We report on the application of a light emitting diode (LED) screen to elicit multifocal ERG on- and off-responses in a patient presenting with the complete type of congenital stationary night blindness (cCSNB): A 63-years old woman was diagnosed with cCSNB by means of standard ERG procedures and dark adaptometry. To confirm this diagnosis and to investigate topographical differences of on- and off-responses a multifocal approach employing long-duration stimuli was added. Results of mfERG-testing were averaged in three groups (a central area of 7.5°, a ring area of 7.5-21.9° and a peripheral ring of 21.9-31.1°). When compared to normal controls (n = 4) on-responses (P1-amplitudes) were severely reduced symmetrically at all eccentricities, while off-responses showed no reduction resulting in an increased off/on-ratio. Furthermore on-latencies of P1 were delayed symmetrically at all eccentricities, whereas off-latencies were normal. To our knowledge this is the first report of multifocal on- and off-responses in a CSNB-patient. Stimulus-generation with a LED-screen provides the advantage of a stable luminance during the long-duration on-phas

Leifert, Dorothee

Palmowski-Wolfe, Anja

Prünte, Chrisitan

Todorova, Margarita

RERO DOC Digital Library

LED-generated multifocal ERG On- and Off-responses in completecongenital stationary night blindness – a case reportDorothee Leifert, Margarita G. Todorova, Chrisitan Pru¨nte & Anja M. Palmowski-WolfeDepartment of Ophthamlology, University Hospital Basel, Mittlere Strasse 91, CH-4056, Basel, SwitzerlandAccepted 7 July 2005Key words: LED, multifocal ERG, night blindness, on- and off-responseAbstractWe report on the application of a light emitting diode (LED) screen to elicit multifocal ERG on- and off-responses in a patient presenting with the complete type of congenital stationary night blindness (cCSNB):A 63-years old woman was diagnosed with cCSNB by means of standard ERG procedures and darkadaptometry. To confirm this diagnosis and to investigate topographical differences of on- and off-re-sponses a multifocal approach employing long-duration stimuli was added. Results of mfERG-testing wereaveraged in three groups (a central area of 7.5, a ring area of 7.5–21.9 and a peripheral ring of 21.9–31.1).When compared to normal controls (n=4) on-responses (P1-amplitudes) were severely reduced symmet-rically at all eccentricities, while off-responses showed no reduction resulting in an increased off/on-ratio.Furthermore on-latencies of P1 were delayed symmetrically at all eccentricities, whereas off-latencies werenormal. To our knowledge this is the first report of multifocal on- and off-responses in a CSNB-patient.Stimulus-generation with a LED-screen provides the advantage of a stable luminance during thelong-duration on-phase.IntroductionCongenital stationary night blindness has beenclassified by Miyake et al. [1] according to theresults of Ganzfeld-ERG testing. Subtypes ofthis non-progressive disorder presenting with aso-called ‘‘negative-shaped’’ ERG (Schubert–Bornschein type) after maximal mixed rod andcone stimulus presentation were separated from‘‘non-negative phenotypes’’, the so-called Riggstype. This type includes mainly members of twolarge families (in France the Nougaret-family [2]and in Denmark the Rambusch-family) and isof autosomal-dominant inheritance [3]. TheSchubert–Bornschein type has been further sub-divided into two forms: A so-called completeform with no rod response under scotopic con-ditions and under dark adaptometry but withonly a slightly reduced cone response (i.e. slight-ly reduced amplitudes under photopic condi-tions, but substantially increased implicit times).In contrast, the so-called incomplete form hasresidual rod function but a more severe decreaseof cone function. Since the negative wave formis the result of a more or less normal photore-ceptor response combined with a diminished toabsent bipolar response the defect has beensubscribed to proximal retinal layers.Several mutations have been identified for thedifferent phenotypes described above: A mutationat the Xp11.4 locus (X-chromosomal-recessiveinheritance) coding for nyctalopin, a protein as-sumed to play a role during the development ofon-synapses, has been assigned to the completeSchubert–Bornschein type (also known as cCSNBPresented in part at the 102nd meeting of the German Academyof Ophthalmology, Berlin (Germany), 22–26 September 2004.Documenta Ophthalmologica (2005) 111: 1–6  Springer 2006DOI 10.1007/s10633-005-2303-1or CSNB type 1) [4, 5]. Another point mutation(Xp11.2 locus, CACNA1F, X-chromosomal-recessive inheritance) affecting the calcium chan-nel of the inner photoreceptor segment was foundto result in the incomplete Schubert–Bornscheintype (also known as iCSNB or CSNB type 2) byinhibition of the signal transduction to bipolarcells [6]. For the autosomal recessive forms ofthese two subtypes no mutations have been iden-tiﬁed so far. Dominant CSNB-forms have beenTable 1. Ganzfeld-ERG testing (according to ISCEV standards) of the CSNB patient (left-hand side) exhibits a negative-shapedERG for the mixed maximal rod and cone response, an absent rod response, as well as a slightly reduced amplitude and increasedimplicit times under photopic conditions (single photopic ﬂash, 30-Hz-ﬂicker) if compared to a representative control (right-handside)Also, the oscillatory potentials were severely diminished. Because of identical results of both eyes only the results of the right eye areshown.2shown to result from mutations within the photo-transduction cascade (type Nougaret: alpha-sub-unit of transducin [7], and type Rambusch:beta-subunit of cGMP-phosphodiesterase [8]).Recently the multifocal ERG has been appliedto differentiate on- and off-bipolar-responsesthrough long-duration stimuli generation [9]. Inhealthy controls an increase of the off-/on-ratiowith eccentricity has been documented [9]. Multi-focal analysis of patients presenting with cCSNBapplying short-duration stimuli revealed changesregarding mainly the P1 implicit times and the N2wave-forms in the ﬁrst order kernels, but most ofall the overall wave-forms of the second-orderkernels [10]. In the Ganzfeld-ERG, stimulationwith long-duration stimuli allows an even morepronounced separation between the complete andthe incomplete CSNB type when compared tostandard ERG recordings [11]. Here we report amultifocal approach in a CSNB patient (completetype) with differentiation of on- and off-responsesthrough long-duration stimuli presentation gener-ated with a LED-screen.PatientA 63-year-old woman presented with night blind-ness and reduced daytime vision since her earlychildhood as well as myopic astigmatism (R:)6.0 sph, )3.0 cyl/80, L: )9.0 sph, )2.0 cyl/90).Apart from low degree myopic posterior segmentchanges and a slight cataract no ocular pathol-ogy, especially no nystagm or squinting, was evi-dent. Her best corrected visual acuity was 20/40(right eye) and 20/50 (left eye). Based on biomi-croscopy, electrophysiological and psychophysi-cal examinations she was diagnosed with thecomplete Schubert–Bornschein type of congenitalstationary night blindness: The Ganzfeld-ERG isshown in Table 1 and exhibits a negative-shapedERG for the mixed maximal rod and coneresponse, an absent rod response, as well as aslightly reduced amplitude and increased implicittimes under photopic conditions (single photopicﬂash, 30-Hz-ﬂicker). The oscillatory potentialswere severely diminished.The results of the dark adaptometry (Gold-mann-Weekers) are seen in Figure 1: A completeabsence of the rod response results in a mono-phasic curve.MethodsFor multifocal ERG recording both eyes ofthe patient and one eye of each control (n=4)were examined in maximal mydriasis (0.5%Figure 1. Dark adaption (Goldmann–Weekers) demonstrates complete absence of the rod response resulting in a monophasic curve(black line). Age-matched normal controls would lie within the grey area.3tropicamide and 0.5% phenylephrine hydrochlo-ride), while the other eye was occluded. Afterlocal anaesthesia (0.5% Alcaine eye drops) abipolar contact lens electrode (GoldLens, Dyag-nosys LLC) was inserted. The ground electrodewas attached to the forehead. The visual stimuluswas generated by a screen of 3232 light emittingdiodes (luminance: 1 (min) – 180 (max) cd/m2)displayed in a pattern of 61 hexagons. To com-pensate for different photoreceptor distributionwith eccentricity these hexagons were scaled insize. On- and off-phases of 100 ms each were alter-nating. MfERGs were recorded with RetiscanTM.The band-pass ﬁlter was set at 10–200 Hz. TotalFigure 2. Multifocal ERG on- and off-responses of the CSNB patient (right eye: left column, left eye: middle column) and a repre-sentative control (right column) after stimulus presentation with the LED-monitor.Table 2. Amplitudes of the on- and off-responses and the off/on-ratio of the CSNB patient and controls (n=4)Ring area ON OFF OFF/ONCSNB (lvolt) controls (lvolt) CSNB (lvolt) controls (lvolt) ratio CSNB ratio controls1 (0–7.5) R 16.6 46.2–69 R 15.2 19.9–28.7 R 0.92 0.36–0.62L 18.8 L 25.0 L 1.332 (7.5–21.9) R 12.2 24–29 R 13.7 8.4–14.6 R 1.12 0.30–0.54L 9.4 L 11.3 L 1.23 (21.9–31.1) R 13.3 20–25 R 16.0 9.0–12.8 R 1.2 0.40–0.59L 7.0 L 11.2 L 1.64recording time was 13.28 min, split up for comfortinto 8 periods of 1.46 min duration. For analysiseach data point was averaged with it’s twoadjacent data points on either side. This smooth-ing procedure was performed twice.ResultsWave forms of the patient’s right and left eye andof a representative control are seen in Figure 2. Inall eccentricities (ring 1 to 3) the amplitudes of theon-responses are severely diminished, while theoff-responses are normal (for values see Table 2).To adjust for interindividual amplitude differencesthe off/on-ratio was calculated. With eccentricitythe off/on-ratio tends to show a slight increase inall subjects tested. The off/on-ratio of the CSNBpatient shows a substantial elevation without anyoverlap with the controls (Table 2, Figure 3). Theincrease with eccentricity is preserved. All laten-cies are listed in Table 3: The implicit time of theP1-off-response was normal in the CSNB patientwhen compared to controls, whereas the P1 of theon-response showed a delay in implicit time(46.9 ms, normal range: 34.7–38.8 ms). Again thiswas found for all eccentricities.DiscussionApplying a multifocal ERG approach with long-duration stimuli facilitated the classification ofour patient to one of the CSNB subtypes andsupported the original diagnose that was basedon standard ERG results. The homogenous pat-tern of amplitude reduction in all eccentricitiesseems to correlate to the congenital type of thisdisorder that involves on-bipolar cells evenlyacross the retina. In contrast, one of our patientswith an acquired retinal damage (MAR) failed toshow such a symmetrical damage pattern (datapresented at the 102nd meeting of the GermanAcademy of Ophthalmology, Berlin). As in stan-dard ERG-testing, implicit times of the multifo-cal ERG responses generated with long-durationstimuli were affected as well. Separating the on-und off-responses suggests that the increase inimplicit time seen in standard ERG recordings ofCSNB patients is a characteristic of the on-re-sponse, since all off-response implicit times werenormal (in all eccentricities). In context of thefast-stimulation mfERG ﬁndings in CSNB (seeFigure 3. Amplitude off/on-ratio of the CSNB patient and controls (n=4), with the dotted line representing the range of normal.The off/on-ratio of the CSNB patient shows a substantial elevation without any overlap with the controls.Table 3. off- and on-latencies of the CSNB patient and cont-rols (n=4).ON OFFCSNBring 1–3 mseccontrols ring1–3 msecCSNBring 1–3 mseccontrols ring1–3 msecR, L 46.9 34.7–38.8 R, L 125.5 122.45introduction), the responses of the slow-stimula-tion mfERG in CSNB reported here are in sup-port of the ﬁndings by Hood et al. [12]. Theypostulated that the P1 peak in fast-stimulationmfERG testing is composed of a positive on-peak,representing the on-bipolar response, partiallysuperimposed by a shortly delayed positive off-peak, representing the off-bipolar response. Withincreasing stimuli length these two positive peaksseparate and can be examined independently. Theuse of a LED screen seems to be a suitableapproach, because it provides the advantage ofstable luminance during the long-duration step-shaped on-stimulus.AcknowledgementSupported by a grand from Pfizer (MT, AP)References1. Miyake Y, Yagasaki K, Horiguchi M, Kawase Y, KandaT. Congenital stationary night blindness with negativeelectroretinogram. A new classiﬁcation. Arch Ophthalmol,1986; 104(7): 1013–20.2. Sandberg MA, Pawlyk BS, Dan J, Arnaud B, Dryja TP,Berson EL. Rod and cone function in the Nougaret formof stationary night blindness. Arch Ophthalmol, 1998;116(7): 867–72.3. Rosenberg T, Haim M, Piczenik Y, Simonsen SE. Auto-somal dominant stationary night-blindness. A large familyrediscovered. Acta Ophthalmol (Copenhagen), 1991; 69(6):694–702.4. Pusch CM, Zeitz C, Brandau O, Pesch K, Achatz H, FeilS, Scharfe C, Maurer J, Jacobi FK, Pinckers A, Andre-asson S, Hardcastle A, Wissinger B, Berger W, Meindl A.The complete form of X-linked congenital stationarynight blindness is caused by mutations in a gene encodinga leucine-rich repeat protein. Nat Genet, 2000; 26(3):324–7.5. Bech-Hansen NT, Naylor MJ, Maybaum TA, Sparkes RL,Koop B, Birch DG, Bergen AA, Prinsen CF, PolomenoRC, Gal A, Drack AV, Musarella MA, Jacobson SG,Young RS, Weleber RG. Mutations in NYX, encoding theleucine-rich proteoglycan nyctalopin, cause X-linked com-plete congenital stationary night blindness. Nat Genet,2000; 26(3): 319–23.6. Jacobi FK, Hamel CP, Arnaud B, Blin N, Broghammer M,Jacobi PC, Apfelstedt-Sylla E, Pusch CM. A novelCACNA1F mutation in a french family with the incom-plete type of X-linked congenital stationary night blind-ness. Am J Ophthalmol, 2003; 135(5): 733–6.7. Muradov KG, Artemyev NO. Loss of the effector functionin a transducin-alpha mutant associated with Nougaretnight blindness. J Biol Chem, 2000; 275(10): 6969–74.8. Muradov KG, Granovsky AE, Artemyev NO. Mutation inrod PDE6 linked to congenital stationary night blindnessimpairs the enzyme inhibition by its gamma-subunit.Biochemistry, 2003; 42(11): 3305–10.9. Kondo M, Miyake Y, Horiguchi M, Suzuki S, TanikawaA. Recording multifocal electroretinogram on and offresponses in humans. Invest Ophthalmol Vis Sci, 2003Mar; 39(3): 574–80.10. Kondo M, Miyake Y, Kondo N, Tanikawa A, Suzuki S,Horiguchi M, Terasaki H. Multifocal ERG ﬁndings incomplete type congenital stationary night blindness. InvestOphthalmol Vis Sci, 2001; 42(6): 1342–8.11. Langrova H, Gamer D, Friedburg C, Besch D, ZrennerE, Apfelstedt-Sylla E. Abnormalities of the long ﬂashERG in congenital stationary night blindness of theSchubert–Bornschein type. Vision Res, 2002; 42(11):1475–83.12. Hood DC, Frishman LJ, Saszik S, Viswanathan S. Retinalorigins of the primate multifocal ERG: implications for thehuman response. Invest Ophthalmol Vis Sci, 2002; 43(5):1673–85.Address for correspondence: Dorothee Leifert, Department ofOphthamlology, University Hospital Basel, Mittlere Strasse 91,CH-4056, Basel, SwitzerlandPhone: +41-61-265-8787; Fax: +41-61-265-8740; E-mail:leifertd@uhbs.ch)6

LED-generated Multifocal ERG On- and Off-responses in Complete Congenital Stationary Night Blindness - A Case Report

http://doc.rero.ch/record/314593/files/10633_2005_Article_2303.pdf

LED-generated Multifocal ERG On- and Off-responses in Complete Congenital Stationary Night Blindness - A Case Report

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library