PATTERN ELECTRORETINOGRAPHY IN RELATION TO KINETIC AND STATIC PERIMETRY AND VISUAL ACUITY IN RETINITIS PIGMENTOSA

Background. This study was conducted to assess whether pattern ERG is a sensitive test in evaluating the retinal function in patients with retinitis pigmentosa. We wanted to determine how pattern ERG, reflecting the activity of inner retinal layers, is related to other psychophysical tests such as perimetry and visual acuity.Methods. An analysis was performed on 50 eyes of 25 patients with typical rod-cone retinitis pigmentosa. The standard Snellen visual acuity was tested. Visual field sensitivity was measured with automated static perimetry (Octopus G2 program) where mean defect was taken as an index of visual field loss. In kinetic perimetry (Goldmann) the average radius of the visual field measured with target II/4 and V/4 was calculated. Transient pattern ERG and all five flash ERG responses were also measured according to ISCEV standards. Amplitudes of pattern ERG P50 and N95 waves were compared to results of visual acuity and visual field testing.Results. In our group of 25 RP patients with visual acuity ranging from 0.16 to 1.0, PERG responses were preserved much better than full field ERGs. 72% of them had still recordable PERG responses, while 48% had cone and only 32% maximal responses. Scotopic rod responses were extinguished in all eyes. The normalized amplitudes of the PERG responses were also much higher (43.5%) than cone (22.5%) or maximal responses (4.5%). A strong correlation of both P50 and N95 amplitudes with Octopus mean defect index was found. In kinetic perimetry the correlation with PERG amplitudes was also high, but it was better with II/4 than with V/4 target. Patients with high preserved ERG responses had good visual acuity. In all patients with visual acuity less than 0.4 both flash and pattern ERG responses were already absent.Conclusions. This study shows that pattern ERG is an objective and sensitive test in evaluating the functional visual loss in retinitis pigmentosa. Amplitudes of P50 and N95 responses are linearly related to the remaining functional retina. The agreement is more pronounced in static than kinetic perimetry. Visual acuity affects the pattern ERG more than flash ERG.</p

ELECTROOCULOGRAPHY AND PATTERN ERG IN THE DIAGNOSTICS OF BEST’S VITELLIFORM DISTROPHY

Background. The aim of the study was to develop electrooculography in accordance with ISCEV standards and to test its accuracy in the diagnosis of Best’s disease, where the EOG results should be invariably abnormal in all affected members. The pathophysiology of Best’s disease is not yet completely understood, so pattern and full field flash ERG responses compared to visual acuity and stage of the disease were used to asses the neurosensory retinal function in different stages of Best’s disease.Patients and methods. The EOG was recorded in accordance with ISCEV standards on 30 healthy individuals to determine normal values of our laboratory. Pattern as well as photopic and scotopic ERG were recorded on 24 eyes of 12 patients with typical Best’s disease with abnormal EOG responses. The results were compared to visual acuity and stage of the disease.Results. Our EOG normative data are comparable with results from other laboratories: the mean value of Arden ratio is 2.32, the range of 2 standard deviations from the mean value is from 1.6 to 3.04. The patients with Best’s disease have statisticaly significant lower values of Arden ratio (the mean value beeing 1.19). 12 patients (24 eyes) with Best’s disease with abnormal EOG values were divided in two groups according to visual acuity. In the first group of 12 eyes with visual acuity &gt; 0.5 PERG P50 and N95 responses were all in the normal range. In the second group of 12 eyes with visual acuity 0.5 or less PERG showed reduced both P50 and N95 responses in 5 eyes, and N95 solely, in two eyes.The photopic and scotopic electroretinographic responses were normal in all patients. Progression of the disease, seen in the deterioration of visual acuity, corresponded well with reduction of both PERG P50 and N95 responses. There was no correlation found between visual acuity and EOG responses.Conclusions. In the study on patients with Best’s disease, it was confirmed that EOG is a very sensitive test for detecting the disease. On the basis of EOG results alone no assumption can be made about the stage of the disease, as EOG is abnormal in all the patients, regardless of the stage of the disease. Pattern ERG is getting abnormal with progression of the disease, indicating relative preservation of neurosensory retina in initial stages of the disease, giving opportunity for electrophysiological determination of the progression of the disease.</p

Leberjeva hereditarna optična nevropatija – pregled bolezni z analizo prisotnosti v Sloveniji

Leberjeva hereditarna optična nevropatija (LHON) je redka dedna mitohondrijska bolezen, ki povzroča slepoto najpogosteje pri mladih odraslih. Navadno se izrazi kot subakutna, neboleča izguba vida na eno oko, ki ji sledi poslabšanje vida drugega očesa v nekaj tednih do mesecih. Bolezen večinoma pušča trajne posledice, le pri nekaterih bolnikih lahko v redkih primerih pride do delnega spontanega izboljšanja vida. Razmerje med moškimi in ženskimi bolniki se ocenjuje na 3 : 1. V zadnjih letih je z razvojem zdravilne učinkovine idebenone možno podporno farmakološko zdravljenje, ki lahko prispeva k delnemu izboljšanju vidne funkcije. Bolezen zaradi svoje redkosti velikokrat ostane ne- ali napačno diagnosticirana. V članku predstavljamo štiri klinične primere bolnikov, pri katerih se je po obsežnem in dolgotrajnem diagnosticiranju izkazalo, da imajo LHON. Od leta 1996 se v Sloveniji vodi baza bolnikov z redkimi dednimi očesnimi boleznimi. Na tej podlagi je ocenjena prevalenca LHON 1/72.000. Ob sumu na bolezen so ključni družinska anamneza slabovidnosti po materini strani, genetsko testiranje in napotitev na obravnavo ter zdravljenje v terciarno ustanovo

Fundus autofluorescence and optical coherence tomography in relation to visual function in Usher syndrome type 1 and 2

Purpose of this study was to characterize retinal disease in Usher syndrome using fundus autofluorescence and optical coherence tomography. Study included 54 patients (26 male, 28 female) aged 7–70 years. There were 18 (33%) USH1 and 36 (67%) USH2 patients. 49/52 (94%) patients were found to carry at least one mutation in Usher genes. Ophthalmological examination included assessment of Snellen visual acuity, color vision with Ishihara tables, Goldmann visual fields (targets II/1–4 and V/4), microperimetry, fundus autofluorescence imaging and optical coherence tomography. Average age at disease onset (nyctalopia) was significantly lower in USH1 than USH2 patients (average 9 vs. 17 years, respectively; p < 0.01); however no significant differences were found regarding type of autofluorescence patterns, frequency of foveal lesions and CME, rate of disease progression and age at legal blindness. All representative eyes had abnormal fundus autofluorescence of either hyperautofluorescent ring (55%), hyperautofluorescent foveal patch (35%) or foveal atrophy (10%). Disease duration of more than 30 years was associated with a high incidence of abnormal central fundus autofluorescence (patch or atrophy) and visual acuity loss

Stargardt-like Clinical Characteristics and Disease Course Associated with Variants in the <i>WDR19</i> Gene

Variants in WDR19 (IFT144) have been implicated as another possible cause of Stargardt disease. The purpose of this study was to compare longitudinal multimodal imaging of a WDR19-Stargardt patient, harboring p.(Ser485Ile) and a novel c.(3183+1_3184-1)_(3261+1_3262-1)del variant, with 43 ABCA4-Stargardt patients. Age at onset, visual acuity, Ishihara color vision, color fundus, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT) images, microperimetry and electroretinography (ERG) were evaluated. First symptom of WDR19 patient was nyctalopia at the age of 5 years. After the age of 18 years, OCT showed hyper-reflectivity at the level of the external limiting membrane/outer nuclear layer. There was abnormal cone and rod photoreceptor function on ERG. Widespread fundus flecks appeared, followed by perifoveal photoreceptor atrophy. Fovea and peripapillary retina remained preserved until the latest exam at 25 years of age. ABCA4 patients had median age of onset at 16 (range 5–60) years and mostly displayed typical Stargardt triad. A total of 19% had foveal sparing. In comparison to ABCA4 patients, the WDR19 patient had a relatively large foveal preservation and severe rod photoreceptor impairment; however, it was still within the ABCA4 disease spectrum. Addition of WDR19 in the group of genes producing phenocopies of Stargardt disease underlines the importance of genetic testing and may help to understand its pathogenesis

Clinical and haplotypic variability of Slovenian USH2A patients homozygous for the c. 11864G>A nonsense mutation

Purpose: to determine a detailed clinical and haplotypic variability of the Slovenian USH2A patients with homozygous c.11864G>A (p.Trp3955Ter) nonsense mutation and to develop sensitive, accurate and rapid screening test. Methods: Ten unrelated homozygous patients with detailed ophthalmological exam were included in our study. The High-Resolution Melting (HRM) method was developed for fast and reliable detection of the c.11864G>A mutation. Results: The c.11864G>A mutation represents the vast majority of pathogenic alleles in Slovenian USH2A-Usher syndrome population (84%). The median age of onset of nyctalopia was 16 years and all patients younger than 40 years had hyperautofluorescent rings on fundus autofluorescence imaging. The Kaplan Meier survival analysis showed a decline of central vision after the age of 40, with 50% patients reaching visual acuity (VA) ≤ 0.05 at the average age of 66 years visual field diameter less than 20° at the average age of 59 years. There was a relatively large phenotypic variability in the retinal and audiological phenotype. Analysis of the p.Trp3955Ter-homozygous patients revealed four different haplotypes, with the frequency of the most common haplotype ~65%. Disease severity did not correlate with the haplotype. Conclusions: According to the natural history of homozygous p.Trp3955Ter patients any therapy aimed to slow disease progression in these patients would be best started before the age of 40. Phenotypic variability suggests the presence of cis and/or trans factors outside the USH2A gene that are able to affect disease severity. High frequency of p.Trp3955Ter mutation in Slovenian USH2A gene pool appears to be initiated from different unrelated founders because of migrations from neighboring populations. The mutation on haplotype 2 seems to be the major founder allele

Clinical and Haplotypic Variability of Slovenian USH2A Patients Homozygous for the c. 11864G>A Nonsense Mutation

International audiencePURPOSE: to determine a detailed clinical and haplotypic variability of the Slovenian USH2A patients with homozygous c.11864G>A (p.Trp3955Ter) nonsense mutation and to develop sensitive, accurate and rapid screening test.METHODS: Ten unrelated homozygous patients with detailed ophthalmological exam were included in our study. The High-Resolution Melting (HRM) method was developed for fast and reliable detection of the c.11864G>A mutation.RESULTS: The c.11864G>A mutation represents the vast majority of pathogenic alleles in Slovenian USH2A-Usher syndrome population (84%). The median age of onset of nyctalopia was 16 years and all patients younger than 40 years had hyperautofluorescent rings on fundus autofluorescence imaging. The Kaplan Meier survival analysis showed a decline of central vision after the age of 40, with 50% patients reaching visual acuity (VA) ≤ 0.05 at the average age of 66 years visual field diameter less than 20° at the average age of 59 years. There was a relatively large phenotypic variability in the retinal and audiological phenotype. Analysis of the p.Trp3955Ter-homozygous patients revealed four different haplotypes, with the frequency of the most common haplotype ~65%. Disease severity did not correlate with the haplotype.CONCLUSIONS: According to the natural history of homozygous p.Trp3955Ter patients any therapy aimed to slow disease progression in these patients would be best started before the age of 40. Phenotypic variability suggests the presence of cis and/or trans factors outside the USH2A gene that are able to affect disease severity. High frequency of p.Trp3955Ter mutation in Slovenian USH2A gene pool appears to be initiated from different unrelated founders because of migrations from neighboring populations. The mutation on haplotype 2 seems to be the major founder allele

Double hyperautofluorescent rings in patients with USH2A-retinopathy

USH2A mutation is the most common cause of retinitis pigmentosa, with or without hearing impairment. Patients most commonly exhibit hyperautofluorescent ring on fundus autofluorescence imaging (FAF) and rod-cone dystrophy on electrophysiology. A detailed study of three USH2A patients with a rare pattern of double hyperautofluorescent rings was performed. Twenty-four patients with typical single hyperautofluorescent rings were used for comparison of the ages of onset, visual fields, optical coherence tomography, electrophysiology, and audiograms. Double rings delineated the area of pericentral retinal degeneration in all cases. Two patients exhibited rod-cone dystrophy, whereas the third had a cone-rod dystrophy type of dysfunction on electrophysiology. There was minimal progression on follow-up in all three. Patients with double rings had significantly better visual acuity, cone function, and auditory performance than the single ring group. Double rings were associated with combinations of null and missense mutations, none of the latter found in the single ring patients. According to these findings, the double hyperautofluorescent rings indicate a mild subtype of USH2A disease, characterized by pericentral retinal degeneration, mild to moderate hearing loss, and either a rod-cone or cone-rod pattern on electrophysiology, the latter expanding the known clinical spectrum of USH2A-retinopathy

Double Hyperautofluorescent Rings in Patients with USH2A-Retinopathy

International audienceUSH2A mutation is the most common cause of retinitis pigmentosa, with or without hearing impairment. Patients most commonly exhibit hyperautofluorescent ring on fundus autofluorescence imaging (FAF) and rod-cone dystrophy on electrophysiology. A detailed study of three USH2A patients with a rare pattern of double hyperautofluorescent rings was performed. Twenty-four patients with typical single hyperautofluorescent rings were used for comparison of the ages of onset, visual fields, optical coherence tomography, electrophysiology, and audiograms. Double rings delineated the area of pericentral retinal degeneration in all cases. Two patients exhibited rod-cone dystrophy, whereas the third had a cone-rod dystrophy type of dysfunction on electrophysiology. There was minimal progression on follow-up in all three. Patients with double rings had significantly better visual acuity, cone function, and auditory performance than the single ring group. Double rings were associated with combinations of null and missense mutations, none of the latter found in the single ring patients. According to these findings, the double hyperautofluorescent rings indicate a mild subtype of USH2A disease, characterized by pericentral retinal degeneration, mild to moderate hearing loss, and either a rod-cone or cone-rod pattern on electrophysiology, the latter expanding the known clinical spectrum of USH2A-retinopathy