PPUUPPIILL AANNDD AACCCCOOMMOODDAATTIIOONN AABBNNOORRMMAALLIITTIIEESS SympatheticSympathetic pathwaypathway ofof pupillarypupillary innervationinnervation PPuuppiillllaarryy lliigghhtt rreefflleexxeess ••PupilPupil diameterdiameter isis subjectsubject toto continuouscontinuous variationsvariations asas aa functionfunction ofof changeschanges inin luminanceluminance,, fixationfixation andand psychosensitivepsychosensitive stimulistimuli..

•• PupilsPupils mustmust bebe studiedstudied byby evaluatingevaluating theirtheir sizesize,, shapeshape,, symmetrysymmetry andand activityactivity ((dilationdilation andand constrictionconstriction).). •• ToTo evaluateevaluate sizesize andand symmetrysymmetry ofof pupilspupils,, patientspatients areare invitedinvited toto fixatefixate aa farawayfaraway objectobject,, whichwhich mustmust notnot bebe aa sourcesource ofof excessiveexcessive lightlight stimulationstimulation.. ••SSuubbsseeqquueennttllyy,, bbyy iilllluummiinnaattiinngg tthhee ppaattiieennttss’’ ffaaccee ffrroomm bbeellooww wwiitthh aa wweeaakk lliigghhtt ssoouurrccee,, bbootthh ppuuppiillss aarree ssiimmuullttaanneeoouussllyy oobbsseerrvveedd aanndd tthheeiirr ddiiaammeetteerrss aarree ddeetteerrmmiinneedd ((mmmm))..

•• IInn tthhee nnoorrmmaall ppooppuullaattiioonn,, ppuuppiill ddiiaammeetteerr tteennddss ttoo bbee ssmmaalllleerr iinn cchhiillddrreenn,, iinn tthhee eellddeerrllyy aanndd iinn ssuubbjjeeccttss wwiitthh ddaarrkk iirriiss.. •In general, which changes with changes of luminance conditions must be considered pathologic, while • anisocoria which remains constant, indipendently from the degree of luminance and is associated to a symmetrical photomotor reflex, is the expression of physiologic or essential anisocoria.

•The photomotor reflex must be evaluated: • the patient fixates a faraway object, to inhibit the near reflex, and each is stimulated by using a high intensity light. • In the presence of a pupil which scarcely reacts to the direct light stimulus, the indirect or consensual reflex must be examined, by stimulating the contralateral eye. •• IfIf thethe reflexreflex arcarc isis intactintact,, thethe directdirect reflexreflex mustmust bebe equalequal toto thethe consensualconsensual reflexreflex (due(due toto thethe doubledouble decussationdecussation ofof thethe pupillarypupillary fibersfibers).). ••TheThe amplitudeamplitude,, latencylatency andand speedspeed ofof pupilpupil constrictionconstriction afterafter aa lightlight stimulusstimulus areare generallygenerally correlatedcorrelated toto thethe visualvisual acuityacuity ofof thethe patientpatient,, exceptexcept inin casescases inin whichwhich thethe visualvisual defectdefect isis secondarysecondary toto aa circumscribedcircumscribed fovealfoveal lesionlesion oror aa bilateralbilateral occipitaloccipital pathologypathology,, inin whichwhich pupilpupil activityactivity isis normalnormal..

TheThe nearnear pupilpupil reflexreflex isis analysedanalysed byby askingasking thethe patientpatient toto fixatefixate aa farawayfaraway objectobject andand thenthen toto fixatefixate aa nearnear objectobject positionedpositioned inin frontfront ofof thethe nosenose.. •• NormalNormal visualvisual functionfunction isis notnot aa necessarynecessary requirementrequirement toto elicitelicit thethe nearnear reflex.reflex. •• TheThe nearnear pupilpupil reflexreflex mustmust bebe onlyonly evaluatedevaluated inin thethe presencepresence ofof anan abnormalabnormal photomotorphotomotor reflex.reflex. •• TheThe dissociationdissociation ofof photomotorphotomotor andand nearnear reflexesreflexes indicatesindicates thethe presencepresence ofof aa mesencephalicmesencephalic pathologypathology ((ParinaudParinaud’’ss syndromesyndrome,, ArgyllArgyll--RobertsonRobertson’’ss pupilpupil)) oror thethe involvementinvolvement ofof postganglionicpostganglionic parasympatheticparasympathetic fibersfibers ((AdieAdie’’ss tonictonic pupilpupil).). ••TheThe doubledouble hemidecussationhemidecussation ofof pupillarypupillary fibersfibers atat thethe levellevel ofof thethe opticoptic chiasmchiasm andand mesencephalusmesencephalus guaranteesguarantees thethe presencepresence andand symmetrysymmetry ofof thethe directdirect andand indirectindirect reflex.reflex. ••EvenEven whenwhen thethe afferenceafference ofof anan eyeeye isis completelycompletely deficientdeficient,, thethe symmetrysymmetry ofof pupilpupil diametersdiameters isis maintainedmaintained byby thethe stimulistimuli originatingoriginating inin thethe contralateralcontralateral eyeeye andand fibersfibers decussatingdecussating inin thethe brainstembrainstem.. ••ForFor thisthis reasonreason,, inin casescases ofof monolateralmonolateral blindnessblindness anisocoriaanisocoria isis nevernever presentpresent.. PPuuppiillllaarryy lliigghhtt rreefflleexx:: nneeaarr ddiissssoocciiaattiioonn iinn PPaarriinnaauudd''ss ssyynnddrroommee ••InIn thethe presencepresence ofof anisocoriaanisocoria anan ophthalmologicophthalmologic examinationexamination isis fundamentalfundamental,, withwith particularparticular attentionattention toto thethe biomicroscopicbiomicroscopic examinationexamination ofof thethe anterioranterior segmentsegment andand thethe measurementmeasurement ofof intraocularintraocular pressurepressure.. •• ItIt isis alsoalso necessarynecessary toto excludeexclude thethe presencepresence ofof ocularocular motilitymotility defectsdefects,, alterationsalterations ofof eyelideyelid positionposition andand activityactivity,, andand trigeminaltrigeminal dysfunctionsdysfunctions ((includingincluding cornealcorneal reflex).reflex). •• TheThe presencepresence ofof aa relativerelative afferentafferent pupillarypupillary reflexreflex (RAPD)(RAPD) isis oneone ofof thethe mostmost importantimportant signssigns inin neurophthalmologyneurophthalmology asas itit providesprovides objectiveobjective evidenceevidence ofof damagedamage toto thethe anterioranterior visualvisual pathwayspathways.. •• ThisThis signsign isis evidentevident inin thethe presencepresence ofof anan asymmetryasymmetry inin thethe functionfunction ofof thethe afferentafferent systemsystem ofof thethe twotwo eyeseyes.. •• IndeedIndeed,, whenwhen lightlight isis positionedpositioned infrontinfront ofof thethe healthyhealthy eyeeye,, bothboth pupilspupils constrictconstrict andand thenthen slowlyslowly dilatedilate;; whenwhen thethe lightlight isis positionedpositioned infrontinfront ofof thethe affectedaffected eyeeye,, thethe constrictionconstriction isis reducedreduced oror absentabsent,, butbut thethe subsequentsubsequent dilationdilation isis immediatelyimmediately evidentevident.. •To correctly search for the presence of a RAPD it is necessary to begin with both in the dark. Each pupil is then rapidly illuminated in an alternating way (for maximum 3 seconds) passing above the nose.

• A monolateral lesion of the is practically always associated to a relative afferent defect, while a bilateral lesion only when strongly asymmetrical

• However, a retinal pathology (eg. Large ) may also determine the presence of a RAPD. A slight RAPD may be present in some large macular lesions and in cases of .

• It is generally not present in acute papilloedema, severe refractive defects, , non-organic visual loss, or cortical lesions. RelativeRelative afferentafferent pupillarypupillary defectdefect (RAPD)(RAPD) RelativeRelative afferentafferent pupillarypupillary defectdefect (RAPD)(RAPD) ••PHYSIOLOGICPHYSIOLOGIC ANISOCORIAANISOCORIA :: •• TheThe mostmost frequentfrequent causecause ofof relativerelative differencedifference inin pupilpupil diameterdiameter.. •• ApproxApprox.. 20%20% ofof thethe generalgeneral populationpopulation presentspresents somesome degreedegree ofof anisocoriaanisocoria •• PhysiologicPhysiologic oror essentialessential anisocoriaanisocoria isis generallygenerally 0,50,5 mm,mm, alwaysalways lessless thanthan 11 mm.mm. •• TheThe prevalenceprevalence ofof anisocoriaanisocoria increasesincreases withwith ageage,, reachingreaching 33%33% inin thethe populationpopulation overover 6060 yearsyears ofof ageage.. •• TheThe differencedifference inin pupilpupil diameterdiameter inin physiologicphysiologic anisocoriaanisocoria isis constantconstant inin differentdifferent conditionsconditions ofof luminanceluminance,, withwith aa slightslight tendencytendency toto bebe moremore evidentevident inin darknessdarkness.. LESIONS of the MESENCEPHALUS • Efferent pupillary defects associated to lesions involving the oculomotor nucleus and its bundle in its mesencephalic pathway • Features: anisocoria (associated to defects of motility and ), and the pupil with greater diameter reacts weakly to light and convergence.

••ArgyllArgyll RobertsonRobertson’’ss pupilpupil:: • • small-sized (<2 mm) and often irregular pupils. • Near dissociation is present, and pupils show scarce dilation after instillation of mydriatic eyedrops. • Similar features, for the presence of near dissociation, are present in diabetes (probably due to a peripheral autonomic neuropathy), chronic alcoholism, encephalitis and some degenerative diseases. Parinaud’s syndrome, or dorsal mesencephalus syndrome • Pupils in medium (4-5 mm), round and regular. • Dissociation between light reflex, which is scarce or absent, and near reflex, which is normal. • A consequence of: Involvement of afferent pupillary fibers at the pretectal level, that is the fibers which, once leaving the visual pathways, direct towards the pretectal nuclei.

Associated to: • paralysis of the upwards gaze, • (convergence-retraction) • retraction (Collier’s sign). The most frequent causes of Parinaud’s syndrome are: • tumors of the pineal gland region, •Multiple sclerosis, ischaemic lesions and hydrocephalus with ventricular dilation. PPuuppiillllaarryy lliigghhtt rreefflleexx:: nneeaarr ddiissssoocciiaattiioonn iinn PPaarriinnaauudd''ss ssyynnddrroommee CCoolllliieerr''ss ssiiggnn LESIONSLESIONS OFOF THETHE PARASYMPATHETICPARASYMPATHETIC SYSTEMSYSTEM • The paralysis of the 3rd CN determines pupil involvement generally associated to ptosis and paralysis of .

• The involved pupil is dilated, and anisocoria is greatest in conditions of high luminance.

• The mydriatic pupil does not react after instillation of low concentrations of cholinergic substances (pilocarpine diluted to 0,125%), while it constricts after normal potency miotic drugs such as 1% pilocarpine.

Pupil dilation may be the only sign of oculomotor nerve paralysis in two extremely rare clinical conditions: •Uncus herniation • basal meningitis (tubercolosis, sarcoidosis, , cryptococcosis). ••TheThe presencepresence ofof pupilpupil involvementinvolvement andand incompleteincomplete paralysisparalysis ofof thethe oculomotoroculomotor nervesnerves inin subjectssubjects withwith lessless thanthan 5050 yearsyears ofof ageage mustmust leadlead toto hypothesizehypothesize thethe presencepresence ofof anan aneurismaneurism inin thethe junctionjunction betweenbetween internalinternal carotidcarotid arteryartery andand posteriorposterior communicatingcommunicating arteryartery.. (MRI(MRI and,and, ifif negative,negative, completecomplete brainbrain angiographyangiography).).

•• InIn aberrantaberrant regenerationsregenerations ofof thethe 3rd3rd CN,CN, especiallyespecially ifif postpost--traumatictraumatic,, aa paradoxalparadoxal innervationinnervation ofof thethe pupilpupil sphynctersphyncter maymay bebe observedobserved,, withwith sectorialsectorial contractioncontraction duringduring abductionabduction.. • The presence of mydriasis may be of traumatic origin. • A contusive trauma may in fact damage the sphyncter muscle, and in these cases, the presence of lacerations of the pupil edge and defects of transillumination of the may be observed. Immediately after trauma, the pupil may be miotic, but changes to medium mydriasis early on, demonstrating a weak reaction to light.

•The monolateral instillation, accidental or volontary, of mydriatic drugs (such as atropin) may be the cause of anisocoria (pharmacological anisocoria). In these cases the dilated pupil weakly reacts to light and to the near reflex. AdieAdie’’ss tonictonic pupilpupil ••PathologyPathology withwith unknownunknown etiologyetiology,, whichwhich determinesdetermines pupilpupil alterationsalterations probablyprobably secondarysecondary toto damagedamage atat thethe levellevel ofof postganglionpostganglion fibersfibers.. ••AsAs thethe fibersfibers innervatinginnervating bothboth thethe pupillarypupillary sphynctersphyncter musclemuscle andand thethe ciliaryciliary musclemuscle areare involvedinvolved,, bothboth pupilpupil reflexesreflexes andand accomodationaccomodation areare compromisedcompromised.. ••TheThe pathologypathology isis characterizedcharacterized byby anan irregularirregular andand dilateddilated pupilpupil,, withwith scarcescarce oror absentabsent reactionreaction toto light.light. OftenOften associatedassociated toto hypohypo--areflexiaareflexia.. AAddiiee''ss ppuuppiill LLEESSIIOONNSS OOFF TTHHEE SSYYMMPPAATTHHEETTIICC SSYYSSTTEEMM HHoorrnneerr’’ss ssyynnddrroommee:: IInntteerrrruuppttiioonn ooff tthhee ooccuullaarr ssyymmppaatthheettiicc ssyysstteemm dduurriinngg iittss ppaatthhwwaayy.. CChhaarraacctteerriizzeedd bbyy:: mmiioossiiss,, sslliigghhtt ppttoossiiss,, ……eennoopphhtthhaallmmuuss AAccqquuiirreedd HHoorrnneerr''ss ssyynnddrroommee CCoonnggeenniittaall HHoorrnneerr''ss ssyynnddrroommee