Search Results (227)

Background: Full field electroretinography (ERG) is an essential tool for assessing retinal function and diagnosing retinal diseases. In recent years, mydriasis-free handheld ERG devices have emerged as portable, non-invasive alternatives to traditional ERG systems. Their main application has been in the screening and monitoring of diabetic retinopathy (DR), particularly in settings with limited access to standard ERG equipment and in pediatric populations where conventional testing may be difficult to perform. This review aims to evaluate the current evidence on handheld ERG devices in ocular diseases, with a focus on their reliability, diagnostic accuracy, and inherent limitations. Methods: A review was conducted to identify studies evaluating handheld ERG devices in diverse clinical settings, including retinal diseases, DR, pediatric populations, and conditions such as glaucoma. A comprehensive search of the Pubmed and Embase databases was performed for studies published up to December 2024. Search terms included “mydriasis free ERG”, “handheld ERG”, “portable ERG”, “RETeval”, “healthy subjects”, “retinal diseases”, “diabetic retinopathy”, “glaucoma”, and “pediatric diseases”, as well as relevant MeSH terms and synonyms. Case reports, conference abstracts, non-human studies, and letters were excluded. After screening titles and abstracts, additional studies not meeting the inclusion criteria were excluded. Of 279 records that were initially identified, 55 met the eligibility criteria and were included in the final review. Results were synthesized narratively due to heterogeneity in the study design, populations, and outcomes. Findings were organized thematically according to clinical context. Results: A total of 57 studies were included in the review: 19 conducted in healthy subjects, 13 in diabetic retinopathy, eight in selected retinopathies, eight in glaucoma, and 14 in pediatric cohorts. Five studies overlapped between groups due to shared populations or study designs. No meta-analysis was performed due to heterogeneity in study design and outcome measures; therefore, findings were summarized narratively across disease categories. Handheld ERG devices have been evaluated in healthy subjects, patients with DR, other retinal pathologies, glaucoma and pediatric cohorts. Evidence indicates that these devices provide a rapid, non-invasive assessment of retinal function and are particularly valuable where conventional ERG is difficult to implement and potentially well-suited for screening purposes. They show good sensitivity and reasonable specificity for detecting functional changes, making them suitable for screening purposes. However, limitations exist: reduced performance in detecting early-stage disease and cone dysfunction, risk of false positives, and variability in waveform morphology and amplitude compared with traditional ERG systems. Reproducibility challenges are noted among pediatric patients and individuals with poor fixation or unstable eye movements. These discrepancies highlight the need for establishing robust normative datasets for both healthy subjects and specific disease states. Conclusions: Handheld ERG devices provide a rapid, accessible and user-friendly option for retinal assessment. While not a replacement for conventional ERG, they serve as complementary tools, particularly in early disease and in contexts where standard testing is less feasible. Further research is required to refine testing protocols, improve diagnostic accuracy, and validate their application across a broader spectrum of ocular diseases. Full article

(1) Background: Modifications of histone methylation could alter chromatin structure and thereby have an impact on gene expressions. (2) Methods: To investigate whether ORY-1001 delay retinal photoreceptor degeneration, rd10 mice were intraperitoneally injected with ORY-1001 (0.075 mg/kg) every second day from the 14th to the 24th day after birth. Full-field electroretinogram detection (ff ERG), optical coherence tomography (OCT), visual behavioral testing, retinal tissue morphology observation, and protein expression detection experiments were performed on the 25th day. Simultaneously, ATAC-seq and RNA-seq were used to test the mice’s retinal tissues, and metabolomics detection and quantitative real-time polymerase chain reaction (qRT-PCR) were carried out. (3) Results: Compared with the rd10 group, in the treatment group, the function in the electroretinogram response and the visual behavioral responses were improved, the nuclear layer morphology of retinal tissue was reserved more, and the protein expression of H3K4me2 and CoREST was increased. Conjoint analysis of our ATAC-seq and RNA-seq results showed that chromatin accessibility was changed, as was gene expression which was involved in metabolism changes. In addition, the effector gene in the retina was Gnat1. (4) Conclusions: ORY-1001 delays retinal photoreceptor degeneration by inhibiting H3K4me2 demethylation in rd10 mice, which suggests that ORY-1001, as a novel epigenetic modifier, has potential for treating RP. Full article

Objectives: To evaluate the changes in retinal function and neural conduction along the visual pathways after 12 months of treatment with Citicoline oral solution in patients with open-angle glaucoma (OAG). Methods: In this randomized, prospective, double-blind study, 29 OAG patients were enrolled. Fifteen patients (Citicoline Group, 15 eyes) received Citicoline oral solution (Neurotidine^®, 500 mg/day), and 14 patients (Placebo Group, 14 eyes) received placebo for 12 months. Visual field (VF), pattern electroretinogram (PERG), visual evoked potentials (VEP), and Retinocortical Time (RCT) were assessed at baseline and after 6 and 12 months. Brain Diffusion Tensor Imaging (DTI)-Magnetic Resonance Imaging (MRI) was performed at baseline and at 12 months. Results: PERG, VEP, and RCT baseline values were comparable between groups (p > 0.01) at baseline. After 12 months of Citicoline treatment, significant (p < 0.01) increases in PERG P50–N95 and VEP N75-P100 amplitudes, and significant shortening of PERG P50, VEP P100 implicit times and RCT were observed. VEP implicit times shortening significantly correlated with the changes in VF Mean Deviation, and RCT shortening was associated with changes in DTI-MRI metrics in the lateral geniculate nucleus and on optic radiations, without reaching the level of significance. No significant changes were found in the Placebo Group. Conclusions: In OAG, Citicoline oral solution enhances retinal function likely through neuromodulation processes and changes post-retinal visual pathway connectivity. This could explain the improvement of visual field defects. Full article

American Staffordshire Terriers (ASTs) with a c.296G>A variant in ARSG develop progressive ataxia, cerebellar atrophy, and neuronal accumulation of autofluorescent storage material. Human subjects with ARSG variants exhibit hearing loss and rod–cone dystrophy without apparent other neurological involvement and arsg knockout mice exhibit progressive ataxia, lysosomal storage, and photoreceptor loss. Owners of 8 of 11 affected ASTs evaluated for the ARSG risk variant reported observing visual impairment in their dogs, suggesting that the canine disease may involve retinal dysfunction consistent with human subjects and mice with ARSG variants. To assess whether this might be the case, electroretinography was performed on four affected and three unaffected ASTs. Three affected dogs that were exhibiting signs of ataxia had attenuated electroretinogram (ERG) amplitudes indicative of rod and cone photoreceptor dysfunction, while ERG responses were not attenuated in a younger dog that had not yet shown signs of ataxia or visual impairment. Autofluorescent inclusions were observed in the retinal pigment epithelium and retinal ganglion cell layer of two affected dogs that were euthanized due to neurological disease progression. The results from these cases indicate that standardized electroretinography can be used to detect retinal dysfunction in dogs with the ARSG-related disorder and in other disorders in which dogs exhibit apparent impairment in visually mediated behavior. Full article

Background/Objectives: Herein, we report the clinical cases of two affected first-degree relatives from a family with highly variable macular dystrophy, expanding the known phenotype spectrum with mutations in the thyroid hormone receptor beta gene (THRB). Methods: Multimodal retinal imaging included wide-field fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) imaging, performed alongside functional testing (visual fields, electroretinogram (ERG)), metabolic blood analyses, and genetic testing of both cases. Results: A 67-year-old female patient presenting with reading difficulties and visual impairment since childhood was referred for evaluation and counseling for potential treatment options. Extensive ophthalmologic examination, including multimodal retinal imaging and functional testing, revealed an occult macular dystrophy. Her 39-year-old son reported similar visual symptoms in combination with mild photophobia. In multimodal retinal imaging, he also showed a macular dystrophy but with a vitelliform phenotype. Genetic testing identified the heterozygous pathogenic variant c.283+1G>A in the thyroid hormone receptor beta gene (THRB) in both patients. Conclusions: This report shows a high intrafamilial variability of macular dystrophy caused by a heterozygous THRB mutation, which has only recently been recognized as a cause of macular dystrophy. Here, we describe a novel clinical presentation characterized by a vitelliform lesion, expanding the phenotypic spectrum of THRB-associated macular dystrophy. Full article

PITPNM3 has been identified as a crucial gene associated with various phenotypes of retinal disease in humans; however, detailed mechanisms through which PITPNM3 mutations result in these conditions are not fully understood. In this study, we aimed to generate such a preclinical mouse model and evaluate its relevance to human PITPNM3-related conditions. Heterozygous mice were bred to obtain a homozygous genotype, aiming to mimic the human genetic condition. Subsequent phenotyping and genetic segregation analyses were conducted along with electrophysiological studies and histological examinations. Full-field electroretinogram analysis revealed a reduced cone response although the severity was not as pronounced as observed in humans with PITPNM3-related conditions. Histologically, the retinal structure appeared largely unchanged, indicating a discordance between functional impairment and morphological changes. In our preclinical mouse model, the observed phenotypic changes were not as severe as those found in humans with PITPNM3-related conditions and this discrepancy points to a potentially different disease progression trajectory in the mouse model. These findings highlight the importance of longer follow-up periods in such studies and the need for further research to elucidate the genotype–phenotype relationship in PITPNM3. Full article

Visual impairments pose a significant global health challenge, and visual electrophysiological (EP) acquisition plays a pivotal role in diagnosing ophthalmic diseases. However, traditional electrodes still encounter limitations such as inadequate mechanical adaptability and reusability. This study proposes a stretchable and transparent electrode (STE) consisting of a conductive paste/indium tin oxide layer on a polymethyl methacrylate substrate. Leveraging an island–bridge design, the STE renders reliable performance even after being subjected to 1000 cycles of 25% lateral strain and 18% diagonal strain, exhibiting exceptional mechanical flexibility and realizing seamless attachment to soft tissue. Furthermore, optimized conductive paste layer thickness yields a signal-to-noise ratio comparable to commercial electrodes, achieving equivalent performance to Ag/AgCl electrodes in electroretinogram (ERG), electrooculography (EOG), and visual evoked potential (VEP) acquisition. The STE’s mechanical suitability and inconspicuous features hold significant potential for widespread clinical adoption in ophthalmic diagnostics and personalized eye healthcare, offering improved comfort, reusability, and diagnostic precision. Full article

Diabetic retinopathy (DR) is a major source of retinal disease and vision loss worldwide. Current treatments fail to address the loss of neurons and are associated with significant side effects. Here, we investigated whether retinal progenitor cells (RPCs) could improve anatomic and functional outcomes in a rat model of DR. Male Long Evans (LE) rats were given streptozotocin (STZ), and the induction of diabetes was confirmed prior to the intravitreal injection of RPCs, either allogeneic (no immunosuppression) or human (with cyclosporin A), at 1 week post-induction. Animals were tested at 6 weeks post-induction via electroretinogram (ERG), optomotor response (OR), and contrast sensitivity (CS). Retinas were harvested post-mortem, 8 weeks post-STZ induction, and analyzed using immunohistochemistry (IHC). In rat RPC-treated eyes, ERG (b-wave, oscillatory potentials), OR, and CS all showed a positive effect for cell treatment versus controls. IHC showed a markedly diminished extravasation of albumin, a decreased VEGF expression, and an improved morphology in cellular and synaptic layers. Human RPC-treated eyes replicated a subset of these results. Together, this provides evidence of both anatomic and functional treatment effects in a rat model of DR, encompassing retinal neuroprotection as well as improved vascular integrity, thereby supporting the further investigation of intravitreal RPCs for the treatment of this condition. Full article

Background: Vitamin A deficiency (VAD) can occur due to malnutrition or reduced intestinal absorption, such as in short bowel syndrome (SBS). The main causes of SBS in adults include post-radiotherapy and surgery (e.g., repeated bowel resections). VAD mostly involves rods producing nyctalopia and reduced amplitudes of the electroretinogram (ERG) in scotopic conditions, with a characteristic negative ERG pattern (b/a < 1). Case Report: We report a 67-year-old woman with a history of gastric adenocarcinoma and several surgeries, who developed a progressive 3-month clinical picture of night blindness. Results: Urgent blood tests, biomicroscopy, intraocular pressure measurements, fundoscopy, and a cranial MRI were all normal. Visual evoked potentials showed increased latencies in both eyes, and full-field ERG showed a significant alteration in responses under scotopic conditions, and, to a lesser extent, under photopic conditions. Laboratory tests confirmed VAD, probably due to post-surgery and radiotherapy SBS. After parenteral vitamin replacement, VAD was clinically, analytically, and electroretinographically resolved. Discussion: VAD diagnosis is based on history, neuro-ophthalmological examination, and serum levels of retinol (<0.3 µg/mL) and/or retinol/retinol-binding protein (<0.8). In cases of a history of SBS, acquired nyctalopia, negative ERG, and clinical, analytical, and electroretinographic improvement with restoration of vitamin A levels, VAD should be suspected. ERG is crucial for early and appropriate management. Conclusions: As far as we know, this is the first reported VAD case secondary to SBS following surgical resections and radiotherapy of gastric adenocarcinoma with neuro-ophthalmological, laboratory, and electroretinographic monitoring of VAD recovery. Full article

The clinical electroretinogram (ERG) is a non-invasive diagnostic test used to assess the functional state of the retina by recording changes in the bioelectric potential following brief flashes of light. The recorded ERG waveform offers ways for diagnosing both retinal dystrophies and neurological disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Parkinson’s disease. In this study, different time-series-based machine learning methods were used to classify ERG signals from ASD and typically developing individuals with the aim of interpreting the decisions made by the models to understand the classification process made by the models. Among the time-series classification (TSC) algorithms, the Random Convolutional Kernel Transform (ROCKET) algorithm showed the most accurate results with the fewest number of predictive errors. For the interpretation analysis of the model predictions, the SHapley Additive exPlanations (SHAP) algorithm was applied to each of the models’ predictions, with the ROCKET and KNeighborsTimeSeriesClassifier (TS-KNN) algorithms showing more suitability for ASD classification as they provided better-defined explanations by discarding the uninformative non-physiological part of the ERG waveform baseline signal and focused on the time regions incorporating the clinically significant a- and b-waves of the ERG. With the potential broadening scope of practice for visual electrophysiology within neurological disorders, TSC may support the identification of important regions in the ERG time series to support the classification of neurological disorders and potential retinal diseases. Full article

Blue-light stimulation of the optic disc has been suggested as a means of myopia prevention by activating dopaminergic amacrine cells via intrinsically photosensitive retinal ganglion cells. This prospective, adequately powered study investigated this approach by examining its effects on pattern electroretinogram (PERG) N95 amplitude and choroidal thickness (ChT), established biomarkers associated with retinal ganglion cell function and myopia progression, respectively. Forty-six healthy adults received one minute of 450 nm blue-light stimulation to either the optic disc or central retina of the right eye, with the fellow left eye serving as control. PERG responses were measured before and 20 min after stimulation (N = 15 per stimulation location), while ChT, using swept-source optical coherence tomography images, was measured before, 20, and 60 min after stimulation (N = 8 per stimulation location). Only retinal stimulation significantly increased PERG N95 amplitude (baseline 16.16 µV, post-stimulation 17.61 µV [p = 0.01]), whereas optic disc stimulation did not (baseline 18.71 µV, post-stimulation 18.81 µV [p = 0.76]). Neither optic disc nor retinal stimulation significantly changed ChT at any time point. No significant differences were observed between myopic and non-myopic participants. Our findings do not support the hypothesis that short-duration blue-light stimulation of the optic disc is a viable strategy to activate retinal dopaminergic pathways for myopia prevention. Full article

Purpose: We previously reported that the systemic administration of preprogrammed mouse hematopoietic bone marrow-derived progenitor cells (HSPCs) improved visual function and restored a functional retinal pigment epithelial (RPE) layer. Here, we investigated the potential impact of donor vs. host age on systemic cellular therapy in a murine model of retinal degeneration. Methods: HSPCs from young (8 weeks) and old (15 months) mice were programmed ex vivo with a lentiviral vector expressing the RPE65 gene (LV-RPE65) and systemically administering into young or old SOD2 KD mice. Visual loss and pathological changes were evaluated by electroretinogram (ERG), optical coherence tomography (OCT), histology, and immunohistochemistry. Results: Old donor HSPCs administered to old manganese superoxide dismutase (SOD2) knockdown (KD) recipient mice offered the least benefit. This was exemplified by the reduced recruitment and incorporation of LV-RPE65 HSPC into the RPE layer, as well as decreased improvement in visual function, retinal thinning, and limited reduction in oxidative damage and microglial activation. LV-RPE65 HSPC from young mice incorporated into the RPE layer of old SOD2 KD mice, though to a lesser extent than young cells administered to young hosts, offered some level of protection. By contrast, LV-RPE65 HSPCs from old mice, located to the subretinal space of young host mice, reduced visual loss, although some retinal pathology was observed. Conclusions: The administration of LV-RPE65 HSPC from old donors to old SOD2 KD mice offered the least improvement. Translational Relevance: Our findings highlight how both donor and recipient age impact the success of HSPC-based retinal therapy and using cells from aged donors for AMD treatment may have some limitations. Full article

Introduction: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign proliferation of the melanin-producing retinal pigment epithelium (RPE). Although often a benign and incidental finding, multifocal CHRPE may mimic lesions associated with familial adenomatous polyposis (FAP). Case Description: We describe an 8-year-old girl presenting with optic disc pallor and widespread multifocal bear track CHRPE observed bilaterally on dilated fundoscopy. Fundus autofluorescence (FAF) imaging showed uniform areas of hypoautofluorescence corresponding to the bear track lesions. Spectral domain optical coherence tomography (SD-OCT) demonstrated normal lamination without atrophy. The full-field electroretinogram (ffERG) was within normal limits. Whole-genome sequencing (WGS) revealed a likely pathogenic heterozygous variant in the STAG2 gene (c.3222dup, p.Ser1075IlefsTer12). Conclusions: We present a rare case of bilateral, panretinal bear track CHRPE in a child with a likely pathogenic variant in STAG2. Using multimodal imaging, we contrast bear track lesions of the retina with FAP-associated CHRPE. We also present possible ophthalmic manifestations in carriers of pathogenic STAG2 variants. Full article

Transcorneal electrical stimulation (TES) is a promising treatment for several retinal degenerative diseases (RDDs). TES involves the application of a controlled electrical current to the anterior surface of the cornea, aimed at activating the retina and posterior ocular structures. Dawson–Trick–Litzkow (DTL) and ERG-JET electrodes are among the most widely used for TES. However, their continuous metallic surface design limits spatial resolution and the ability to perform selective ES. In this work, we present the development of a transcorneal electrical stimulation (TES) electrode that, unlike conventional electrodes, enables spatially selective TES. The proposed electrode design consists of an array of 20 independent microelectrodes distributed across the central and paracentral regions of the cornea. The fabrication process combines surface micromachining and flexible electronics technologies, employing only three structural materials: aluminum (Al), titanium (Ti), and polyimide (PI). This material selection is critical for achieving a simplified, reproducible, and low-cost fabrication process. The fabricated electrode was validated through electrical and electrochemical testing. The results show a relatively high electrical conductivity of Al/Ti structures, low electrochemical impedance values—ranging from 791 kΩ to 1.75 MΩ for the clinically relevant frequency range (11 to 30 Hz)—and a high charge storage capacity of 1437 mC/cm². The electrode capacity for electrical signal transmission was demonstrated through in vitro testing. Finally, the applicability of the TES electrode for electroretinogram (ERG) recording was evaluated by measuring its optical transmittance across the visible wavelength range. Full article

Background/Objectives: The aim of this study was to evaluate the relationship between foveal avascular zone (FAZ) enlargement, retinal ganglion cell (RGC) dysfunction, and structural retinal measurements in glaucoma suspects (GS), using pattern electroretinogram (PERG) and optical coherence tomography angiography (OCTA) parameters. Methods: Thirty-one eyes (20 subjects) of GS status underwent comprehensive ophthalmologic evaluation including steady-state PERG, optical coherence tomography (OCT), and OCTA. FAZ area was measured using ImageJ software (version 1.54p), and PERG parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) were analyzed. Partial correlation analyses were performed to assess associations between FAZ area, PERG parameters, and structural metrics including retinal nerve fiber layer (RNFL), ganglion cell layer–inner plexiform layer (GCL + IPL), and macular thickness. Results: After controlling for age, sex, central corneal thickness (CCT), intraocular pressure (IOP), and spherical equivalent, partial correlation analysis showed that FAZ area was significantly associated with both lower Magnitude (r < −0.503, p < 0.05) and MagnitudeD (r < −0.507, p < 0.05) values. PERG parameters were significantly correlated with superior and average RNFL thickness, as well as superior and superior temporal GCL + IPL thickness. FAZ area was significantly associated with multiple GCL + IPL and macular thickness sectors, but not with RNFL thickness. Conclusions: FAZ enlargement is significantly associated with RGC dysfunction and inner retinal layer thinning in GS. Full article