A Novel Approach to the Assessment of Afferent Pupillary Defects

Transcription

1 Eye (1991) 5, A Nvel Apprach t the Assessment f Afferent Pupillary Defects M. T. BENSON, M. E. NELSON, 1. A. CUNLIFFE, I. G. RENNIE Sheffield Summary The pupil respnse t a flashing light stimulus was bserved fr a grup f 26 healthy vlunteer cntrls, and 15 patients with relative afferent pupillary defects (RAPDs). Fr the cntrl grup, the mean interval between flashes which wuld just prduce a perceptible pupil respnse was 295 millisecnds (ms). The mean difference between right and left eyes was 8.84 ms. The mean difference between nrmal and abnrmal eyes f the APD grup was 78.6 ms. The difference between these results and thse f the cntrl grup are highly significant statistically (p<o.ooi), and we cnclude that this test may be f use in the assessment f defects f the afferent light pathways. The relative afferent pupillary defect (RAPD) is an extremely useful clinical sign, giving infrmatin in a wide range f cnditins which invlve the pre-geniculate visual pathways Assessment f a RAPD may aid diagnsis and influence management. In rder t chart the curse f a disease, and t enable a cmparisn between the affected eyes f different patients, it is useful t measure the amunt f RAPD present. Sme clinicians assign a numerical grade t the RAPD. Such rugh rating systems are highly subjective and prne t errr. 14 The measurement f RAPDs using neutral density (ND) filters has been strngly advcated by sme authrs. 14,15,16 Hwever, there are technical prblems assciated with this methd. The quantificatin f RAPDs with ND filters is influenced by the test light used,17 and causes asymmetric bleaching f the retinas.14 The 'blanket' reductin in afferent input prduced by ND filters is nt necessarily the same afferent defect as the ne t be matched. The pupil cycle time has been suggested as a useful clinical test fr assessment f ptic nerve functin. 1 8, 19,2 0 This test utilises efferent and afferent pathways fr the eye under bservatin. Whereas the RAPD is a relative sign, which disappears if the ther eye develps a matching dysfunctin, the pupil cycle time is bjective fr each eye individually and can be used even in mncular patients. Hwever, the pupil cycle time is a difficult and time-cnsuming test t perfrm. Mrever, it is a relatively insensitive indicatr f ptic nerve disease.3 It was ur aim t prduce a test f afferent visual pathway functin which was easy and quick t perfrm, and which wuld allw the measurement f the RAPD directly. Pupillgraphic studies f afferent pupillary defects shw that when the affected eye is stimulated the pupillary cntractin has a lnger latent perid and a smaller amplitude than when the unaffected eye is stimulated. 9 Since the abnrmal respnse is f greater latency and reduced amplitude, we reasned that the bserved pupillary respnse t a flashing light wuld be diminished, and that disappearance f visible respnse with increasing flash fre- Frm: Department f Ophthalmlgy, University f Sheffield; and Ryal Hallamshire Hspital, Sheffield. Crrespndence t: Mr M. T. Bensn, Department f Ophthalmlgy, Ryal Hallamshire Hspital, Sheffield SlO2JF.

2 THE ASSESSMENT OF AFFERENT PUPILLARY DEFECTS 41 Table I. Age, sex and pupil respnse measurements in millisecnds f cntrl ppulatin N Age Sex 22 F 32 M 21 F F 30 M 25 M 45 F 42 M 37 F 3(1 M F 29 F 58 F F 24 F 26 M 21 F 24 F 22 F 75 M 70 M 76 F 78 M Right Left Difference 40 quency culd be used as an end-pint fr assessment f RAPDs. Methd Subjects were enrlled fr the study frm the general phthalmic utpatient clinic. Assessment f RAPDs was carried ut by nting any asymmetry f pupillary escape during the winging flashlight test, using a bright light in a dim rm with the patient fixating a distant target.l The cntrl ppulatin cmprised healthy vlunteers with n histry f cular disease. Fr all subjects a full medical, drug and phthalmic histry was btained. Visual acuity, refractive errr, and pupil size were recrded. Pupil respnses were stimulated with flashes f white light frm a strbscpe cntaining a xenn flash-tube, which subjects were asked t view thrugh an eyepiece. The unstimulated eye fixated a distant target in a mirrr. Flashes were f 7.5 micrsecnds duratin, and since, at the utset, it was nt knwn if flash intensity wuld be a significant factr, tw intensities were used, namely 42 and 670 cd/s/m 2. The mean backgrund illuminatin was 15 cd/m 2. The respnse f the unstimulated eye was bserved. The interval between flashes f light was initially 500 millisecnds. This interval was then decreased in 0 millisecnd decrements until the pupil respnse f the unstimulated eye was n lnger perceptible. The interval between flashes at which this ccurred was recrded and the test was then perfrmed n the ther eye. Fr each eye the test was then repeated starting at the first end-pint and increasing the interval between flashes by millisecnd increments until a pupil respnse was just bserved. The interval between flashes at which this ccurred was recrded as the final end-pint. The test was carried ut fr each intensity f stimulating light, and the bserver was masked with respect t any pupillary abnrmality f the subject, and t the flash frequency being used at any particular time. Results It was fund that the results fr the tw different flash intensities were almst identical, and therefre nly ne set f results (thse using the 670 cd/s/m 2 flash) are presented here. Twenty-six healthy vlunteer subjects (Table I) were recruited fr the study. The mean age f this grup was 33.8 years (range -76) (Table II). Fr cntrl subjects the mean interval between flashes at which a pupil respnse was just perceptible was 295 millisecnds (321 fr males and 283 fr females) (Table III). The mean difference between the end-pint fr right and left eyes was 8.84 millisecnds (5.5 fr males and.5 fr females) (Table IV). There was n psitive crrelatin Table II. Age distributin f cntrls and patients with afferent pupillary defects. M = male, F = female Cntrls RAPD grup Mean age Range n [M36.6, F32.3] [M25-68, F-76] [M9, F17] [M74.3, F76.8] [M61-86, F70-82] [MIO, F5]

3 42 M. T. BENSON ET AL. Table III. Pupil respnses, in millisecnds f interval, f cntrl ppulatin. SD = standard deviatin Right Left Bth Mean (SD) fr all 294 (37.5) 295 (38.0) 295 (38.2) Means (SDs) fr sexes [M317 (19.2), F281 (39.2) 1 [M323 (17.3), F284 (41.5) 1 [M321 (18.0), F283 (39.8) 1 between the difference in end-pint between the tw eyes f this grup, and the age f the subjects. Fifteen patients with RAPDS (Table V) were recruited fr the study. The mean age f these patients was 75.1 years (range 61-86) (Table II). Fr this grup the mean difference in end-pint between the nrmal and abnrmal eyes was 78.6 millisecnds (Table VI). The difference between the results fr the cntrl and the RAPD ppulatins is highly significant statistically (p<o.ool using a ne-sided Mann-Whitney test). Discussin Since it indicates an imbalance in the pregeniculate light pathways, the RAPD may prvide useful clinical infrmatin in a wide range f cnditins, including ptic neuritis, 1.2 ischaemic r cmpressive ptic neurpathy/, 3 cclusin f the central retinal artery r vein, 1 asymmetrical glaucmatus damage,<h'l. 9 bl 1 0. am ypla,', 11 cntra I ateral t an ptic tract lesin, 12 large macular lesins, 5 retinal detachment,i,5,1 3 and extensive rganic disease f the retina. 1 In patients with unilateral ptic neurpathy the RAPD is mre sensitive than the visual evked ptential (VEP) and the pupil cycle time as an indicatr f disease. 3 Hwever, the RAPD is f use nly when the disease is unilateral, and bilateral disease may be missed, i.e, it des nt replace the YEP in detecting past ptic neuritis, The numerical grading f RAPDs, e.g. frm 1+ t 4+, is subject t errr, e,g, because f pupil size (small pupils make the RAPD seem less), 1 4 and because it is highly subjective, The measurement f RAPDs with neutral density filters has been recmmended, Using this technique the smallest defect that can be measured with cnfidence is 0.3 lg units, 1 4 This methd is nt free frm technical prblems, Abve 1.2 lg units, the filter is s dense that it becmes necessary t lk arund it t see the pupil mve.14 The quantificatin f RAPDs with ND filters is influenced by the test light used, 17 and causes asymmetric bleaching f the retinas, 1 4 Als, the ND filters cause a reductin in the incident light acrss the entire retina, which is nt necessarily the same afferent defect as the ne t be matched. One disadvantage f the RAPD is that it is a relative sign, and therefre disappears if the ther eye develps a matching dysfunctin. In patients wh are strngly suspected f having an RAPD but in whm pupillary testing is nt pssible, brightness cmparisn testing can be helpful, and in sme subgrups it can reliably predict the presence r absence f an RAPD, but it is very subjective, 2 S The pupil cycle time may be used t assess ptic nerve functin. 1& -2 0 A small beam f light fcussed at the pupillary margin induces regular, persistent scillatins f the pupil. One hundred cycles may be timed with a stpwatch t the nearest 0.1 sec, and the average time in millisecnds fr a single cycle is then termed the pupil cycle time, 1 & -2 0 The pupil cycle time is bjective fr each eye individually. Hwever, it is a difficult test t perfrm, and can be time-cnsuming because f blinking and lsses f fixatin, and it is a relatively insensitive indicatr f ptic nerve disease,3 Our test demnstrated remarkable cnsistency between the end-pints fr the tw eyes f the cntrl subjects, and between different subjects (Tables I and III). It shuld be emphasised that the bserver was masked with regard t the flash frequency being used, The end-pints fr individual eyes shw a bimdal distributin, the cause fr which is nt clear, but seems t be related t sex ' insfar as all male cntrls fall int the less rapid respnse grup, whereas the females are predminantly in the mre rapid grup (Tables I Table IV. Mean difference in pupil respnse between individuals' eyes, in millisecnds f interval, fr cntrls Male Female All Mean Difference

4 THE ASSESSMENT OF AFFERENT PUPILLARY DEFECfS 43 Table V. Age, sex, diagnsis and pupil measurements in millisecnds f interval f RAPD grup. AMD = agerelated macular degeneratin; POAG = primary pen-angle glaucma; CRVO = central retinal vein cclusin; CRAO = central retinal artery cclusin; AION = anterir ischaemic ptic neurpathy; OA = ptic atrphy. Diagnsis in brackets = cncurrent cnditin (* = cnditin in ther eye) N. Age Sex Diagnsis 1 81 M AMD 2 78 F POAG 3 82 F CRVO 4 86 M CRVO 5 74 F CRAO (BRVO)* 6 76 M CRVO (POAG) 7 79 M CRVO 8 70 F AION 9 69 M AION (POAG) 81 M CRVO F CRVO (POAG) M OA M CRVO M CRVO M CRVO (POAG) Affected Unaffected Eye Eye Difference and III). This is cnsistent with the finding that females tend t have a shrter latency n testing f the visual evked ptential than males. There was n significant difference between the tw Bash intensities used in this study with regard t eliciting these end-pints. Althugh the mean age f ur cntrl subjects was less than that f the RAPD ppulatin, it was evident frm ur cntrl ppulatin that there was n psitive crrelatin between subject age and difference in end-pint between the tw eyes. The difference between nrmal and abnrmal eyes f thse subjects with RAPDs was highly significant statistically (Table VI). It is pssible that the end-pint fr this test is determined in part by the bserver's threshld f bservatin, just as it is when ND filters are used, but as lng as the same bserver defines the end-pint fr the tw eyes f a patient this shuld nt matter, as the test is a measure f the difference between the tw Table VI. Mean difference in pupil respnse between 'nrmal' and 'abnrmal' eyes, in millisecnds f interval, fr patients with RAPD Nrmal Abnrmal Difference Mean Difference eyes. Prvided the same stimulus is used fr bth eyes f a patient, the value fr the pupil respnse difference culd be cmpared t the values fr ther patients. In cnclusin, this test appears t be f value in measuring the pupil respnse directly, giving remarkably cnsistent and highly significant results with a masked bserver. Althugh it requires much further evaluatin, including cmparisn with established techniques fr pupil assessment, it is hped that this test may be f use in the assessment f defects f the afferent light pathways. References [ Levatin P: Pupillary escape in disease f the retina r ptic nerve. Arch Ophthalml1959, 62: Stanley JA and Baise GR: The swinging flashlight test t detect minimal ptic neurpathy. Arch Ophthalml1968, 80: Cx TA, Thmpsn HS, Hayreh SS, Synder JE: Visual evked ptential and pupillary signs. Arch Ophthalml1982, 0: Kabak MB, Burde RM, Becker B: Relative afferent pupillary defect in glaucma. Am J Ophthalml 1976, 81: Thmpsn HS: Pupillary signs in the diagnsis f ptic nerve disease. Trans Ophthalml Sc UK 1976, 96: Quigley HA, Addicks EM, Green WR: Optic nerve damage in human glaucma: III. Quantitative crrelatin f nerve fiber lss and visual field defect in glaucma, ischemic neurpathy, papilledema, and txic neurpathy. Arch Ophthalml 1982, 0:

5 44 M. T. BENSON ET AL. 7 Khn AN, Mss AP, Pds SM: Relative afferent pupillary defects in glaucma withut characteristic field lss. Arch Ophthalml1979, 77: Jhnsn LN, Hill RA, Barthlmew MJ: Crrelatin f afferent pupillary defect with visual field lss n autmated perimetry. Ophthalmlgy 1988,95: "Thmpsn HS: Afferent pupillary defects. Pupillary findings assciated with defects f the afferent arm f the pupillary light reflex arc. Am J Ophthalml1966, 62: Prtny JZ, Thmpsn HS, Lennarsn L, Crbett 11: Pupillary defects in amblypia. Am J Ophthalml 1983, 96: II Greenwald MJ and Flk ER: Afferent pupillary defects in amblypia. J Pediatr Ophthalml Strabismus 1983, : O'Cnnr PS, Kasdn D, Tredici TJ, Ivan DJ: The Marcus Gunn pupil in experimental tract lesins. Ophthalmlgy 1982, 89: Bvin JA and Burtn TC: Measurement f the relative afferent pupillary defect in retinal detachment. Am J Ophthalml1980, 90: '4Thmpsn HS, Crbett 11, Cx TA: Hw t measure the relative afferent pupillary defect. Surv Ophthalml1981, 26: Thmpsn HS: Putting a number n the relative afferent pupillary defect. In Thmsn HS (ed): Tpics in Neur-Ophthalmlgy, Baltimre, Williams & Wilkins, 1979, Fineberg E, Thmpsn HS: Quantitatin f the afferent pupillary defect. In: Smith JL (ed) Neur-phthalmlgy fcus 1980, New Yrk, Massn publishing, 1980: Brwning DJ and Tiedeman JS: The test light affects quantitatin f the afferent pupillary defect. Ophthalml1987, 94: IR Miller SD and Thmpsn HS: Pupil cycle time in ptic neuritis. Am J Ophthalml1978, 85: Miller SD and Thmpsn HS: Edge-light pupil cycle time. Br J Ophthalml1978, 62: Miller SD and Thmpsn HS: The pupil cycle time. In Thmsn HS (ed): Tpics in Neur-Ophthalmlgy, Baltimre, Williams & Wilkins, 1979, Cx TA. Pupillgraphy f a relative afferent pupillary defect. Am J Ophthalml1986, 1: Lwenstein 0 and Friedman ED: Pupillgraphic studies. Arch Ophthalml1942, 27: Smith SA and Smith SE: Cntractin aniscria: nasal versus tempral illuminatin. Br J Ophthalml 1980, 64: Cx TA: Pupillgraphic characteristics f simulated relative afferent pupillary defects. Invest Ophthalml Vis Sci 1989, 30: Brwning DJ and Buckley EG: Reliability f brightness cmparisn testing in predicting afferent pupillary defects. Arch Ophthalml 1988, 6: