Masaru Yoshii

A Basic Investigation of Multifocal Electroretinogram : Reproducibility and Effect of Luminance

PURPOSE To investigate the reproducibility as well as the effect of luminance in multifocal electroretinogram (mERG). METHODS Multifocal electroretinogram recordings were repeated on different days in 6 normal subjects using the Veris III system. The mean luminance of the monitor displaying the stimuli was randomly varied by five kinds of neutral density (ND) filters. RESULTS The standard deviation of mERG amplitude from the macular region was approximately 10% of the mean value for each normal subject. Reproducibility largely depended on the condition of the subject and placement of the contact lens electrode. With decreases in the mean luminance of the monitor, the amplitude of mERG decreased exponentially, whereas the peak latency increased linearly. mERGs elicited from a patient with mild cortical cataract resembled the mERGs obtained from the control group using an ND filter between -0.30 and -0.52 log, whereas two patients with typical retinitis pigmentosa showed much lower response densities in mERGs. CONCLUSIONS It is necessary to pay attention to the reproducibility and the luminance effect to obtain reliable mERGs.

REP-1 gene mutations in Japanese patients with choroideremia

Abstract · Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients.

Relationship between visual field defect and multifocal electroretinogram.

We investigated the effect of artificial parafoveal scotomata on the multifocal electroretinogram (M-ERG). M-ERGs were recorded from normal subjects using a monitor with several different sizes of black paper attached. A lower response density area around the 10 to 15 degree parafoveal region was not recognized for scotomata up to 3 degrees but was observed in scotomata above 5 degrees (visual angle) in the field topography of M-ERG. The shape of the scotomata was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration accorded well with this basic study.

VISUAL FUNCTION AND GENE ANALYSIS IN A FAMILY WITH OGUCHI'S DISEASE

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi’s disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi’s disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 cases, but no mutation was observed for the rhodopsin gene. A homozygous deletion 1147 (1147de1A) in codon 309 of the arrestin gene was commonly observed in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi’s disease, respectively.

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa

SummaryHeterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT→AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

Multifocal electroretinograms in early primary open-angle glaucoma

PURPOSE To determine the utility of multifocal electroretinograms (mfERGs) in patients with early primary open-angle glaucoma (POAG) with unilateral visual field abnormalities. METHODS mfERGs were recorded from 24 eyes of 12 cases of early POAG (stage I for 1 eye and stage II for the other eye on the Kosaki scale). The implicit times and amplitudes of the second-order kernel summed for the whole visual field, for the superior and inferior hemi-fields, and for quadrantic fields of the stage I and stage II eyes were compared. RESULTS Neither the first- nor the second-order kernels of the mfERGs showed any changes reflecting glaucomatous visual field abnormalities. The implicit times and amplitudes of the second-order kernel summed for the whole visual field, the superior and inferior hemi-visual fields, and quadrantic visual fields of the stage I and stage II eyes were also not significantly different. CONCLUSIONS We conclude that because the second-order kernel of the mfERG does not correlate with the visual field abnormality in early POAG, the second-order kernel of the mfERG that can be recorded at present is highly unlikely to reflect the function of the ganglion cells in the inner retinal layers.

Visual function in retinitis pigmentosa related to a codon 15 rhodopsin gene mutation

To determine the phenotype of a Japanese family in which retinitis pigmentosa cosegregates with a rhodopsin gene mutation, i.e. an asparagine-to-serine change at codon 15 (Asn-15-Ser), 5 affected and 5 unaffected members of one pedigree underwent several ophthalmic examinations as well as Ganzfeldelectroretinography (ERG) and multifocal ERG. Genomic DNA samples were analyzed by PCR amplification, sequencing and restriction enzyme digestion. A codon 15 rhodopsin gene mutation (Asn-15-Ser) was found in all affected members. The region of pigmentary degeneration was localized in the lower hemiretina, and visual field defects corresponded to the retinal pigmentary changes. Scotopic ERG amplitudes, rather than photopic ERG amplitudes, were reduced. Multifocal ERG revealed a low magnitude of response density, even for the upper hemiretina, which showed no bony corpuscle pigmentation. Visual function in sectorial retinitis pigmentosa associated with rhodopsin gene codon 15 mutation is on the basis of the rod-cone dystrophy, regardless of differences in phenotypic expression.

Nonlinear Component of the Electroretinogram Recorded from the Posterior Pole of Normal and Highly Myopic Human Eyes

To extract the nonlinear component of the electroretinogram (ERG) from the posterior pole (pp) of the human ocular fundus and to evaluate the possibility of its clinical application, three types of stimulus modes – double-flash, single-flash, and delayed single-flash stimuli – were produced using a conventional electrophysiological system. A large hexagonal element was presented on a CRT monitor, and ppERGs were recorded from 14 normal eyes and 16 eyes of eight highly myopic patients. The nonlinear component of the ppERG was obtained by subtracting the single-flash ERG and delayed single-flash ERG responses from the double flash ERG response. Three peaks were commonly observed in the nonlinear component of ppERG, all of which were significantly depressed in patients with high myopia. ppERGs that can be obtained using a simple algorithm might be useful in clinical applications.

Artifact removal procedure distorts multifocal electroretinogram.

PURPOSE To study whether the Artifact Removal procedure available for eliminating artifacts in multifocal electroretinograms (mERG) works correctly or not. METHODS A test response was made using a photo-diode circuit. mERGs were recorded from 3 well-trained normal subjects using the Veris III system, and were then analyzed by the procedure that is included in the Veris Science (Artifact Removal) software program. The stimuli consisted of densely arranged arrays of 103 or 37 hexagonal elements. It took a total of 8 minutes to obtain one mERG record, and 16 sessions were required to complete this record. The first-order as well as the second-order kernel response components were extracted by Veris Science software, and the Artifact Removal procedure was used for both components. RESULTS The Artifact Removal procedure influenced both the test response on the center element as well as the neighboring traces just around the test response. After the repetitions of the Artifact Removal procedure, the shape of the test response changed considerably. Some of the traces of the second-order kernel response components elicited from a normal subject changed irregularly when the Artifact Removal procedure was repeatedly used. The noise increased at the first iteration of the Artifact Removal procedure. CONCLUSION This procedure has been considered useful for eliminating artifact distortion in mERG, but should be carefully checked by well-established testing methods before clinical use.

The relation between the after-negative potential of the pattern electroretinogram and the visually evoked cortical potential

The relationship between the after-negative potential of the pattern electroretinogram (PERG) and the visually evoked cortical potential (VECP) was studied. The PERG was recorded through the use of Torays high water content, soft contact lens electrode. The PERG consisted of an initial positive potential, a subsequent negative potential and then a slow positive potential. To reduce or avoid contamination of the VECP on the PERG, the most important factor was found to be the reference electrode position; special attention was paid in cases where the amplitude of the VECP was large. In the steady-state condition, the PERG was thought to be modulated by the VECP when the ear lobe was used as the reference electrode position; when the temple was used as the reference electrode position, the amplitude of the PERG was thought to represent that of the after-negative potential.