Yozo Miyake

Guidelines for basic multifocal electroretinography (mfERG)

Michael F. Marmor1, Donald C. Hood2, David Keating3, Mitsuhiro Kondo4, Mathias W. Seeliger5 & Yozo Miyake4 (for the International Society for Clinical Electrophysiology of Vision) 1Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA; 2Department of Psychology, Columbia University, New York, New York, USA; 3Department of Ophthalmology, Gartnavel General Hospital, Glasgow, UK; 4Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan; 5Department II, University Eye Hospital, Tubingen, Germany

Refractive errors and factors associated with myopia in an adult Japanese population.

PURPOSE To investigate the refractive status and factors associated with myopia by a population-based survey of Japanese adults. METHODS A total of 2168 subjects aged 40 to 79 years, randomly selected from a local community, were assessed in a cross-sectional study. The spherical equivalent of the refractive error was calculated and used in a multiple logistic regression analysis to evaluate the relationships between myopia and possible related factors. RESULTS The mean (+/- SD) of the spherical equivalent was -0.70 +/- 1.40 diopters (D) in men, and -0.50 +/- 1.44 D in women. Based on +/- 0.5 D cutoff points, the prevalence of myopia, emmetropia, and hypermetropia were 45.7%, 40.8%, and 13.5% in men, and 38.3%, 43.1%, and 18.6% in women, respectively. A 10-year increase in age was associated with reduced risk of myopia [men: odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.44-0.62; women: OR = 0.65, 95% CI: 0.54-0.78]. In men, myopia was significantly associated with higher education (high school: OR = 1.6, 95% CI: 1.1-2.3; college: OR = 2.0, 95% CI: 1.3-3.1) and management occupations (OR = 1.6, 95% CI: 1.0-2.4). For women, high income (OR = 1.5, 95% CI: 1.1-2.2), and clerical (OR = 1.5, 95% CI: 1.0-2.4) and sales/service occupations (OR = 1.7, 95% CI: 1.1-2.6) were also associated with myopia. CONCLUSIONS The prevalence of myopia in a Japanese population was similar to that in other Asian surveys but higher than in black or white populations. Our study confirmed a higher prevalence of myopia among younger vs. older populations, and a significant association with education levels and socioeconomic factors.

Occult macular dystrophy

PURPOSE Occult macular dystrophy is a hereditary macular dystrophy without any visible abnormality of the fundus or abnormality indicated by fluorescein angiography even when visual acuity is decreased. Normal full-field electroretinogram in both cone and rod components with abnormal focal macular cone electroretinogram is the key to diagnosing this disorder. The purpose of this study was to identify the function of the macular rods and to provide detailed clinical findings in occult macular dystrophy. METHODS Thirteen patients from eight families were examined. The fundi of 12 patients were essentially normal (occult macular dystrophy), and the oldest patient in one family disclosed bulls eye maculopathy. In the 12 patients, including the patient with bulls eye maculopathy, the profiles of cone and rod absolute thresholds were performed across the 60-degree horizontal meridian of the posterior pole. RESULTS All 12 patients showed cone sensitivity loss only in the macular area. Six relatively young patients revealed normal rod sensitivity, whereas six older patients showed borderline rod sensitivity or abnormal rod sensitivity in the macular area. CONCLUSIONS The pathology of occult dystrophy involves either only the macular cone system or macular cone and rod systems without any visible abnormality. This difference of the pathology suggests a different clinical entity or a different stage of occult macular dystrophy.

A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants.

Abstract. Incomplete X-linked congenital stationary night blindness (CSNB) is a recessive, non-progressive eye disorder characterized by abnormal electroretinogram and psychophysical testing and can include impaired night vision, decreased visual acuity, myopia, nystagmus, and strabismus. Including the 20 families previously reported (Bech-Hansen et al. 1998b), we have now analyzed patients from a total of 36 families with incomplete CSNB and identified 20 different mutations in the calcium channel gene CACNA1F. Three of the mutations account for incomplete CSNB in two or more families, and a founder effect is clearly demonstrable for one of these mutations. Of the 20 mutations identified, 14 (70%) are predicted to cause premature protein truncation and six (30%) to cause amino acid substitutions or deletions at conserved positions in the α1F protein. In characterizing transcripts of CACNA1F we have identified several splice variants and defined a prototypical sequence based on the location of mutations in splice variants and comparison with the mouse orthologue, Cacna1f.

Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice.

The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1(-/-) mice. The amplitudes of the a- and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1(-/-) mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1(-/-) mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1(-/-) and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1(-/-) mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1(-/-) mice also present progressive retinal degeneration. Our results indicate that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration.

Retinal Dysfunction in Basigin Deficiency

PURPOSE To examine the retina of basigin (Bsg) knockout mice by electrophysiological and histologic methods and thereby to determine the possible function of Bsg in phototransduction and retinal development. METHODS Scotopic and photopic electroretinograms (ERGs) were recorded from 11 wild-type, 12 heterozygous, and 8 homozygous Bsg gene knockout mice of different ages. The retinas were also examined by histologic and immunolabeling methods. RESULTS Bsg knockout mice of 5 to 41 weeks of age showed a decrease in the amplitude of all components of both the photopic and scotopic ERGs. In contrast, the fundus and the fluorescein fundus angiography and morphology of the retina at the light microscopic level appeared to be normal until 8 weeks of age in Bsg knockout mice. Thereafter, the length of outer segment and outer nuclear layers decreased with increasing age. Immunohistochemical analysis localized Bsg protein in a variety of cells in the retina, especially in the pigment epithelium, the upper outer plexiform layer and the inner segments of photoreceptor cells. CONCLUSIONS The results demonstrated that both rod and cone function were severely affected from an early age by the targeted disruption of the Bsg gene. In spite of abnormal ERGs, the photoreceptor cells maintained normal morphology up to 8 weeks. Thereafter, the photoreceptor cells degenerated gradually and were almost ablated by 41 weeks.

Multifocal electroretinogram in occult macular dystrophy

PURPOSE Occult macular dystrophy (OMD) is an unusual macular dystrophy presenting with an essentially normal fundus and fluorescein angiography but with progressive central visual loss. The authors studied the function of local retinal areas in the posterior pole of patients with OMD using multifocal electroretinograms (ERGs). METHODS Multifocal ERGs were recorded using the Visual Evoked Response Imaging System with 61 hexagonal elements within a visual field of 30 degrees radius from 8 OMD patients and 20 age-matched, normal subjects. The amplitudes and implicit times of the patients and normal control subjects were compared at the various retinal eccentricities. RESULTs. The amplitudes of the multifocal ERGs in the OMD patients were markedly reduced in the central 7 degrees of the fovea. The difference of the ERG amplitudes between OMD and normal subjects became smaller toward the peripheral retina. Most OMD patients had slight but significantly delayed implicit times across the whole testing field, and the differences between the OMD and the normal subjects did not change with retinal eccentricity. CONCLUSIONS Our results for multifocal ERG amplitudes support the idea that OMD patients have localized retinal dysfunction distal to the ganglion cells in the central retina. The delayed implicit times across the whole test field suggest that the retinal dysfunction has a broader boundary than expected by ERG amplitudes and psychophysical perimetric results.

Dominant Mutations in RP1L1 Are Responsible for Occult Macular Dystrophy

Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. Typical OMD is characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina. Linkage analysis of two OMD families was performed by the SNP High Throughput Linkage analysis system (SNP HiTLink), localizing the disease locus to chromosome 8p22-p23. Among the 128 genes in the linkage region, 22 genes were expressed in the retina, and four candidate genes were selected. No mutations were found in the first three candidate genes, methionine sulfoxide reductase A (MSRA), GATA binding 4 (GATA4), and pericentriolar material 1 (PCM1). However, amino acid substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in three OMD families and p.Trp960Arg in a remaining OMD family. These two mutations were detected in all affected individuals but in none of the 876 controls. Immunohistochemistry of RP1L1 in the retina section of cynomolgus monkey revealed expression in the rod and cone photoreceptor, supporting a role of RP1L1 in the photoreceptors that, when disrupted by mutation, leads to OMD. Identification of RP1L1 mutations as causative for OMD has potentially broader implications for understanding the differential cone photoreceptor functions in the fovea and the peripheral retina.

Age-related Change in Contrast Sensitivity Among Japanese Adults

PURPOSE To evaluate the age-related change in contrast sensitivity seen in a middle-aged to elderly Japanese population. METHODS Contrast sensitivity and visual acuity were measured in subjects aged 40 to 79 years randomly recruited from a community in Aichi prefecture near Nagoya, Japan. Contrast sensitivity tests were performed using the Vistech contrast sensitivity test chart (VCTS 6500). The results were statistically analyzed relative to age. RESULTS A statistically significant decrease in contrast sensitivity was seen with advancing age at each spatial frequency (Cochran-Mantel-Haenszel: P<.001). This trend was detected even when the subjects were limited to only those having a corrected visual acuity of 1.0 or better (Cochran-Mantel-Haenszel: P<.001). Overall, 9.4% of the eyes with good visual acuity had poor contrast sensitivity at a high spatial frequency, while in the 70-79-year-old group, the percentage with poor contrast sensitivity reached 21.1%. CONCLUSIONS The age-related decrease in contrast sensitivity was confirmed at all frequencies in our population, even when adjusted for visual acuity. Our results suggest that contrast sensitivity tests, especially at high frequencies, assess aspects of visual function that cannot be determined in the elderly population from visual acuity tests alone.

Optical coherence tomography and focal macular electroretinogram in eyes with epiretinal membrane and macular pseudohole

PURPOSE To determine the morphology of macular pseudoholes (MPHs) and the relationship of morphology to macular function. DESIGN Observational case series. METHODS Optical coherence tomography (OCT) was performed on 42 eyes of 42 consecutive patients with an epiretinal membrane (ERM) and an MPH. The diameters of the MPH, and the thickness of the foveal and parafoveal retina were measured. Of these 42 eyes, focal macular electroretinograms (FMERGs) were recorded from 22 eyes of 22 patients with a 15 degree stimulus; FMERGs were also recorded with a 5 degree stimulus from 9 eyes of these 22 eyes. RESULTS In 42 eyes, the mean +/- Standard deviation (SD) diameter (437.7 +/- 172.8 microm) and geometrical shape of the MPHs were not significantly correlated with the visual acuity. The MPHs were divided into 2 types from the OCT images at the base of MPHs; group A had normal thickness (100-199 microm; n = 29), and group B (n = 13) had thicknesses of >or= 200 microm, or thickness < 100 microm, or irregular base. The visual acuity in group A (logarithm of the minimum angle of resolution [log MAR] mean +/- SD:.083 +/-.144) was significantly better than group B (log MAR,.407 +/-.212, P <.0001). There was a significant reduction in the amplitude of all components of FMERGs elicited by the 15 degree stimulus in the affected eyes (mean +/- SE, A-wave: 1.26 +/-.12 microv, B-wave: 3.07 +/-.27 microv, oscillatory potentials: 1.23 +/-.25 microv) compared with the normal fellow eyes (A-wave: 1.58 +/-.13 microv, B-wave: 4.14 +/-.27 microv, oscillatory potentials: 2.35 +/-.29 microv). A significant correlation was found between the relative amplitudes of the B-wave elicited by the 5 degree stimulus and the visual acuity (r =.918, P =.0005). CONCLUSIONS In eyes with an ERM and an MPH, the visual acuity is generally correlated with the OCT images. Macular function of eyes with an MPH resembles eyes with an ERM without an MPH. The effect of the ERM appears to be different on the base and parafovea of the MPHs.