Clinical Review & Education

JAMA Ophthalmology Clinical Challenge

Visual Field Loss in a Patient With Optic Disc Cupping

James T. Walsh, MD, PhD; Shira L. Robbins, MD; Peter J. Savino, MD

A Fundus photograph, right eye B Fundus photograph, left eye

C Automated perimetry, left eye D Automated perimetry, right eye

Figure. A, Fundus photographs show cupping with optic nerve pallor in both
eyes and a supratemporal optic nerve pit in the right eye (arrowhead).
B, Automated perimetry demonstrating temporal hemianopia respecting the
vertical midline in the left eye with cecocentral scotoma in the right eye,
consistent with a junctional scotoma.

A 52-year-old man was referred to the neuro-ophthalmology clinic for evaluation of

visual field loss. He had exotropia and amblyopia of the left eye. He was diagnosed as hav- WHAT WOULD YOU DO NEXT?
ing glaucoma 6 months prior to presentation owing to optic nerve cupping and visual field
deficits on automated perimetry and was taking latanoprost. His medical history was sig- A. Observation
nificant for pyruvate dehydrogenase deficiency, and his family history was notable for
glaucoma in his grandmother. He was being treated by the neurology department for his
B. Magnetic resonance imaging
pyruvate dehydrogenase deficiency with thiamine, vitamin C, and oxaloacetate. His sys-
of the brain/orbits
temic symptoms included hyperhidrosis and episodes of hand tremors, ataxia, and dysar-
thria that occur every 2 to 3 years.
Best-corrected visual acuity was 20/40 −2 OD and 20/100 +2 OS, with a relative C. Referral to endocrinology
afferent pupillary defect in the left eye. Intraocular pressure (IOP) was 16 mm Hg OU,
and pachymetry was 611 μM OD and 592 μM OS (normal mean [SD], 542.4 [33.5] D. Repeated visual fields with IOP
μM). He identified 8/8 OD and 3/8 OS Ishihara color plates. He had an exotropia check in 1 month
with full range of motion in both eyes. His nuclear sclerotic cataracts were not
consistent with visual acuity in both eyes; his anterior segment examination was
otherwise within normal limits. His dilated examination was normal except for
cupping and pallor in both eyes with a supratemporal optic nerve pit in the
right eye. The optic discs and automated perimetry are shown in the Figure.
Optical coherence tomography (OCT) of the retinal nerve fiber layer showed a
mean thickness of 64 μM OD and 47 μM OS (normal mean [SD], 97.3 [9.6] μM),
and OCT of the macula showed perifoveal thinning with normal foveal
thickness in both eyes.

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 Clinical Review & Education JAMA Ophthalmology Clinical Challenge

Diagnosis nase lead to a decrease in aerobic respiration causing lactic acido-

Chiasmal syndrome secondary to pyruvate dehydrogenase
deficiency
What To Do Next
B. Magnetic resonance imaging of the brain/orbits
Discussion
Junctional scotomas are visual field defects affecting the central or
cecocentral visual field in 1 eye with a contralateral temporal deficit
that respects the vertical midline. These scotomas localize to the
junction of the optic nerve and chiasm and are not compatible with
the diagnosis of glaucoma. The most frequent cause of junctional
syndrome is pituitary adenoma,1 but it has also been reported in
trauma, substance abuse, infection, inflammatory disease such as
sarcoidosis or multiple sclerosis, meningioma, or aneurysm.2-4 Any
patient with a junctional scotoma should undergo magnetic reso-
nance imaging of the optic chiasm.
Observation and repeating visual fields in 1 month (options A
and D) are not appropriate because mass lesions, including pitu-
itary apoplexy and aneurysm, frequently cause chiasmal syndrome
and would require urgent treatment. Referral to endocrinology (op-
tion B) would not be appropriate at this time. Although the most com-
mon cause of chiasmal syndrome is a pituitary adenoma that would
benefit from endocrinology consult, it would be inappropriate to
make this referral without further evidence of a pituitary lesion.
The pyruvate dehydrogenase complex is found in the mito-
chondria and is responsible for converting pyruvate to acetyl
coenzyme A, thus producing the substrate for the tricarboxylic
acid cycle and aerobic respiration. Deficits in pyruvate dehydroge-
sis and an increase in plasma concentrations of pyruvate. Owing to
the high metabolic demand of the central nervous system tissue,
neurologic manifestations of pyruvate dehydrogenase deficiency
include peripheral neuropathy, ataxia, and seizures.5 Pyruvate
dehydrogenase deficiency is a rare cause of optic neuropathy, and
to our knowledge, there have only been 2 cases of optic neuropa-
thy reported owing to pyruvate dehydrogenase deficiency.6,7
Similar to our case, both of these patients had ocular motility defi-
cits with stable vision for many years before their acute visual loss
owing to optic neuropathy. Owing to the rarity of patients surviv-
ing with pyruvate dehydrogenase deficiency to adulthood, there
are no treatments that have been proven in prospective trials, but
case reports have suggested that there are a subset of patients
who respond to thiamine supplementation,8 activators of pyru-
vate dehydrogenase such as dichloroacetate,9 or a ketogenic
diet.10
Patient Outcome
Magnetic resonance imaging of the brain did not reveal abnormali-
ties of the optic nerves or chiasm but did demonstrate atrophy of
the cerebellum. Repeated serologic testing demonstrated
increased levels of lactate and pyruvate. After 5 years of follow-up,
his visual acuity remained stable at 20/30 OD and 20/70 OS. Ishi-
hara color plates were 7/8 OD and 3/8 OS. His maximum IOP dur-
ing this period was 17 mm Hg OU while receiving latanoprost. His
fundus examination remained unchanged, and his mean deviation
on visual fields remained stable in both eyes between his initial
visit to his last follow-up (−10.00 dB to −9.34 dB OD and −16.23 dB
to −16.69 dB OS).

ARTICLE INFORMATION
Author Affiliations: Viterbi Department of
Ophthalmology; University of California, San Diego
(Walsh, Robbins, Savino); Ratner Children's Eye
Center at the Shiley Eye Institute, University of
California, San Diego (Robbins).
Corresponding Author: Peter J. Savino, MD,
Shiley Eye Institute, University of California,
San Diego, 9415 Campus Point Dr, San Diego, CA
92093 (psavino@ucsd.edu).
Published Online: May 23, 2019.
doi:10.1001/jamaophthalmol.2019.1173
Conflict of Interest Disclosures: Dr Robbins
reported support from US Department of Health
and Human Services, other support from Nevakar,
Prometic, the American Academy of Pediatrics,
Elsevier, and Springer and grants from Retrophin
and the Hartwell Foundation outside the submitted
work. No other disclosures were reported.
Additional Contributions: We thank the patient for
granting permission to publish this information.
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