BACKGROUND
Symmetric optic neuropathy (SON) is commonly seen in neuro-ophthalmic practice and is often discovered incidentally. Although multiple investigations might be performed to discover the underlying cause, they are not always indicated. The aim of this study was to report a clinically reasonable and cost-effective approach to investigating patients with SON.
METHODS
SON was defined as bilateral optic neuropathy with normal and/or symmetrically decreased central visual acuity, absence of relative afferent pupillary defect, presence of symmetric optic disc pallor, symmetric thinning of peripapillary retinal nerve fiber layer on optical coherence tomography, and absence of other identifiable causes of optic neuropathy. Records of all patients diagnosed with SON seen at a tertiary university-affiliated neuro-ophthalmology practice from 2016 to 2022 were reviewed to identify the yield of various investigations. Clinical data from the initial and last follow-up visit were obtained. Subgroup analysis was performed to ascertain whether diagnostic yield is higher in patients with severe visual loss (central acuity worse than 20/40) compared with those with mild visual loss (acuity 20/40 or better).
RESULTS
One hundred thirty-six patients met inclusion criteria. Testing for OPA1 and OPA2 mutations had the highest diagnostic yield (16.0%), followed by mitochondrial genome sequencing (13.6%), serum vitamin B12 (6.1%), and serum folate (1.6%). MRI brain was performed in 54.4% of patients and had a diagnostic yield of only 5%. Both patients who had abnormal MRI had symptoms of demyelination at presentation. Patients were followed for a mean of 15.0 (SD 21.3) months. The most frequently identified etiologies of SON were Leber hereditary optic neuropathy (8.1%), alcohol/tobacco amblyopia (7.4%), vitamin B12 deficiency (5.9%), and dominant optic atrophy (2.9%). Patients with severe visual impairment were more likely to have a final diagnosis compared with those with milder visual impairment (63.9% vs 12.0%, P < 0.001).
CONCLUSIONS
The diagnostic yield of investigating SON in patients with preserved visual function, normal diet, and absence of other neurological symptoms is very low. It is reasonable to observe patients with SON with mild visual impairment, reserving costly investigations for those with the visual acuity worse than 20/40 or progressive course.
[1]
K. Ahmadi,et al.
Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls
,
2021,
Critical reviews in clinical laboratory sciences.
[2]
P. Freund,et al.
Clinicopathological Correlates: Chronic Arsenic Toxicity Causing Bilateral Symmetric Progressive Optic Neuropathy.
,
2020,
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.
[3]
K. Small,et al.
Nuclear genetic regulation of the human mitochondrial transcriptome
,
2019,
eLife.
[4]
H. Blom,et al.
Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency
,
2016,
Front. Mol. Biosci..
[5]
G. Wollstein,et al.
Profile and predictors of normal ganglion cell-inner plexiform layer thickness measured with frequency-domain optical coherence tomography.
,
2011,
Investigative ophthalmology & visual science.
[6]
Pradeep Sharma,et al.
Toxic optic neuropathy
,
2011,
Indian journal of ophthalmology.
[7]
N. Newman,et al.
Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies.
,
2011,
Ophthalmology.
[8]
Robert W. Taylor,et al.
The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.
,
2010,
Ophthalmology.
[9]
N. Newman.
Hereditary optic neuropathies: from the mitochondria to the optic nerve.
,
2005,
American journal of ophthalmology.
[10]
D. Turnbull,et al.
Nuclear genes and mitochondrial translation: a new class of genetic disease.
,
2005,
Trends in genetics : TIG.
[11]
P. Chinnery.
Searching for nuclear-mitochondrial genes.
,
2003,
Trends in genetics : TIG.
[12]
T. Rosenberg,et al.
A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy.
,
2002,
Investigative ophthalmology & visual science.
[13]
C. Hoyt,et al.
Autosomal dominant optic atrophy. A spectrum of disability.
,
1980,
Ophthalmology.
[14]
N. Newman.
Optic disc pallor: a false localizing sign.
,
1993,
Survey of ophthalmology.