no.
Age/
sex
1
45/M Second day
24 h
Gastrointestinal ⫹
neurological
2
53/M Second day
24 h
Gastrointestinal ⫹
neurological
3
45/M Second day
24 h
Gastrointestinal ⫹
neurological
4
46/M Second day
24–48 h
Gastrointestinal
5
47/M Third day
24–48 h
Gastrointestinal ⫹
neurological
6
60/F
24–48 h
Gastrointestinal
7
48/M Fourth day
24–48 h
Gastrointestinal
8
46/M Seventh day
Third day
After 48 h None
Treatment given
IV Methylprednisolone ⫹ oral prednisolone
⫹ IV ethanol ⫹ hemodialysis ⫹ folinic
acid and multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ IV ethanol ⫹ hemodialysis ⫹ folinic
acid and multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ IV ethanol ⫹ sodium bicarbonate ⫹
folinic acid and multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ IV ethanol ⫹ sodium bicarbonate
folinic acid and multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ sodium bicarbonate ⫹ folinic acid and
multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ folinic acid and multivitamins
IV Methylprednisolone ⫹ oral prednisolone
⫹ sodium bicarbonate ⫹ folinic acid and
multivitamins
Oral prednisolone ⫹ folinic acid and
multivitamins
VEP, visually evoked potential.
Optometry and Vision Science, Vol. 89, No. 2, February 2012
Other special
tests done
CT scan ⫹ arterial pH,
VEP, ERG
CT scan ⫹ arterial pH
CT scan ⫹ arterial pH,
VEP, ERG
CT scan (abnormal
findings) ⫹ arterial
pH
CT scan ⫹ arterial pH,
VEP, ERG
CT scan ⫹ arterial pH
CT scan (abnormal
findings) ⫹ MRI
CT scan
180 Methanol Poisoning: Ocular and Neurological Manifestations—Sharma et al.
TABLE 2.
Summary of the ocular findings
PVA
VA at 1 yr
Pupil
OD
Fundus
S. N.
OD
OS
OD
OS
OS
1
NLP
⬍20/200
3/60
6/24
3 mma
3 mm
2
NLP
NLP
LFU
LFU
4 mma,b
4 mma,b
3
4
5
6
20/400
NLP
HM
NLP
HM
20/400
⬍20/200
NLP
6/24
LFU
6/36
HM
6/60
LFU
6/60
HM
3 mm
4 mma,b
3 mma
3 mma,b
Mid dilateda,b
4 mma
3 mma
3 mma
7
8
NLP
LP
NLP
LP
LFU
LFU
LFU
LFU
5 mm fixed
3 mma
5 mm fixed
3 mma
OD
Hyperemic disc
edema
Hyperemic disc
edema
Normal
Disc edema
Normal
Hyperemic disc
edema
Disc edema
Hyperemic disc
edema
OS
with NFL
Normal
with NFL
Hyperemic disc with
NFL edema
Normal
Normal
Normal
Hyperemic disc with
NFL edema
Disc edema
Disc edema
with NFL
with NFL
a
Sluggish pupillary reaction.
Relative afferent pupillary defect (RAPD).
VA, visual acuity; PVA, presenting visual acuity; NPL, no light perception; LP, light perception; NFL, nerve fibre layer; LFU, lost to
follow-up.
b
light reflexes. Fundoscopy revealed normal appearance in six
eyes (37.5%), hyperemic optic disc with nerve fiber layer edema
in six eyes (37.5%), and disc edema in four eyes (25%). Three
eyes with disc edema progressed to optic atrophy after the
1-month follow-up.
Visually evoked potentials were recorded in three patients of
which two had abnormal b-wave amplitudes and increased peak III
latencies whereas results were inconclusive in one patient. Similarly, scotopic ERGs were recorded in three cases. The scotopic
ERG was subnormal with diminished a- and b-waves.
Six patients underwent arterial blood pH testing of whom four
had metabolic acidosis at presentation. Arterial blood pH was not
assessed in two cases who presented after 4 days with only ocular
complaints. All patients showed the presence of methanol in their
blood. The blood methanol level was ⬎40 mg/dl in two cases.
Six patients had normal CT scans. One patient showed a B/L
hypodense area in the lenticular nucleus and another patient had
dilated ventricles. Magnetic resolution imaging was performed in
one patient at 1-month follow-up. The imaging was normal. Gastrointestinal symptoms such as nausea, abdominal pain, and
vomiting were present in seven patients. However, neurological
manifestations, which included headache, ataxia, and drowsiness,
were seen in only four cases.
Four eyes (25%) were lost to follow-up 1 week after discharge.
Six eyes (38%) were lost to follow-up at 1 month. Only eight eyes
(50%) were followed up for 1 year. At the time of discharge, a total
of 13 eyes improved (81.25%) among which five eyes improved
from no light perception to light perception and hand movement
(HM). Eyes with light perception and HM also improved to HM
and 20/400, respectively. At 1-week follow-up, there was a significant improvement in visual acuity. Eyes with HM and 20/400
further improved to 20/200. Patients with visual acuities of 20/200
and 20/400 improved to 20/120 and 20/80, respectively. However, vision in two eyes deteriorated at 1 month, and one remained
unchanged. Excluding those lost to follow-up, 87.5% of patients
showed at least two lines of improvement of visual acuity at 1-year
follow-up.
DISCUSSION
Even small amounts of ingested methanol can cause severe visual
dysfunction and death through acute destruction of parts of the
central nervous system or may lead to permanent neurological
dysfunction and irreversible blindness. Without treatment, ingestion of 30 ml (0.5 mg/kg body weight) of pure methanol usually
results in death and as little as 4 ml can result in blindness.1 As
methanol metabolism proceeds, the serum bicarbonate falls concomitantly with a rise in the anion gap and a fall in the serum
osmolality. Formic acid, the primary toxin, accounts for the majority of anion gap metabolic acidosis and ocular toxicity.2 The
ocular changes are reported to correlate with the degree of acidosis.
Retinal damage is believed to be due to the inhibition of retinal
hexokinase by formaldehyde, an intermediate metabolite of methanol.7 After entering into the retinal circulation, formic acid inhibits cytochrome oxidase in the retina. It then impairs mitochondrial
function resulting in decreased ATP production and finally leads
to disruption of axoplasnic flow and swelling of axons in the optic
disc and subsequently retinal nerve fiber layer edema. These events
cause marked visual impairment.8
The diagnosis of methanol poisoning is based on a positive
history of methanol ingestion or a ingestion of a methanolcontaining product. The early non-specific symptoms of methanol
consumption are nausea, headache, abdominal discomfort, generalized weakness, and deterioration of the level of consciousness.
This picture can then proceed to blindness, coma, and death because of profound metabolic acidosis.9 The serum methanol concentration, anion gap metabolic acidosis, and an osmolal gap
confirm the diagnosis. The electrophysiological tests support the
diagnosis. In our case series, we measured the scotopic ERG and
found that a- and b-waves were diminished, as was reported by
Optometry and Vision Science, Vol. 89, No. 2, February 2012
Methanol Poisoning: Ocular and Neurological Manifestations—Sharma et al.
McKellar et al.10 It has been emphasized that pupillary status provides the best prognostic information for both morbidity and mortality.11 In our patients, pupillary involvement was 100% of whom
87.5% had some amount of improvement in vision over a time
period of 1 year. Fixed, dilated pupils, and optic atrophy, with or
without excavation, are the most common findings reported.12 We
observed sluggish to fixed pupillary reactions.
Different studies have reported varying fundus changes. Patel
and Narang12 report neuroretinitis with peripapillary retinal
edema in 34% of cases. We found hyperemic optic discs with nerve
fiber layer edema in six eyes (37.5%) and disc edema in four eyes
(25%) at presentation. Cases with disc edema and fixed pupillary
reaction progressed to disc pallor and narrowed vessels within 4
weeks. Roe13 observed that the fundus is usually normal with occasional blurring of the disc margins and vessel tortuosity. He
reported that the disc pallor and narrowing of the blood vessels
start within 6 to 12 weeks and pallor proceeds to narrowing of the
vessels.
Of the four cases (50%) with neurological symptoms at presentation, only one had ataxia at 1-month follow-up. One study noted
that severe poisoning causes necrosis of the basal ganglion, particularly the putamen.14 We observed one patient with a hypodense
area in the lenticular nucleus on the CT scan.
The essential therapy of methanol poisoning is adequate alkalinization and ethanol administration. Ethanol competes with
methanol for the enzyme alcohol dehydrogenase (ADH) in the
liver thereby inhibiting the accumulation of toxic metabolites of
methanol in the body. The three primary goals of therapy are
treatment of metabolic acidosis, inhibition of the methanol metabolism, and enhanced elimination of the unmetabolized compound
and existing toxic metabolites.15 Currently recommended management aims to delay methanol metabolism by using intravenous
ethanol infusion, gastric lavage, ADH enzyme blockade by means
of fomepizole, hemodialysis, alkalinization, and use of cofactors
such as folic acid.9,16,17 Folic acid enhances the metabolism of
formic acid.18
Ethanol and fomepizole are specific antidotes. These agents
block the conversion of methanol to formic acid. Bicarbonate and
hemodialysis are used to correct the systemic acidosis. Fomepizole
(4-methylpyrazole) has ⬃500 to 1000 times greater affinity for
ADH than ethanol and can completely inhibit ADH at a much
lower serum concentration.19
Intravenous high doses of steroids are reported to benefit the
visual status provided that the interval between the consumption of
methanol and start of treatment is short.20,21 We treated most of
the cases with intravenous high-dose steroids and attained good
results (87.5% showed improvement) that depended on the severity of the acidosis, pupillary involvement, and stage at presentation. We could not treat our patients with fomepizole because it
was unavailable.
Fifty percent of our cases presented after more than 24 h. This
may be attributable to the lack of awareness about the potentially
dangerous effect of the alcohol ingested. Patients who presented
within 48 h and were treated with ethanol and steroids had a better
outcome, an observation also noted by Hassanian-Moghaddam et
al.22 Our cases who presented later had severe metabolic acidosis,
had fixed and dilated pupils, who required hemodialysis and bicar-
181
bonate, and those with severe visual impairment did not have as
good an outcome.
Fifty percent of our cases were lost to follow-up within the
1-year study duration. Among those who followed up, 87.5% had
some visual acuity improvement. This reflects the gradual improvement of visual acuity as observed by other authors.23 We
could not trace those cases that were lost to follow-up because they
were from remote districts. Seven of the eyes (43.75%) had visual
acuity of ⬍20/400.
CONCLUSIONS
All patients in our case series presented with visual symptoms.
Pupillary abnormality was observed in all cases. Edema of the optic
disc and nerve fiber layer were common fundus findings. Most
patients showed an improvement of vision with the use of methylprednisolone. Early presentation with prompt treatment has a
significant role in preservation and improvement of visual acuity in
acute methanol poisoning. Where fomepizole is unavailable, ethanol, which serves as an antidote, and high-dose intravenous
methyprednisolone can be used as alternative treatments that improve visual outcome.
ACKNOWLEDGMENTS
The authors have received no outside financial support and declare no conflict
of interest with any of the products or devices mentioned in the manuscript.
The paper has been presented orally at the “26th Asia Pacific Academy of
Ophthalmology Congress” at Sydney, Australia on 20 –24th March, 2011.
Received March 3, 2011; accepted September 28, 2011.
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Optometry and Vision Science, Vol. 89, No. 2, February 2012
Ranjana Sharma
Kathmandu University Hospital
Dhulikhel Hospital
Dhulikhel, Nepal
e-mail: [email protected]