To report the clinical characteristics of asymptomatic cases with RP1L1 gene mutations in four families with occult macular dystrophy (OMD).
Four asymptomatic cases from four families were selected ...from a cohort of 40 subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four asymptomatic cases and three symptomatic patients in the same families were reviewed. The three asymptomatic cases did not have any visual symptoms in either eye, and one was unilaterally affected. Ophthalmologic examinations, including spectral-domain optical coherence tomography (OCT) were performed, and the morphologic characteristics of the photoreceptor layer of the asymptomatic cases were compared to those of the symptomatic patients within the same family.
The OCT images demonstrated photoreceptor abnormalities in the parafoveal regions in all of the four asymptomatic cases (i.e., absence of the interdigitation zone and blurring of the ellipsoid zone). However, these microstructures were preserved at the foveal center. The longitudinal reflectivity profiles clearly identified this distinct pattern in the asymptomatic cases. In contrast, no distinct abnormalities were detected by other examinations including perimetry, fundus autofluorescence images, and multifocal electroretinograms (ERGs).
The sparing of the central foveal photoreceptor layer accounts for the well-preserved visual acuity in the asymptomatic patients. The sparing may represent either the initial phase of typical OMD or a subtype of macular lesion associated with OMD. It is necessary to examine asymptomatic subjects in families with OMD because some of them may progress to the typical phenotype of OMD.
Purpose. Previous cross-sectional Japanese studies have shown that intraocular pressure (IOP) decreases with age. However, central corneal thickness (CCT) variation should also be considered when ...examining the relationship between age and IOP, since tonometry has an inherent measurement error due to CCT variations. This study investigates the influence of CCT variation on the age-IOP relationship in a Japanese population. Methods. The right eyes of 1317 subjects from 40 to 80 years old selected from a general population using a random sampling method were assessed in cross-section. The IOP was measured with a non-contact tonometer, and CCT was measured with a specular microscope. The relationships between age, IOP, and CCT were assessed using correlation analyses, while the relationship between age and IOP controlled for CCT, blood pressure, and body mass index was investigated using multivariate regression analyses. Results. The mean (± SD) IOP value was 13.6 (± 2.6) mmHg in men and 13.3 (± 2.6) mmHg in women. The IOP correlated inversely with age in men (r = -0.14, p <0.001), but showed only a marginal inverse correlation in women (r = -0.07, p = 0.066). The mean (± SD) CCT value was 518.3 (± 33.2) µm in men and 511.1 (± 33.0) µm in women. Only in men was an inverse correlation seen between CCT and age (r = -0.10, p = 0.009), but both genders had positive correlations between CCT and IOP (man: r = 0.44, p < 0.001; woman: r = 0.48, p < 0.001). In multivariate analyses, CCT was shown to have an effect on IOP measurement, however, it was shown that IOP still decreases with age in both sexes even when adjusted for CCT (p = 0.001). Conclusions. The IOP decreases with age in the Japanese, and CCT variation has practically no effect on the unique age-IOP relationship.
To evaluate the changes in the focal macular electroretinogram (FMERG) and foveal retinal thickness after vitrectomy for diabetic macular edema (DME).
FMERGs were elicited from 25 eyes of 21 patients ...(ages 29-75 years) who underwent vitrectomy for DME by a 15 degrees stimulus. A posterior vitreous detachment (PVD) was created during surgery in 19 eyes (group 1), and 4 eyes had a PVD before surgery (group 2). In the remaining 2 eyes, a PVD could not be created (group 3). FMERGs were recorded before and 3, 6, and 12 months after vitrectomy. The foveal thickness, determined by optical coherence tomography (OCT), and visual acuity were measured on the same day as the FMERG recordings.
The postoperative visual acuity (logarithm of the minimum angle of resolution logMAR) improved gradually after the surgery and was significantly better at 12 months in eyes in group 1 (P = 0.0393). The postoperative mean foveal thickness was significantly less at 3 months after surgery in group 1 eyes (P = 0.0006), and there was a further decrease thereafter. In the 2 eyes in group 3, the decreased foveal thickness 3 and 6 months after surgery became thicker at 12 months. The mean b-wave amplitude of the FMERGs increased significantly at 12 months in group 1 eyes (P = 0.0297). The mean implicit time of a- and b-waves was more delayed at 3 months, and the change in a-wave was statistically significant in group 1 eyes (P = 0.0474). There was a wide range of changes in the b-wave amplitude at 12 months, however, the increase in the b-wave was correlated with the decrease in foveal thickness (r =.49, P = 0.012).
A disparity in the time course and degree of recovery of the foveal thickness and macular retinal function was found in eyes with DME after vitrectomy. Part of the functional recovery could be attributed to decreased retinal thickness and the absorption of the subretinal fluid.
To study the effect of aging on astigmatism in adult Japanese.
Measurements of refractive errors and keratometry were performed on 2161 randomly selected subjects (aged 40-79 years). The relation ...between age and the net value in diopters (D) of astigmatism was evaluated with a trend test. The relation between age and the polar value was also examined by linear regression analysis.
The mean (+/-SD) value of total and corneal astigmatism was -0.97 +/- 0.72 D and -0.86 +/- 0.63 D, respectively, and the net value of both increased with age (P trend < 0.001). The prevalence of either type of astigmatism also increased with age, according to the Cochran-Mantel-Haenzel test (P < 0.0001 for total and P < 0.01 for corneal astigmatism). The prevalence of against-the-rule astigmatism increased with age for either type of astigmatism (P < 0.0001 for total, P < 0.0001 for corneal). According to the analysis of polar values by age, the regression coefficient (+/-SE) for total and corneal astigmatism was -0.024 +/- 0.002 (P < 0.0001) and -0.028 +/- 0.002 (P < 0.0001), respectively. There was no statistical difference between these two regression coefficients.
The prevalence of astigmatism increases and the axis turns to against-the-rule with age. The result of the linear regression analysis indicates that the age-related change in astigmatism is mainly associated with changes in the cornea.
To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD).
International, multicenter, retrospective cohort studies.
A ...total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea.
A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions.
Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants.
Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2-73), and the median age at the latest examination was 46.0 years (range, 11-86). The median VA (logMAR) was 0.65 (range, -0.08-1.22) in the right eye and 0.65 (-0.08-1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196-1201).
There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population.
Purpose
To report the findings in two patients with unilateral cone-rod dysfunction with the a-wave larger than the b-wave, i.e., negative-type, full-field electroretinogram (ERG).
Methods
Standard ...ophthalmological examinations were performed including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and perimetry. ERG examinations were carried out with the ISCEV standard. Immunoblot analysis using the patient’s sera was performed to determine the presence of the recoverin1 antibody.
Results
The common findings in these two patients were: unilateral, male sex, sudden onset of photophobia or a reduction in the vision at an advanced age, preserved visual acuity, no complaint of night blindness, normal fundus appearance, negative-type dark-adapted 3.0 ERGs with reduced a-wave amplitudes, absent light-adapted 3.0 ERGs, and very reduced but recordable dark-adapted 0.01 ERGs. In addition, the multifocal ERGs in all areas except that in a hexagonal area within a 2.5° radius of the fovea were very reduced. Patients with similar findings have been reported earlier, but the subnormal a-wave of the dark-adapted 3.0 ERGs and extensive morphological alterations of the retina in the posterior pole in the OCT images were different from those of the reported patients. The OCT images showed an indistinct interdigitation zone and discontinuous ellipsoid zone. Anti-recoverin antibodies were not detected.
Conclusions
Negative ERGs with severely reduced cone and rod components suggest that both the cone and rod bipolar cell visual pathways may be disturbed. Slightly decreased a-wave suggests minor abnormality of photoreceptors. It is important to determine whether these patients represent a new clinical entity or a phenotypic variation of an already described retinal disorder.
To evaluate the age-related change in contrast sensitivity seen in a middle-aged to elderly Japanese population.
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.
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%.
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.
To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD).
International, multicenter, retrospective cohort studies.
A ...total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea.
A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions.
Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants.
Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2–73), and the median age at the latest examination was 46.0 years (range, 11–86). The median VA (logMAR) was 0.65 (range, –0.08–1.22) in the right eye and 0.65 (–0.08–1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196–1201).
There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196–1201 in the RP1L1 gene were confirmed in the East Asian population.
Occult macular dystrophy (OMD) is a hereditary retinal disease characterized by a normal fundus, normal full-field electroretinograms (ERGs), progressive decrease of visual acuity, and abnormal focal ...macular ERGs. The purpose of this study was to report pattern-reversal visual-evoked potential (pVEPs) findings in OMD patients.
The pVEPs recorded from four patients with OMD (aged 42-61 years; 2 men and 2 women) were reviewed. The visual acuities ranged from 20/200 to 20/30. The amplitudes of the N-75 and P-100 (P2 amplitude) and the latency of the N-75 components (N1 latency) were analyzed.
The mean (±SD) P2 amplitude was 2.7 ± 1.9 μV for the 5', 4.8 ± 2.9 μV for the 10', 3.2 ± 2.1 μV for the 20', and 4.4 ± 3.5 μV for the 40' checkerboard stimuli. The N1 latency was 122.2 ± 6.4 ms for the 5', 105.0 ± 11.5 ms for the 10', 97.7 ± 10.0 ms for the 20', and 91.0 ± 13.7 ms for the 40' checkerboard stimuli. The mean P2 amplitude was reduced and the N1 latency was delayed in comparison with the laboratory standard for the Keio University Hospital.
The delayed latency and reduced amplitude suggest a major contribution of the central cone pathway to the pVEPs.
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