Optic Neuropathies

Can Kocasarac, MD, has a unique role. As part of the Neuro-Ophthalmology Service at the UPMC Eye Center – which he joined this last year — the Clinical Assistant Professor of Ophthalmology at the University of Pittsburgh specializes in vison issues related to the nervous system.

His April 20th webinar, hosted by the Eye & Ear Foundation, was entitled, “Optic Neuropathies: A Crucial Messenger and its Disorders.”

Optic Nerve

The optic nerve is a bundle of more than 1,000,000 fibers and acts as a messenger to the brain. It is the only nerve that can be seen in an exam.

Optic Neuropathies

Optic neuropathy is damage to the optic nerve. There are many kinds:

  • Vascular ischemic optic neuropathies: arteritic/non arteritic
  • Hereditary
    • Autosomal dominant/recessive optic atrophy
    • Leber hereditary optic neuropathy
  • Inflammatory optic neuropathies
    • Demyelinating diseases (multiple scelerosis, neuromyelitis optica)
    • Infections
    • Systemic inflammatory diseases
  • Compressive/infiltrative optic neuropathies
  • Toxic nutritional
  • Traumatic
  • Glaucoma

Some optic neuropathies have rapid onset, like demyelinating diseases, inflammatory diseases, ischemic, traumatic, and hereditary. Gradual onset optic neuropathies include glaucoma, toxic/nutritional, infiltrative/compressive, and hereditary, though exceptions can occur.

Optic Neuritis – Demyelinating Disease

Conditions that fall under this category include:

  • MS
  • Neuromyelitis (NMOSD)
  • Myelin oligodendrocyte glycoprotein (MOG) antibody disorder
  • Clinically isolated syndrome

Symptoms are as follows:

  • Reduced visual acuity
  • Altered color vision
  • Visual field defects
  • Impaired pupillary light reflex
  • Pain with eye movements
  • Flashes

Information from the following is taken for diagnosis:

  • Medical history
  • Ophthalmologic exam
  • Visual acuity
  • Color vision
  • Visual field test
  • Neurologic exam
  • Testing, labs, MRI imaging

There are many medical treatment options for demyelinating diseases and more potential therapies in development today than at any other time in history.

Ischemic Optic Neuropathies

Ischemic optic neuropathies include anterior and posterior, arteritic anterior (A-AION), and non arteritic anterior (NA-AION). This kind of optic neuropathy presents with sudden painless vision loss.

Arteritic Anterior Ischemic Optic Neuropathy

  • Inflammation of the arteries
  • Giant Cell Arteritis (GCA)/Temporal arteritis
  • 5-10% of AION
  • More common in women 3:1
  • Exclusively affects people over age 50

To diagnose this condition:

  • Medical history:
    • Pain in the temples
    • Pain when chewing
    • Scalp pain or tingling
    • Neck pain
    • Muscle aches & pains
    • General fatigue
    • Loss of appetite
    • Unexplained loss of weight
    • Fever
  • Ophthalmologic exam
  • Lab tests (inflammatory markers)
  • Temporal artery biopsy

Treatment involves high dose steroids.

Non Arteritic Anterior Ischemic Optic Neuropathy

  • Most common form of ION
  • Men/women ratio 1:1
  • Risk factors:
    • Diabetes mellitus
    • High blood pressure
    • High cholesterol
    • Smoking
    • Sleep apnea

A diagnosis is made after taking a medical history, giving an ophthalmologic exam that includes a visual field test, blood tests, and imaging if necessary. There is no proven effective treatment. Aspirin can be used. The second eye has a 15-20% chance of being affected in the following five years. The main way of treating this is to manage the risk factors.

Hereditary Optic Neuropathies

  • Genetic defects
  • Leber Hereditary Optic Neuropathy (LHON)
  • Autosomal Dominant Optic Atrophy
  • Autosomal Recessive Optic Atrophy

Leber Hereditary Optic Neuropathy

This is the most common inherited mitochondrial disease. It is inherited from the mother. Its prevalence is 1:50,000, male>female (9:1). Age of onset is typically between 10-30 years with subacute vision loss of one eye. It progresses to bilateral vision loss in less than a year. Vision is usually less than 20/200. There are visual field defects and color vision loss.

The following is needed for a diagnosis:

  • Medical history
  • Ophthalmologic exam
  • Imaging
  • Genetic tests
  • Three common mitochondrial mutations (G11778A, G3460A, T14484C)

Coenzyme Q10 and idebenone are used in treatment, along with nutritional supplements like vitamin B12, vitamin C, and lutein. Alcohol and tobacco must be avoided.

Autosomal Dominant Optic Atrophy

This is the most common hereditary optic neuropathy, with an estimated prevalence of 1:12,000 to 1:50,000. Kjer’s optic neuropathy is another name for it.

These are the criteria for diagnosis:

  • Typical onset of visual loss in first or second decade
  • Bilateral, symmetric, insidious visual loss
  • Vision better than 20/200
  • Color vision loss
  • Visual field defects
  • Mutations in the OPA1 gene

There is no established treatment. Similar to Leber’s, patients are given CoQ10, idebenone, nutritional supplements, and told to avoid alcohol and tobacco.

Clinical Trials

Dr. Kocasarac shared some clinical trial results:

Stem Cell Opthalmology Treatment Study II (SCOTS2)

  • Evaluated 5 patients
  • Significant improvement in visual acuity
  • Count fingers to 20/100 and hand motion to 20/200
  • Visual field improvement

Rescue and Reverse Gene Therapy Trials

  • RESCUE 39 patients, REVERSE 37patients
  • Vision loss less than 6 mos vs vision loss between 6 mos-1 year
  • One eye received gene therapy
  • Significant improvement in visual acuity in both eyes

Reflect Gene Therapy Trial

  • First affected eye – gene therapy
  • Second affected eye – gene therapy vs placebo
  • Better visual acuity improvements in bilateral treatment

There will be a new multi-center genetic trial, Dr. Kocasarac announced, though the details have not been disclosed yet. “I am very excited about being part of this study,” he said.

He also referred to the Louis J. Fox Center for Vision Restoration, which is doing exciting things with optic nerve regeneration.


Eye & Ear Foundation CEO Lawton Snyder talked about a few things that stood out to him from Dr. Kocasarac’s presentation. There are very different ways people can develop vision loss, with multi-faceted solutions. “I am excited to hear there are a lot of things being tried,” he said, including “gene therapy work for inherited conditions.”

Dr. Kocasarac said there is a great collaboration with his neurology colleagues. He also said there are many current studies. In the near future, there will be options for patients with optic nerve damage, but the science may take some time. Nonetheless, “I’m very hopeful and excited about it,” he said.