Supernormal scotopic ERG in cone dystrophy

British Journl of Ophthlmology, 1984, 68, 69-78 Supernorml scotopic ERG in cone dystrophy KENNETH R. ALEXANDER AND GERALD A. FISHMAN From the Deprtment of Ophthlmology, University ofillinois Eye nd Er Infirmry, Chicgo, USA SUMMARY Three ptients with ull's-eye mculr lesion nd other signs chrcteristic of cone dystrophy gve n unusul ERG finding. In response to white flsh of moderte intensity the scotopic -wve mplitude ws considerly lrger thn norml. One ptient hd elevted rod thresholds nd nyctlopi, while the other 2 hd norml rod sensitivity ssocited with the supernorml scotopic -wve mplitude. In the ltter 2 ptients the norml ERG pttern ws unchnged for 4 yers nd 7 yers respectively. This typicl finding, of supernorml scotopic -wve mplitude in response to light of moderte intensity, ppers to chrcterise sugroup of ptients with cone dystrophy, proly of utosoml recessive inheritnce. The pthogenesis of the norml ERG remins uncertin. Cone dystrophy is group of disorders often chrcterised y n trophic mculr lesion, typiclly ull's-eye-like in ppernce, ssocited with reduced visul cuity, poor colour vision, light sensitivity, nd in some instnces nystgmus. ' The dystrophy my e diffuse, with reduced or nondetectle photopic ERG, or loclised in the mcul, with norml photopic electroretinogrm (ERG).4 Anormlities of rod function re sometimes lso pprent, including scotopic ERG which is reduced in mplitude (cone-rod dystrophy).7" Recently n unusul type of.cone dystrophy hs een reported in which the rod ERG is sunorml t low flsh intensities ut is supernorml with righter flshes. 1 In the 2 ptients descried the cone dystrophy occurred in ssocition with nyctlopi. The purpose of this report is to descrie 3 cses of supernorml scotopic ERG ssocited with n trophic mculr lesion. One cse is similr to those ofcone dystrophywith nyctlopi reported y Gours et l. The other 2 cses seem to represent previously unreported clinicl entity of cone dystrophy with supernorml scotopic ERG without nyctlopi. The ltter ptients demonstrte tht supernorml scotopic ERG cn occur without impired rod function. Mterils nd methods The procedures for recording the ERG hve een descried elsewhere. " Briefly, the ptients' pupils Correspondence to Dr Gerld A. Fishmn, University of Illinois Eye nd Er Infirmry, 1855 W. Tylor Street, Chicgo, IL 6612, USA. were dilted with 1% phenylephrine nd 1% cyclopentolte drops, following the ppliction of 5% proprcine hydrochloride s topicl nesthetic. The ERGs were recorded with Burin-Allen monopolr electrode wetted with methylcellulose. Responses were elicited y Grss PS-22 photostimultor tht illuminted diffusing sphere to provide Gnzfeld stimultion. Signls were mplified y Grss premplifier nd y Tektronix dul trce mplifier. Results were displyed on n oscilloscope nd photogrphed with n oscilloscope cmer. Sujects were dpted for 5 minutes to Gnzfeld illumintion of 1-7 log cd m2, nd then single-flsh photopic response ws recorded ginst ckground of 1-4 log cd m2, using the unttenuted I-16 setting, which hd nominl intensity of 1 5 x 11 cndle power nd durtion t hlf-mplitude of 1,us. The ckground ws extinguished, nd single-flsh recordings were otined fter 5, 1, 15, 2, nd 3 minutes of drk dpttion, gin with the use of the unttenuted 1-16 setting. A single-flsh response to dim lue light (produced y Wrtten 47 nd 5 log unit neutrl density filters nd ni-4 setting) ws lso otined fter 3 minutes of drk dpttion to stimulte the rod system preferentilly. An mplitude-intensity function ws then otined. The 1-16 flsh intensity ws ttenuted y 3.5 log units of neutrl density filtering, nd single-flsh white-light ERG response ws recorded. The flsh intensity ws then systemticlly incresed in -5 log unit steps, nd the ERG ws recorded t ech intensity. A rief period of drk dpttion of pproximtely 2 minutes' durtion followed ech flsh presenttion. 69 Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

7 Sttic profile perimetry ws performed with Tuinger perimeter. The ptients' pupils were dilted s ove, nd then ptients were drk-dpted for t lest 4 minutes. Asolute thresholds were otined cross the visul field for test stimulus (TS) tht ws 14' in dimeter, 5 ms in durtion, nd either of long wvelength (Oculus glss filter, ndpss >62 nm) or middle wvelength (Oculus interference filter, Xmx=5OO nm). The reltive threshold vlues for the 2 chromtic stimuli t ech retinl loction indicte whether rods or cones determine the solute threshold.'2 The sensitivity of the cone system ws further ssessed y light-dpted flicker perimetry."3 The threshold luminnce for detecting flicker cross the visul field ws mesured with 25 Hz white TS, 14' in dimeter nd 3 seconds in durtion, presented ginst Gnzfeld ckground of 5 log cd m-2 to suppress the rod system. Cse reports nd results CASE 1: CONE-ROD DYSTROPHY A 19-yer-old lck womn ws referred for poor visul cuity of pproximtely 2 yers' durtion. The ptient's only other complint ws tht she seemed to tke longer thn usul to djust to drkness. She gve no specific history of poor colour vision or photosensitivity. The ptient hd noted no further reduction in centrl cuity, or incresed difficulty in djusting to drkness over the pst 2 yers. The ptient ws in good helth nd hd no known systemic disorders. She ws tking Ortho-Novum (tlets contining norethisterone) for irth control. A review of the fmily pedigree indicted tht the ptient hs rother, ge 26, who lso hs reduced visul cuity tht is uncorrectle with glsses. He ws unville for exmintion. Two other rothers nd two sisters were, y history, norml. Vision ws correctle to 2/1+1 OD with -1-75 nd 2/1+1 OS with -3 5. The ptient could red J-2 t 6 inches without correction. Externl exmintion showed 2 prism dioptres of left exotropi for ner nd distnce, ut ws otherwise norml. Slit-lmp exmintion of the corne, nterior chmer, iris, nd lens ws similrly norml. The vitreous ws modertely firillr ut otherwise unremrkle. Fundus exmintion showed norml optic discs. The retinl rterioles were mildly ttenuted. Both mculs showed ilterl trophiclooking lesions tht hd ull's-eye ppernce (the right fundus is shown in Fig. 1). Exmintion of the peripherl retin showed no evidence of pigmentry normlities. Visul field testing, with the 4-e-II nd 2-e-II test trgets on Goldmnn perimeter, showed no peripherl depression or centrl scotoms. Colour Kenneth R. Alexnder nd Gerld A. Fishmn Fig. 1 Fundus photogrph of the right eye ofptient 1, showing ull's-eye-like mculr lesion. vision ws norml, with lrge increse in the numer of errors on the FM 1-hue test (with no specific xis), nd shift towrd the red setting on the Ngel nomloscope. Asolute thresholds cross the horizontl meridin of the visul field re shown in Fig. 2. Dt re plotted in photopic units; coincident dt points for the middle nd long wvelength test stimuli represent -1 E X -2 V O -3 I -4 cm -J -5!MITIT R - BG 8 8 4 2 2 4 6 8 Nsl Retinl Temporl Fig. 2 Asolute thresholds cross the horizontl meridin ofthe righteye ofptient I for long wvelength (filled circles) nd middle wvelength (open circles) test stimuli. Shded regions represent the rnge ofthresholds for 5 norml oservers. Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

Supernorml scotopic ERG in cone dystrophy _3- E ( 1 8 6 4 2. 2 4 6 8 Nsl Retinl Temporl Fig. 3 Light-dptedflicker thresholds cross the horizontl meridin of the right eye ofptient I for 25 Hz white test stimulus (open circles). Shded region represents the rnge offlicker thresholds forfour norml oservers. cone-medited solute thresholds, wheres verticl seprtion of 2-6 log units indictes rod-medited thresholds for oth test stimuli. Intermedite verticl seprtions indicte tht cones detect the long wvelength TS, while rods detect the middle wvelength TS. 11 Dotted regions in Fig. 2 represent the rnge of solute threshold settings for 5 norml sujects. For this ptient solute Tle 1 Photopicflsh (white) Summry of ERG responses Ptient no. -wve -wve thresholds re medited y rods throughout the horizontl meridin. (The sence of centrl region of cone-medited thresholds is due to the ptient's use of nonfovel region for fixtion.) Rod thresholds re elevted y t lest 2 log units throughout the retin, supporting the ptient's complint of nyctlopi. Cone sensitivity cross the horizontl meridin of the visul field, s mesured y light-dpted flicker perimetry, is shown in Fig. 3, with the dotted region representing the rnge of flicker thresholds for 4 norml oservers. The ptient hd loss of cone sensitivity t ll tested loctions, indicting the diffuse nture of the dystrophy. The ptient's ERG responses in comprison with those of norml suject re shown in Fig. 4. Verticl rs on the norml trcings represent 9% confidence limits for the men of 21 (photopic white flsh), 18 (scotopic white flsh), or 23 (lue flsh) norml responses. The top trcing shows the light-dpted photopic ERG. The -wve is norml in mplitude ut prolonged in implicit time, while the -wve mplitude is reduced to pproximtely 5% of norml, nd the implicit time is prolonged (see Tle 1). The next 3 trcings show the single-flsh ERG response fter 5, 15, nd 3 minutes of drk dpttion. The -wve mplitude nd implicit time re Amplitude* Implicit timet Amplitude: Implicit time 1 Norml Prolonged (24 ms) Reduced (5,uV) Prolonged (42 ms) 2 Norml Norml Norml Norml 3 Norml Norml Norml Norml Scotopicflsh Ptient no. White flsh Blueflsh -wve -wve -wve Amplitude Implicit time Amplitude** Implicit time Amplitudett Implicit timett 1 Norml Norml Supernorml Norml Reduced Prolonged (75 AV) (8,uV) (18 ms) 2 Norml Norml Supernorml Norml Supernorml Norml (8 AV) (46 MV) 3 Norml Norml Supernorml Norml Norml Norml (82 AV) *'Norml' indictes tht the vlue ws within 9% confidence limits for the men. t9% confidence limits= 14 to 2 ms, n=3. 1:9% confidence limits= 1 to 18,uV, n=21. 9% confidence limits=26 to 34 ms, n=21. **9% confidence limits=4 to 61 AV, n= 18. tt9o% confidence limits= 19 to 3,uV, n=29. #49% confidence limits=8 to 92 ms, n=21. 71 Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

72 Fig. 4 ERG responses for the right eye ofptient 1 (left column) nd for typicl norml oserver (right column) under the conditions indicted. Verticl rs represent 9% confidence limits for the men of the norml responses. Clirtion rs re shown t the \ top. within norml limits, ut the -wve mplitude is clerly supernorml, lthough norml in implicit time (Tle 1). The ottom trcing represents the ERG response to dim lue flsh fter 3 minutes of drk dpttion. While the -wve mplitude to right flsh is supernorml, the -wve response to the dim lue flsh is sunorml in mplitude nd prolonged in implicit time. The -wve mplitude-intensity functions for this ptient nd for 2 norml sujects re shown in Fig. 5. At low flsh intensities the - wve mplitude for the cone-rod dystrophy ptient is sunorml, ut the mplitude rpidly overtkes the norml response nd ecomes supernorml t high flsh intensities. CASE 2: CONE DYSTROPHY 2 Y/O BF A 3-yer-old white womn first noted lurred vision in ech eye t pproximtely ge 23. The lurred vision slowly incresed in severity over the ensuing 3 yers. When first seen y the uthors t ge 26 she gve no history of photosensitivity, poor colour vision, or nyctlopi. The ptient ws otherwise in good helth nd ws not tking ny mediction. A Kenneth R. Alexnder nd Gerld A. Fishmn CONE - ROD DYSTROPHY 1 Pv L 2 ms Scotopic Scotopic Scotopic White White White in. Scotopic Blue NORMAL AS review of the fmily history ws pertinent in tht her mternl grndprents were first cousins. There were no other known fmily memers with oculr disese. When the ptient ws initilly seen, visul cuity ws correctle to 2/4+2 OD with + 1 - nd 2/4-2 OS with + 1 -. Externl exmintion showed no normlities of oculr motility. Slit-lmp exmintion of the corne, nterior chmer, lens, nd vitreous were norml. Fundus exmintion disclosed norml optic discs nd retinl vessels. There ws no evidence of ny peripherl pigmentry normlities. However, the ptient hd ilterl ull's-eye mculr lesions (Fig. 6). The ull's-eye ppernce ws ccentuted on fluorescein ngiogrphy (Fig. 7). The ptient ws seen susequently t ge 3, 4 yers fter her initil exmintion. Visul cuity hd decresed to 2/2 OD ut ws still 2/4-2 OS. Grossly, the ull's-eye lesions were somewht more extensive thn on her initil exmintion. The optic discs, retinl vessels, nd peripherl retin remined norml. At this time visul field testing with the 2-e-II trget on Goldmnn perimeter showed norml Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

Supernorml scotopic ERG in cone dystrophy 2 I-.E -3.5-3. -2.5-2. - 1.5-1. -.5. Log Reltive Intensity Fig. 5 A -wve mplitude-intensity function for the left eye ofptient I (filled circles) ndfor 2 norml oservers (open symols). Dshed line connects the men ofthe 2 norml vlues. peripherl oundries ut ilterl centrl scotoms. Colour vision testing with the FM 1-hue nd D-15 tests showed norml findings. On the Ngel nomloscope the ptient showed shift towrd red in the Ryleigh eqution. Fig. 6 Fundus photogrph of the right eye ofptient 2, showing ull's-eye-like mculr lesion. Fig. 7 Fluorescein ngiogrm of the right eye ofptient 2, in which hyperfluorescent window defect ccentutes the ull's-eye mculr lesion shown in Fig. 6. 73 Asolute thresholds cross the horizontl meridin of the visul field re shown in Fig. 8. The fovel threshold for the long wvelength (cone-detected) TS is somewht elevted. In the prfovel nd peripherl retin solute thresholds re rodmedited nd within norml limits. Cone thresholds otined y flicker perimetry re shown in Fig. 9. In the fove the flicker threshold is elevted, ut cone flicker thresholds re within norml limits outside the - -~ - 1- 'D 1-2 - -o m -3- co I--4- -J -5 R e BG 8 6 4 2 2 4 6 8 Nsl Retinl Temporl Fig. 8 Asolute thresholds cross the horizontl meridin ofthe right eye ofptient2for long wvelength (filled circles) nd middle wvelength (open circles) test stimuli. Shded regions represent the rnge ofthresholds for 5 norml oservers. Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

74 *.R* 1 I- -J 3-2- 1-1 - I 8 6 4 2 2 4 6 8 Nsl Retinl Temporl Fig. 9 Light-dptedflicker thresholds cross the horizontl meridin of the right eye ofptient2for 25 Hz white test stimulus (open circles). Shded region represents the rnge offlicker thresholds for 4 norml oservers. fove. In contrst to ptient 1 this ptient hs dystrophy tht is loclised in the mcul nd ffects primrily cone photoreceptors. The ptient's ERG ws tested on the initil visit nd then ws retested 4 yers lter, with the findings 3 Y/O WF Kenneth R. Alexnder nd Gerld A. Fishmn unchnged. The most recent results re shown in Fig. 1. The photopic - nd -wves (top trcing) re within norml limits, oth in mplitude nd in implicit time, consistent with the loclised nture of the dystrophy. Under drk-dpted conditions (next 3 trcings), the -wve mplitude nd implicit time re norml, s is the -wve implicit time, ut the -wve mplitude is supernorml, even with the lowintensity lue flsh (Tle 1). The -wve mplitudeintensity function (Fig. 11) confirms these findings. At low flsh intensities the -wve is somewht lrger thn norml nd ecomes considerly lrger thn norml with higher flsh intensities. CASE 3: CONE DYSTROPHY A 31-yer-old white womn's chief complint ws poor centrl cuity, which she hd experienced since 5 yers of ge. The ptient did not complin of photosensitivity, poor colour vision, or nyctlopi, nd specificlly mentioned tht her cuity ws etter t night. The ptient ws otherwise in good helth nd ws not tking ny mediction. A review of the fmily pedigree ws noninformtive, since the ptient ws dopted. CONE Fig. 1 ERG responses for the right eye ofptient2 (left column) ndfor typicl norml oserver (right column) underthe conditions indicted. Verticl rs represent 9% confidence limits for the men ofthe norml responses. Clirtion rs re shown t the top. 5 mi. Scotopic White DYSTROPHY 1 JvAL 2 ms \2 min Scotopic White min Scotopic Blue NORMAL Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

Supernorml scotopic ERG in cone dystrophy 97 8 o -1-7- 3 o 6.E 5Q V Q) 3 ' 3 E 4-2- 1- n /,,I._,./.1.9-3.5-3. -2.5-2. -1.5-1.o -.5. Log Reltive Intensity Fig. 11 A -wve mplitude-intensity function for the right eye ofptient 2 (filled circles) ndfor 2 norml oservers (open symols). Dshed line connects the men of the 2 nornl vlues. Visul cuity ws correctle to 1/6(+1 OD with +4-75+-5x1, nd 1/5+1 OS with +5 25+ -25 x7 using Feinloom chrt. The ptient red J-7 t 12 inches (3 cm). Externl exmintion showed no normlities of oculr motility. Slit-lmp Fig. 12 Fundus photogrph ofthe left eye ofptient 3, depicting n trophic mculr lesion. Fig. 13 Fluorescein ngiogrm of the left eye ofptient 3, showing window defects within the mcul. exmintion of the corne, nterior chmer, lens, nd vitreous ws norml. Fundus exmintion showed norml optic discs nd retinl vessels. There ws no evidence of ny peripherl pigmentry normlities. The foves exhiited ilterl, somewht sutle trophic chnges tht hd the ppernce of ull's-eye pttern (Fig. 12). Fluorescein ngiogrphy showed ilterl window defects within the fove, which somewht highlighted the ull's-eye ppernce of her trophic chnges (Fig. 13). Visul field testing with the 4-e-II nd 2-e-II test - E 2 ' p ) /:j Reo BGo 8 6 4 2 2 4 6 8 Nsl Retinl Temporl Fig. 14 Asolute thresholds cross the horizontl meridin ofthe right eye ofptient3for long wvelength (filled circles) nd middle wvelength (open circles) test stimuli. Shded regions represent the rnge ofthresholds fors norml oservers. 75 Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

76 E V SI. co -J 3-2- 1- - -1-8 6 4 2 2 4 6 8 Nsl Retinl Temporl Fig. 15 Light-dptedflicker thresholds cross the horizontl meridin ofthe right eye ofptient 3for 25 Hz white test stimulus (open circles). Shded region represents the rnge offlicker thresholds for 4 norml oservers. trgets on Goldmnn perimeter showed no evidence of peripherl depression ut did show ilterl centrl scotoms. Colour vision testing with the FM 1-hue test demonstrted ilterl tritn (lue-yellow) defect. The ptient ws techniclly unle to perform on the Ngel nomloscope. Fig. 16 ERG responsesfor the right eye ofptient3 (left column) ndfor typicl norml oserver (right column) under the conditions indicted. Verticl rs represent 9o% confidence limits for the men ofthe norml responses. Clirtion rs re shown t the top. Kenneth R. Alexnder nd Gerld A. Fishmn Asolute thresholds cross the horizontl meridin re rod-medited (Fig. 14). As with ptient 1, the profile missed the ntomicl fove due to nonfovel fixtion pttern. Within the centrl 4 solute thresholds were elevted compred with norml, ut returned to norml vlues t the greter eccentricities. Cone flicker thresholds re presented in Fig. 15. There ws slight loss of cone sensitivity in regions ner the fove ut norml cone sensitivity t greter eccentricities. As with the previous ptient, the dystrophy ws confined to the mculr region. The ERG pttern for this ptient hs een unchnged for 7 yers. The most recent results re shown in Fig. 16. The photopic ERG shows mplitudes nd implicit times tht re within norml limits, consistent with the loclised nture of the dystrophy. The drk-dpted -wve mplitudes nd implicit times, s well s the -wve implicit times, re norml (Tle 1). The -wve response to the dim lue flsh is within norml limits. However, the -wve elicited y the white flsh is of supernorml mplitude. An mplitude-intensity function (Fig. 17) shows tht the drk-dpted -wve is norml t low flsh intensities, ut ecomes supernorml with right flshes. CONE DYSTROPHY AvL 2 ms 31 Y/O WF NORMAL While min. Scotopic White min. Scotopic Blue White Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

Supernorml scotopic ERG in cone dystrophy 777 9 2 6 8-7- E 5- E 4-3o 2 11 - -3.5-3. -2.5-2. -1.5-1. -.5. Log Reltive Intensity Fig. 17 A -wve mplitude-intensity function for the right eye ofptient 3 (filled circles) ndfor 2 norml oservers (open symols). Dshed line connects the men oft-he 2 normnl vlues. Discussion The 3 ptients with cone dystrophy descried in this report hve supernormnl drk-dpted -wve response to modertely intense light flsh. A considertion of inheritnce ptterns suggests tht the dystrophy my e n utosoml recessive trit. In severl respects ptient 1 resemles the 2 ptients reported y Gours et l.'1 Ptient 1 hs reduced cuity, decresed colour vision, nyctlopi, diminished photopic ERG, nd drk-dpted - wve mplitude tht is sunorml with dim flshes nd superonorl with righter flshes. Unlike the 2 ptients reported previously' ptient 1 hs ull'seye mculr lesion (rther thn nonspecific mculr grnulrity), with n sence of sensitivity to light. Ptients 2 nd 3 lso hve supernorml drkdpted -wve, ut they pper to represent different type, or perhps stge, of cone dystrophy. For oth ptients the dystrophy is restricted to the mculr region rther thn eing diffuse cone-rod loss. The scotopic -wve is normnl or lrger thn norml t low flsh intensities, rther thn sunorml s with ptient 1. T'he pthogenesis of the supernorml scotopic - wve is uncertin. The ERG -wve is thought to rise predominntly from the Mueller cells in response to chnges in the concentrtion of extrcellulr potssium tht result from the ctivity of retinl neurons.'4 The supernorml scotopic -wve oserved in these ptients with cone dystrophy my e due to n normnlity in this process. Alterntively 'Gours et l.' hve suggested tht the norml ERG my result from n increse in the level of cyclic gunosine monophosphte (cgmp) in the rod photoreceptors, which in turn leds to n norml photoreceptor response. Other conditions esides cone dystrophy hve een reported in ssocition with supernorml ERG in humns, including linism,'" hyperthyroidism,'6 corticosteroid dministrtion,"7 optic trophy,'8 nd retinl vsculr disorders.'91 We hve not een le to implicte ny of these fctors in the norml ERG response in our ptients. A supernorml -wve hs lso een reported to ccompny n increse in Po, in the isolted perfused ct eye." However, the reltionship etween this finding nd the results from our ptients is uncertin. Although the pthogenesis of the supernorml scotopic -wve in these ptients with cone dystrophy is uncler, the norml -wve represents dignostic device tht my prove useful in the clinicl delinetion of cone dystrophy genocopies, which currently pper to e heterogeneous group of conditions under the sme dignostic lel. Supported y NIH Trining Grnt EY738, NIH Core Grnt EY1792, nd grnt from the Ntionl Retinitis Pigmentos Foundtion. We thnk Dr M. F. Golderg nd Ms M. Gere for helpful comments on the mnuscript. Refeirences 1ISorsy A, Dvey HE. Dominnt mculr dystrophy. Br J Ophthlmol 1955; 39: 385-97. 2 Goodmn, Ripps H, Siegel IM. Cone dysfunction syndromes. Arch Ophthlmol 1963; 7:214-31. 3 Berson EL, Gours P, Gunkel RD. Progressive cone degenertion, dominntly inherited. Arch Ophthlmol 1968; S: 77-83. 4 Krill AE, Deutmn AF. Dominnt mculr degenertions; the cone dystrophies. AmiJ Ophthlmol 1972; 73: 352-69. 5 Krill AE, Deutmn AF, Fishmn M. The cone degenertions. Doc Ophthlmol 1973; 35: 1-8. 6 Frneois J, DeRouck A, Verriest G, et l. Progressive generlized cone dysfunction. Ophthlmologic 1974; 169: 255-84. 7 Berson EL, Gours P, Gunkel RD. Progressive cone-rod dystrophy. Arch Ophthlmol 1968; 8: 68-76. 8 Hittner HM, Murphree AL, Grci CA, et L. Dominnt conerod dystrophy. Doc Ophthlmol 1975; 39: 29-52. 9 Fishmn GA. Progressive humn cone-rod dysfunction (dystrophy). Trns Am Acd Ophthlmol Otolryngol 1976; 81: 716-24. 1 Gours P, Eggers HM, McKy CJ. Cone dystrophy. nyctlopi nd supernorml rod responses: new retinl degenertion. Arch Ophthlmol 1983; 11: 718-24. 11Fishmn GA, Buckmn G, Vn Every T. Fundus flvimcultus: clinicl clssifiction. Doc Ophthlmol Proc Ser 1977; 13: 213-2. 12 Mssof RW, Finkelstein D. Two forms of utosoml dominnt primry retinitis pigmentos. Doc Ophthlmol 1981; 51: 289-346. Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.

78 Kenneth R. Alexnder nd Gerld A. Fishmn 13 King-Smith PE, Crden D. Luminnce nd opponent-color contriutions to visul detection nd dpttion nd to temporl nd sptil integrtion. J Opt Soc Am 1976; 66: 79-17. 14 Kline R, Ripps H, Dowling JE, Genertion of -wve currents in the skte retin. Proc Nd Acd Sci USA 1978; 75: 5727-31. 15 Krill AE, Lee GB. The electroretinogrm in linos nd crriers of the oculr lino trit. Arch Ophthlmol 1963; 69: 32-8. 16 Perlmn JT, Burin HM. Electroretinogrphic findings in thyroid dysfunction. Am J Ophthlmol 1964; 58: 216-25. 17 Zimmermn TJ, Dwson WW, Fitzergld CR. Electroretinogrphic chnges in norml eyes during dministrtion of prednisone. Ann Ophthlmol 1973; 5: 757-65. 18 Feinsod M, Rowe H, Auerch E. Chnges in the electroretinogrm in ptients with optic nerve lesions. Doc Ophthlmol 1971; 29: 169-2. 19 Henkes HE. Electroretinogrphy. An evlution of the influence of the retinl nd generl metolic condition on the electricl response of the retin. Am J Ophthlmol 1957; 43: 67-81. 2 Niemeyer G. ERG dependence on flow rte in the isolted nd perfused mmmlin eye. Brin Res 1973; 57: 23-7. Br J Ophthlmol: first pulished s 1.1136/jo.68.2.69 on 1 Ferury 1984. Downloded from http://jo.mj.com/ on 15 Novemer 218 y guest. Protected y copyright.