2,072 research outputs found
Investigating the potential of Zernike polynomials to characterise spatial distribution of macular pigment
It has been postulated that particular patterns of macular pigment (MP) distribution may be associated with the risk for eye diseases such as age-related macular degeneration (AMD). This work investigates the potential of Zernike polynomials (ZP) to characterise the level and distribution of MP, and their suitability as a representation for analysis of the effects of age and AMD on MP patterns. As the case study, MP distribution maps computed using an experimental method based on fundus reflectance (MRIA) were obtained for ninety volunteers representing three groups: under-fifty without AMD, fifty and over without AMD, and fifty and over with AMD. ZP with 105 coefficients were fitted to the maps using least-squares optimisation and found to represent MP maps accurately (RMSE<10-1). One-way MANOVA analysis carried out on ZP representations showed that the three subject groups have significantly different means (Wilk's Lambda 0.125, p<0.0001). Linear discriminant analysis with leave-one-out scheme resulted in accuracy, sensitivity and specificity of classification according to, respectively, disease status regardless of age (81% all); disease status in the age-matched groups (87%, 88%, 86%); age irrespective of disease status (81%, 83%, 73%); and age for subjects without AMD (83%, 88%, 80%). Mean MP distributions computed from ZP coefficients for the three groups showed more elevated and more peaked MP for the healthy under-fifty group; more irregular and more elevated peripheral levels in over-fifty AMD group than in over-fifty non-AMD group; and moderate radial asymmetry in non-AMD over-50 group. The results suggest that ZP coefficients are capable of accurately representing MP in a way that captures certain spatial patterns of its distribution. Using the ZP representation MP maps could be classified according to both age and disease status with accuracy significantly greater than chance, with peak elevation, pattern irregularity and radial asymmetry identified as important features
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
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
Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy
ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update)
This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023
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
Electrophysiology as a prognostic indicator of visual recovery in diabetic patients undergoing cataract surgery
Purpose: Visual outcomes after cataract surgery in diabetic patients with retinal or visual pathway disease are difficult to predict as the fundus may be obscured, and assessment of visual potential is challenging. This study assessed the value of visual electrophysiology as a prognostic indicator of visual recovery in diabetic patients with cataract, prior to cataract surgery. Methods: Forty-one diabetic patients (aged 52–80; 74 eyes) and 13 age-matched non-diabetic control patients (21 eyes) were examined prior to cataract surgery. Pre-surgical examinations included best-corrected visual acuity (BCVA), slit-lamp bio-microscopy, ISCEV-standard full-field electroretinography (ffERG), and flash visual evoked potential (flash VEP) testing. Electrophysiological assessments included quantification of the DA and LA ERG, oscillatory potentials (OPs; OP1, OP2, OP3, OP4) and flash VEP P1, P2, and P3 components. Post-operative BCVA was measured in all cases and the diabetic patients grouped according to the severity of visual acuity loss: mild (logMAR ≤ 0.1), moderate (0.1 < logMAR < 0.5), or severe (logMAR ≥ 0.5). A fourth group included those without diabetes. The pre-surgical electrophysiological data was compared between the four groups by analysis of variance. Results: The severity of post-surgical visual acuity loss in the diabetic patients was classified as mild (N=22 eyes), moderate (N=31 eyes), or severe (N=21 eyes). In the group without diabetes, post-surgical visual impairment was classified as mild (N=21 eyes). The pre-operative DA 10.0 ERG a-wave amplitudes, DA 3.0 ERG OP2 amplitudes, and the LA 3.0 a- and b-wave amplitudes showed best significant differences among the four groups. The flash VEP did not show significant difference between groups. Conclusion: Electrophysiological assessment of diabetic patients with cataract can provide a useful measure of retinal function. Full-field ERG components, including the DA 10.0 ERG a-wave, DA 3.0 ERG OP2 component, and the LA 3.0 a- and b-wave amplitudes, are of prognostic value in predicting post-surgical visual acuity, and may inform the surgical management of cataract patients with diabetes. [Figure not available: see fulltext.]
High-resolution optical coherence tomography imaging in KCNV2 retinopathy
ABSTRACT Aim To report novel spectral domain optical coherence tomography (SD-OCT) findings and new mutational data in patients with 'cone dystrophy with supernormal rod electroretinogram', a recessive childhood onset retinal dystrophy consequent upon mutation in the KCNV2 gene. Design/methods This was a comparative case series study of 12 patients with clinical and/or electrophysiological findings in keeping with KCNV2 mutation. Clinical examination and electrophysiological testing results were reviewed. Fundus photography and autofluorescence imaging were performed. Retinal layer appearance and thickness were evaluated using SD-OCT. The coding region and introneexon boundaries of KCNV2 were screened by direct sequencing. Results Mutations in KCNV2 were detected in all families; five of these changes were novel. Pattern electroretinograms were undetectable and full-field electroretinograms showed findings specific for the disorder
Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy
In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with “cone-first” retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs∗2];[Glu529Valfs∗2], and c.[401delT(;)3354G>A], p.[Leu134Argfs∗45(;)Trp1118∗]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543∗) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families
- …