Full-field Electroretinogram Research Articles

Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon.

Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening. Retrospective observational case series of 5 patients who experienced TBVL on awakening seen in the neuro-ophthalmology clinic at the Mayo Clinic between 2016 and 2020. Patients who described generalized blurred vision and those with monocular transient vision loss were excluded. The median age was 81.4 years (range, 68-92 years), and all were male. Every patient described a stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126-728 episodes) before evaluation in the neuro-ophthalmology clinic. All patients had normal optic nerves, and no plaques were noted in the retinal vessels. All 5 had macular drusen, which were predominantly extrafoveal and mild. Two patients underwent electrophysiology testing, which were both normal on full-field electroretinogram (ERG), but there was blunted central wave forms on multifocal ERG. Two patients underwent dark adaptation testing, which showed both prolong and diminished dark adaptation. Neuroimaging and thromboembolic workup were unrevealing. TBVL is a distinct phenomenon from TMVL on awakening, which has a different demographic and symptomology. The etiology is unclear but seems to be a focal macular process in conjunction with an autoregulatory failure resulting in a supply-demand mismatch during low-light conditions.

Phenotyping of ABCA4 Retinopathy by Machine Learning Analysis of Full-Field Electroretinography.

PurposeBiallelic pathogenic variants in ABCA4 are the commonest cause of monogenic retinal disease. The full-field electroretinogram (ERG) quantifies severity of retinal dysfunction. We explored application of machine learning in ERG interpretation and in genotype–phenotype correlations.MethodsInternational standard ERGs in 597 cases of ABCA4 retinopathy were classified into three functional phenotypes by human experts: macular dysfunction alone (group 1), or with additional generalized cone dysfunction (group 2), or both cone and rod dysfunction (group 3). Algorithms were developed for automatic selection and measurement of ERG components and for classification of ERG phenotype. Elastic-net regression was used to quantify severity of specific ABCA4 variants based on effect on retinal function.ResultsOf the cohort, 57.6%, 7.4%, and 35.0% fell into groups 1, 2, and 3 respectively. Compared with human experts, automated classification showed overall accuracy of 91.8% (SE, 0.169), and 96.7%, 39.3%, and 93.8% for groups 1, 2, and 3. When groups 2 and 3 were combined, the average holdout group accuracy was 93.6% (SE, 0.142). A regression model yielded phenotypic severity scores for the 47 commonest ABCA4 variants.ConclusionsThis study quantifies prevalence of phenotypic groups based on retinal function in a uniquely large single-center cohort of patients with electrophysiologically characterized ABCA4 retinopathy and shows applicability of machine learning. Novel regression-based analyses of ABCA4 variant severity could identify individuals predisposed to severe disease.Translational RelevanceMachine learning can yield meaningful classifications of ERG data, and data-driven scoring of genetic variants can identify patients likely to benefit most from future therapies.

Fast and slow light-induced changes in murine outer retina optical coherence tomography: complementary high spatial resolution functional biomarkers.

Fast (seconds) and slow (minutes to hours) optical coherence tomography (OCT) responses to light stimulation have been developed to probe outer retinal function with higher spatial resolution than the classical full-field electroretinogram (ERG). However, the relationships between functional information revealed by OCT and ERG are largely unexplored. In this study, we directly compared the fast and slow OCT responses with the ERG. Fast responses [i.e. the optoretinogram (ORG)] are dominated by reflectance changes in the outer segment (OS) and the inner segment ellipsoid zone (ISez). The ORG OS response has faster kinetics and a higher light sensitivity than the ISez response, and both differ significantly with ERG parameters. Sildenafil-inhibition of phototransduction reduced the ORG light sensitivity, suggesting a complete phototransduction pathway is needed for ORG responses. Slower OCT responses were dominated by light-induced changes in the external limiting membrane to retinal pigment epithelium (ELM-RPE) thickness and photoreceptor-tip hyporeflective band (HB) magnitudes, with the biggest changes occurring after prolonged light stimulation. Mice with high (129S6/ev) vs. low (C57BL/6J) ATP(adenosine triphosphate) synthesis efficiency show similar fast ORG, but dissimilar slow OCT responses. We propose that the ORG reflects passive physiology, such as water movement from photoreceptors, in response to the photocurrent response (measurable by ERG), whereas the slow OCT responses measure mitochondria-driven physiology in the outer retina, such as dark-provoked water removal from the subretinal space.

Full-field electroretinogram in evaluation of the outer retina in patients with multiple sclerosis

Background: Background: Optic nerve inflammation may contribute to the pathology of multiple sclerosis (MS) (retrograde trans-synaptic degeneration) However, within the past ten years, some investigations have indicated that primary retinopathy may be brought on by MS. This study used a full-field electroretinogram to test the function of the outer retinal layers in people with relapsing remitting multiple sclerosis (RRMS) (ff-ERG). Methods: This is a case- control study, conducted on 30 RRMS patients and 30 healthy controls. RRMS patients were subjected to neurological, ophthalmological, and radiological assessment. Both RRMS patients and controls were subjected to full field ERG. Results: The ff-ERG showed a significant delay of latencies of a and b-waves of both light and dark-adapted condition with reduction of their amplitudes compared to control. ERG responses were significantly affected in MS patients with or without optic neuritis compared to control. Most of ff-ERG parameters showed non statistically significant difference between optic neuritis and non-optic neuritis eyes. Conclusion: There is functional affection of the bipolar and the photoreceptors layers in the outer retina in optic neuritis and non-optic neuritis eyes of MS. Therefore, the outer retina could be a site for primary pathology in MS, unrelated to the optic nerve affection.

Сase of congenital cataract development in a child with Farh disease

INTRODUCTION: Fahr disease is a rare idiopathic neurodegenerative disorder characterized by the calcification of the basal ganglia, cerebellar dentate nuclei, and surrounding white matter leading to progressive nervous system dysfunction. Cases of congenital cataracts are not described.
 AIM: To describe a clinical case of congenital cataract in a pediatric patient with Farh disease.
 MATERIAL AND METHODS: Congenital atypical progressive metabolic cataract was diagnosed in a 9-year-old child. Congenital cataract extraction with intraocular lens implantation was performed.
 RESULTS: Refraction before operation was sph+2.0 cyl+1.5 ax 107 and sph+0.25 cyl+1.25 ax 74, respectively. The preoperative visual acuity for both eyes was 0.5 log MAR and 1.0 log MAR, respectively. Crystalline lenses were cloudy with atypical star-shaped infusions. Full-field electroretinogram (ERG) a-wave and b-wave were normal for OD and abnormal for OS, and flicker ERG was normal for both eyes. Visually evoked potentials were prolonged for both eyes. The intraocular pressure was normal for both eyes. The axial lengths were 22.60 mm and 22.62 mm, respectively. Exudative reaction was noted postoperatively, and the logMar visual acuity improved to 0.2 for both eyes.
 CONCLUSION: Congenital cataracts may be diagnosed in patients with Fahr disease. Dynamic examination of the child with a wide pupil is necessary to identify initial changes in the lens and to refer him/her for surgical treatment. There is an increased risk of exudative reactions in the early postoperative period.

Full field electroretinography with skin electrodes to diagnose inherited retinal disease in pediatric patients

A single-site retrospective study was undertaken to validate a handheld electroretinogram (ERG) system utilizing skin electrodes to complete full-field ERGs as a stand-alone test in the workup for inherited retinal disease.

Deep learning to distinguish Best vitelliform macular dystrophy (BVMD) from adult-onset vitelliform macular degeneration (AVMD)

Initial stages of Best vitelliform macular dystrophy (BVMD) and adult vitelliform macular dystrophy (AVMD) harbor similar blue autofluorescence (BAF) and optical coherence tomography (OCT) features. Nevertheless, BVMD is characterized by a worse final stage visual acuity (VA) and an earlier onset of critical VA loss. Currently, differential diagnosis requires an invasive and time-consuming process including genetic testing, electrooculography (EOG), full field electroretinogram (ERG), and visual field testing. The aim of our study was to automatically classify OCT and BAF images from stage II BVMD and AVMD eyes using a deep learning algorithm and to identify an image processing method to facilitate human-based clinical diagnosis based on non-invasive tests like BAF and OCT without the use of machine-learning technology. After the application of a customized image processing method, OCT images were characterized by a dark appearance of the vitelliform deposit in the case of BVMD and a lighter inhomogeneous appearance in the case of AVMD. By contrast, a customized method for processing of BAF images revealed that BVMD and AVMD were characterized respectively by the presence or absence of a hypo-autofluorescent region of retina encircling the central hyperautofluorescent foveal lesion. The human-based evaluation of both BAF and OCT images showed significantly higher correspondence to ground truth reference when performed on processed images. The deep learning classifiers based on BAF and OCT images showed around 90% accuracy of classification with both processed and unprocessed images, which was significantly higher than human performance on both processed and unprocessed images. The ability to differentiate between the two entities without recurring to invasive and expensive tests may offer a valuable clinical tool in the management of the two diseases.

Phenotype Characterization of a Mice Genetic Model of Absolute Blindness.

Recent technological development requires new approaches to address the problem of blindness. Such approaches need to be able to ensure that no cells with photosensitive capability remain in the retina. The presented model, Opn4−/− × Pde6brd10/rd10 (O×Rd) double mutant murine, is a combination of a mutation in the Pde6b gene (photoreceptor degeneration) together with a deletion of the Opn4 gene (responsible for the expression of melanopsin in the intrinsically photosensitive retinal ganglion cells). This model has been characterized and compared with those of WT mice and murine animal models displaying both mutations separately. A total loss of pupillary reflex was observed. Likewise, behavioral tests demonstrated loss of rejection to illuminated spaces and a complete decrease in visual acuity (optomotor test). Functional recordings showed an absolute disappearance of various wave components of the full-field and pattern electroretinogram (fERG, pERG). Likewise, visual evoked potential (VEP) could not be recorded. Immunohistochemical staining showed marked degeneration of the outer retinal layers and the absence of melanopsin staining. The combination of both mutations has generated an animal model that does not show any photosensitive element in its retina. This model is a potential tool for the study of new ophthalmological approaches such as optosensitive agents.

Optic neuropathy and retinopathy due to advanced cobalt toxicity

We report a rare case of cobalt toxicity resulting in a combined optic neuropathy and retinopathy. A 58-year-old woman with a recent revision of a hip implant presented with profound loss of vision. Although her initial exam was structurally unremarkable, she developed progressive outer retinal atrophy and optic nerve pallor. Abnormalities were also demonstrated in the full-field electroretinogram and optic nerve sheath on magnetic resonance imaging (MRI). Cobalt levels in the serum were severely elevated (734 μg/L) from the dysfunctional metal-on-metal (MoM) hip implant. Removal of the implant led to a rapid reduction in cobalt levels and stabilization of her declining vision.

Clinical and visual electrophysiological characteristics of vitelliform macular dystrophies in the first decade of life.

Purpose:To evaluate patterns of pediatric vitelliform macular dystrophy (PVMD).Methods: This is a retrospective analysis of Indian children with vitelliform macular dystrophy (VMD) presenting within the first decade of life. Records were evaluated for clinical findings, family screening, and investigative findings including optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinogram (ERG) and electrooculogram (EOG). Electrophysiology was scrutinized and audited for acquisition and interpretation errors. Findings on follow-up were also recorded.Results: 46 eyes of 24 patients were included. Mean age at presentation was 7.17 ± 2.17 years. Mean follow-up duration was 1.55 ± 1.69 years. Best disease was the commonest type of VMD detected (21 patients), while autosomal recessive bestrophinopathy was seen in three cases. Mean logMAR BCVA was 0.364 which decreased to 0.402 on follow-up. Hyperopia was noted in 29 out of 46 eyes (mean being +3.87 D, range ebing +0.75 to +8.75 D). Four eyes of four children had choroidal neovascular membrane at presentation, while another child developed while in follow-up. Solid type subretinal deposit was the commonest OCT finding (n = 29/38) and central hyper FAF was the commonest pattern (n = 18/32). EOG was available for review in 32 eyes, but was unreliable in 11 eyes. Seven eyes demonstrated complete absence of light rise on EOG.Conclusion: PVMD can present in advanced forms. Progression to complications with loss of visual acuity can happen within the first decade of life. EOG shows grossly suppressed waveforms in the light phase in a large number of such children.

Changes in Functional Activity of Rabbit’s Retina During Flicker Photostimulation with Scale-free Dynamics

Neuroplasticity-based stimulation therapy assists in restoring the visual system in neurodegenerative disorders. Scale-free fluctuations peculiar to healthy physiological rhythms disappear as the disease progresses. Fractal visual stimuli positively influence CNS plasticity and increase the efficiency of visual rehabilitation. To determine the effect of a lengthy course of fractal photostimulation (FS) on the electroretinogram (ERG) in healthy rabbits, a device for FS was created. For twelve healthy rabbits, 20-minute FS sessions were conducted once a day from 9 to 11 a.m., five times a week. Before and after 1, 4, and 12 weeks of FS, full-field ERGs, flicker ERGs, and the pattern-ERGs were registered. The observed positive impact of FS consisted of shortening peak latency of the maximal scotopic ERG b-wave and a significant increase in the amplitude of the cone ERG a- and b-waves and low-frequency flicker ERGs (p<0.05). For the first time, we describe the effect of FS on the ERG. The long-term FS does not impair retinal activity and can be safely used in the clinic. The dynamics of the positive influence of FS on retinal activity argue that the duration of the FS course of 1 to 4 weeks is optimal for subsequent studies.

Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage.

PurposeHeat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model.MethodsMale C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury.ResultsONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa.ConclusionsInhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy.

Full-field and multifocal electroretinogram in non-diabetic controls and diabetics with and without retinopathy.

To compare retinal function assessed by full-field electroretinography (ffERG) and multifocal electroretinography (mfERG) in diabetes without retinopathy, diabetes with moderate non-proliferative diabetic retinopathy (NPDR) and in the absence of diabetes. Scotopic and photopic ffERG and mfERG was made in non-fasting volunteers, including 26 diabetic participants without retinopathy, 22 diabetic participants with moderate NPDR and 22 participants without diabetes using full International Society for Clinical Electrophysiology of Vision protocols. Of the ffERG responses, significant deviation (p ≤ 0.05, corrected for multiple sampling and other relevant confounders) from the non-diabetic participants was seen in the diabetic participants only for the OP1-OP3 oscillatory amplitudes and the OP2 implicit time. This finding was independent of whether retinopathy was present or not. For the mfERG, minor amplitude or implicit time deviations were found for a small number of rings (R2, R4 and R5). Receiver of operating characteristic analysis showed that the single most prominent abnormality of the ffERG in diabetes, regardless of whether retinopathy was present or not, was the OP2 implicit time (area under the curve ≥ 0.80). This bi-modal study of electroretinographic characteristics found that the most prominent anomaly associated with diabetes was a prolongation of the implicit time of the OP2 of the scotopic ffERG, while the most prominent added effect of non-proliferative diabetic retinopathy was a further prolongation of the OP2 implicit time. Although the variation in ERG characteristics is far too large for diagnostic purposes, the close association of the oscillatory potentials with the amacrine cells of the retina indicate that their function is particularly sensitive to diabetes.

Atypical chorioretinal lesions in Siberian Husky dogs with primary angle-closure glaucoma: a case series

BackgroundA number of etiologies for different canine chorioretinal lesions have been proved or suggested but some fundic lesions remain unclear in terms of an etiologic diagnosis, treatment options and prognosis. The purpose of this case series is to describe atypical chorioretinal lesions observed in dogs with primary angle-closure glaucoma (PACG).Case presentationTwo spayed-female Siberian Huskies (3- and 4-year-old) and one Siberian Husky/Australian Shepherd mixed breed dog (11-month-old) that had multifocal depigmented retinal lesions and PACG were included. Procedures: Ophthalmic examination, gross, and histopathologic examination findings are described. One of the dogs underwent further clinical diagnostics. Advanced clinical diagnostics on the fellow, presumed to be non-glaucomatous eye of a dog revealed: pectinate ligament dysplasia by gonioscopy, retinal thinning in the depigmented area and wedge shaped retinal thinning with delayed choroidal vascular perfusion by optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography. Quantifiable maze testing for the same eye revealed mild nyctalopia but the full-field electroretinogram showed no generalized decrease of retinal function. Genetic testing for mutations within the retinitis pigmentosa GTPase regulator gene causing X-linked progressive retinal atrophy in Siberian Huskies was negative. Histopathologic evaluations on enucleated eyes in two dogs confirmed goniodysgenesis, PACG with optic nerve head cupping, and diffuse inner retinal atrophy. In addition, segmental profound retinal atrophy, loss of retinal pigment epithelium, and adhesion of the retina to Bruch’s membrane was observed and coincided with multifocal depigmented lesions noted on fundic examination.ConclusionsTo our knowledge, this is the first case series with clinical and histopathologic data of chorioretinal lesions, most likely caused by severely impaired choroidal perfusion. Further studies are warranted to elucidate the etiology and pathophysiology, including its possible association with PACG.

Multifocal Electroretinogram Photopic Negative Response: A Reliable Paradigm to Detect Localized Retinal Ganglion Cells' Impairment in Retrobulbar Optic Neuritis Due to Multiple Sclerosis as a Model of Retinal Neurodegeneration.

The measure of the full-field photopic negative response (ff-PhNR) of light-adapted full-field electroretinogram (ff-ERG) allows to evaluate the function of the innermost retinal layers (IRL) containing primarily retinal ganglion cells (RGCs) and other non-neuronal elements of the entire retina. The aim of this study was to acquire functional information of localized IRL by measuring the PhNR in response to multifocal stimuli (mfPhNR). In this case-control observational and retrospective study, we assessed mfPhNR responses from 25 healthy controls and from 20 patients with multiple sclerosis with previous history of optic neuritis (MS-ON), with full recovery of visual acuity, IRL morphological impairment, and absence of morpho-functional involvement of outer retinal layers (ORL). MfPhNR response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), and 20–25° (R5) from retinal sectors (superior-temporal (ST), superior-nasal (SN), inferior-nasal (IN), and inferior-temporal (IT)); between 5° and 20° and from retinal sectors (superior (S), temporal (T), inferior (I), and nasal (N)); and within 5° to 10° and within 10° and 20° from the fovea. The mfPhNR RAD values observed in all rings or sectors in MS-ON eyes were significantly reduced (p < 0.01) with respect to control ones. Our results suggest that mfPhNR recordings may detect localized IRL dysfunction in the pathologic condition of selective RGCs neurodegeneration.

ISCEV Standard for full-field clinical electroretinography (2022 update)

The full-field electroretinogram (ERG) is a mass electrophysiological response to diffuse flashes of light and is used widely to assess generalized retinal function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical ERG testing. Minimum protocols for basic ERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis, monitoring and inter-laboratory comparisons, while also responding to evolving clinical practices and technology. The main changes in this updated ISCEV Standard for clinical ERGs include specifying that ERGs may meet the Standard without mydriasis, providing stimuli adequately compensate for non-dilated pupils. There is more detail about analysis of dark-adapted oscillatory potentials (OPs) and the document format has been updated and supplementary content reduced. There is a more detailed review of the origins of the major ERG components. Several tests previously tabulated as additional ERG protocols are now cited as published ISCEV extended protocols. A non-standard abbreviated ERG protocol is described, for use when patient age, compliance or other circumstances preclude ISCEV Standard ERG testing.

Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease

To describe the longitudinal progression and phenotypic association of bilateral foveomacular vitelliform lesions in the setting of ABCA4 disease. Case report and cross-sectional cohort study. Nineteen patients with confirmed ABCA4 disease exhibiting an optical gap phenotype. Multimodal retinal imaging across multiple visits included autofluorescence imaging, spectral-domain OCT (SD-OCT), and OCT angiography. Electro-oculogram (EOG) and full-field electroretinogram testing results were analyzed. Exome sequencing was performed for diagnostic confirmation and the verification of other variations. Light-peak-to-dark-trough ratio (Arden ratio) on EOG; thickness and en face maps of various retinal layers on SD-OCT; area measurements on 488- and 787-nm autofluorescence images; and the presence of variation in vitelliform-associated genes identified using exome sequencing. A 25-year-old White man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid. The result of EOG testing was inconsistent with bestrophinopathy (Arden ratio= 1.62), and no generalized rod or cone dysfunction was detected on full-field electroretinogram. Exome sequencing identified the pathogenic variants c.5882G>A (p.(Gly1961Glu)) and c.4139C>T (p.(Pro1380Leu)) in ABCA4 and no other vitelliform-associated genes. Significant thinning and abnormal reflectivity of photoreceptor-attributable layers as well as near-infrared autofluorescence abnormalities were found in lesion-adjacent areas. Complete resorption of the vitelliform fluid occurred after 30 months, after which the optical gap lesions exhibited an enlarged and "cavitated" appearance. Phenotypic screening for additional cases from a large ABCA4 disease database (n= 602) identified 18 additional patients at various stages of optical gap lesion formation, most of whom harbored the c.5882G>A (p.(Gly1961Glu)) variant (P < 0.001), although none had apparent vitelliform fluid. At least 5 of the 18 (31.6%) patients exhibited optical gap lesions with the distinct "cavitated" appearance, whereas the lesions remained unperturbed in the other patients over the course of examination. Foveomacular vitelliform deposition is a mechanistically congruent but rare manifestation of ABCA4 disease. Specifically, this disease phenotype may be clinically associated with the c.5882G>A (p.(Gly1961Glu)) allele and optical gap lesions.

Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1.

PurposeRetinal and choroidal abnormalities in neurofibromatosis type 1 (NF1) remain poorly studied. It has been reported, however, that the function of the retinal pigment epithelium (RPE) in NF1 was abnormal, with a supra-normal Arden ratio of the electro-oculogram (EOG). This study aims to evaluate the function of the RPE, using EOG, first in patients with NF1 compared to controls and second in patients with NF1 with choroidal abnormalities compared to patients with NF1 without choroidal abnormalities.MethodsThis prospective case-control study included 20 patients with NF1 (10 patients with choroidal abnormalities and 10 patients without) and 10 healthy patients, matched for age. A complete ophthalmologic assessment with multimodal imaging, an EOG, and a full-field electroretinogram were performed for each included patient. The main outcome measured was the EOG light peak (LP)/dark trough (DT) ratio.ResultsThe LP/DT ratio was 3.02 ± 0.52 in patients with NF1 and 2.63 ± 0.31 in controls (P = 0.02). DT values were significantly lower in patients with NF1 than in controls (240 vs. 325 µV, P = 0.02), while light peak values were not significantly different (P = 0.26). No difference was found for peak latencies. No significant correlation between the surface and number of choroidal abnormalities and EOG parameters was demonstrated.ConclusionsThis study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2+ ion flux and an abnormal polarization of the RPE.

Increase in b-wave amplitude after light stimulation of the blind spot is positively correlated with the axial length of myopic individuals

Altered retinal dopamine and ON-pathway activity may underlie myopia development. It has been shown that the stimulation of the blind spot with short-wavelength light increases the electroretinogram (ERG) b-wave amplitude of myopic eyes and may engage the retinal dopaminergic system. This study evaluated the impact of various durations of blind spot stimulation on the electrophysiological response of the myopic retina and their relationship to axial length. Six myopic individuals underwent three short-wavelength blue light blind spot stimulation protocols (10 s, 1 min, 10 min) using a virtual reality headset. As a control condition, no stimulation was shown for 1 min. The b-wave amplitude of the photopic full-field ERG was measured at baseline and 10, 20, 30, 40, 50, and 60 min after each condition. A significant increase in b-wave amplitude was observed for all stimulation protocols compared to the control. The peak b-wave amplitude was observed 20 min after the 1-min stimulation protocol and 60 min after the 10-min stimulation protocol. A significant positive correlation was found between axial length of the eye and percent change in b-wave amplitude for the 10-min stimulation protocol. A rapid and a delayed b-wave time course responses were observed following 1 min and 10 min of blind spot stimulation, respectively. Overall, these results indicate that light stimulation of the blind spot for various durations elevates ON-bipolar cell activity in the retina and as such is assumed to reduce the myopic response. These findings could have implications for future myopia treatment.

Use of extended protocols with nonstandard stimuli to characterize rod and cone contributions to the canine electroretinogram.

In this study, we assessed several extended electroretinographic protocols using nonstandard stimuli. Our aim was to separate and quantify the contributions of different populations of retinal cells to the overall response, both to assess normal function and characterize dogs with inherited retinal disease. We investigated three different protocols for measuring the full-field flash electroretinogram-(1) chromatic dark-adapted red and blue flashes, (2) increasing luminance blue-background, (3) flicker with fixed frequency and increasing luminance, and flicker with increasing frequency at a fixed luminance-to assess rod and cone contributions to electroretinograms recorded in phenotypically normal control dogs and dogs lacking rod function. Temporal separation of the rod- and cone-driven responses is possible in the fully dark-adapted eye using dim red flashes. A- and b-wave amplitudes decrease at different rates with increasing background luminance in control dogs. Flicker responses elicited with extended flicker protocols are well fit with mathematical models in control dogs. Dogs lacking rod function demonstrated larger amplitude dark-adapted compared to light-adapted flicker responses. Using extended protocols of the full-field electroretinogram provides additional characterization of the health and function of different populations of cells in the normal retina and enables quantifiable comparison between phenotypically normal dogs and those with retinal disease.