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A. Characterizing Diseases navigator

  1. Nature of Visual Loss
    1. Sudden
    2. Gradual
    3. Postural
    4. None
  2. Swelling of Optic Disk
    1. Called Papilledema
    2. Often with pallor
    3. Blurred margins
    4. Hyperemia
    5. Dilated vessels with loss of spontaneous venous pulsation
  3. Optic Nerve Signs/Symptoms
    1. Decreased visual acuity
    2. Decreased color vision
    3. Afferent pupillary defect
    4. Monocular visual field defects which do not usually respect vertical midline
  4. Glaucoma is considered separately
    1. Open angle glaucoma (POAG) - chronic progressive visual field loss and blindness
    2. Acute angle closure glaucoma (PACG) - acute loss, usually in one eye

B. Papilledema [4] navigator

  1. Specific term for optic nerve swelling
    1. Neurological emergency
    2. requires immediate neuroimaging followed in some settings by lumbar puncture
  2. Caused by increased intracranial pressure (ICP)
    1. Usually bilateral changes but may be assymmetric
    2. Headache, Nausea, Vomiting are common
    3. Rare vision loss in acute stage - if occurs, is usually transient and posturally dependent
    4. Vision loss can occur in long term and is gradual
    5. Pseudotumor Cerebri (see below)
    6. Note that glaucoma is characterized by elevated intraocular pressure (IOP)
  3. Symptoms and Signs
    1. No visual acuity loss unless macular region affected - may note enlarged blind spot
    2. May have loss if chronic or if distal visual processing areas affected (such as optic chiasm)
    3. Patient may describe amaurosis fugax symptoms
    4. Optic disk swelling - usually bilateral
  4. Evaluation
    1. Physical exam with emergent CT/MRI to rule out mass lesion
    2. If CT/MRI is negative then lumbar puncture (spinal tap) should be performed
  5. Treatment
    1. Underlying lesion if mass
    2. Reduce intraocular and/or intracranial pressure
    3. Acetazolamide (Diamox®), Furosemide (Lasix®), Mannitol, shunt or decompression

C. Pseudotumor Cerebri navigator

  1. Triad of:
    1. Increased ICP on lumbar puncture
    2. Normal neuroimaging
    3. Normal composition of cerebrospinal fluid
  2. Symptoms
    1. Headache
    2. Visual disturbance such as diplopia, transient obscurations, or field loss (inferonasal)
    3. Ataxia / Dizziness
    4. Mental Status Changes
  3. Patient Characteristics
    1. Usually women, aged 20-40
    2. Associated with COPD, pregnancy, obesity, use of outdated tetracycline, vitamin A
  4. Treatment
    1. Weight loss and cessation of any implicated drugs
    2. Diuretics such as acetazolamide or furosemide
    3. Frequent lumbar punctures with drainage
    4. Surgical shunt placement
    5. Optic nerve sheath fenestration

D. Suddent Visual Loss Syndromes [1]navigator

  1. Optic Neuritis: inflammation, infection
  2. Ischemic Optic Neuropathy
  3. Compressive Optic Neuropathy
  4. Toxic/Deficient Optic Neuropathy

E. Optic Neuritis [1,3,4] navigator

  1. Characteristics
    1. Primary inflammation of optic nerve
    2. Associated primarily with multiple sclerosis (MS)
    3. Also more weakly associated with a variety of other autoimmune disorders
    4. Recurrence rate ~30% over 10 years after initial event
    5. Risk of MS ~38% over 10 years (without interferon treatment); 60% after 40 years [4]
    6. MS can also preceed optic neuritis and increases risk for recurrence
  2. Clinical Presentation
    1. Periocular pain in ~70% of patients
    2. Pain typically worse with eye movement
    3. Women more commonly affected than men
    4. Ages 15-45
    5. Optic disk swelling (anterior neuritis) in ~30%
    6. Usually (70%) unilateral
    7. Typically subacute progressive course
  3. Etiology
    1. Inflammation of optic nerve, probably with demyelination
    2. Related to central nervous system demyelination as in MS
    3. Thus, the main association of optic neuritis is with MS
    4. Also occurs in Guillain-Barre syndrome and various other rare neurological conditions
    5. Lyme disease, sarcoid, syphilis, giant cell arteritis cause related but distinct diseases
    6. Systemic lupus erythematosus assocatied with optic neuritis in ~1% of SLE patients
    7. Invasive infection or malignancy can also present a similar syndrome [9]
  4. Diagnosis
    1. Central scotoma is rule; other field defects possible
    2. Afferent pupillary defect present unless bilateral disease
    3. Optic disk swelling as above in ~35% of cases; normal optic disk in remainder
    4. Uhthoff's symptom may be present
    5. Uhthoff's is transient visual obscuration with exertion or increased body temperature
    6. Retrobulbar optic neuritis has increased disk pallor over time with no initial swelling
    7. Magnetic resonance imaging (MRI) with gadolinium enhancement should be performed to rule out early sub-clinical MS
  5. Differential Diagnosis
    1. Acute demyelinating optic neuritis
    2. Anterior ischemic optic neuropathy (see below)
    3. Leber's hereditary optic neuropathy: no pain, ~85% male, age 26-37, progression weeks to months; mitochondrial DNA abnormality
    4. Leber's congenital amaurosis (LCA) are a group of recessive, severe, infantile-onset rod-cone dystrophies that lead to progressive blindness before age 30
    5. Transfer of RPE65 wild type cDNA to retina of LCA type 2 patients can improve vision [13,14]
  6. Treatment [3]
    1. Methylprednisolone (SoluMedrol®) 250mg intravenous (IV) q6 hours x 3 days
    2. Followed by 11d prednisone oral 1mg/kg
    3. Rate of progression to MS was 7.5% in IV group at 2 years
    4. Contrast with 14.7% in po prednisone only (14d) versus 16.7% for controls
    5. Oral prednisone alone should NOT be used
    6. High dose IV glucocorticoids generally well tolerated therapy with low risk of side effects
    7. IV methylprednisolone reduced MS progression at 2 years but NOT at 5 years [7]
    8. Interferon ß (IFN-ß) is currently the mainstay of chronic therapy
    9. IV pulse cyclophosphamide 0.5-1 gm/m2 is effective in severe SLE disease [6]
    10. Mitoxantrone IV is also used in severe MS ± optic neuritis
  7. Optic Neuritis and MS
    1. Strongly consider use of IFNß1a or IFNß1b following initial episode if any evidence of MS [3]
    2. IFN-ß1a (Avonex®) weekly after first clinical event (including optic neuritis) in patients with evidence of early MS prevents onset of clinical MS [8]
    3. IFN-ß1a (Rebif®) given subcutaneously weekly after first clinical event (including optic neuritis) reduces onsetof definite MS by ~20% and delays progression [12]
    4. Patients with optic neuritis and MRI evidence of MS should consider treatment for MS
    5. Use of high dose glucocorticoids must consider risks and potential benefits [1]
  8. Prognosis
    1. Rapid loss of vision with gradual improvement 6 weeks - 6 months
    2. High rate of progression to MS within 2 years of attack ~20%; within 40 years ~60% [4]
    3. High dose IV glucocorticoid therapy may quicken visual recovery in 2-3 weeks
    4. IV glucocorticoid therapy does not show significant improvement at 6 months versus placebo
    5. Apparent protective effect of glucocorticoids against development of MS is no longer statistically significant at 5 years of followup after initial neuritis [7]
    6. IFN-ß1a will delay frank MS in patients with one episode of optic neuritis (see above) [8,12]

F. Ischemic Optic Neuropathy [1,4] navigator

  1. Characteristics
    1. Most patients >55 years
    2. Men and women equally affected
    3. Afferent pupillary defect always present
    4. Sight lost as if "curtain came down" - altitudinal
    5. Sudden onset typically painless (except with giant cell arteritis)
  2. Types
    1. Anterior ischemic optic neuropathy
    2. Posterior ischemic optic neuropathy
    3. Giant Cell Arteritis (GCA)
    4. Diabetes mellitus: diabetic retinopathy [10]
  3. Etiology
    1. Under age 40: Diabetes, systemic lupus, migraine, severe hemorrhage
    2. Over age 40: Hypertension and diabetes
    3. Over age 60: Must consider GCA (obtain ESR)
  4. Signs
    1. Most cases show optic disk swelling (anterior ischemic optic neuropathy)
    2. Loss of vision
    3. Flame shaped hemorrhage may occur
  5. Prognosis and Treatment
    1. High dose glucocorticoids in GCA
    2. No treatments demonstrated benefit in non-GCA ischemic optic neuropathy
    3. Usually no improvement of vision
    4. Education that second eye may be affected in 25-30% of patients
    5. Optic nerve sheath decompression not beneficial, may be harmful [5]

G. Toxin and Nutritional Optic Neuropathynavigator

  1. Usually bilateral and Symmetric
  2. Signs and Symptoms
    1. Optic disks may be mildly pale temporally or normal
    2. Severe color vision loss in most cases
    3. Papilledema may occur in toxin states but not in nutritial deficiency
    4. No afferent pupillary defect because both eyes affected
    5. Classic field defect is central or near-central scotoma
  3. Toxins
    1. Chloramphenicol
    2. Ethambutol, Isoniazid (INH)
    3. Lead
    4. Alcohol (MeOH, EtOH)
    5. Tobacco
  4. Deficiency States
    1. Vitamin B12 (cyanocobalamin)
    2. Vitamins B1 (thiamine)
    3. Folic Acid (may be a cofactor)
    4. Cerebral folate deficiency (see below)
  5. Treatment
    1. Stop Toxin - may have reversal of visual loss over several months
    2. Patients should get thiamine, folate and multivitamins
    3. Consider heavy metal screen
    4. Check RBC B12 / Folate levels if anemia present
    5. Neuroimaging if assymmetric loss or any supicion of compressive etiology
  6. Consider Leber's Hereditary optic neuropathy (mitochondrial DNA abnormality)

H. Cerebral Folate Deficiency [11]navigator

  1. Infantile onset syndrome with reduced cerebral (normal peripheral) levels of folate metabolite
  2. Specifically, reduced levels of 5-methyltetrahydrofolate (5MTHF)
  3. Normal folate metabolism outside of CNS
  4. Symptoms develop age 4-6 months after birth
    1. Irritability, slow head growth, psychomotor retardation
    2. Cerebellar ataxia, pyramidal tract signs, dyskinesias
    3. Minority of cases with seizures
    4. Progression to optic atrophy and blindness
  5. Dysfunctional membrane associated folate receptors in CNS
    1. Receptor is required for folate transport into CNS
    2. Most cases due to blocking autoantibodies to folate receptors
  6. Diagnosis with demonstration of reduced CSF (but normal peripheral) 5MTHF levels
  7. Effectively treated with 0.25-0.5mg/kg po bid folinic acid

I. Other Causes of Papilledemanavigator

  1. Compression
    1. Glioma or meningioma
    2. Pituitary Tumors
    3. Thyroid ophthalmopathy
    4. Metastatic tumors
    5. arterial aneurysms
    6. Sinus mucocoele
  2. Infiltration - sarcoid, leukemia, metastatic disease, mucormycosis (fungal) [9]
  3. Posterior Uveitis / Scleritis
  4. Central Retinal Venous Occlusion
  5. Malignant Hypertensive Retinopathy
  6. Benign Papillophlebitis
  7. Pseudopapilledema
    1. Optic disk drusen
    2. Hyperoptic full disk
    3. Other disk anomalies such as tilted disk, colobomas

References navigator

  1. Hickman SJ, Dalton CM, Miller DH, Plant GT. 2002. Lancet. 360(9349):1953 abstract
  2. Bainbridge JW, Smith AJ, Barker SS, et al. 2008. NEJM. 358(21):2231 abstract
  3. Balcer JC. 2006. NEJM. 354(12):1273 abstract
  4. Miller NR and Newman NJ. 2004. Lancet. 364(9450):2045 abstract
  5. Ischemic Optic Neuropathy Decompression Trial Research Group. 1995. JAMA. 273:625 abstract
  6. Galindo-Rodriguez G, Avina-Zubieta A, Pizarro S, et al. 1999. Am J Med. 106(1):65 abstract
  7. Kaufman DI, Trobe JD, Eggenberger ER, Whitaker NJ. 2000. Neurology. 54:2039 abstract
  8. Jacobs LD, Beck RW, Simon JH, et al. 2000. NEJM. 343(13):898 abstract
  9. Bienfang DC and Karluk D. 2002. NEJM. 346(12):924 (Case Record) abstract
  10. Frank RN. 2004. NEJM. 350(1):48 abstract
  11. Ramaekers VT, Rothenberg SP, Sequeria JM, et al. 2005. NEJM. 352(19):1985 abstract
  12. Comi G, Filippi M, Barkhof F, et al. 2001. Lancet. 357(9268):1576 abstract
  13. Bainbridge JW, Smith AJ, Barker SS, et al. 2008. NEJM. 358(21):2231 abstract
  14. Maguire AM, Simonelli F, Pierce EA, et al. 2008. NEJM. 358(21):2240 abstract