Ischemic Optic Neuropathies

14 Pages·2008·1.14 MB·English

R A
EVIEW RTICLE
Ischemic Optic Neuropathies
Katie Luneau, MD,* Nancy J. Newman, MD,*†‡ and Vale´rie Biousse, MD*†
Abstract: Anterior ischemic optic neuropathy (AION) is the most
commoncauseofacuteopticneuropathyafterage50,butmayalso Ischemic optic neuropathies can be divided into
occur in younger patients. The diagnosis is clinical and includes
painless visual loss associated with a relative afferent pupillary nonarteritic and arteritic etiologies.
defect and disc edema. In almost all cases, there is an underlying
crowded optic nerve with a small cup-to-disc ratio. The visual
prognosis is usually poor, although up to 43% of patients may
Ischemic optic neuropathies can also be divided into
improve over time. The fellow eye is involved in up to 15% of
nonarteriticandarteriticetiologies.ArteriticION,classically
patientswithin5years,buttheriskofrecurrenceinthesameeyeis
duetogiantcellarteritis(GCA),isanophthalmologicemer-
lessthan5%.ThereisnotreatmentforacutenonarteriticAIONbut
gency,requiringpromptrecognitionandtreatmenttoprevent
it is essential to evaluate these patients for underlying treatable
devastating permanent blindness.1
atheromatous vascular risk factors. A coagulation workup should
Knowledgeofthevascularanatomyoftheopticnerveis
alsobeconsideredinyoungerpatients.Itisessentialtoruleoutgiant
helpfultounderstandthemechanismsofischemicopticneurop-
cell arteritis in all patients over the age of 50 with ischemic optic
athies.Theopticnervebloodsupplycomesfromtheophthalmic
neuropathies. Posterior ischemic neuropathy (in which the optic
artery,abranchoftheinternalcarotidartery.Thefirstbranchof
nerveisnormalacutely)israreandshouldbeconsideredadiagnosis
theophthalmicartery,thecentralretinalartery,enterstheoptic
ofexclusion.
nerve approximately1cmbehindtheeye,andsuppliestheinner
KeyWords:ischemicopticneuropathy,nonarteriticischemic partoftheretina.Theouterpartoftheretinaissuppliedseparately
opticneuropathy,arteriticischemicopticneuropathy,giantcell bythechoroidalarteries,whichoriginatefromtheposteriorciliary
arteritis,temporalarteritis arteries.Theposteriorciliaryarteriesrunalongtheopticnervefrom
theophthalmicarterytothechoroid,supplyingtheopticnervewith
(TheNeurologist2008;14:341–354)
smallpenetratingbranches.Theposteriorpartoftheopticnerveis
supplied by a surrounding pial plexus derived from these small
branchesofftheophthalmicandposteriorciliaryarteries.Theoptic
Ischemic optic neuropathies are the most common acute nerve head receives its arterial blood supply from an anastomic
optic neuropathies in patients over 50 years of age. The arterial circle (the circle of Zinn-Haller), formed by anastomoses
term ischemic optic neuropathy (ION) is used as a general between side branches of the short posterior ciliary arteries,
term to refer to all presumed ischemic causes of optic neu- branchesfromthenearbypialarterialnetwork,andfromchoroidal
ropathy. Depending on the segment of optic nerve affected, vessels (Fig. 3).1 The result of hypoperfusion of these vascular
ION is divided into anterior ischemic optic neuropathy networks is optic nerve ischemia, with varying clinical presenta-
(AION) and posterior ischemic optic neuropathy (PION). tions,dependingonthesegmentofopticnerveinvolved.
Optic disc edema from ischemia to the anterior nerve is, by
Nonarteritic Anterior Ischemic
definition, present in AION (Figs. 1, 2) and absent in PION.
Optic Neuropathy
AION is much more common than PION, accounting for
90% of cases of optic nerve ischemia.1 Nonarteriticanteriorischemicopticneuropathy(NAION)is
presumably secondary to small vessel disease of the short
FromtheDepartmentsof*Ophthalmology,†Neurology,and‡Neurological
Surgery,EmoryUniversitySchoolofMedicine,Atlanta,Georgia.
Supported in part by a department grant (Department of Ophthalmology) Nonarteritic anterior ischemic optic neuropathy
fromResearchtoPreventBlindness,Inc.,NewYork,NewYork,andby
a core grant P30-EY06360 (Department of Ophthalmology) from the is secondary to small vessel disease of the short
NationalInstitutesofHealth,Bethesda,Maryland.ResearchtoPrevent
BlindnessLewR.WassermanMeritAward(toN.J.N.). posterior ciliary arteries, with resultant
Reprints: Vale´rie Biousse, MD, Neuro-Ophthalmology Unit, EmoryEye
Center, 1365-B Clifton Rd, N.E. Atlanta, GA 30322. E-mail: vbiouss@ hypoperfusion and infarction of the anterior
emory.edu.
Copyright©2008byLippincottWilliams&Wilkins optic nerve.
ISSN:1074-7931/08/1406-0341
DOI:10.1097/NRL.0b013e318177394b
TheNeurologist (cid:127) Volume14,Number6,November2008 341
Luneauetal TheNeurologist (cid:127) Volume14,Number6,November2008
posterior ciliary arteries, with resultant hypoperfusion and
infarction of the anterior optic nerve.1 Diagnosis is pri-
marily clinical, and, despite its high incidence, NAION
remains untreatable. The Ischemic Optic Neuropathy De-
compression Trial (IONDT), a large, multicentered pro-
spectivetreatmenttrial,hasprovidedvaluableinformation
on the natural history of NAION.2–5
Diagnosis
NAION typically occurs after the age of 50 years, but
cases in younger patients and even children are well docu-
mented.1,6Incidenceisestimatedat2.3to10.2casesperyear
per 100,000 persons aged 50 and older, and 95% of cases
occur in whites.1 The typical presentation is that of sudden,
painless monocular visual loss that progresses over hours to
weeks. Premonitory transient visual loss and ocular discom-
fort are infrequent in NAION.1,7
Examination in typical NAION reveals an optic neu-
ropathy, with decreased visual acuity, a relative afferent
pupillary defect, visual field loss, and optic disc edema,
often with peripapillary hemorrhages. Disc edema may be
diffuse or segmental, involving only the superior or infe-
rior portion of the optic disc (Figs. 1, 2). This may
correspondwithadivisionofthecircleofZinn-Hallerinto
distinct upper and lower halves.1 Similarly, the corre-
sponding visual field defect is often an inferior (most
common) or superior altitudinal or arcuate defect (Fig. 1).
Initial visual acuity varies widely from 20/20 to no light
perception. It is better than or equal to 20/64 in 31% to
52% of patients and worse than or equal to 20/200 in 34%
to54%ofpatients.1,7Fourto6weeksaftervisualloss,disc
edema resolves and optic disc pallor develops, often in a
sectoral pattern (Figs. 1, 2).1
Although the onset of visual loss is classically sudden
(as in all vascular events), progressive worsening of vision
over a few days or weeks is not uncommon in NAION. The
IONDTalsoshowedthatupto43%ofpatientswhopresented
withvisualacuityworsethan20/64spontaneouslyregained3
lines of visual acuity at 6 month follow-up, with 31% sus-
taining that benefit at 24 months.2–5
An important examination finding, usually
considered essential to the diagnosis of
nonarteritic anterior ischemic optic neuropathy,
is the presence of a small optic nerve with a
FIGURE1.Anteriorischemicopticneuropathy.A,Optic
nerveappearanceduringtheacutephaseshowingdiffuse small or absent physiologic cup in the
discedemawithperipapillaryhemorrhages.B,Twomonths
later,thediscedemahascompletelyresolvedandthereis unaffected eye.
superiorsegmentalopticnervepallorcorrespondingtothe
inferiorvisualfielddefectshowninC.C,Humphreyvisual
fieldoftherighteyeshowinganinferiorarcuatedefectin
thispatientwithnonarteriticanteriorischemicopticneurop-
An important examination finding, usually consid-
athy.Visualacuityis20/40inthateye,thereisarightrela-
ered essential to the diagnosis of NAION, is the presence
tiveafferentpupillarydefectandcolorvisionisnormal.
of a small optic nerve with a small or absent physiologic
342 ©2008LippincottWilliams&Wilkins
TheNeurologist (cid:127) Volume14,Number6,November2008 IschemicOpticNeuropathies
FIGURE2.Anteriorischemicopticneuropathy.Nonarteriticanteriorischemicopticneuropathyofthelefteyeinthesettingof
severeanemiafromdysfunctionaluterinebleeding.A,Opticnerveappearanceattheacutephaseshowingdiscedemaofthe
lefteye.B,Oppositeeye(righteye)showingtheabsenceofdiscedemaandtheclassicdisc-at-riskconfiguration(smallcup-
to-discratioof(cid:1)0.1).C,Twomonthslater,thediscedemainthelefteyeisresolvingandthereissuperiorsegmentalopticnerve
pallor.
cup (termed “disc-at-risk”) in the unaffected eye (Figs. 2, nerve or optic nerve sheath should suggest an alternative
4).1,8,9 Therefore, it is imperative to examine both optic diagnosis other than NAION.1
nervesandtobeabletorecognizethisabsenceofcupping.
It is thought that an anatomically small, crowded optic
Risk Factors and Recurrence
nerve predisposes patients to NAION via mechanical fac-
tors such as crowding with impaired axonal flow and Although the precise pathophysiology of NAION re-
resultant compromise of the laminar microcirculation.1,8,9 mains unknown, studies have reported the association of
Whites tend to have small cup-to-disc ratios, which may NAION with optic nerve anomalies and systemic disorders
explain why they predominate among AION patients.1,10 (Table 2).1,8 Many even consider NAION to be a form of
The absence of a disc-at-risk appearance in a patient with ischemic stroke. However, even if NAION and intracranial
presumed NAION should raise the possibility of arteritic cerebrovascular disease share similar risk factors, they rep-
AION or another cause of optic neuropathy. resent 2 different entities and they do not share the same
NAION must be differentiated from other causes of mechanisms.1
acute optic neuropathies, such as idiopathic optic neuritis, Asemphasizedabove,themainriskfactorforNAION
infectious optic neuritis or compressive optic neuropathies is the presence of an anomalous optic nerve. A disk-at-risk
(Table 1).1,11,12 Occasionally, fat suppressed magnetic reso- (smallopticnervewithasmallorabsentphysiologiccup)is
nance imaging (MRI) of the optic nerve (with contrast) may usuallypresenteveninpatientswhomayhaveanotherreason
be helpful, wherein the finding of enhancement of the optic to develop NAION (such as perioperative AION or AION
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Luneauetal TheNeurologist (cid:127) Volume14,Number6,November2008
FIGURE3.Vascularsupplytotheop-
ticnerve.Theeyehasadualvascular
supply,witharterialcontributions
fromboththechoroidalandcentral
retinalcirculations,bothofwhich
originatefromtheophthalmicartery,
abranchoftheinternalcarotidartery.
ReprintedwithpermissionfromThe
RequisitesinOphthalmology—Neuro-
Ophthalmology.Missouri:Mosby,
2000.
occurring in association with medication use). Other optic occlusive disease (especially dissections) and poor collateral
nerve anomalies such as papilledema, or optic nerve head blood supply.20 It is therefore not necessary to routinely
drusen, can also be complicated by AION, most likely be- obtain a carotid ultrasound examination in patients who
cause of impaired axonal flow, and resultant compromise of develop AION. However, if the patient complains of visual
the laminar microcirculation.1,8,13 symptomssuggestiveofhypoperfusionoftheeye(ie,blurred
vision with changes of posture, with bright light or during
exercise), or if the AION was preceded by, or associated
with, contralateral neurologic symptoms and signs, transient
Systemic diseases associated with an increased monocular visual loss, Horner syndrome, or orbital pain,
noninvasive carotid imaging should be obtained to identify
risk of nonarteritic anterior ischemic optic
patients at risk for further embolic or hemodynamic
neuropathy include systemic hypertension events.1,20
Rarely, hypercoagulable states have been associated
and diabetes.
with NAION; however, case-controlled studies have given
various results. It is suggested that thrombotic factors, in
particularhomocysteine,bemeasuredinpatientslessthan45
yearsoldwithNAIONwithoutothervascularriskfactors,in
Systemic diseases associated with an increased risk of
bilateral simultaneous NAION, in NAION recurrent in the
NAION include systemic hypertension (in about 50%) and
sameeye,inNAIONwiththeabsenceofasmallcup-to-disc
diabetes (in about 25%).1,4,8,14–16 Ischemic heart disease,
ratio, and in familial NAION.1,21–25
hypercholesterolemia, stroke, tobacco use, sleep apnea, and
Acute bleeding with anemia and systemic hypoten-
systemic atherosclerosis have also been associated,1,17,18 but
sion can result in unilateral or bilateral AION (Fig. 2) (see
few rigorous population-controlled studies have been per-
below). Similarly, fluctuations in blood pressure, espe-
formed.
cially in anemic patients, such as those with chronic renal
Nonarteritic AION is a disease of the small vessels
insufficiency receiving dialysis, may precipitate AION.1,8
supplyingtheopticnerveheadandisclinicallynotassociated
Hayreh reported that visual loss in AION was most fre-
withipsilateralinternalcarotidarterystenosis;embolicAION
isextremelyrare.1,16,19Aswithsmallvesseldiseaseaffecting quently recognize upon awakening, and proposed noctur-
thecentralnervoussystem,someassociationbetweencarotid nal hypotension as a mechanism.26 This finding was not
occlusivediseaseandacuteAIONhasbeensuggested.How- confirmed in the IONDT.4
ever,inmostcasesofAION,theopticneuropathyisasignof Multiple medications have been implicated in the
widespread atherosclerosis affecting both large and small occurrence of NAION, such as amiodarone, interferon-(cid:1),
vessels,reflectingsharedriskfactorssuchashypertensionor nasal decongestants, various vasopressors or vasocon-
diabetesmellitus.Exceptionally,opticnerveinfarctionresults stricting drugs, and phosphodiesterase inhibitors erectile dys-
from reduced perfusion pressure secondary to severe carotid function drugs.1,27–32 However, establishing a direct relation-
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TheNeurologist (cid:127) Volume14,Number6,November2008 IschemicOpticNeuropathies
In the past few years, the association of erectile dys-
function drugs and NAION has been of particular interest.
The World Health Organization standards suggest a possible
association, but there is not enough data to establish a
cause-and-effect relationship. Furthermore, there is no evi-
dencethatsupportsthepracticeofscreeningerectiledysfunc-
tiondrugusersforasmallcup-to-discratio,afeaturepredis-
posing to spontaneous NAION.32
Acute elevation of intraocular pressure, such as during
ocular surgeries or during an attack of angle closure glau-
coma, may also precipitate NAION.1,33–35
NAION recurs in the affected eye in less than 5% of
patients.5ItispossiblethatatrophyofthenerveafterNAION
relieves crowding and reduces recurrence risk. Because pa-
tients often have a disc-at-risk in both eyes, it is not uncom-
mon to observe bilateral NAION, usually sequentially rather
than simultaneously. The risk of second eye involvement is
12% to 15% at 5 years and seems to be related to poor
baselinevisualacuityinthefirsteyeandtodiabetes,butnot
to age, sex, smoking history, or aspirin use.1,5,8 There is a
modest correlation of final visual acuities between eyes in
bilateral, sequential NAION, with approximately 50% of
patients having Snellen visual acuities within 3 lines of one
another.5
Treatment
ThereisnoestablishedtreatmentforNAION,although
a number of medical and surgical treatments have been
evaluated. The clinician’s primary role in managing patients
with this disorder is exclusion of GCA and to detect and
control vascular risk factors.1
Subtenon injection of vasodilators, intravenous or
topicalintraocularpressure-loweringagents,vasopressors,
stellate ganglion block, levodopa, carbidopa, diphenylhy-
dantoin, anticoagulants, aspirin, oral corticosteroids, hy-
perbaric oxygen, transvitreal optic neurotomy (opening of
the scleral canal), optic nerve sheath decompression, and
intravitreal injection of corticosteroids have been used in
FIGURE4.Illustrationofthecup-to-discratio.Theratioof some cases with NAION and have not proven useful for
cupsizetothediameteroftheopticdiscdeterminesifthe the treatment of acute NAION (Table 3 summarizes the
patienthasa“disc-at-risk”forNAION.A,Smallopticdisc most recent studies).2,5,36–48 However, most studies were
withcup-to-discratioof(cid:1)0.1.Thisistheclassicdisc-at-risk retrospective, nonrandomized, and small. Although it has
inNAION.B,Largecup-to-discratio(0.85)suchasoften been suggested that neuroprotective agents (especially
seeninpatientswithglaucoma. those that can be administered topically or directly in the
eye) may be efficacious in acute treatment of NAION, this
remainstobedemonstratedinacontrolledstudy.Although
ship between use of a specific medication and NAION is afewretrospectivestudieshavesuggestedthataspirinmay
problematic because most patients have concurrent vascu- help prevent fellow eye involvement, this remains unre-
lar risk factors and an underlying disc-at-risk. When pos- solved. However, because aspirin is beneficial in primary
sible, it is generally recommended to discontinue such med- and secondary prevention of most atherosclerosis-related
ications in patients with AION. A recent study31 proposed vascular diseases, it is reasonable to prescribe aspirin in
some criteria to help differentiate amiodarone optic neu- NAION patients.1
ropathy from NAION, including bilateral onset or atypical
features of NAION, such as an insidious onset of symp- Diabetic Papillopathy and Pre-AION Optic
toms, milder optic nerve dysfunction and disc edema, or a Disc Edema
generous cup-to-disc ratio in the fellow eye of patients. In Patients may develop disc swelling from AION before
suspected cases, amiodarone, when possible, should be theyhaveanyvisualsymptoms.1,49,50Theasymptomaticdisc
discontinued under medical attention. swelling(“premonitory”or“incipient”AION)isoftennoted
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TABLE1. ClinicalCharacteristicsofInflammatoryOpticNeuritis,NonarteriticAIONandArteriticAION
OpticNeuritis AIONNonarteritic AIONArteritic
Ageofpatients Younger Older((cid:2)50yr) Older((cid:2)65yr)
Race Nodifference Nodifference Morecommoninwhites
Sex Morecommoninwomen Nodifference Morecommoninwomen
Laterality Unilateral Unilateral Uni-orbilateral
Visualloss Rapidlyprogressive Acute Acute
Acuityrarelyspared Acuityvariable Severevisualloss
Pain Orbitalpainfrequentwitheyemovements Paininfrequent Headachecommon
Colorvision Commonlyabnormal Commonlysparedifvisiongood Correlateswithvisualacuity
Visualfield Centraldefects Altitudinaldefect Anydefect(severe)
Opticdisc
Acute Normal(2/3)ordiscedema(1/3) Discedema,segmental;small Discedema,pallid;
cup-to-discratio retinal/choroidalinfarction
Late Temporalpallor Segmentalpallor Diffusepallor,cupping
Visualprognosis Good Variable Poor
25%recurrencerisk 15%secondeyeat5yr 75%secondeyewithin2wk
Systemicdiseases Riskofmultiplesclerosis HTN(51%),DM(24%) GCA/PMR
GCAtoberuledout 25%havenoGCAsymptoms
GCAindicatesgiantcellarteritis;HTN,hypertension;DM,diabetesmellitus;PMR,polymyalgiarheumatica.
inthefelloweyeofapatientwithaprevioushistoryofAION.
TABLE2. DisordersandDrugsSuggestedtobeAssociated The mechanism of disc swelling in these cases is presumed
WithAION ischemic.1,49,50
Arteriticanteriorischemicopticneuropathy Similarly, young patients with diabetes mellitus may de-
Giantcellarteritis(cid:3)(cid:3)(cid:3) velop disc swelling in 1 eye with no or very mild visual loss,
Periarteritisnodosa so-called diabetic papillopathy. The swelling may be unilateral
Churg-Strausssyndrome orbilateralandthevisualprognosisisusuallyexcellent.Inmore
Wegener’sgranulomatosis than80%ofreportedcases,diabeticretinopathyispresentatthe
Connectivetissuediseasessuchassystemiclupuserythematosus time of onset of diabetic papillopathy. The mechanism remains
Rheumatoidarthritis unknown,althoughischemiaoftheopticnerveheadismostlikely.
Relapsingpolychondritis Anotherpotentialcauseofopticnerveswellingintheseandother
Non-Arteriticanteriorischemicopticneuropathy patientsisvitrealtraction.1,49
Anomalousopticnerve
“Disc-at-risk”:smallcrowdedopticnerve Arteritic Ischemic Optic Neuropathy
Papilledema AIONisthemostcommonophthalmicmanifestationof
Opticnerveheaddrusen GCA(Table4).1ArteriticAIONisaneuro-ophthalmicemer-
Elevatedintraocularpressure(acuteglaucoma,ocularsurgery)
Radiation-inducedopticneuropathy
Diabetesmellitus/diabeticpapillopathy
Othervascularriskfactors(atherosclerosis) Arteritic anterior ischemic optic neuropathy is
Hypercoagulablestates*
a neuro-ophthalmic emergency, which is
Acutesystemichypotension/anemia
Bleeding
exceedingly important to recognize and
Cardiacarrest
Perioperative(especiallycardiacandspinesurgeries) differentiate from nonarteritic anterior
Dialysis
ischemic optic neuropathy, to prevent further
Sleepapnea
Drugs devastating visual loss.
Amiodarone
Interferon-(cid:1)
Vasoconstrictoragents(suchasnasaldecongestant)
Erectiledysfunctiondrugs(phosphodiesteraseinhibitors) gency, which is exceedingly important to recognize and
*HypercoagulablestatesarerarelyresponsibleforAIONandshouldonlybetested differentiate from NAION, to prevent further devastating
forinyoungerpatientsunderage50withoutotherriskfactorsforAION. visual loss. Although GCA is the most common cause of
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TABLE3. StudiesEvaluatingtheTreatmentofNAIONPublishedSince1996
Study
Author Year Treatment Type No.Patients Outcome ConclusionsoftheStudy
AcutetreatmentofAION
IONDT2 1995 ONSF P 258total(127 Nodifferenceinvisual ThereisnoroleforONSFin
treated,131 outcome;24%ofsurgical acuteNAIONtreatment
untreated) patientsworsened
Arnoldetal36 1996 Hyperbaric P 22treated,27 Nosignificantdifferencein Hyperbaricoxygendoesnot
oxygen untreated finalVA improvevisualoutcomeof
affectedeye
Botelhoetal37 1996 Aspirin R 78total(23treated, Nosignificantdifferencein Aspirindoesnotimprove
55untreated) finalVA visualoutcomeofaffected
eye
Johnsonetal38 2000 Levodopa R 37total(18treated, ImprovedVAat6mo Levodopamayimprove
19untreated) 76.9%oftreated visualoutcomeofaffected
30%ofuntreated eye
NochangeinVF
Soheilianetal39 2003 Transvitrealoptic R 7treated 6of7patientshadsome Transvitrealopticneurotomy
neurotomy improvementinVA maybehelpfulinAION
withseverevisualloss
Fazzoneetal40 2003 Topical R 31total(14treated, Thegrouptreatedwith Topicalbrimonidinedoes
brimonidine 17untreated) brimonidinehadworse notimprovevisual
visualfunctionat8–12wk outcomeofaffected
eye
Simseketal45 2005 Levodopaand P 24total — Levodopaandcarbidopadoes
carbidopa notimprovevisual
outcomeofaffectedeye
Wilhelmetal44 2006 Topical P 36total(29 Nosignificantdifferencein Topicalbrimonidineisnot
brimonidine analyzed)(18 finalVA harmful,butdoesnot
treated,11 improvevisualoutcomeof
untreated) affectedeye
Jonasetal46 2007 Intravitreal P 3treated Maynotbemarkedlyeffective Needrandomizedcontrolled
triamcinolone inincreasingVA trials
Kaderlietal47 2007 Intravitreal P 10total(4treated,6 Thetreatedgroupshowed Alargertrialismeritedby
triamcinolone untreated) relativelyimproved theresultofthissmall
recoveryofVAandrapid pilotstudy
reductioninopticdisc
edema—nomarkedchange
inVF
SecondarypreventionofAION(preventionoffelloweyeinvolvement)
Kupersmithetal41 1997 Aspirin R 100total:57treated, NAIONinfelloweye:at2yr Aspirinmaydecreaseriskof
43untreated (17.5%oftreated,53.5% AIONinthefelloweye
ofuntreated)
Becketal42 1997 Aspirin R 431total:153 NAIONinfelloweye:at2yr Aspirindoesnotdecrease
treated,278 (7%oftreated,15%of riskofAIONinthefellow
untreated untreated)andat5yr eye
(17%oftreated,20%of
untreated)
Salomonetal43 1999 Aspirin R 52total:36treated, NAIONinfelloweye:22.2% Aspirinmaydecreaseriskof
16untreated oftreated,50%of AIONinthefelloweye
untreated
IONDT5 2002 Aspirin P* 326total:at NAIONinfelloweye:aspirin Aspirindoesnotdecrease
baseline†(87 atbaseline(20%of riskofAIONinthefellow
treated,237 treated,13%ofuntreated); eye
untreated);and aspirinafterbaseline(15%
afterbaseline‡(86 oftreated,15%of
treated,240 untreated)
untreated)
*AlthoughtheIONDTwasaprospectivetrialtoevaluateopticnervesheathdecompression,itwasnotaprospectivetrialtoevaluateaspirintherapy.Aspirindataareobservational
only.
†Reportedstartingregularaspirinuse(cid:2)1mobeforeonsetofsymptomsatbaselinevisit.
‡Respondedpositivelyto“startedregularuse”ofaspirinonatleast1studyvisitafterbaseline.
Rindicatesretrospective;P,prospective;VA,visualacuity;VF,visualfield;ONSF,opticnervesheathfenestration.
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ofvisuallosstendstobemoresevereinarteriticAION,with
TABLE4. OphthalmologicManifestationsofGiant
initial visual loss being between count fingers and no light
CellArteritis
perception in 54% of patients, compared with 26% of
Ischemicopticneuropathy NAION patients1,54 if untreated, arteritic AION becomes
Anteriorischemicopticneuropathy bilateralwithindaystoweeksinatleast50%ofcases1,54;(5)
Posteriorischemicopticneuropathy theaffectedswollenopticnerveisoftenpaleacutelyinGCA
Choroidalinfarction (Fig. 5), whereas pallor is delayed in NAION1; and (6) a
Centralretinalarteryocclusion disc-at-riskisnotnecessaryforarteriticAION,butifpresent,
Branchretinalarteryocclusion doesnothelptodifferentiatearteriticAIONfromNAION.1,7
Cilioretinalarteryocclusion Indeed, the absence of a crowded optic nerve in the fellow
Ophthalmicarteryocclusion eye of a patient with AION should make the diagnosis of
Ischemicocularsyndrome NAION unlikely and should raise the possibility of arteritic
Cornealedema AION.Athoroughhistory(lookingforsystemicsymptoms),
Anterioruveitis and a careful ocular examination evaluating the cup-to-disc
Cataract ratio and looking for other signs of ocular ischemia, are of
Irisneovascularization paramount importance in the diagnosis of arteritic AION. In
Ocularhypertension(neovascularglaucoma) difficult cases, retinal fluorescein angiography can be very
Ocularhypotony helpful at detecting choroidal hypoperfusion and delayed
Retinalhemorrhages(venousstasisretinopathy) choroidal filling (Fig. 5).1
Retinalneovascularization
Orbitalischemia Diagnostic Tests
Orbitalpain
Laboratory testing may be useful in the diagnosis of
Diplopia(ischemiaoftheextraocularmuscles)
arteritic AION. An elevated erythrocyte sedimentation rate
Proptosis
(ESR) is generally well accepted in the diagnosis of GCA.
Cranialnerveischemia
However, different studies have shown a better sensitivity
Diplopia(III,IV,andVInerveischemia)
for diagnosis when ESR is combined with C-reactive
Cerebralischemia
protein (CRP). Together, they have been reported to be
Brainstemischemia(diplopia)
highly predictive of biopsy-proven GCA, with a combined
Occipitallobeinfarction(cerebralblindness) sensitivity of 97%.56
Visualhallucinations
Tonicpupil
Hornersyndrome
Other tests must be obtained in addition to
arteriticAION,othervasculitidessuchasperiarteritisnodosa
should also be considered (Table 2).1 erythrocyte sedimentation rate when giant cell
arteritis is suspected; C-reactive protein,
Diagnosis
Temporalarteritisoccurspredominantlyinwomenand fibrinogen, complete blood count, and platelets
inwhites.TheprevalenceofGCAincreaseswithageandthe
should always be obtained in addition to the
annual incidence is approximately 20 per 100,000 persons
aged50yearsorolder.51,52Mostpatientsareoverage65,but erythrocyte sedimentation rate.
GCAmustbesuspectedineverypatientover50.Upto50%
ofpatientswithGCApresentwithocularsymptoms;ofthose,
70% to 80% have arteritic AION (Table 4).1,51 The clinical
presentation of arteritic AION is similar to that of NAION,
but numerous red flags should raise clinical suspicion for Because normal values of ESR are known to increase
arteritic AION rather than NAION (Table 1),1,7,53–55: (1) with age, and are higher in women, the ESR should be
systemicsymptomssuchasjawclaudication,headache,scalp adequatelyadjusted(Table5).56,57AnelevatedESRisuseful
tenderness, neck pain, proximal weakness, malaise, weight because it correlates with the disease process, hence facili-
loss,andfevermayprecedevisuallossbymonths;however, tating monitoring of the disease. The ESR is greater than 40
about 25% of patients with positive temporal artery biopsies mm/hinatleast77%ofpatientswithactive,untreatedGCA.
do not exhibit these systemic symptoms54; (2) permanent However, the ESR is a nonspecific marker of a variety of
visual loss from arteritic AION is sometimes preceded by inflammatory, infectious, and neoplastic disorders, and may
episodes of transient visual loss (30%) or transient diplopia be normal in 7% to 20% of patients with GCA before
(5%–10%) secondary to ischemia to the optic nerve head, treatment. Therefore, a normal ESR does not rule out GCA,
extraocular muscles, or cranial nerves54,55; (3) the finding of andthelevelofelevationofESRdoesnotcorrelatewiththe
peripapillary,retinal,orchoroidalischemiainadditiontothe severity of the disease.51,52,58 Therefore, other tests must be
AIONishighlysuspiciousforGCA(Fig.4)1;(4)thedegree obtained in addition to ESR when GCA is suspected; CRP,
348 ©2008LippincottWilliams&Wilkins
TheNeurologist (cid:127) Volume14,Number6,November2008 IschemicOpticNeuropathies
FIGURE5.Normalappearingopticnervesinapatientwithgiantcellarteritis.Funduscopicexaminationofapatientwhohad
1episodeoftransientvisuallossinthelefteye,associatedwithnewonsetheadacheandjawclaudication.A,Normalappear-
ingfundusrighteye.B,Normalappearingfunduslefteye.C,Retinalfluoresceinangiographyofthesamepatientshowing
delayedandpatchychoroidalfillinginthelefteye(normalchoroidsshouldappear“white”(filledwithfluorescein)approxi-
mately30secondsafterinjection;inthispatient,fillingisdelayedinferiorlymorethan1minuteafterinjection).
provides a slightly greater sensitivity for the diagnosis of
TABLE5. FormulasProposedtoDeterminetheNormalESR
GCA (sensitivity of 99%) than the use of either test alone.
BasedonthePatient’sAge
In active inflammatory disease, fibrinogen and platelet
Hayrehetal56 countarefrequentlyelevated,mostpatientswillpresentwith
Men:17.3(cid:3)(0.18(cid:4)age) Women:22.1(cid:3)(0.18(cid:4)age) a mild-to-moderate anemia, and approximately one third of
Milleretal†57 patientswillhavemildlyabnormalliver-functiontests.51,52,58
Men:ageinyears/2 Women:(ageinyears(cid:3)10)/2 Fluorescein angiography is often very useful in the
*Basedonastudyof363patientswithsuspectedGCA,106ofwhomhadbiopsy diagnosisofGCA(Fig.5).Itisawidelyavailable,safe,and
provendiseaseand749controls. relatively inexpensive diagnostic tool for many retinal, cho-
†Basedonastudyof27,912individualsaged20–65.
roidal, and optic nerve disorders. As opposed to NAION
(which tends only to affect the posterior ciliary circulation),
fibrinogen,completebloodcountandplateletsshouldalways themultifocalnatureofarteriticAIONoftenleadstoinvolve-
be obtained in addition to the ESR.58 ment of both the posterior ciliary and choroidal circulations;
The CRP is an acute phase plasma protein of hepatic therefore, when extensive choroidal hypoperfusion is identi-
origin that rises before ESR in most disease states, and is fiedbyfluoresceinangiography(Fig.5)inthesettingofION,
often elevated in GCA. Studies have shown several advan- an arteritic etiology is highly likely.1,58
tages of CRP over ESR, including higher sensitivity and MRI is not a classic diagnostic test for AION. How-
specificity (98.6% and 75.7%, respectively), and relative ever, MRI of the orbits is often obtained as a component of
insensitivity to age, gender, and other hematologic parame- the diagnostic evaluation for a unilateral optic neuropathy.
ters.59 A recent study,60 showed that most patients with AlthoughtheMRIisnormalinNAION,orbitalfatenhance-
biopsy-provenGCAhavebothanelevatedESRandCRP,but ment and optic nerve and nerve sheath enhancement have
that there can be nonconcordance between those 2 tests, been reported in arteritic AION.1,58
either an elevated ESR with normal CRP, or a normal ESR Thetemporalarterybiopsy(TAB)isthegoldstandard
withanelevatedCRP.Theyshowedthattheuseofbothtests for definitive diagnosis of GCA. Although diagnosis of ar-
©2008LippincottWilliams&Wilkins 349
Luneauetal TheNeurologist (cid:127) Volume14,Number6,November2008
TABLE6. TherapeuticTrialsinArteriticAIONSince2000,ComparingIVSteroidsWithOralSteroidsinTermsof
VisualOutcome
Author Year StudyType No.PatientsandTreatment Outcome ConclusionoftheStudy
Chevaletetal63 2000 P 164total;1pulseof240mgIVof Samecumulativesteroids NobenefitofIVsteroids
methylprednisolonefollowedby dosesinbothgroupsat1yr. versuspo
posteroidsorposteroidsalone Nodifferenceintimeto
normalizelabsorsteroids
sideeffects
Changetal64 2001 R 73total;IVfollowedbyposteroids Improvementinvision:40%of Steroidscanimprovevision,
(43)orposteroidsalone(30), IVtreated,13%ofpo withsuperiorresultsforIV
differentregimensoftreatment treated steroidscomparedtopo
HayrehandZimmerman65 2003 LO 145total;IVfollowedbyPO Nodifferenceinvisual NobenefitofIVsteroids
steroids(48)orposteroidsalone outcomeorcumulativedose versuspo
(97),differentregimensof
treatment
Pindicatesprospective;R,retrospective;LO,longitudinalobservational;IV,intravenous;po,peros.
teritic AION may be suspected on clinical grounds, TAB steroids followed by high dose oral steroids are recom-
confirmation of GCA is mandatory, especially given the mended, although only a few prospective studies have
complication rate associated with the necessary subsequent evaluated this regimen, with different conclusions (Table
long-term corticosteroid therapy.1,51,52,58,61 Treatment must 6).63–65BeginningtreatmentwithIVcorticosteroidswhile
be promptly instituted while the diagnosis is suspected and the patient is hospitalized has several advantages, partic-
should not be delayed for TAB. Although treatment with ularly in an older population with multiple comorbidities,
corticosteroids will ultimately diminish the histopathologic who present with new onset visual impairment. It permits
findingsofactivearteritisonaTAB,itwillnotsubstantially achievement of a complete work-up, and better control of
change the sensitivity of a biopsy performed within 2 weeks corticosteroid side effects, such as elevations and fluctua-
ofinstitutedtreatment.Anegativeunilateralbiopsydoesnot tions in blood sugar levels.
necessarily rule out GCA. An adequate specimen must be Iforalprednisonealoneisused,dosesintherangeof1
submittedforpathology(aminimumof2cmlongisrecom- to2mg/kg/daresuggested.Maintenancetherapyinthisdose
mendedbecauseofskiplesions).Instronglysuspectedcases, range should be continued for at least 4 to 6 weeks, until
a second biopsy (on the opposite side) should be performed, normalization of laboratory inflammatory markers occurs, to
with an up to 5% chance of positivity.62 be followed by a slow taper over the next 12 to 18 months,
with careful follow-up of ESR and CRP. The rate of corti-
Treatment and Outcome costeroid taper is approximately 10 mg per month initially,
Corticosteroid-responsiveness and improved outcome then decreased to 5 mg per month, and even as low as 1 mg
with early treatment make immediate and aggressive initia- permonth,onceadoseof10or15mgperdayisreached.A
tionoftherapythegoaltopreventpermanentvisualloss.The maintenance dose of 5 to 7.5 mg per day is generally
following treatment suggestions are those generally recom- adequate after the first 6 to 12 months of therapy. Alternate
mended by neuro-ophthalmologists confronted with patients day corticosteroid regimens are not recommended, because
with a substantial risk of severe visual morbidity. rebound arteritis has been associated with this regimen.1
Arecentstudy66lookedinaprospectivemanneratthe
impactofinductiontherapywithhighdoseIVcorticosteroids
compared with oral treatment, as regards the course of ther-
In a patient with arteritic anterior ischemic apy. Twenty-seven patients with biopsy-proven GCA were
randomized to receive IV methylprednisolone (15 mg/kg of
optic neuropathy, systemic corticosteroids ideal body weight per day) or IV saline for 3 consecutive
days,andallpatientswerestartedon40mg/dofprednisone,
should be promptly instituted upon suspected
followed by a taper schedule. However, because of the
diagnosis and should not be delayed for relatively low dose of prednisone used, patients with GCA-
related vision loss, amaurosis fugax or cerebrovascular acci-
temporal artery biopsy. dents were excluded from the study. It was concluded that
initial treatment with IV methylpredisolone had long-term
benefits,suchasamorerapidtaperingoforalcorticosteroids
and a higher rate of sustained remission.
In a patient with arteritic AION, systemic corticoste- The response of GCA systemic symptoms to cortico-
roidsshouldbepromptlyinstituteduponsuspecteddiagnosis steroidsisusuallyrapidanddramatic,withreliefofheadache
and should not be delayed for TAB. In the setting of visual andmalaisewithin24hours.Unfortunately,only4%to15%
loss, high dose (1–2 g/d for 2–3 days) intravenous cortico- of patients with arteritic AION experience improvement in
350 ©2008LippincottWilliams&Wilkins