Occult macular dystrophy Miyake, Yozo; Tsunoda, Kazushige
Japanese journal of ophthalmology,
03/2015, Letnik:
59, Številka:
2
Journal Article
Recenzirano
Occult macular dystrophy (OMD) was first reported in 1989 as a hereditary macular disease without visible fundus abnormalities. Patients with OMD are characterized by a progressive decrease of visual ...acuity but have normal fundus and fluorescein angiograms with both the rod and cone components of the full-field electroretinograms (ERGs) essentially normal. However, the focal macular ERGs and multifocal ERGs are severely attenuated. These findings indicate that the retinal dysfunction is confined to the macula. Optical coherence tomography (OCT) has shown structural changes in the outer nuclear and/or photoreceptor layers. Genetic analyses of OMD pedigrees have identified dominant mutations in the
RP1L1
gene. However, the same mutations were not detected in sporadic cases, suggesting that several independent mutations can lead to the OMD phenotype. The purpose of this paper is to review the history of OMD, the visual functions determined psychophysically, ERG findings, OCT characteristics and genetic findings in patients with OMD.
To determine the course of occult macular dystrophy (OMD, Miyake's disease) and to propose stages of OMD based on the optical coherence tomographic (OCT) findings.
Sixty-one patients from 33 families ...with OMD who carried one of the proven variants of the RP1L1 gene were studied at seven centers in Japan. Ophthalmological examinations including the best-corrected visual acuity (BVCA) and OCT were performed.
The median age at the last visit was 50 years with a range of 10 to 88 years, and the median age at the symptom onset was 30 years with a range of 3 to 60 years. There were significant negative correlations between the duration of OMD and BCVA, the central retinal thickness (CRT) and the thickness between external limiting membrane and retinal pigment epithelium (ERT). The BCVA gradually decreased for 10 years after symptom onset and was stable thereafter. Kaplan-Meier survival curves of the BCVA and retinal thickness showed that all of the patients had retained a vision of 1.0 logMAR, and over 80% of the patients had retained 50% thickness of the normal CRT and ERT for at least 60 years after symptom onset. The stages of OMD based on the visual symptoms and OCT findings are proposed.
The photoreceptors do not become completely atrophic even at the late stage, which may account for the good retinal pigment epithelium (RPE) structure and normal-appearing fundus. The proposed stages facilitate the investigation of the pathogenicity of OMD and provide information to determine the effectiveness of therapeutic procedures.
Purpose
To establish with negative electroretinogram (ERG) the clinical entity of eight patients with unilateral severe photophobia, essentially normal fundus, good visual acuity, and severe cone and ...rod dysfunction.
Study design
Multicenter retrospective observation case series.
Methods
Comprehensive ophthalmologic examinations were performed, including best-corrected visual acuity (BCVA), full-field ERGs and multifocal ERGs (mfERGs), fundus photographs, and OCT. Systemic and genetic examinations were performed.
Results
The mean (± SD) age at the onset was 60.0 ± 8.4 years, and the six patients noticed severe photophobia in the affected eye in spite of almost normal fundus appearance and good BCVA. The dark-adapted bright flash ERGs in the affected eye had relatively well-preserved a-waves and depressed b-waves, i.e., a negative ERG. Cone ERGs and both b- and d-waves of the photopic long-duration ERGs were almost undetectable. Rod ERGs were severely reduced; however, only two patients complained of night blindness. In five patients, the mfERGs were extinguished in the periphery but preserved in the central retina, resulting in good BCVA. Electrophysiological findings indicated a severe diffuse dysfunction of the inner retina affecting bipolar cells of both ON- and OFF-pathways, and in five patients there was a reduction in the thickness of the inner nuclear layer. In seven patients the retinal arteries were attenuated. Anti-retinal antibodies were detected in the serum of two patients. No genetic causes were found.
Conclusions
The common features in the eight patients with unilateral negative ERGs suggest a new disease entity of unilateral acute inner retinal layer dysfunction. In most patients, the only subjective complain was photophobia.
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.
Purpose
This study was performed to assess the impact of dry eye on patients’ quality of life (QOL) and to analyze the association between subjective symptoms and ocular surface findings of dry eye.
...Methods
The study population consisted of 158 patients with dry eye aged 20 years or older who visited any of the 15 medical care facilities enrolled in the study. The backgrounds and ocular findings of the patients were investigated, and their QOL was evaluated with the Japanese version of the 25-item National Eye Institute Visual Functioning Questionnaire (VFQ-25) and of the Medical Outcomes Study (MOS) 8-item Short-Form Health Survey (SF-8) to examine the association between subjective symptoms and ocular surface findings.
Results
Of the patients enrolled, 15 were men and 143 were women, and their average age was 62.5 ± 12.6 years. Sixty patients (38.0%) had comorbid Sjögren syndrome (SS). The results of Schirmer testing, fluorescein staining, and rose bengal staining for SS patients were significantly worse than those for the non-SS patients, but the VFQ-25 and SF-8 scores were not significantly different between the SS and non-SS patients. In the ocular surface findings, a weak association between the fluorescein staining scores and general vision scores, a subscale of the VFQ-25, was found. However, the ocular surface findings and VFQ-25/SF-8 results in the simple correlation analysis as well as in the multiple linear regression analysis showed no significant associations.
Conclusions
Ocular surface findings and QOL scores of patients with dry eye appear to disagree. Therefore, it is necessary to address subjective symptoms and QOL scores in addition to examination findings when evaluating dry eye.
Abstract This document presents recommendations and guidelines for the use of visual electrophysiological testing in the clinical assessment of visual pathway function.
To describe a new technique to record focal macular electroretinograms (FMERGs) during vitrectomy to assess macular function.
Intraoperative FMERGs (iFMERGs) were recorded in ten patients (10 eyes) ...who undergo vitrectomy. iFMERGs were elicited by focal macular stimulation. The stimulus light was directed to the macular area through a 25 gauge (25G) glass fiber optic bundle. Background light was delivered through a dual chandelier-type light fiber probe. Focal macular responses elicited with combinations of stimulus and background luminances were analyzed.
A stimulus luminance that was approximately 1.75 log units brighter than the background light was able to elicit focal macular responses that were not contaminated by stray light responses. Thus, a stimulus luminance of 160 cd/m2 delivered on a background of 3 cd/m2 elicited iFMEGs from only the stimulated area. This combination of stimulus and background luminances did not elicit a response when the stimulus was projected onto the optic nerve head. The iFMERGs elicited by a 10° stimulus with a duration of 100 ms and an interstimulus interval of 150 ms consisted of an a-, b-, and d-waves, the oscillatory potentials, and the photopic negative response (PhNR).
Focal ERGs with all components can be recorded from the macula and other retinal areas during vitreous surgery. This new technique will allow surgeons to assess the function of focal areas of the retina intraoperatively.
The temperature of the vitreous has been reported to vary during cataract and vitreous surgery. We measured intraocular temperature at four intraocular sites; the anterior chamber (AC), just behind ...the crystalline lens, mid-vitreous, and just anterior to the optic disc (OD) at the beginning of vitrectomy with a thermoprobe in 48 eyes. The temperatures were compared in three groups; eyes that underwent vitrectomy for the first time (Group V, n = 30), eyes that had previous vitrectomy and the vitreous cavity had been filled with balanced salt solution (BSS; Group A, n = 12), and eyes that had previous vitrectomy and the vitreous cavity was filled with silicone oil (Group S, n = 6). There was a gradient in the temperature in all groups, i.e., it was lowest in the AC, and it increased at points closer to the retina. The intraocular temperature was significantly correlated with the type of fluid in the vitreous cavity. The mean intraocular temperatures were not significantly different in Groups V and A, but they were significantly higher in Group S. Clinicians should be aware of the differences in the temperature at the different intraocular sites because the temperatures may affect the physiology of the retina and the recovery process.
The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X‐linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2‐associated ...retinal disorder (RP2‐RD) from four Japanese families in a nationwide cohort. A systematic review of RP2‐RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10–47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52–2.0)/1.10 (0.52–1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2‐RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement.
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.
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