Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation

To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutatio

Blue cone monochromacy: causative mutations and associated phenotypes.

PurposeTo perform a phenotypic assessment of members of three British families with blue cone monochromatism (BCM), and to determine the underlying molecular genetic basis of disease.MethodsAffected members of three British families with BCM were examined clinically and underwent detailed electrophysiological and psychophysical testing. Blood samples were taken for DNA extraction. Molecular analysis involved the amplification of the coding regions of the long (L) and medium (M) wave cone opsin genes and the upstream locus control region (LCR) by polymerase chain reaction (PCR). Gene products were directly sequenced and analyzed.ResultsIn all three families, genetic analysis identified that the underlying cause of BCM involved an unequal crossover within the opsin gene array, with an inactivating mutation. Family 1 had a single 5'-L-M-3' hybrid gene, with an inactivating Cys203Arg (C203R) mutation. Family 3 had an array composed of a C203R inactivated 5'-L-M-3' hybrid gene followed by a second inactive gene. Families 1 and 3 had typical clinical, electrophysiological, and psychophysical findings consistent with stationary BCM. A novel mutation was detected in Family 2 that had a single hybrid gene lacking exon 2. This family presented clinical and psychophysical evidence of a slowly progressive phenotype.ConclusionsTwo of the BCM-causing family genotypes identified in this study comprised different hybrid genes, each of which contained the commonly described C203R inactivating mutation. The genotype in the family with evidence of a slowly progressive phenotype represents a novel BCM mutation. The deleted exon 2 in this family is not predicted to result in a shift in the reading frame, therefore we hypothesize that an abnormal opsin protein product may accumulate and lead to cone cell loss over time. This is the first report of slow progression associated with this class of mutation in the L or M opsin genes in BCM

Curvature contraction of convex hypersurfaces by nonsmooth speeds

We consider contraction of convex hypersurfaces by convex speeds, homogeneous of degree one in the principal curvatures, that are not necessarily smooth. We show how to approximate such a speed by a sequence of smooth speeds for which behaviour is well known. By obtaining speed and curvature pinching estimates for the flows by the approximating speeds, independent of the smoothing parameter, we may pass to the limit to deduce that the flow by the nonsmooth speed converges to a point in finite time that, under a suitable rescaling, is round in the C² sense, with the convergence being exponential.The research of the second author was supported by an Australian Postgraduate Award. The research of the first, third, fourth and fifth authors was supported by Discovery Project grant DP120100097 of the Australian Research Council

Quantum Control of Interacting Bosons in Periodic Optical Lattice

We study the avoided crossings in the dynamics of quantum controlled excitations for an interacting two-boson system in an optical lattice. Specifically, we perform numerical simulations of quantum control in this system where driving pulses connect the undriven stationary states in a manner characteristic of Stimulated Raman Adiabatic Passage (STIRAP). We demonstrate that the dynamics of such a transition is affected by chaos induced avoided crossings, resulting in a loss in coherence of the final outcome in the adiabatic limit.Comment: Accepted for publication in Physica E. Typo corrections to final versio

Curvature contraction of convex hypersurfaces by nonsmooth speeds

We consider contraction of convex hypersurfaces by convex speeds, homogeneous of degree one in the principal curvatures, that are not necessarily smooth. We show how to approximate such a speed by a sequence of smooth speeds for which behaviour is well known. By obtaining speed and curvature pinching estimates for the flows by the approximating speeds, independent of the smoothing parameter, we may pass to the limit to deduce that the flow by the nonsmooth speed converges to a point in finite time that, under a suitable rescaling, is round in the C^2 sense, with the convergence being exponential

ISCEV standard for clinical pattern electroretinography—2007 update

The pattern electroretinogram (PERG) is a retinal response evoked by viewing a temporally alternating pattern, usually a black and white checkerboard or grating. The PERG is important in clinical and research applications because it provides information both about retinal ganglion cell function and, because the stimulus is customarily viewed with central fixation, the function of the macula. The PERG can therefore facilitate interpretation of an abnormal pattern VEP by revealing the retinal responses to a similar stimulus to that used for the VEP. However, practitioners may have difficulty choosing between the different techniques for recording the PERG that have been described in the literature. The International Society for Clinical Electrophysiology of Vision published a standard for clinical PERG recording in 2000 to assist practitioners in obtaining good quality reliable responses and to facilitate inter-laboratory communication and comparison. This document is the scheduled revision of that standard

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

Purpose To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. Methods Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), “cone dystrophy with supernormal rod ERG” (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM). Results In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change. Conclusions Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease

Published: March 13, 2023Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage. Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD)were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC). Results: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained fromwedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar 2.5 degrees: 0.88±0.11;wedge/ring<2.5 degrees: 0.89 ± 0.12 wedge/ring; >2.5 degrees: 0.86 ± 0.10) for the peripheral visual field. Conclusions: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.Supported by the Austrian Science Fund (FWF); KLI 670-B3

A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

PurposeTo describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.MethodsUsing direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.ResultsOnly one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.ConclusionsMutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2