Kenji Yanashima

Clinical features of autosomal dominant retinitis pigmentosa with rhodopsin gene codon 17 mutation and retinal neovascularization in a Japanese patient

A 49-year-old Japanese man had autosomal dominant retinitis pigmentosa with a point mutation in codon 17 of the rhodopsin gene, resulting in a threonine-to-methionine change, and retinal neovascularization in both eyes. Pigmentary degeneration mainly in the inferior area of the fundus, and severe loss in the upper portion of the visual field were observed. Moderately preserved rod and cone functions were demonstrated by electroretinograms. These findings differed from those of Japanese and white patients with autosomal dominant retinitis pigmentosa with a codon 347 mutation and were almost the same as those of white patients with the codon 17 mutation. Our study indicates that phenotypic similarities exist among patients with the same mutation, but of different racial backgrounds. The neovascularization in the right eye diminished over a two-year period in conjunction with the progression of retinal degeneration.

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.

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.

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.

A Japanese pedigree of autosomal dominant congenital stationary night blindness with variable expressivity

Three cases in three successive generations of one family with autosomal dominant congenital stationary night blindness are presented. Case 1, the proband, and Case 3, his grandfather had the same electroretinographic responses: nonrecordable scotopic electroretinogram (ERG), normal but slightly diminished flicker ERG, and negative-shaped single bright-flash ERG. Their dark adaptation curves were monophasic with no rod segment. However, Case 2, the probands father, showed different ERG findings; a moderately diminished scotopic ERG, a normal flicker ERG, and a biphasic dark adaptation curve with an elevated final rod threshold. The authors believe that these differences reflect variations in the expressivity of a single gene mutation with the lowest expressivity being seen in Case 2.

Association of ectodermal dysplasia, ectrodactyly and macular dystrophy: EEM syndrome (case report).

The authors reported a 41-year-old female patient with EEM (ectodermal dysplasia, ectrodactyly and macular dystrophy) syndrome with hypotrichosis, teeth anomaly, split hand complex and retinal changes with prominent pigmentations located in the posterior pole of the retina. Retinal degeneration had shown minimal progression during 11 years. A longer follow-up period was necessary to make a definite diagnosis of these fundus changes. This is an isolated case born from a consanguineous marriage.

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.

An atypical Leber's hereditary optic neuropathy with the 11778 mutation.

excluded; and (3) the patients were breast fed by their mothers although the mothers died many years ago and no serological tests had been performed. The familial clustering has been reported in a number of autoimmune diseases in which the genetic predisposition plays a role in the disease susceptibility. The present case with familial occurrence of HTLV-I uveitis may suggest an involvement of infectious/autoimmune overlap in the pathogenesis of the disease. The transmission ofHTLV-I carrier state and the presence of HTLV-I infected cells in the eye are essential for the development of the disease. However, clinical disease was apparent in only a few of the seropositive family member. The presence of disease only in certain HTLV-I infected family members, therefore, suggests that host factors also play a role in the disease development. It has been reported that immunogenetic factors in the host determine susceptibility to HAM/TSP.II Therefore, the survey of immunogenetic factors in HTLV-I uveitis may provide us with further information to understand the pathogenesis of the disease and this is now in progress.