You have some Nerve: Is it A Glaucoma or a Neurological case?

Steven Ferrucci, O.D., Matt Kay, M.D., & Geetha Vedula, M.D.

Abstract:  Many other optic nerve etiologies can mimic the appearance of glaucoma, some having a neurological cause that may represent a serious condition. This course will give the participant knowledge to differentiate glaucoma from other neurologic diseases affecting the disc, and the tools to properly manage  these conditions. Clinical pearls related to VF testing, imaging and appropriate workup and co-management approach is provided.

Objectives

1. To understand common neurologic disorders of the ONH that mimic glaucoma
2. To learn which tests that help differentiate glaucoma from more serious neurologic disorders of the nerve
3. To gain knowledge in regards to best practices for managing cases presented

Outline

1. Introductions and disclosures
   1. Strategies to help differentiate
      1. Get a thorough, detailed history
      2. Do a careful exam Include
         1. Pupils
         2. Color vison
         3. Ancillary testing
            1. OCT
            2. VF
            3. MRI

• Note the speed of progression

1. Don’t rely on one single piece of information
2. Look for pallor and severity
3. What about the disc cupping

• Are there vascular changes
• Remember pt may have more than one disease

1. Diagnosis of Glaucoma straightforward if:
   1. elevated intraocular pressure (most often but not always)
   2. glaucomatous excavation of the disc

• pink neural rim

1. characteristic nerve fiber bundle defects on visual field testing
2. Cupping precedes pallor
3. Is bilateral in most cases. May be asymmetric but bilateral

• Tends to progress more slowly
• Uncommon in pts less than 50

1. Visual fields patterns

1. The questions
   1. Always carry an index of suspicion for an alternative non-glaucomatous process and critically evaluate the optic nerves and visual fields
      1. Is the degree of visual loss consistent with the optic nerve changes?
      2. Is the character of the visual field loss compatible with glaucomatous change?

• Are additional investigations warranted, and if so, what studies should be performed?

1. Is the progression of visual field loss out of proportion to the optic nerve changes regardless of the IOP? (Baseline detailed drawings of the optic nerve disc photographs)

• Evaluation
  1. optical coherence tomography (OCT) of the nerve fiber layer is insufficient as an isolated imaging modality because any progressive optic neuropathy will lead to progressive thinning of the peripapillary nerve fiber layer (e.g. compressive, infiltrative, toxic)
  2. Essential to follow optic nerve appearance in terms of: cupping, excavation&color of the neural rims
  3. disc photographs are particularly important in the setting of progressive visual field loss Anterior Optic Neuropathies

1. Neuropathies
   1. Glaucoma
   2. Anterior Optic Neuropathies
   3. Disc drusen
   4. Papillitis
   5. Papilledema
   6. Toxic/nutritionalON
      1. Toxic:
         1. Methanol
         2. Ethambutol/isonizad
         3. Tobacco
         4. Others
      2. Nutritional
         1. Thiamin B1
         2. B12
         3. Niacin B3
         4. Riboflavin

1. Distinction Between Glaucoma and Non-Glaucomatous O.N.
   1. Color of neural rim: pink in glaucoma
   2. Visual acuity
   3. Color vision
   4. APD
      1. In Glaucoma
         1. Asymmetric cupping of ≥ 0.3
         2. Significant VF asymmetry
      2. VF
         1. Temporal VF Loss and Glaucoma
         2. Temporal wedge defects can rarely occur in glaucoma

• Any VF defect > temporally should alert to possible chiasmal pathology

1. Which diseases have altitudinal defects?

1. Optic Atrophy
   1. Not a disease of itself, but rather a sign of a potentially more serious disease
      1. Tumor
      2. Compressive lesion
   2. Differentiating factors
      1. Pallor greater than cupping
      2. Other neurological sings

• Key tests
  1. MRI vs CT
  2. which is better for what

1. Treatments
   1. Treat underlying cause
2. Prognosis
   1. Depends on cause
3. Clinical pearls

• Anterior Optic Neuropathies
  1. nerve fiber bundle defects on visual field loss of retinal ganglion cells
     retinal nerve fiber layer lossoptic atrophy
  2. Cupping in Non-glaucomatous O.N.
     1. Arteritic AION (92%)
        1. Arteritic vs non-arteritic nerve characteristic
        2. Associated symptoms and underlying systemic disease
        3. Clinical picture
     2. Pallor Optic neuritis

• Dominant OA

1. Compressive lesions – NOT TO BE MISSED
2. Meningioma
3. Pituitary adenoma

• Craniopharyngioma
• Aneurysm

• Cases
  1. Optociliary Shunt Vessels ONSM
     1. OAG
     2. CRVO

• Meningioma

1. Testing for a patient presents with unexplained unilateral optic atrophy.
   1. Carotid ultrasound to r/o embolic source
   2. Observation unless evidence for progressive optic neuropathy

• MRI Orbits with contrast to exclude a compressive lesion

1. Serial OCT of nerve fiber layer

1. Diagnose Compressive Lesions
   1. 30% of delayed diagnosis of mass lesion misdiagnosed as NTG All patients had neural rim pallor
   2. 80% exhibited cavernous degeneration of O.N.

• Most with bitemporal VF defects

1. 75% with ↓ V.A. out of proportion to cupping

1. NTG vs Compression
   1. Features highly specific for compression
   2. V.A. < 20/40

• VF defects aligned along vertical meridian ON pallor in excess of cupping

1. Age < 50

1. Shock-induced Optic Neuropathy
   1. Hx of severe blood loss and/or hypotension
   2. May masquerade as glaucoma/NTG

• NFB defects c/w optic neuropathy

1. ON pallor > cupping
2. Most commonly post-surgical complication (orthopedic procedures, CABG)

1. Hereditary
   1. Optic Neuropathy LHON: 73% glaucomatous via HRT – C:D 0.7-0.9 (small series)
   2. DOA
      1. Temporal Excavation ≈ 75% pts
      2. Prominent pallor (temporal or diffuse) –C:D > 0.5 in 88% pts

• Mean VA 20/80
  1. Central defects w/ peripheral sparing – Young age at dx

1. Hx of severe blood loss and/or hypotension
   1. May masquerade as glaucoma/NTG
   2. ON pallor > cupping

1. Challenges
   1. Glaucoma Prophylaxis in Setting of Non-Glaucomatous ON
      1. Ocular HTN in 2-3% > 40 yo
      2. Similar % of pts w/ non-glc ON will have ocular HTN (e.g. compressive ON, post- inflammatory OA, prior AION, etc)

• ↓ VF progression in pts w/ disc drusen when given topical glaucoma rx (21.4 mo)

1. ↑ VF progression in disc drusen eyes w/ ocular HTN vs. normal IOP
2. Consider prophylactic topical IOP therapy in setting of ocular HTN and co-existing non- glaucomatous ON

1. Neuroprotection
   1. Brimonidine (alpha-2 agonist) of theoretical benefit
      – Randomized trial in NAION in 36 pts w/i one week of visual loss
   2. No significant benefit in visual outcome
      Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):551-8 Wilhelm B et al

• Memantine (Namenda) Glutamate antagonist – Monkeys

1. ↓ LGN shrinkage in experimental glaucoma – Rats
2. Neuroprotective in ON crush injuries – Rabbits
3. Neuroprotective in ON ischemia – Humans

• No benefit vs. placebo in OAG

1. Occipital CVA with HH will impede ability to assess nasal VF in eye ipsilateral to involved visual cortex (i.e. contralateral to involved hemifield)
   1. Therefore, essential to carefully monitor ONH appearance, NFL analysis, etc
   2. Glaucoma patient with right occipital stroke and left homonymous hemianopia Patient’s discs with asymmetric cupping, left eye greater than right

• Dense left homonymous hemianopia, superimposed upon arcuate defects from glaucoma

1. Assessing for Glaucomatous Change with Co-existing Homonymous VF Defects