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Neuro-ophthalmology

Ocular Symptoms of SIBO

SIBO (Small Intestinal Bacterial Overgrowth) is a condition characterized by abnormal bacterial proliferation in the small intestine. Causative organisms include Escherichia coli, Enterococcus, Klebsiella pneumoniae, and Proteus mirabilis.

Although gastrointestinal symptoms (indigestion, abdominal pain, nausea, vomiting) are predominant, the overgrown bacteria parasitically consume essential nutrients, leading to malabsorption. Deficiencies of thiamine (B1), pyridoxine (B6), folate, and vitamin B12 can cause nutritional optic neuropathy.

Vitamin B12 plays an essential role in myelin synthesis. Its deficiency is associated with myelopathy, peripheral neuropathy, and optic atrophy1). In the United States, the prevalence of vitamin B12 deficiency is reported to be at least 3% in adults aged 20–39, 4% in those aged 40–59, and 6% in those aged 60 and older2).

Q What kind of disease is SIBO?
A

SIBO is a disease in which bacteria abnormally proliferate in the small intestine, causing digestive symptoms such as indigestion, abdominal pain, and nausea. The proliferating bacteria consume essential vitamins, leading to nutritional deficiencies, which can result in ophthalmic complications such as nutritional optic neuropathy.

Digestive symptoms often precede ocular symptoms. The following ocular symptoms are observed.

  • Bilateral symmetric vision loss: Painless and slowly progressive.
  • Color vision abnormality (dyschromatopsia): Perceived as a change in how colors appear.

Clinical findings (findings confirmed by physician examination)

Section titled “Clinical findings (findings confirmed by physician examination)”
  • Centrocecal scotoma: Detected on visual field testing as a scotoma connecting the center and the blind spot. This visual field change is characteristic of nutritional optic neuropathy.
  • Temporal pallor of the optic disc: In vitamin B₁₂ deficiency optic neuropathy, the temporal side of the optic disc becomes pale, and nerve fiber bundle defects are observed.
  • Optic atrophy: In advanced cases, it leads to optic atrophy. This is an irreversible change that occurs when diagnosis is delayed.

Bacteria proliferating in the small intestine consume essential nutrients such as thiamine, pyridoxine, folate, and vitamin B₁₂ from the host, significantly reducing the amount available for absorption. This malabsorption is the underlying cause of nutritional optic neuropathy.

  • Bariatric surgery (especially Roux-en-Y gastric bypass): Creates a blind loop, a major predisposing factor for SIBO. Malabsorptive procedures carry a higher risk of ocular complications than restrictive procedures.
  • High-FODMAP diet: A diet rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) promotes the development and recurrence of SIBO.
Q After bariatric surgery, should I also watch for eye symptoms?
A

Bariatric surgeries such as Roux-en-Y gastric bypass are major risk factors for SIBO and can cause optic neuropathy through nutritional deficiencies like vitamin B₁₂. After surgery, it is important to monitor vitamin levels regularly and promptly see an eye doctor if vision loss or color vision abnormalities occur.

  • Hydrogen/Lactose breath test: After ingesting a fixed amount of sugar, the amount of methane and hydrogen produced by intestinal bacteria is measured in the breath. This is a non-invasive test used for diagnosing SIBO.
  • Serum vitamin level measurement: Measure serum levels of thiamine, pyridoxine, folate, and vitamin B₁₂.
  • Metabolic markers: Low folate and vitamin B₁₂ levels may appear as elevated methylmalonic acid and homocysteine.
  • Visual acuity test and visual field test: Visual field tests (Goldmann perimetry or automated perimetry) are performed to detect central scotomas.
  • Color vision test: Assesses the presence and degree of color vision deficiency.

In diagnosing nutritional optic neuropathy, it is necessary to differentiate it from other optic neuropathies.

Optic neuropathy due to vitamin B₁₂ or B₁ deficiency is rare, but it is important to include it in the differential diagnosis for unexplained bilateral optic neuropathy.

Treatment of SIBO (Collaboration with Gastroenterology)

Section titled “Treatment of SIBO (Collaboration with Gastroenterology)”
  • Antibiotic therapy (rifaximin): Highly effective for treating SIBO, leading to reduction of abdominal symptoms. Referral to the attending physician or gastroenterologist is recommended.
  • Low FODMAP diet: Introduced to suppress bacterial regrowth after antibiotic treatment.

Vitamin supplementation is performed after bacterial growth is sufficiently suppressed.

  • Vitamin B₁₂ oral or intramuscular administration: This is the basis of treatment for nutritional deficiency optic neuropathy. If malabsorption persists, intramuscular administration is chosen.
  • Thiamine (vitamin B₁) supplementation: Administer thiamine 100–1,000 mg to prevent and treat Wernicke encephalopathy (ocular motility disorders, gaze-evoked nystagmus).
  • Other vitamin supplementation: Pyridoxine (B₆), folic acid, and others are supplemented as needed.
Q How long does it take for vision to recover?
A

Recovery of visual function in nutritional optic neuropathy is slow, taking about six months to two years. Early diagnosis and initiation of SIBO treatment and vitamin supplementation are key to visual recovery. Delayed diagnosis may lead to irreversible optic atrophy.

6. Pathophysiology and detailed mechanisms of onset

Section titled “6. Pathophysiology and detailed mechanisms of onset”

The pathogenesis of nutritional optic neuropathy is not fully understood, but it is thought that vitamin deficiency inhibits oxidative phosphorylation and causes oxidative stress.

Vitamin B₁₂ is essential for myelin synthesis, and its deficiency is associated with myelopathy, peripheral neuropathy, and optic atrophy 1). The correspondence between each vitamin deficiency and ocular findings is shown below.

The correspondence between each vitamin deficiency and major ophthalmic findings is as follows.

VitaminOphthalmic findings
B₁ (thiamine)Optic atrophy, ocular motility disorders due to Wernicke encephalopathy (abducens nerve palsy, gaze-evoked nystagmus)
B6 (pyridoxine)Optic neuropathy (excessive intake can cause sensory disturbances and optic neuropathy)
B12 (cobalamin)Nutritional deficiency optic neuropathy, optic atrophy
Nicotinic acid (niacin)Ocular motor disorders

Bacterial parasitic nutrient uptake plays a central role in the pathology. Bacteria proliferating in the small intestine preferentially consume essential host nutrients, significantly reducing the amount of vitamins available for absorption from the intestine. This leads to metabolic disorders in neural tissues, including the optic nerve.


  1. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5:949-60.
  2. Shipton MJ, Thachil J. Vitamin B12 deficiency - A 21st century perspective. Clinical medicine (London, England). 2015;15(2):145-50. doi:10.7861/clinmedicine.15-2-145. PMID:25824066; PMCID:PMC4953733.

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