The Diagnostic Accuracy of Photopic Negative Responses Evoked by Broadband and Chromatic Stimuli in a Clinically Heterogeneous Population

Purpose: To compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort. Methods: Adults referred for electrophysiological investigations were recruited consecutively for this single-centre, prospective, paired diagnostic accuracy study. PhNRs were recorded to red flashes (1.5 cd·s·m−2) on a blue background (10 cd·m−2) and to white flashes on a white background (the latter being the ISCEV standard LA 3 stimulus). PhNR results were compared with a reference test battery assessing RGC/optic nerve structure and function including optical coherence tomography (OCT) retinal nerve fibre layer thickness and mean RGC volume measurements, fundus photography, pattern electroretinography and visual evoked potentials. Primary outcome measures were differences in sensitivity and specificity of the two PhNR methods. Results: Two hundred and forty-three participants were initially enrolled, with 200 (median age 54; range 18–95; female 65%) meeting inclusion criteria. Sensitivity was 53% (95% confidence intervals [CI] 39% to 68%) and 62% (95% CI 48% to 76%), for WW and RB PhNRs, respectively. Specificity was 80% (95% CI 74% to 86%) and 78% (95% CI 72% to 85%), respectively. There was a statistically significant difference between sensitivities (p = 0.046) but not specificities (p = 0.08) of the two methods. Receiver operator characteristic (ROC) area under the curve (AUC) values were 0.73 for WW and 0.74 for RB PhNRs. Conclusion: PhNRs to red flashes on a blue background may be more sensitive than white-on-white stimuli, but there is no significant difference between specificities. This study highlights the value and potential convenience of using white-on-white stimuli, already used widely for routine ERG assessment

WFS1-Associated Optic Neuropathy : Genotype-Phenotype Correlations and Disease Progression

center dot OBJECTIVE: To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON).center dot DESIGN: Multicenter cohort study. center dot METHODS: The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmologic assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. Main Outcome Measures: WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile.center dot RESULTS: Twenty-two recessive and 5 dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. center dot CONCLUSIONS: WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe, vision and RGC loss compared with heterozygous variants. Abnormal cleftlike lamination of the OPL is a distinctive OCT feature that strongly points toward dominant WON. (Am J Ophthalmol 2022;241: 927. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))Peer reviewe

Chiasmal Misrouting in Infantile Nystagmus Syndrome (INS): Phenotypes in Patients With Molecular Diagnoses

Chiasmal misrouting, once believed to be pathognomonic for albinism, has been reported in cases of INS, independent of melanin pathway disruption. The purpose of this study is to test the hypothesis that there are clinical-electrophysiological parameters that correlate with particular genotypes in INS

The diagnostic accuracy of photopic negative responses evoked by broadband and chromatic stimuli in a clinically heterogeneous population.

PURPOSE: To compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort. METHODS: Adults referred for electrophysiological investigations were recruited consecutively for this single-centre, prospective, paired diagnostic accuracy study. PhNRs were recorded to red flashes (1.5 cd·s·m-2) on a blue background (10 cd·m-2) and to white flashes on a white background (the latter being the ISCEV standard LA 3 stimulus). PhNR results were compared with a reference test battery assessing RGC/optic nerve structure and function including optical coherence tomography (OCT) retinal nerve fibre layer thickness and mean RGC volume measurements, fundus photography, pattern electroretinography and visual evoked potentials. Primary outcome measures were differences in sensitivity and specificity of the two PhNR methods. RESULTS: Two hundred and forty-three participants were initially enrolled, with 200 (median age 54; range 18-95; female 65%) meeting inclusion criteria. Sensitivity was 53% (95% confidence intervals [CI] 39% to 68%) and 62% (95% CI 48% to 76%), for WW and RB PhNRs, respectively. Specificity was 80% (95% CI 74% to 86%) and 78% (95% CI 72% to 85%), respectively. There was a statistically significant difference between sensitivities (p = 0.046) but not specificities (p = 0.08) of the two methods. Receiver operator characteristic (ROC) area under the curve (AUC) values were 0.73 for WW and 0.74 for RB PhNRs. CONCLUSION: PhNRs to red flashes on a blue background may be more sensitive than white-on-white stimuli, but there is no significant difference between specificities. This study highlights the value and potential convenience of using white-on-white stimuli, already used widely for routine ERG assessment

Differential Changes in Color and Motion-Onset Visual Evoked Potentials from Both Eyes in Early-and Late-Onset Strabismic Amblyopia

PURPOSE. To examine changes in color-and motion-related visual function in patients with strabismic amblyopia. METHODS. Motion-onset and color visual-evoked potentials (VEPs) were recorded in 16 adult patients with strabismic amblyopia which had an early onset, before 18 months of age, and 14 patients with amblyopia of later onset. The results are compared with those from 21 normal adults. RESULTS. The peak times of motion-onset VEPs in the amblyopic eye were longer those than in the fellow eye in patients with both early-and late-onset strabismic amblyopia, but peak times in both amblyopic and fellow eyes were shorter than those in normal eyes. In patients with late-but not early-onset amblyopia, the peak times for color VEPs were significantly longer in amblyopic than in fellow and normal eyes. CONCLUSIONS. The patterns of abnormality for motion-onset and color VEPs in patients with strabismic amblyopia are different, probably indicating differential changes in function in magno-and parvocellular pathways. These abnormalities affect both the amblyopic and fellow eyes and are different in patients with an onset of amblyopia before or after 18 months of age. (Invest Ophthalmol Vis Sci. 2008;49:4418 -4426

Isolated rod dysfunction associated with a novel genotype of CNGB1

Purpose: To describe the clinical and electrophysiological features of an unusual retinopathy in a patient with a novel genotype of CNGB1, mutations in which are implicated in autosomal recessive retinitis pigmentosa (rod-cone dystrophy). Observations: A 61-year old asymptomatic woman was referred to the inherited retinal disorders clinic because of peripheral retinal pigmentary changes. She had normal visual acuity and color vision. Clinical examination and detailed imaging of the macula were normal, but there was atrophy of the outer retina in the periphery with sparse intra-retinal pigmentation. Electroretinography (ERG) revealed undetectable rod responses, with normal cone-mediated responses. The pattern ERG was normal. Genetic analysis identified two previously unreported variants in CNGB1: (c.2258T > A, p.[Leu753*] and c.807G > C, p.[Gln269His]), shown to be in trans. Conclusions and importance: This report describes a functionally cone-isolated retina in an adult, apparently hemizygous for a novel missense mutation in CNGB1, a novel phenotype for this gene. The p.[Gln269His] allele is the first missense change, within the glutamic acid-rich protein (GARP) domain of CNGB1, to be associated with retinal disease in humans. Keywords: Cone-isolated retina, Cyclic nucleotide-gated channels, Glutamic-acid rich protein (GARP), Night blindness, Retinitis pigmentosa, Rod dysfunctio

Electroretinogram measures in a septuagenarian population.

This study reports electroretinogram (ERG) data in a septuagenarian population. Fifty healthy adults without diabetes or dementia aged 70-79 years underwent standardised electrophysiological testing incorporating current ISCEV Standards as baseline assessment for the OPAL (Older People And n-3 Long-chain polyunsaturated fatty acids) study. These data were compared with those from 53 healthy adults aged 20-50 years. Amplitudes and peak times of the major components were assessed. There were no significant differences in amplitude or peak time between sexes or between eyes. ERG amplitudes were 25-40% smaller and peak-times were longer in the older compared with the younger age group. In all participants, the bright flash ERG b-wave amplitude had the highest variability; the bright flash ERG a-wave peak time had the lowest. ERGs in a septuagenarian age group show 25-40% lower amplitude than those of a 20 to 50-year-old group and are of longer peak time. With an increasingly ageing population involved in clinical trials, and the potential use of ERG in the assessment both of efficacy and safety in forthcoming therapeutic interventions, it is important that the effects of age are given adequate consideration