Masamichi Saga

A novel Cys-214-Ser mutation in the peripherin/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa

We have screened for possible disease-causing mutations in the peripherin/retinal degeneration slow (RDS) gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ADRP). Using polymerase chain reaction-single strand conformation polymorphism analysis, a novel mutation at codon 214 was found in which the highly conserved cysteine was replaced with a serine in one family. The mutation at codon 214 was found in all three affected siblings of this family, but none of the 40 normal control individuals had this mutation. These results strongly suggest, that the mutation is pathogenic for RP in this family. The clinical phenotype for this family is a late-onset form of ADRP.

Autosomal dominant retinitis pigmentosa: A mutation in codon 1 81 (Glu → Lys) of the rhodopsin gene in a Japanese family

The PCR/restriction endonuclease digestion (RE) assay and PCR/SSCP analysis of the rhodopsin gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ad RP) revealed a G-A substitution of the first nucleotide of codon 181, replacing Glu (GAG) with Lys (AAG), in one family. The proband showed an early onset of symptoms in childhood with a diffuse loss of rod and cone function and a relatively good preservation of cone function, corresponding to the type with relatively rapid progression to blindness (type I category of ad RP).

Correlation between Contrast Sensitivity and Visual Acuity in Retinitis pigmentosa Patients

Purpose: High-contrast figures such as Landolt rings are insufficient to evaluate the function of the foveal cones of retinitis pigmentosa (RP) patients. We investigated the correlation between visual function as determined with Landolt rings and with the Vistech Contrast Sensitivity Function Test (VCTS) at various spatial frequencies, in addition to the Cambridge Low Contrast Grating (CLCG). Methods: The study included 30 retinitis pigmentosa patients (53 eyes). All patients were assessed with Landolt rings, the Vistech method, and the CLCG. We estimated the relative contribution of contrast sensitivity to visual acuity by VCTS at each spatial frequency and by CLCG by simple linear regression analysis. Results: The results of the regression analysis of VCTS at 1.5, 3.0, and 6.0 cycles/degree showed a significant correlation between Landolt rings and VCTS and between CLCG and VCTS that was strongest at 6.0 cycles/degree. There was no significant correlation between Landolt rings and VCTS or between CLCG and VCTS at 12.0 and 18.0 cycles/degree. Patients with a visual acuity of 20/25 and CLCG greater than 100 were divided into two groups according to their contrast sensitivity at 18.0 cycles/degree on VCTS. Conclusions: The VCTS at the highest frequency was useful for evaluating the foveal visual function in RP patients having good visual acuity with the Landolt rings. Thus, contrast sensitivity should be useful in detecting minute impairment or improvement of visual function in RP.

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.

Gene analysis and evaluation of the single founder effect in Japanese patients with Oguchi disease.

PurposeTo analyze mutations of the arrestin/S-antigen (SAG) gene in nine newly identified Oguchi disease patients, and to examine whether the 926delA (formerly called 1147delA) mutation in the SAG gene is inherited from a single founder.MethodsDNA samples were assayed for mutations around nucleotide 926 of the SAG gene by direct sequencing, and analyzed for polymorphisms at codon 403 and IVS6-18 of the SAG gene by restriction analysis of polymerase chain reaction products.ResultsAll nine newly identified patients were homozygous for the 926delA mutation and had the same haplotype at codon 403 and IVS6-18. These findings are identical to those of previous reports of four Japanese Oguchi disease patients.ConclusionsMutation 926delA of the SAG gene is the main cause of Oguchi disease in Japanese. This mutation appears to have been inherited from a single founder.

Risk of false-positive molecular genetic diagnosis of Leber's hereditary optic neuropathy.

PURPOSE/METHODS The most common pathogenic mitochondrial mutation at nucleotide 11778 in Lebers hereditary optic neuropathy is usually detected by the loss of an SfaNI restriction site. To evaluate a false-positive diagnostic error in this molecular genetic assay, we investigated SfaNI polymorphism in 120 patients with bilateral optic atrophy. RESULTS/CONCLUSIONS The ratio of false-positive to true-positive results was 1:36. Mitochondrial DNA polymorphism at nucleotide 11779 reflects a false-positive genetic error.

Progression of Visual Field Loss in Patients with Retinitis pigmentosa of Sporadic and Autosomal Recessive Types

Purpose: We examined the natural course of patients with retinitis pigmentosa of the eight sporadic and five autosomal recessive forms over 5 years. Methods: We measured the areas of the visual fields by Goldmann perimetry using a digitizer and a computer software. Results: The visual field of V-4 isopters in 4 sporadic cases was approximately 200 cm2 during 30 years after the initial examination, but decreased down to 40 cm2 in the next 10 years. The visual field was reduced to half the normal field in 3 autosomal recessive cases early below the age of 25 years. In 4 sporadic and 2 autosomal recessive cases, the inferior temporal visual field was the widest at the onset of the disease, but exhibited the most severe loss. The superior nasal area was the narrowest initially, and showed the mildest progression. Conclusions: The visual field in retinitis pigmentosa is constricted age-dependently with severe loss of the inferior temporal visual area and mild damage to the superior nasal area.

Association of Retinal Artery and Other Inner Retinal Structures With Distribution of Tapetal-like Reflex in Oguchi's Disease.

PURPOSE To report novel ophthalmoscopic features of patients with Oguchis disease, and to describe how they may be related to the unusual tapetal-like fundus appearance. METHODS Twenty-one eyes of 11 patients who were diagnosed with Oguchis disease were investigated. Genetic screening of seven cases showed homozygous mutations in the SAG gene (c.926delA). The retinal appearance was retrospectively assessed in the fundus photographs, and the optical coherence tomographic (OCT) and fundus autofluorescence (AF) images. RESULTS In 11 eyes of 7 patients, clearly demarcated dark regions without tapetal-like reflex were observed in the midperipheral retinal regions. In the dark regions, OCT showed lower reflectances in the photoreceptor layer but the AF images had normal reflectances. In nine eyes of six patients, the dark regions were partially demarcated by retinal arteries but not by veins. In nine eyes of five patients, the extent of the dark regions either increased or decreased during the course of the disease process, and these changes were not due to the state of adaptation or a posterior vitreous detachment. In all eyes, the peripheral retinal arteries but not veins had either high or low reflective regions along one side. CONCLUSIONS Although the alterations of the outer retinal layers are believed to be most responsible for the abnormal tapetal-like reflex in patients with Oguchis disease, these ophthalmoscopic features cannot be explained solely by the abnormality of the outer retina. Our findings suggest that the appearance of tapetal-like reflex is strongly affected by alterations of structures in the inner retinal layers.

Phenotype associated with an R120X nonsense mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa

We examined a Japanese family with X-linked retinitis pigmentosa (RP) associated with a nonsense mutation, R120X, in the RP2 gene. The 26-year-old proband presented at the age of seven years with a two-year history of night blindness. Visual disability worsened with increasing age. At age 24, visual acuity was 0.08 in both eyes. Testing for refractive error indicated mild myopia. Visual fields showed bilateral-constriction to 10 degrees. He had central macular areolar sclerosis in both eyes. Two maternal uncles had vision of light perception to hand movement in their early forties together with dense bilateral cataracts. The ocular phenotype of this family with R120X was considered severe; reported phenotypes associated with this mutation have not been uniform.

A Prospective, Randomized Trial of Two Mucin Secretogogues for the Treatment of Dry Eye Syndrome in Office Workers

The purpose of the study was to compare the two mucin secretogogues, diquafosol (DQS) and rebamipide (RBM), for the treatment of dry eye syndrome (DES) in office workers. Dry eye patients using computers for >4 h/day were randomly assigned treatment with either DQS or RBM. Main outcomes measures included changes in tear film break-up time (TBUT) and subjective symptoms assessed by the Dry Eye-Related Quality of Life Score (DEQS). The subjects had scheduled examinations at 0 and 4 weeks, and the examinations at 2 and 8 weeks were optional. Changes in keratoconjunctival fluorescein score and a patient satisfaction questionnaire were also recorded. Both groups showed significant improvements in the DEQS scores at 2, 4, and 8 weeks following the initiation of the study. Both groups showed significant increases in the TBUT at 2 and 4 weeks. No significant difference was found between the DQS and RBM groups at any time periods. Patients reported more comfort with the use of DQS compared with the use of RBM. No local or systemic side effects were noted. The results of the present study indicated that both DQS and RBM were effective for the treatment of DES in office workers.