315 ISCHEMIC OPTIC NEUROPATHIES

Neuropathies Optic Ischemic • 315 CHAPTER

Nerve Optic • 28 SECTION

●Patients with NAION, unlike AAION, do not have preceding episodes of amaurosis fugax or symptoms of temporal arteritis such as jaw claudication, fever, polymylagia, weight loss, or scalp tenderness.

●The natural history is classically described as nonimproving and non-deteriorating. However, the IONDT report suggested a modest level of improvement in up to 40% of patients.

●Involvement of the second eye months or years later is not uncommon; studies have suggested rates up to 41%, though the IONDT suggests that 15% will go bilaterally blind.

DIAGNOSIS

NAION is diagnosed by a good clinical history of sudden and painless unilateral visual loss in the absence of the constitutional symptoms of GCA. The patient usually has some cardiovascular risk factors such as diabetes or hypertension. The examination generally reveals an unilateral optic neuropathy, an altitudinal visual field defect and unilateral disc edema with peripapillary hemorrhages. Furthermore, the contralateral asymptomatic eye will show a very small cup-to-disc ratio.

In the setting of a classic presentation of NAION, an MRI is not required; however, the patient may need evaluation for hypertension, diabetes mellitus, and anemia. In atypical presentations (or if the patient is a poor historian), neuroimaging should be performed.

TREATMENT

No effective treatment for NAION is available. The following modalities have been tried, but none have been proved beneficial:

●Anticoagulation;

●Systemic and retrobulbar corticosteroids;

●L-Dopa;

●Pentoxyfilline;

●Optic nerve sheath decompression;

●Hyperbaric oxygen.

REMARKABLE FEATURES OF NAION

●Most patients with NAION have vasculopathic risk factors such as diabetes, hypertension, or high serum cholesterol.

●Although NAION is a vasculopathic disorder, these patients do not have an increased incidence of myocardial infarction, cerebrovascular accident, or sudden death.

●The incidence of NAION peaks in the 60s. Most age related diseases (AAION, glaucoma, etc.) continue to increase in incidence with age.

●In 98% of cases, NAION occurs only once per eye.

●There is a 15–41% incidence of visual loss in the fellow eye.

●Visual loss may be preceded by posterior vitreous detachment in a small percentage of patients.

●Emboli are almost never seen, suggesting that the ischemia is usually due to watershed hypoperfusion.

●The branches of the central retinal artery just peripheral to the area of the disc edema and subsequent pallor often

become focally attenuated and sheathed. Why such a response occurs in the retinal circulation is unknown, especially when the ciliary arteries are believed to be the primary site of difficulties.

DIFFERENTIATION BETWEEN AAION AND NAION

●Patients with GCA (AAION) are usually much older than patients with NAION.

●Patients with GCA generally have more severely affected visual acuity and visual field loss. NAION usually results in inferior or superior altitudinal visual field loss.

●Patients with GCA may have amaurosis fugax or double vision before a fixed visual deficit. NAION is not preceded by these symptoms.

●Patients with GCA are often systemically ill with headache, fever, malaise, weight loss, arthralgias, and myalgias. In particular, clinicians should be attentive to signs of jaw claudication. Patients with NAION are constitutionally well.

●Patients with NAION develop hyperemic optic disc edema with peripapillary hemorrhages. In contrast, in GCA there is pallid disc edema.

●Patients with NAION have a greatly increased incidence of a congenitally anomalous optic nerve in the contralateral asymptomatic eye. Detection of a contralateral optic nerve with a normal cup-to-disc ratio should raise the clinician’s index of suspicion for GCA or another cause of the patient’s visual loss instead of NAION.

REFERENCES

Albert DM, Searl SS, Craft L: Histologic and ultrastructural characteristics of temporal arteritis. Ophthalmology 89:1111–1126, 1982.

Arnold AC: Ischemic optic neuropathy, diabetic papillopathy, and papillophlebitis in Ophthalmology. 2nd edn. London, Yanoff & Duker 2003:1268–1274.

Hayreh SS, Podhajsky PA, Zimmerman B: Ocular manifestations of giant cell arteritis. Am J Ophthalmol 125:509–520, 1998.

Johnson LN, Arnold AC: Incidence of nonarteritic and arteritic anterior ischemic optic neuropathy: population-based study in the state of Missouri and Los Angeles County, California. J Neuroophthalmol 14:38– 44, 1994.

The Ischemic Optic Neuropathy Decompression Trial Research Group: Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy is not effective and may be harmful. JAMA 273:625– 632, 1995.

316 OPTIC NEURITIS 317.28

Simon J. Hickman, MA, PhD, MBBChir, MRCP

Sheffield, England

Optic neuritis is an inflammatory demyelinating condition of the optic nerve that usually presents as a sub-acute painful unilateral impairment of vision, although bilateral visual loss can occur.

Neuritis Optic • 316 CHAPTER

Nerve Optic • 28 SECTION

ETIOLOGY/INCIDENCE

The incidence is 1–5 per 100,000/year. The age group principally affected is 20–49 years with females being more commonly affected. Most cases of optic neuritis are due to idiopathic inflammatory demyelination, which may occur in isolation, as a manifestation of multiple sclerosis (MS) or, rarely, as part of neuromyelitis optica. The causes of optic neuritis/MS are currently unknown. A genetic predisposition exists, as suggested by the epidemiology of the condition. Environmental factors, in particular exposure to viruses, are probably also important although, as yet, no reliable candidates have been identified. Childhood cases are seen, a higher proportion of which are bilateral with less of an association with MS.

COURSE/PROGNOSIS

The natural history of acute optic neuritis is for the pain to last for only a few days and the vision to deteriorate over a period of a few days to two weeks before spontaneously improving. Most patients show a good functional recovery. The visual acuity at one year was 20/40 or better in 95% of the placebo group of the Optic Neuritis Treatment Trial (ONTT) with a median visual acuity of 20/16. The cumulative probability of having recurrent optic neuritis after ten years’ follow-up in the ONTT was 35% for either eye, although the overall visual prognosis was good with the median visual acuity being 20/16–2. The risk of MS developing at ten years in those who had clinically isolated optic neuritis on entry to the trial was 38%. The risk increased if asymptomatic brain lesions were seen on baseline magnetic resonance imaging (MRI). The risk of MS was 22% in those with no lesions and 56% when one or more lesions were present.

DIAGNOSIS

Clinical signs and symptoms

Optic neuritis usually presents as an acute unilateral impairment of vision with retro-ocular pain and pain on eye movement, although in about 10% of cases it is painless. The degree of visual loss varies from minor blurring to no perception of light in the affected eye. Decreased colour vision, a central or para-central scotoma and a relative afferent pupillary defect are also usually seen on examination. The optic disc may appear swollen but is often normal in appearance (Figure 316.1).

Laboratory findings

In the main, optic neuritis is a clinical diagnosis and in typical cases further investigation is not essential in making the diagnosis. If any atypical features for optic neuritis lead to suspicion of an alternative diagnosis then prompt investigations are required.

Orbital MRI, particularly if gadolinium-enhanced, will usually demonstrate the symptomatic lesion. The principal use of MRI is to assess the brain for asymptomatic lesions which can help to define the risk for the future development of MS as described above. Visual evoked potentials (VEP) may not be helpful in differentiating between different causes of optic neuropathies in the acute phase, although the combination of VEP with a pattern electroretinogram may be useful in differentiating macular from optic nerve disorders. A cerebrospinal fluid (CSF) examination is useful when there is clinical doubt and

FIGURE 316.1. Typical swollen optic disc in a patient with acute optic neuritis.

an infectious or other inflammatory optic neuropathy needs to be excluded. Testing the CSF for oligoclonal bands may also help in counseling the patient about their risk for the development of MS.

Differential diagnosis

●Inflammatory corticosteroid-dependent optic neuropathy.

●Neuromyelitis optica.

●Compressive optic neuropathy.

●Infectious optic neuropathy.

●Anterior ischemic optic neuropathy.

●Leber’s hereditary optic neuropathy.

●Toxic optic neuropathy.

●Nutritional optic neuropathy.

●Posterior scleritis.

●Central serous retinopathy.

●Acute zonal occult outer retinopathy (AZOOR).

●Big blind spot syndrome.

PROPHYLAXIS

The β-interferons can be used to delay the onset of MS and, thereby possibly, prevent further relapses of optic neuritis.

TREATMENT

Systemic medical treatment may be used.

Corticosteroids

High-dose parenteral corticosteroids speed up visual recovery in acute optic neuritis but do not affect long-term outcome. Intravenous methylprednisolone (IVMP) is usually administered in a dose of 1 g/day for three days, which may be followed by oral prednisolone 1 mg/kg/day for 11 days and a short dose-taper.

A meta-analysis showed that steroids reduced the number of patients without clinical improvement at 30 days (odds ratio 0.60, range 0.42–0.85) but did not cause long-term improvement in disability (odds ratio 0.96, range 0.71–1.31). The ONTT randomized patients to receive IVMP, oral prednisolone, or placebo. The benefit of IVMP in speeding up visual recovery was greatest between days four to 15 but the treatment advantage declined such that by one year no treatment benefit was seen. When the presenting visual acuity was 20/40 or better then IVMP conferred no benefit, even during the initial stages of recovery. Oral prednisolone produced no significant improvements in the rate of recovery and its use was associated with a persistent increased risk of recurrence of optic neuritis compared with IVMP or placebo.

The use of IVMP seemed to decrease the risk of the development of MS in the ONTT after two years in those patients with an abnormal brain MRI. However, the findings were based on a retrospective analysis with an open-label treatment (there was no intravenous placebo arm) with only small numbers developing MS. Also, 50 patients were lost to follow-up, which may have had a confounding effect. The apparent beneficial effect of IVMP was lost by 3 years and the use of IVMP did not affect the eventual development of neurological disability from MS.

The prognosis following childhood optic neuritis is generally excellent and in a case with mild visual impairment then the child may merely be observed. In a case with severe visual loss then three days of 15 mg/kg/day IVMP may help to improve vision, although trial data are lacking.

β-Interferons

Two recent trials have demonstrated that the β-interferons can slow down the progression to MS following an isolated demyelinating event. The CHAMPS study recruited 383 patients (192 with optic neuritis) who, in addition, had two or more clinically silent brain lesions on MRI and randomized them to receive once weekly 30 μg intramuscular interferon β-1a or placebo injections. The trial was stopped early after an interim analysis since the cumulative probability of the development of MS during the three-year follow-up period was significantly lower in the interferon group than in the placebo group (rate ratio 0.56; 95% CI 0.38–0.81; p = 0.002). There was also a relative reduction in new lesion activity on MRI in the interferon group (p < 0.001). In the ETOMS study, 309 patients (98 with optic neuritis) with four asymptomatic white matter lesions (or three if one was enhancing after administration of gadolinium) were randomized to receive once weekly subcutaneous 22 μg interferon β-1a or placebo injections. After two years the odds ratio for conversion to MS was 0.61 (95% CI 0.37–0.99; p = 0.045) in the treatment group compared with the placebo group, again with less new lesion formation in the treatment group (p < 0.001).

These results are consistent with previously reported trials of the β-interferons in relapsing-remitting MS suggesting that, in patients at high risk of developing MS, the β-interferons have reduced the relapse rate, but not necessarily the eventual occurrence of MS. Longer-term follow-up is needed to ascertain whether the development of persistent disability is delayed by early introduction of a β-interferon.

The absolute risk of developing MS after optic neuritis, even with asymptomatic brain lesions on MRI, is still relatively small and many physicians wait and re-image patients after an interval to see if new brain lesions have developed. This may then lead to a diagnosis of MS according to the McDonald cri-

teria and a potentially greater absolute benefit of treatment with a β-interferon, although trial data to support this approach do not at present exist.

COMPLICATIONS

Corticosteroids are generally well-tolerated. Common minor adverse effects reported include insomnia, mild mood changes, stomach upsets, facial flushing, acne, edema and weight gain. However, serious side effects following their use have been reported including psychosis, acute pancreatitis, avascular necrosis of the femoral head and deaths in two children from chicken pox. The β-interferons have been particularly reported to cause influenza-like symptoms, depression and injection-site reactions, although serious adverse events are rare.

COMMENTS

Optic neuritis usually causes acute painful unilateral visual disturbance with most patients making good spontaneous recoveries. Parenteral corticosteroids can speed up the visual recovery but without affecting long-term visual prognosis; IVMP may delay the onset of MS, but this remains controversial. As significant side effects can occur with the use of highdose corticosteroids, their use is not obligatory and an expectant approach is reasonable. The β-interferons are generally well tolerated and can delay the development of MS in patients after an isolated episode of optic neuritis if they have asymptomatic brain lesions on MRI. However, the effects on long-term development of disability are not known.

SUPPORT GROUPS

The National Multiple Sclerosis Society, 733 Third Avenue, New York, NY 10017, USA.

www.nationalmssociety.org

Multiple Sclerosis Society of Great Britain and Northern Ireland, MS National Centre, 372 Edgware Road, London, NW2 6ND, UK.

www.mssociety.org.uk

REFERENCES

Beck RW, Cleary PA, Anderson MM, Jr, et al: A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 326,581–588, 1992.

Comi G, Filippi M, Barkhof F, et al: Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576–1582, 2001.

Hickman SJ, Dalton CM, Miller DH, et al: Management of acute optic neuritis. Lancet 360:1953–1962, 2002.

Jacobs LD, Beck RW, Simon JH, et al: Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 343:898–904, 2000.

McDonald WI, Compston A, Edan G, et al: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127, 2001.

The Optic Neuritis Study Group: Visual function more than 10 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. Am J Ophthalmol 137:77–83, 2004.

Neuritis Optic • 316 CHAPTER

Nerve Optic • 28 SECTION

317 PAPILLEDEMA 377.00

Andrew W. Lawton, MD

Little Rock, Arkansas

ETIOLOGY/INCIDENCE

Papilledema is swelling of the optic discs due to increased intracranial pressure (ICP). A small percentage of patients with increased ICP in part of the subarachnoid system will have normal optic discs with spontaneous venous pulsations or a single elevated disc.

COURSE/PROGNOSIS

The early recognition of increased ICP is critical. Headaches may be the most intrusive sign of elevated ICP. Optic nerve destruction can occur, however, with devastating swiftness, even in those with few symptoms.

Causes of optic nerve damage include alteration of axoplasmic flow with interruption of the intracellular pumping process from the axon to the intraocular cell, venous stasis due to retardation of outflow through the central retinal vein, and interference with autoregulation of the central retinal artery circulation, evidenced by transient obscurations of vision. As nerve tissue is lost, the appearance of optic nerve swelling decreases until a heavily damaged optic nerve flattens out. A 4+ swollen disc may function normally while a non-edematous disc may be completely nonfunctional.

DIAGNOSIS

Clinical signs and symptoms

Patients may be unaware of visual loss despite permanent optic nerve damage. The initial visual change is enlargement of the blind spot on perimetry. In severe papilledema, encroachment of intraretinal fluid and exudates on the macula reduces central vision (Figure 317.1). The first true sign of compromise of optic nerve health is peripheral perimetric depression, particularly in the inferonasal region which may expand into arcuate bundle scotomas. Eventually, nerve fiber loss progresses until the papillomacular bundle suffers and central vision deteriorates.

Characteristic symptoms include holocranial headaches (worst on awakening) associated with neck and back pain, transient obscurations of vision, intermittent or constant diplopia, pulsatile tinnitus, and nausea with vomiting.

Initial findings on posterior segment examination include opacification of the peripapillary nerve fiber layer, venous dilation, and loss of retinal spontaneous venous pulsations. As the papilledema worsens, the optic disc develops peripheral elevation with preservation of the central cup. Hemorrhages may occur on the optic disc surface and peripapillary nerve fiber layer. The retina and choroid become distorted with the formation of Paton’s lines. Chronic optic disc edema results in a haze of the anterior disc surface from gliosis, progressive optic disc pallor due to optic atrophy, and the development of pale areas (pseudo-drusen).

FIGURE 317.1. Papilledema.

Laboratory findings

The definition of ‘elevated intracranial pressure’ and the risk of injury are affected by fluctuations in ICP levels throughout the day. A pressure below 20 cm water is normal, over 25 cm abnormal, and between 20 cm water and 25 cm water potentially abnormal based on visual function. Serial lumbar punctures provide little assistance in patient care once IIH is diagnosed. In IIH, the CSF composition is normal.

Differential diagnosis

Idiopathic intracranial hypertension (IIH, pseudotumor cerebri) is elevation of intracranial pressure without a discernable etiology. Patients tend to be female, of childbearing age, and overweight. Neuro-imaging studies are normal but may show compressed ventricles. The brain shows both intracellular and extracellular edema. IIH is a diagnosis of exclusion: the MRI and the CSF composition must be normal.

Intracranial masses and hydrocephalus produce a papilledema with a higher likelihood of permanent visual loss. The mechanism underlying this process is different from that of IIH. Interruption of cerebrospinal fluid egress that can occur through infectious agents, subarachnoid hemorrhage, proteins secreted by tumors, and other intermediaries results in an extracellular accumulation of fluid. Without the counterbalancing effect of the intracellular edema present in IIH, the ventricular system and subarachnoid space expand. This imbalance puts stress on the lamina cribrosa and optic nerve vascular supply. Circadian fluctuation increases the impact by forcing the lamina cribrosa to move back and forth. External agents that may cause elevation of ICP include antibiotics (tetracycline derivatives, naladixic acid), vitamin A and its analogues, and corticosteroids. Medical conditions include severe iron deficiency anemia, sleep apnea, chronic renal disease with or without dialysis, pregnancy, arteriovenous fistulas, and dural sinus thrombosis.

TREATMENT

Systemic

The clinician should address any specific underlying cause. Discontinuation of offending medications, CPAP therapy and/