experimental animals : a total of 66 ms were included in the present study . fifty - two of these were brought for examination , because the owner suspected visual 
 impairment , and were diagnosed with pra at the veterinary medical teaching hospital , seoul 
 national university , south korea , from january 2006 to december 2010 . therefore , 
 medical records were studied , and cases with a history of acute blindness , polyphagia , 
 polydipsia and weight gain were excluded from the study . fourteen normal ms were presented 
 by their owners for ocular examination in order to exclude pra before breeding and were 
 selected to be included in the present study to compare retinal function between normal and 
 pra - affected ms using erg . the normal ms dogs were divided into 3 age groups for description 
 of normal erg data : 2 , 3 to 5 and 6 to 9 years by the retinal maturity and evidence of 
 nuclear sclerosis in dogs [ 22 , 23 ] . clinical evaluation : all animals included underwent ocular examinations to 
 diagnose and/or confirm ocular disease . menace responses were evaluated by making a 
 threatening gesture with a hand toward the eye , taking care not to touch the vibrissae or 
 cause air currents . results of the test were divided into a normal blink , delayed and a 
 non - blink response . pupillary light reflexes ( plrs ) were evaluated subjectively by using a 
 focal light source ( heine 6 - 21 - 301 , heine , berlin , germany ) under scotopic 
 conditions . the results of the test were divided into normal , delayed and dilated / fixed 
 plrs . intraocular pressure ( iop ) was measured to differentiate pra from retinal degeneration 
 due to glaucoma using a tonometer ( tonopen xl , mentor , norwell , ma , u.s.a . ) . the 
 anterior segments were examined using a slit lamp biomicroscope ( sl-202p , 
 shin - nippon commerce , tokyo , japan ) , 20 min after instillation of tropicamide 
 ( mydriacyl , alcon inc . , puurs , belgium ) , followed by fundus examination , using 
 an indirect ophthalmoscope ( vantage , keeler instruments inc . , broomall , pa , 
 u.s.a . ) . fundus photographs were taken using a fundus camera ( kowa hand - held fundus 
 camera , genesis , kowa co. , tokyo , japan ) more than 1 hr prior to 
 the erg . the diagnosis of pra was based on the ophthalmoscopic findings and the results of 
 erg recordings . preparation of animals for erg : fifteen ms with visual impairment or 
 blindness and 14 normal ms underwent erg ( retiport , roland consult , brandenburg , 
 germany ) examination after permission by the owner . all animals were fasted for at least 12 
 hr prior to performing the erg recordings . maximal pupillary dilation was obtained by 
 applying 1 drop of 1% tropicamide ( mydriacyl , alcon inc . ) to the test eye every 
 30 min from at least 1 hr prior to beginning the erg session . the canine protocol endorsed 
 by the european college of veterinary ophthalmologists was utilized for 28 dogs ( 14 normal 
 ms and 14 pra - affected ms ) all under general anesthesia . the dogs were premedicated with atropine sulfate ( je - il atropine sulfate , je - il 
 pharmacy , daegu , korea ) administrated subcutaneously at the dose of 0.04 mg / kg . xylazine 
 ( rompun , bayer korea , ansan , korea ) was administered intramuscularly using a 
 sedative dose of 2.0 mg / kg . the dogs were kept in a cage in a silent area under ambient 
 light for approximately 10 min . generalized anesthesia was induced with ketamine ( yuhan 
 ketamine , yuhan corporation , gunpo , korea ) injected intramuscularly at the 
 dose of 10 mg / kg . after induction of anesthesia , the dogs were positioned on their sternal 
 recumbency throughout the recordings and the head positioned using packs of towels for the 
 erg recordings . erg procedures : ergs were recorded from the left eye of each dog using the 
 erg system . platinum subdermal needle electrodes ( model f - e2 , grass instrument 
 division , astro - med . inc . , west warwick , ri , u.s.a . ) were used to record the erg ; a 
 reference electrode and a ground electrode were placed approximately 2 cm caudal to the 
 lateral canthus of the tested eye and over the external occipital protuberance , 
 respectively . the cornea was anesthetized by topical 0.5% proparacaine hydrochloride 
 ( alcaine , alcon inc . ) . a contact lens electrode with built - in white 
 light - emitting diodes ( led , kooijman / damhof erg lens , medical workshop bv , 
 groningen , netherland ) was placed on the cornea after application of 0.3% hydroxypropyl 
 methylcellulose ( artear , unimed pharm . , a piece of tape was used 
 to keep the contact lens in a correct and stable position on the eye during the recordings . the electrodes were connected to a preamplifier , and signals were amplified with a band pass 
 filter between 1 and 300 hz . all lights in the examining room were turned off at the 
 initiation of the erg test . for the dog protocol , the built - in white led with a contact lens electrode for the erg 
 system used in the study delivered white flashes of light 1 cm from the cornea . two different responses were evaluated for scotopic ergs : rod ( r ) response 
 with scotopic low intensity stimuli ( 0.025 cdsec / m ) and standard mixed rod and 
 cone ( mrc ) responses using scotopic standard intensity ( 2.5 cdsec / m ) . the r 
 responses were designated r1 , r5 , r10 , r15 and r20 elicited 1 , 5 , 10 , 15 and 20 min after 
 the initiation of dark adaptation , respectively . for the evaluation of the cone system , 
 photopic ergs were performed with 2 different stimuli after 10 min of light adaptation 
 ( background luminance : 25 cd / m ) : pure cone ( c ) responses using photopic single 
 flash and 31 hz cone flicker ( cf ) responses from cones and cone pathways with 2.5 
 cdsec / m flash under the same background luminance . the cf responses lasted 
 for 300 msec and recorded 9 flashes for each dog tested . erg evaluation : the amplitude and implicit time were measured for each a- 
 and b - wave erg component . the a - wave amplitude was measured from the baseline to the first 
 negative peak , and the b - wave amplitude was measured from the negative peak of the a - wave to 
 the following positive peak . implicit times for a- and b - waves were measured from the onset 
 of light stimulus to the peak of these a- and b- waves , respectively . for the r responses 
 and cf response , only b - waves were obtained and analyzed . amplitudes of cf responses were 
 measured from the baseline to the positive peak and implicit times from the light onset to 
 the positive peak . statistical analysis : data were analyzed using a commercial statistical 
 package ( spss for windows version 12.0 , spss inc . , chicago , il , u.s.a . ) . descriptive 
 statistics were reported as mean and standard deviation ( sd ) for age , and median and range 
 of the 5th and the 95th percentiles for the erg data to avoid errors by non - normal 
 distribution of data of small sample size . clinical findings : for normal dogs , the mean age  sd was 4.1  2.4 years 
 ( 1 to 9 years of age ) , and there were no ocular abnormalities on the basis of ocular 
 examination . the mean age  sd of dogs with pra was 
 4.3  1.1 years ( 2 to 7 years of age ) at the first presentation for examination ; but 44 of 
 52 dogs with pra ( 84.6% ) were 3 to 5 years of age ( table 1table 1.age distribution in pra - affected dogsage ( years)234567totalnumber of dogs2724133352 ) . the median period between onset and the diagnosis of pra was 2 months 
 ranging from 0.5 to 24 months in 48 dogs affected . seven spayed female , 26 female , 11 male 
 neutered and 8 male dogs were examined . all of the dogs diagnosed with pra showed normal 
 blink ( n=1 , 1.9% ) , delayed ( n=7 , 13.5% ) or non - blink ( n=44 , 84.6% ) menace responses . they displayed normal ( n=6 , 11.5% ) , 
 delayed ( n=21 , 40.4% ) or dilated / fixed ( n=25 , 48.1% ) direct and indirect plrs ( table 2table 2.results of menace responses and pupillary light reflexes in pra - affected dogs 
 ( n=52)age ( years)menace responsedirect and indirect pupillary light reflexesnormal blinkdelayednon - blinknormal reflex delayeddilated / fixed2 ( n=2)00200235 ( n=44)17365201967 ( n=6)006114total174462125a ) consisted of 1 delayed and 4 non - blink menace responses ; b ) 1 normal , 5 delayed 
 and 14 non - blink menace responses ; and c ) 1 delayed and 18 non - blink menace 
 responses . ) . there were no abnormalities in the anterior segment or iop readings in any 
 of the dogs examined . of the 52 dogs with pra , posterior subcapsular incipient cataract and 
 incipient nuclear cataract were identified in 3 dogs ( 2 dogs aged 6 years and 1 dog aged 7 
 years ) and 1 dog aged 4 years , respectively , at the initial presentation . a ) consisted of 1 delayed and 4 non - blink menace responses ; b ) 1 normal , 5 delayed 
 and 14 non - blink menace responses ; and c ) 1 delayed and 18 non - blink menace 
 responses . for the normal dogs , the ophthalmoscopic examination showed normal reflectivity of the 
 tapetal region , normal vascular size and normal coloration of the tapetal fundus . ophthalmoscopic changes noted in the pra - affected ms included one or more of the following 
 changes : diffuse hyperreflectivity of the tapetal area ( n=52 , 100.0% ) , moderate or severe 
 attenuation of major venules and arterioles ( n=52 , 100.0% ) , severe tan - brown discoloration 
 of the tapetal fundus ( n=8 , 15.4% ) , depigmentation in non - tapetal area ( n=7 , 13.5% ) and 
 optic disc atrophy ( n=9 , 17.3% ) ( table 
 3table 3.ophthalmoscopic findings in pra - affected dogs at the first presentation 
 ( n=52)ophthalmoscopic findingsnumber of dogs ( % ) diffuse hyperreflectivity in the tapetal area52 ( 100.0%)attenuation of major venules and arterioles52 ( 100.0%)severe tan - brown discoloration in the tapetal fundus8 ( 15.4%)depigmentation in non - tapetal area7 ( 13.5%)optic disc atrophy9 ( 17.3% ) , fig . 1fig . 1.fundus photographs of pra - affected miniature schnauzers at 2 years ( a ) , 4 years ( b ) 
 and 6 years ( c ) of age . the fundus abnormalities observed in the affected dogs are : 
 diffuse hyperreflectivity ( in a and b ) and severe vascular attenuation ( in a , b and 
 c ) . ) . the signs of retinal degeneration were symmetrical for both eyes in each dog , and 
 the severity of the ophthalmoscopic fundus abnormalities was somewhat variable among the 
 affected dogs . fundus photographs of pra - affected miniature schnauzers at 2 years ( a ) , 4 years ( b ) 
 and 6 years ( c ) of age . the fundus abnormalities observed in the affected dogs are : 
 diffuse hyperreflectivity ( in a and b ) and severe vascular attenuation ( in a , b and 
 c ) . 2.representative erg waveforms recorded using the dog protocol in 4 years old normal 
 and pra - affected ms . scotopic ergs ( a and b , e and f ) and photopic ergs ( c and d , g and h ) are shown . r 
 responses ( 0.025 cdsec / m , a and e ) , were designated r1 ( 1 min ) , r5 ( 5 
 min ) , r10 ( 10 min ) , r15 ( 15 min ) and r20 ( 20 min ) after the initiation of dark 
 adaptation ( from top to bottom in a and e ) , and mrc responses ( 2.5 
 cdsec / m , b and f ) . the c responses ( 2.5 cdsec / m , c and g ) 
 and cf responses ( 2.5 cdsec / m , d and h ) were obtained after 10 min of 
 light adaptation using 25 cd / m of background light . displays examples of typical normal and non - recordable erg responses obtained from 
 two 4-year - old normal ms dogs and pra - affected ms , respectively , for the scotopic and 
 photopic ergs . for the erg waveforms of normal ms , the r responses had a prominent b - wave 
 that increased in amplitude and in implicit time during the 20-min of dark adaptation . the mrc responses had prominent a- 
 and b - waves , and oscillatory potentials were observed during the ascending phase of the 
 b - wave for the normal dogs . the c response had a smaller but faster b - wave than that of the 
 r response , and the cf responses consisted of b - waves only . the erg data with age - related 
 change of normal ms dogs were shown ( table 
 4table 4.median and 5th and 95th percentiles of amplitude ( v ) and 
 implicit time ( msec ) of a - and b - waves by dog protocol in normal ms dogs ( n=14)responsewave2 years ( n=2)35 years ( n=9)69 years ( n=3)amplitudeimplicit timeamplitudeimplicit time amplitudeimplicit timer1b62.8 ( 59.965.6)45.5 ( 38.852.3)49.8 ( 25.670.5)43.0 ( 41.057.2)50.3 ( 39.865.9)46.0 ( 40.650.5)r 5b81.3 ( 46.4116.1)47.0 ( 42.551.5)86.9 ( 38.0126.0)54.0 ( 39.663.6)84.0 ( 43.188.9)51.0 ( 46.564.5)r 10b135.5 ( 110.8160.3)55.0 ( 50.559.5)134.0 ( 62.4163.4)55.0 ( 48.867.8)106.0 ( 73.0113.2)61.0 ( 52.071.8)r 15b192.0 ( 183.0201.0)63.0 ( 56.769.3)161.0 ( 91.7188.4)62.0 ( 55.070.0)129.0 ( 84.1138.9)73.0 ( 66.775.7)r 20b229.5 ( 227.3231.8)64.0 ( 63.164.9)203.0 ( 97.9221.8)64.0 ( 54.870.0)127.0 ( 79.5157.6)74.0 ( 68.674.9)mrca108.6 ( 97.4119.8)12.5 ( 12.113.0)121.0 ( 53.4153.8)12.0 ( 11.015.0)79.0 ( 67.2127.6)15.0 ( 11.419.5)b310.0 ( 286.6333.4)60.5 ( 57.463.7)246.0 ( 115.8298.4)55.0 ( 33.664.8)147.0 ( 102.5225.3)65.0 ( 61.466.8)ca14.7 ( 10.718.6)10.0 ( 8.211.8)11.7 ( 7.921.5)10.0 ( 8.012.0)11.2 ( 10.813.5)11.0 ( 10.112.8)b60.1 ( 53.466.7)25.5 ( 24.226.9)45.5 ( 42.258.6)25.0 ( 22.026.0)33.2 ( 30.156.1)25.0 ( 23.225.9)cfb75.9 ( 71.180.7)25.0 ( 25.025.0)72.7 ( 56.984.6)23.2 ( 19.823.2)66.3 ( 56.775.9)23.2 ( 21.623.2)rod ( r ) responses were obtained using 0.025 cdsec / mof light stimulation 
 during 20 min of dark adaptation , which was designated r1 , r5 , r10 , r15 , and r20 . standard mixed rod cone ( mrc ) responses were thereafter obtained at 2.5 
 cdsec / m . photopic ergs consisted of a photopic single flash cone ( c ) 
 response and 31 hz cone flicker ( cf ) responses , both at 2.5 cdsec / m after 
 10 min of light adaptation using 25 cd / m of background 
 light . ) . for the erg recordings of pra - affected ms tested , all erg responses were 
 non - recordable in all of the pra - affected dogs for all light intensities used . representative erg waveforms recorded using the dog protocol in 4 years old normal 
 and pra - affected ms . scotopic ergs ( a and b , e and f ) and photopic ergs ( c and d , g and h ) are shown . r 
 responses ( 0.025 cdsec / m , a and e ) , were designated r1 ( 1 min ) , r5 ( 5 
 min ) , r10 ( 10 min ) , r15 ( 15 min ) and r20 ( 20 min ) after the initiation of dark 
 adaptation ( from top to bottom in a and e ) , and mrc responses ( 2.5 
 cdsec / m , b and f ) . the c responses ( 2.5 cdsec / m , c and g ) 
 and cf responses ( 2.5 cdsec / m , d and h ) were obtained after 10 min of 
 light adaptation using 25 cd / m of background light . rod ( r ) responses were obtained using 0.025 cdsec / mof light stimulation 
 during 20 min of dark adaptation , which was designated r1 , r5 , r10 , r15 , and r20 . standard mixed rod cone ( mrc ) responses were thereafter obtained at 2.5 
 cdsec / m . photopic ergs consisted of a photopic single flash cone ( c ) 
 response and 31 hz cone flicker ( cf ) responses , both at 2.5 cdsec / m after 
 10 min of light adaptation using 25 cd / m of background 
 light . canine pra is a group of inherited retinal diseases with genetic heterogeneity in different 
 breeds and even within breeds . this study was 
 performed to investigate the clinical and electroretinographic features of the retina in 
 normal ms dogs and in groups of ms diagnosed with pra in south korea . the pra in ms dogs of 
 south korea was associated with visual impairment up to the age of 7 years and was mostly 
 observed at the age of 3 to 5 years in the present study . this result may be caused by the 
 comparatively small group of imported dogs used for breeding purposes , and further 
 inbreeding s performed , including parent and offspring matings . clinical and erg findings 
 from the present study are comparable with the clinical findings of pra cases reported in 
 the breed mainly in u.s.a . previous investigations in the breed including histopathologic and electroretinographic 
 findings showed that the type of pra found was an early - onset disorder . functional and morphologic abnormalities were shown 
 to be evident at an age when the normal retina is approaching the end of postnatal 
 differentiation . therefore , the disease was described as a photoreceptor dysplasia 
 ( pd ) , because it affects both rod and cone photoreceptors , and well 
 before the time of retinal maturation . the ms previously studied were night blind and had 
 compromised day vision by 3 years of age . the blindness observed in affected ms by the 
 previous investigators did not develop until after 4 to 5 years of age . there was no 
 evidence for any sex predilection for the disease [ 2 , 
 20 ] . in the present study , the age range of dog 
 with pra was 2 to7 years , with a mean age  sd was 4.3  1.1 years ; 44 of 52 dogs with pra 
 ( 84.6% ) were 3 to 5 years of age . the present study showed that there was a presence of the menace responses and plrs in some 
 dogs suffering from visual impairment due to pra . comparison of both types of observations 
 used in the present study showed that the menace response gave much better estimation for 
 loss of retinal function than the plrs . the results of both observations allowed us to 
 deduce that conventional retinal testing routinely performed in the clinic was not always 
 trustworthy ; also , it emphasized the importance of more objective testing techniques , such 
 as use of the erg . the plr required fewer intact axons than conscious perception of vision , 
 and therefore , in partial lesions of the proximal visual pathway , the situation may exist 
 where there is loss of vision but the plr is spared . detailed studies have shown that a full plr can still occur in mice lacking both 
 rod and cone photoreceptors , even when there is reduced sensitivity . recently , a new theory on the plr - induced retinal cells was 
 presented : both the vitamin - based photosensitive pigment ( melanopsin ) in retinal ganglion 
 cells and rod - cone photoreceptive systems were associated with plrs in mice . it was also described in another study that there 
 was a presence of intrinsic melanopsin - mediated plr activity induced by high light - intensity 
 and an absence of rod - cone - mediated plr elicited by low light intensities in dogs with 
 retinal degeneration . this phenomenon could 
 explain why there was a presence of plrs in dogs with pra in the present study . posterior subcapsular cataracts commonly occur secondarily to advanced stages of pra in 
 many canine breeds   and in rp in humans . results of several previous studies showed that the 
 lipid peroxidation mechanism might be associated with lens opacity due to retinal diseases , 
 such as pra and rp [ 6 , 9 ] . the differences in metabolic accumulation may give rise to variations in the 
 age of onset of the secondary cataracts in different canine breeds . tibetan terriers and 
 miniature poodles with late - onset forms of pra have lens opacities at older ages . the mean age of cataract onset in ms of south korea 
 was at the age of 5.4 years which was significantly lower than that seen in other breeds 
 . according to the previous studies , even though ophthalmoscopic abnormalities can be 
 detected in some affected animals as early as at 14 months of age conclusive ophthalmoscopic 
 lesions were not found in affected dogs until 2 to 5 years of age . it appears that a misdiagnosis could be made in early stages of the 
 disease process , due to variable clinical findings in affected ms dogs . therefore , erg is a 
 valuable tool that gives an objective evaluation of retinal function and is readily 
 available for clinicians or retinal researchers . erg can be used to show if photoreceptors achieve functional maturity , and whether 
 development is normal or not . further , the process of phototransduction can be monitored 
 using this equipment . according to previous 
 studies regarding the ms , erg recordings showed that pra - affected ms had functional deficits 
 as early as at 8 weeks of age . further , 
 conclusive changes in erg parameters were clearly recognized at 15 to 19 weeks of age . 
 comparing the time point of the ophthalmoscopic abnormalities mentioned above with the erg 
 changes observed , it is clear that erg can be objectively used to detect the subtle changes 
 in the fundus very early and prior to the onset of fundoscopic abnormalities . it is an 
 established concept that configuration of the erg waveform is changed when phototransduction 
 is abnormal . in summary , it was shown that the mean age  sd of ms affected with pra was 4.3  1.1 years 
 at the first presentation for examination , and most of the pra - affected dogs had no menace 
 responses and/or plrs . ophthalmoscopic abnormalities noted in pra - affected dogs included 
 several retinal changes previously described in conjunction with pra . erg responses in the 
 pra - affected dogs tested were non - recordable for all levels of light stimuli used in the 
 dark and light adapted states . the present study showed that pra in the ms was observed in 
 adult dogs at 3 to 5 years of age and that there were functional abnormalities of both the 
 rod and the cone systems at the ages studied .
abstractthe purpose of the study was to describe the clinical and electroretinographic features 
 of clinical cases of progressive retinal atrophy ( pra ) in miniature schnauzer ( ms ) of 
 south korea . 
 sixty - six ms ( 14 normal and 52 affected ) were included . 
 all animals underwent 
 routine ocular examinations . 
 electroretinogram ( erg ) was recorded in the 14 normal and 15 
 affected dogs . for normal dogs , 
 the mean age  sd was 4.1  2.4 years ( 1 to 9 years ) , and 
 there were no ocular abnormalities on the basis of ocular examinations and erg results . 
 for the pra - affected dogs , it was shown that the mean age  sd was 4.3  1.1 years ( 2 to 7 
 years ) , and 44 dogs ( 84.6% ) were 3 to 5 years old . 
 most of the pra - affected dogs had 
 abnormal menace responses ( 98.1% ) and pupillary light reflexes ( plrs , 88.5% ) ; some dogs 
 showed normal menace response ( 1.9% ) and plrs ( 11.5% ) . 
 ophthalmoscopic abnormalities in 
 the affected group included one or more of the following changes : hyperreflectivity and 
 discoloration of the tapetal area , attenuation of retinal vessels , depigmentation in 
 non - tapetal area and optic disc atrophy . 
 erg in the affected dogs showed non - recordable 
 responses in all cases tested with clinical signs of pra . 
 the present study showed that 
 pra in ms was mainly observed between the age of 3 to 5 years . 
 erg revealed abnormal rod 
 and cone responses in affected dogs at the ages studied .