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.
Intrinsic signal imaging (ISI) detects light-induced microstructural or metabolic changes in retinal tissues. Thus, activities of the rod and cone systems could be mapped topographically. However, no ...direct evidence indicates the cellular origin of the signals. The purpose of this study was to determine whether and how retinal ganglion cells (RGCs) contribute to ISI.
In anesthetized macaque monkeys, the properties of intrinsic signals were investigated by simultaneous measurement of the retina and the primary visual cortex (V1) with different wavelengths of observation light, measurement of the flash-induced blood flow changes by laser Doppler flowmetry, and intravitreal injection of tetrodotoxin (TTX).
Slow components of ISI correspond well to the flash-induced blood flow increase. Intrinsic signals of the posterior retina are partially decreased, and the signal of the optic disc is completely abolished by intravitreal injection of TTX at a concentration that should reduce the neural activities of RGCs. The intrinsic signal at the fovea did not change significantly after TTX injection.
Photoreceptors in the outer retina and RGCs in the inner retina are major contributors to the intrinsic signals, and the activity of the RGCs can be mapped by using fast and slow components of the signal in the posterior retina. The functional organization of the RGC layer has not been objectively mapped; results presented here indicate that the ISI has the potential to do this.
To report the outcome of transcorneal electrical stimulation (TES) of the visual system on long-standing retinal artery occlusion (RAO).
Open labeled, case series.
Two patients with central RAO (15 ...and 33 months respectively) and one with branch RAO (26 months) underwent TES therapy. Subjective and objective ophthalmological evaluations were performed before and after the TES. The ages of the patients were 38, 49, and 63 years. The TES (20 Hz biphasic pulses, 30 minutes, up to 1100 uA) was delivered by a bipolar contact lens electrode once a month for 3 months. Perimetric and/or electrophysiological examinations were performed as outcome measures.
The visual acuity improved by more than 0.2 logMAR units in two cases, and the visual fields were improved in all three cases. The multifocal ERGs which had been reduced in the loci corresponding to the ischemic retinal area were improved after the treatment in two cases. Neither ocular nor systemic adverse effects were observed except for transient superficial keratitis.
TES of the retina can improve retinal function in eyes with long-standing RAOs.
To map the distribution of cone- or rod-induced retinal responsiveness by optical imaging from macaque retina.
The light reflectance changes in the posterior retina after a flash stimulus in ...anesthetized rhesus monkeys were measured by a modified fundus camera system equipped with a charge-coupled device (CCD) camera. The response topography of the optical signals was obtained in either light- or dark-adapted conditions.
With infrared observation light, the whole posterior pole became darkened after the stimulus. The response topography in light-adapted conditions demonstrated a steep peak of darkening at the fovea, together with the gradual decrease of signal intensity away from the fovea toward the periphery. In dark-adapted conditions, the optical signal showed additional peaks along the circular region surrounding the macula at the eccentricity of the optic disc, together with the central peak at the fovea. A statistically significant positive correlation was obtained between the light reflectance changes in infrared observation light and the focal responses in multifocal electroretinogram (mfERG) at the corresponding retinal locations.
The response topography in the retina, obtained by optical imaging, was consistent with psychophysical cone or rod sensitivity in humans and anatomic cone or rod distribution in humans and macaques. The cone- or rod-induced retinal responsiveness within the posterior pole region was noninvasively recorded within a short recording time.
To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan.
Retrospective case series.
We analyzed 62 patients with clinical ...features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote.
Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC exon7del, the most common mutation in the East Asian population, with those of the patients with other genotypes.
Best-corrected visual acuity, visual field (VF), and their changes during follow-up.
The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy.
Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.
To report clinical and genetic features of a Japanese patient with end-stage retinitis pigmentosa (RP) caused by a homozygous
variant.
We performed comprehensive ophthalmic examinations. Whole exome ...sequencing analysis was used to investigate the RP patient with parental consanguinity. The pedigree included 4 RP patients in the two generations, which suggests presumed pseudo-autosomal dominant inheritance.
A
variant (p.R653X) was identified to be homozygous and disease-causing in the patient. Homozygosity mapping revealed the homozygous region including the variant and confirmation of autosomal recessive inheritance. The patient reported night blindness at 4 years of age and exhibited typical RP fundus appearance with macula involvement during the follow-up period from at the age of 52-69 years. At the age of 52, the patient exhibited a loss of visual acuity and had severely constricted visual fields, with a further gradual deterioration of her vision until she was 69 years old. At the age of 69, funduscopy showed severe chorioretinal degeneration in the area from the posterior pole to the peripheral retina.
This is the first report that the
variant (p.R653X) has been identified as one of the causes of autosomal recessive RP in the Japanese population. Longitudinal natural history/end-stage findings demonstrated early-onset and a severe RP phenotype with macula involvement when the patient was in her 50s and severe chorioretinal degenerations in her late 60s.
We investigated object representation in area TE, the anterior part of monkey inferotemporal (IT) cortex, with a combination of optical and extracellular recordings in anesthetized monkeys. We found ...neurons that respond to visual stimuli composed of naturally distinguishable parts. These neurons were sensitive to a particular spatial arrangement of parts but less sensitive to differences in local features within individual parts. Thus these neurons were activated when arbitrary local features were arranged in a particular spatial configuration, suggesting that they may be responsible for representing the spatial configuration of object images. Previously it has been reported that many neurons in area TE respond to visual features less complex than natural objects, but it has remained unclear whether these features are related to local features of object images or to more global features. These results indicate that TE neurons represent not only local features but also global features such as the spatial relationship among object parts.
Purpose
To present the characteristics and pathology of a patient with congenital achromatopsia.
Patient and methods
The patient was a 22-year-old Japanese woman who was 8 years old when she first ...visited our clinic. Comprehensive ophthalmic examinations including visual acuity measurements, perimetry, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, electroretinography (ERG), and color vision tests were performed. Her genomic DNA was used as the template for the amplification of exons of five candidate genes for achromatopsia;
CNGA3
,
CNGB3
,
GNAT2
,
PDE6C,
and
PDE6H
, and the amplified products were sequenced. A missense mutation, found in the
CNGA3,
was studied both electrophysiologically and biochemically.
Results
Her phenotype was typical of congenital complete achromatopsia. She was followed for 14 years, and her vision and fundus findings were stable. However, the scotopic ERG b-waves at age 22 were smaller than those at age 8, and her FAF images showed increased autofluorescence in both maculae. Genetic examinations revealed combined heterozygous mutations of c.997_998delGA and p.M424V in the
CNGA3
gene. The homomeric channel consisting of the CNGA3 subunit with the p.M424V mutation had a weak cGMP-activated current in patch-clamp recordings. In heterologous expression analyses, the expression at the cell surface of the mutant CNGA3 subunit was about 28 % of the wild type.
Conclusions
The two novel mutations found in the
CNGA3
gene, c.997_998delGA and p.M424V, can cause complete achromatopsia. The vision of the patient was stationary until the third decade of life although the FAF was altered at the age of 22 years.
We describe focal choroidal excavation (FCE) in a case of Vogt-Koyanagi-Harada (VKH) disease and compare the findings with different chorioretinal conditions. A 55-year-old man was diagnosed with VKH ...based on panuveitis and exudative retinal detachments. Spectral-domain optical coherence tomography demonstrated a dome-shaped protrusion with a nonconforming pattern at the fovea, which had been detected as a conforming pattern 1 year before the onset. The FCE pattern returned into a conforming pattern following corticosteroid therapy. These findings suggest that the natively existent FCE could be affected by pathophysiological changes of VKH as well as other chorioretinal conditions.
Abstract Purpose To determine the efficacy of internal limiting membrane (ILM) peeling during vitrectomy for rhegmatogenous retinal detachment (RRD) regarding post-vitrectomy epiretinal membrane ...(ERM) development and visual outcomes. Design Retrospective, interventional, comparative case series. Methods Setting : Institutional. Study Population : A-hundred-and-two consecutive eyes with RRD treated with vitrectomy and followed for at least 6 months. ILM was peeled without using dye such as indocyanine green (ICG). Observational Procedures : Patients were divided into two groups based on postoperative ERM development: Group 1, 81 eyes without ERM formation; Group 2, 21 eyes with ERM development. Patients also were divided into two subgroups: those with and without ILM peeling (58 and 44 eyes, respectively). Statistical analyses were performed between the two groups with/without ERM formation and between the two subgroups with/without ILM peeling for five preoperative factors including foveal involvement of the RRD, four intraoperative factors including ILM peeling, baseline best-corrected visual acuity (BCVA), and final BCVA. Main Outcome Measures : An association of ILM peeling with ERM prevention and the influence of ILM peeling on visual outcomes. Results ILM peeling was significantly ( P <0.001) associated with ERM prevention. There was no significant difference in the final BCVA between subgroups with and without ILM peeling. Conclusions ILM peeling without ICG staining during the initial vitrectomy for RRDs may prevent postoperative ERM formation with favorable visual outcomes.
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