Full-field electroretinograms (ERGs) are used to evaluate retinal function in patients with various types of hereditary and acquired retinal diseases. However, ERG recordings require relatively ...invasive procedures, including pupillary dilation and the use of contact lens electrodes. Thus, it would be helpful to have a simpler and noninvasive screening method. The purpose of this study was to determine whether a new, handheld, portable ERG device, RETeval™, can be used to screen patients for cone dysfunction.
Thirty-five eyes of 35 patients who had reduced cone responses ascertained by a conventional ERG system using contact lens electrodes were studied. The causative diseases included achromatopsia, cone dystrophy, cone-rod dystrophy, retinitis pigmentosa, choroidal dystrophy, autoimmune retinopathy, and Stargardt disease. The flicker ERGs were recorded with the RETeval™ under undilated conditions with skin electrodes (stimulus strength, 3.0 cd·s/m(2); frequency, 28.3 Hz), and the responses were compared to that of 50 healthy eyes. The amplitudes and implicit times of the fundamental component of the flicker ERGs were analyzed in three age groups: Group A, ≤20 years; Group B, 21-40 years; and Group C, ≥41 years.
In all of the age groups, the amplitudes of the ERGs were significantly smaller and the implicit times significantly longer in patients with cone dysfunction than in the control eyes. All but one of the patients had flicker amplitudes lower than the mean -2.0 standard deviation of control eyes.
The RETeval™ has a potential of being used to screen for cone dysfunction. The entire examination takes <5 minutes and does not require pupil dilatation or a contact lens electrode. Although the flicker responses do not provide information on the scotopic functions, the RETeval™ device can be used to determine which patients require additional full-field ERG testing with dilated pupils under both scotopic and photopic conditions.
Variants in the retinitis pigmentosa GTPase regulator (RPGR) gene are a major cause of X-linked inherited retinal disorder (IRD). We herein describe the clinical and genetic features of 14 patients ...from 13 Japanese families harboring
variants in a nationwide cohort. Comprehensive ophthalmological examinations were performed to classify the patients into one of the phenotype subgroups: retinitis pigmentosa (RP) and cone rod dystrophy (CORD). The mean age of onset/at examination was 13.8/38.1 years (range, 0-50/11-72), respectively. The mean visual acuity in the right/left eye was 0.43/0.43 (range, 0.1-1.7/-0.08-1.52) LogMAR unit. Eight patients had RP, and six had CORD. Whole-exome sequencing with target analyses identified 13
variants in 730 families with IRD, including 8 novel variants. An association between the phenotype subgroup and the position of variants (cutoff of amino acid 950) was revealed. To conclude, the clinical and genetic spectrum of
-associated retinal disorder was first illustrated in a Japanese population, with a high proportion of novel variants. These results suggest the distinct genetic background of RPGR in the Japanese population, in which the genotype-phenotype association was affirmed. This evidence should be helpful monitoring and counseling patients and in selecting patients for future therapeutic trials.
Purpose. To illustrate a data-driven deep learning approach to predicting the gene responsible for the inherited retinal disorder (IRD) in macular dystrophy caused by ABCA4 and RP1L1 gene aberration ...in comparison with retinitis pigmentosa caused by EYS gene aberration and normal subjects. Methods. Seventy-five subjects with IRD or no ocular diseases have been ascertained from the database of Japan Eye Genetics Consortium; 10 ABCA4 retinopathy, 20 RP1L1 retinopathy, 28 EYS retinopathy, and 17 normal patients/subjects. Horizontal/vertical cross-sectional scans of optical coherence tomography (SD-OCT) at the central fovea were cropped/adjusted to a resolution of 400 pixels/inch with a size of 750 × 500 pix2 for learning. Subjects were randomly split following a 3 : 1 ratio into training and test sets. The commercially available learning tool, Medic mind was applied to this four-class classification program. The classification accuracy, sensitivity, and specificity were calculated during the learning process. This process was repeated four times with random assignment to training and test sets to control for selection bias. For each training/testing process, the classification accuracy was calculated per gene category. Results. A total of 178 images from 75 subjects were included in this study. The mean training accuracy was 98.5%, ranging from 90.6 to 100.0. The mean overall test accuracy was 90.9% (82.0–97.6). The mean test accuracy per gene category was 100% for ABCA4, 78.0% for RP1L1, 89.8% for EYS, and 93.4% for Normal. Test accuracy of RP1L1 and EYS was not high relative to the training accuracy which suggests overfitting. Conclusion. This study highlighted a novel application of deep neural networks in the prediction of the causative gene in IRD retinopathies from SD-OCT, with a high prediction accuracy. It is anticipated that deep neural networks will be integrated into general screening to support clinical/genetic diagnosis, as well as enrich the clinical education.
Purpose
To report the findings in 3 cases of bilateral negative electroretinograms (ERGs) with acute onset of photophobia.
Study design
Retrospective case series.
Methods
The medical charts of the 3 ...patients were reviewed.
Results
A 43-year-old woman, a 68-year-old woman, and a 41-year-old woman were referred to Nagoya University Hospital. Their main symptom was bilateral acute photophobia. None of the patients had any systemic diseases or specific medical history. The decimal best-corrected visual acuity (> 0.8) and Humphrey visual fields (mean deviation > -3 dB) were relatively well preserved in all 3 patients. The optical coherence tomography (OCT) and fundus autofluorescence findings were essentially normal. Fluorescein angiography showed mild leakage in 1 patient but no abnormality in the other 2 patients. However, the ERGs of the 3 patients had the features of abnormal ERGs found in patients with incomplete congenital stationary night blindness (CSNB). Exome analyses found no pathogenic variants related to known CSNB-related genes. The symptoms and ERGs of the 3 patients have not progressed or recovered after a relatively long follow-up period.
Conclusion
The ERG characteristics of 3 patients with bilateral photophobia were similar to those of incomplete CSNB, suggesting post-phototransductional abnormalities. The symptoms and genetic analyses indicated the possibility of an acquired condition rather than a hereditary retinal disease.
X-linked congenital retinoschisis (XLRS) is an inherited retinal disorder characterized by reduced central vision and schisis of the macula and peripheral retina. XLRS is caused by mutations in the
...gene. We have identified 37 different mutations in the
gene, including 12 novel mutations, in 67 Japanese patients from 56 XLRS families. We present clinical features of these patients in relation to the associated mutations.
Purpose
The enhanced S-cone syndrome (ESCS) is a rare hereditary retinal degeneration that has enhanced short wavelength-sensitive cone (S-cone) functions. The longitudinal clinical course of this ...disease has been rarely reported, and the genetic aspects of ESCS have not been well investigated in the Japanese population. In this report, we present our clinical and genetic findings for 2 patients with ESCS.
Patients and methods
The patients were 2 unrelated Japanese men. Standard ophthalmic examinations and mutation screening for the
NR2E3
gene were performed.
Results
Patient 1 was a 36-year-old man, and his clinical findings were typical of ESCS. His decimal best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS after removal of cataracts. Genetic investigations revealed a homozygous truncation frameshift, the p.I307LfsX33 mutation. Patient 2 was an 11-year-old boy when he was first examined by us. His clinical findings were typical of ESCS except for uveitis in the left eye. His decimal BCVA at the age of 39 years was maintained at 1.5 in each eye, although the retinal degeneration and visual field impairments had progressed during the follow-up period. The genetic investigations revealed homozygous mutations of p.R104Q in the
NR2E3
gene.
Conclusions
The frameshift mutation, p.I307LfsX33, in the
NR2E3
gene is a new causative mutation for ESCS. The clinical observations for patient 2 are the longest ever reported. The retinal degeneration caused by this mutation is slowly progressive, and these patients maintained good vision with maintenance of the foveal structure until their late thirties.
The purpose of this study is to determine the topography of bleaching in rods, middle/long-wavelength (M/L) and short-wavelength (S) cones in the macaque retina by using a modified retinal ...densitometry technique.
A modified commercial digital fundus camera system was used to measure continuously the intensity of the light reflectance during bleaching with band pass lights in the ocular fundus of three adult Rhesus monkeys (Macaca mulatta) under general anesthesia. The topography of bleaching in rods, M/L-, and S-cones was obtained separately by considering the characteristic time course of the reflectance changes, depending on the wavelengths of light and retinal locations.
The distribution of M/L-cones response had a steep peak at the foveal center and was elongated horizontally. The distribution of rod responses was minimum at the foveal center and maximum along a circular region at the eccentricity of the optic disc. The distribution of S-cone responses was highest at the fovea and was excavated centrally. There was a circular region with the maximal responses at 0.38 to 1.0 degrees from the foveal center.
With the current imaging technique, not only the steep peak of the M/L-cone responses at the fovea, but the ring-shaped distribution of rod responses in the periphery and the central reduction of S-cone response could be determined with good resolution.
Intrinsic signal imaging is a newly developed technique that can map the neural activity of tissues noninvasively. It has been used to map the functional organization of the retina by recording ...flash-induced light reflectance changes in the cone and rod photoreceptors. The purpose of this study was to investigate the properties of the intrinsic signals in the monkey's retina. To accomplish this, the intrinsic signals and the electroretinograms (ERGs) evoked by the same stimuli were measured under different recording conditions.
The fundus of macaque monkeys was observed with infrared light and recorded with a charge-coupled device (CCD) camera. The intrinsic signals were measured as retinal light reflectance changes induced by diffuse or focal flash stimuli. ERGs were recorded under the same stimulating conditions. The reflectance changes induced by different flash intensities, flash intervals, and background luminance were compared.
The intrinsic signals were categorized into different groups based on the location in the fundus. Fast signals (peak: approximately 100 ms) were recorded from the posterior retina including the fovea, and slow signals (peak: 5.0-6.0 seconds) were recorded from the optic disc and nonfoveal posterior retina. The threshold of the slow signal changes was comparable to that of the ERG b-wave, and the thresholds of the fast signals were higher than that of the ERG a- and b-waves.
The retinal intrinsic signals are composed of several components with different response properties and different sources. This recording technique may be useful for mapping the retinal function in eyes with various disorders.
Purpose
Several
OPA1
variants cause dominant optic atrophy (DOA), the most common hereditary optic atrophy. Here, we describe a newly discovered
OPA1
deletion in 3 patients with DOA.
Methods
A female ...proband, her brother, and her mother underwent complete ophthalmologic examinations that included optical coherence tomography and visual field assessments using a Humphrey Field Analyzer with both standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Genomic DNA from each patient was examined to detect genomic rearrangements involving
OPA1
; the genetic analysis involved both multiplex ligation probe amplification and conventional Sanger sequencing.
Results
Each patient had temporal optic disc pallor and significant thinning of the retinal nerve fiber layer in both eyes, although there was phenotypic variability among the patients that ranged from asymptomatic to moderately decreased visual acuity. For the affected brother and mother, the mean deviation values from SAP were within the normal range, whereas those from SWAP were significantly below the normal range (
P
< .05). The genetic analysis identified a newly discovered heterozygous deletion that encompasses exons 9–14 and revealed a breakpoint junction that directly connects intron 8 to intron 14.
Conclusions
This newly described deletion is likely to lead to loss of function in the functionally important GTPase domain encoded by exons 9–16, and the heterozygosity suggested that haploinsufficiency caused the phenotypes. The deletion may be associated with mild DOA phenotypes ranging from asymptomatic to moderately decreased visual acuity.
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