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In this work, we introduce a diurnal rodent, the Mongolian gerbil (Meriones unguiculatus) (MG) as an alternative to study retinal cone system physiology and pathophysiology in mice. The cone system is of particular importance, as it provides high-acuity and color vision and its impairment in retinal disorders is thus especially disabling. Despite their nocturnal lifestyle, mice are currently the most popular animals to study cone-related diseases due to the high availability of genetically modified models. However, the potential for successful translation of any cone-related results is limited due to the substantial differences in retinal organization between mice and humans. Alternatively, there are diurnal rodents such as the MG with a higher retinal proportion of cones and a macula-like specialized region for improved visual resolution, the visual streak. The focus of this work was the evaluation of the MG’s cone system functionality using full-field electroretinography (ERG), together with a morphological assessment of its retinal/visual streak organization via angiography, optical coherence tomography (OCT), and photoreceptor immunohistochemistry. We found that rod system responses in MGs were comparable or slightly inferior to mice, while in contrast, cone system responses were much larger, more sensitive, and also faster than those in the murine counterparts, and in addition, it was possible to record sizeable ON and OFF ERG components. Morphologically, MG cone photoreceptor opsins were evenly distributed throughout the retina, while mice show a dorsoventral M- and S-opsin gradient. Additionally, each cone expressed a single opsin, in contrast to the typical co-expression of opsins in mice. Particular attention was given to the visual streak region, featuring a higher density of cones, elongated cone and rod outer segments (OSs), and an increased thickness of the inner and outer retinal layers in comparison to peripheral regions. In summary, our data render the MG a supreme model to investigate cone system physiology, pathophysiology, and to validate potential therapeutic strategies in that context.

The electroretinogram (ERG) is a clinical test that records the retina's electrical response to light. Analysis of the ERG signal offers a promising way to study different retinal diseases and disorders. Machine learning-based methods are expected to play a pivotal role in achieving the goals of retinal diagnostics and treatment control. This study aims to improve the classification accuracy of the previous work using the combination of three optimal mother wavelet functions. We apply Continuous Wavelet Transform (CWT) on a dataset of mixed pediatric and adult ERG signals and show the possibility of simultaneous analysis of the signals. The modern Visual Transformer-based architectures are tested on a time-frequency representation of the signals. The method provides 88% classification accuracy for Maximum 2.0 ERG, 85% for Scotopic 2.0, and 91% for Photopic 2.0 protocols, which on average improves the result by 7.6% compared to previous work. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation. Animals: Thirty-three client-owned German Spitz dogs were included. Procedures: All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced. Results: Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study. Conclusion: We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is the most typical cause of permanent blindness. POAG, or primary open angle glaucoma, is the most common type. The pattern electroretinogram (PERG) has become a promising technique for detecting glaucoma early-on. The goal of this study was to assess the ability of PERG to diagnose POAG, especially in early, difficult-to-diagnose cases in comparison with other already established diagnostic methods.Methods: 150 participants (300 eyes) were enrolled in a cross-sectional study at ophthalmology department at Menoufia University Hospital in August 2022 to February 2023. All recruited participants underwent comprehensive ophthalmological and PERG exams. The studied eyes were divided into three groups as 100 normal eyes (Group I), 100 eyes with preperimetric glaucoma (Group II), and 100 eyes with established perimetric glaucoma (Group III).Results: OCT-RNFL average thickness had a significant positive correlation with P50 latency (r=0.289, p=0.041) or P50 amplitude (r=0.302, p=0.018) and N95 amplitude (r=0.640, p=0.001) among group (II). Also, RNFL thickness had negative correlation with P50 amplitude (r= − 0.268, p=0.043) among group (III). RNFL thickness and P50 and N95 amplitude showed highest AUC values in detecting preperimetric glaucomatous eyes vs normal eyes (AUC=0.927, 0.952, 904), and for detecting established perimetric glaucomatous eyes vs normal eyes (AUC=1.00, 0.957, 0.983 respectively) compared with VF MD which showed AUC (0.458 and 0.901 respectively).Conclusion: Glaucoma patients exhibit PERG alterations (comparable to RNFL thickness changes) so, it could be used as an accurate diagnostic method in POAG. Because PERG alterations occur before visual field abnormalities, it could be relied on as an early diagnostic tool in preperimetric glaucoma. We can use both RNFL thickness assessment by OCT with PERG parameters as complementary tests for accurate diagnosis of preperimetric glaucoma which represents the most difficult diagnostic challenge in glaucoma diagnosis. [ABSTRACT FROM AUTHOR]

To explore fundus autofluorescence (FAF) imaging as an alternative to electroretinography as a noninvasive, quick, and readily interpretable method to predict disease progression in Stargardt disease (STGD). Retrospective case series of patients who attended Moorfields Eye Hospital (London, United Kingdom). Patients with STGD who met the following criteria were included: (1) biallelic disease-causing variants in ABCA4 , (2) electroretinography testing performed in house with an unequivocal electroretinography group classification, and (3) ultrawidefield (UWF) FAF imaging performed up to 2 years before or after the electroretinography. Patients were divided into 3 electroretinography groups based on retinal function and 3 FAF groups according to the extent of hypoautofluorescence and retinal background appearance. Fundus autofluorescence images of 30° and 55° were reviewed subsequently. Electroretinography and FAF concordance and its association with baseline visual acuity (VA) and genetics. Two hundred thirty-four patients were included in the cohort. One hundred seventy patients (73%) were in electroretinography and FAF groups of the same severity, 33 (14%) were in a milder FAF than electroretinography group, and 31 (13%) were in a more severe FAF than electroretinography group. Children < 10 years of age (n = 23) showed the lowest electroretinography and FAF concordance at 57% (9 of the 10 with discordant electroretinography and FAF showed milder FAF than electroretinography), and adults with adult onset showed the highest (80%). In 97% and 98% of patients, 30° and 55° FAF imaging, respectively, matched with the group defined by UWF FAF. We demonstrated that FAF imaging is an effective method to determine the extent of retinal involvement and thereby inform prognostication by comparing FAF with the current gold standard of electroretinography. In 80% of patients in our large molecularly proven cohort, we were able to predict if the disease was confined to the macula or also affected the peripheral retina. Children assessed at a young age, with at least 1 null variant, early disease onset, poor initial VA, or a combination thereof may have wider retinal involvement than predicted by FAF alone, may progress to a more severe FAF phenotype over time, or both. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

This study quantified age-related changes to retinal autophagy using the CAG-RFP-EGFP-LC3 autophagy reporter mice and considered how aging impacts autophagic responses to acute intraocular pressure (IOP) stress. IOP was elevated to 50 mm Hg for 30 minutes in 3-month-old and 12-month-old CAG-RFP-EGFP-LC3 (n = 7 per age group) and Thy1-YFPh transgenic mice (n = 3 per age group). Compared with younger eyes, older eyes showed diminished basal autophagy in the outer retina, while the inner retina was unaffected. Autophagic flux (red:yellow puncta ratio) was elevated in the inner plexiform layer. Three days following IOP elevation, older eyes showed poorer functional recovery, most notably in ganglion cell responses compared to younger eyes (12 months old: −33.4 ± 5.3% vs. 3 months mice: −13.4 ± 4.5%). This paralleled a reduced capacity to upregulate autophagic puncta volume in the inner retina in older eyes, a response that was seen in younger eyes. Age-related decline in basal and stress-induced autophagy in the retina is associated with greater retinal ganglion cells' susceptibility to IOP elevation. [ABSTRACT FROM AUTHOR]

Purpose. To explore the value of visual electrophysiology in evaluating the fundus function of mature cataract patients. Methods. 124 mature cataract patients (153 eyes) were examined before cataract surgery; the examinations included best corrected visual acuity (BCVA), pattern visual evoked potential (PVEP), full-field electroretinogram (ffERG), and multifocal electroretinogram (mfERG). According to the postoperative fundus conditions, the subjects were divided into two groups: the no fundus disease group and the fundus disease group. Approximately one month after the operation, BCVA was measured, and visual electrophysiology was performed on subjects who had a stable fundus condition and had not received treatment for fundus disease. Results. One month after cataract surgery, BCVA ≤ 0.3 logMAR was found in 60 eyes (96.8%) without fundus disease and 59 eyes (64.8%) with fundus disease. Compared with the group without fundus disease, the preoperative electrophysiological examination of the group with fundus disease showed that the amplitude of ffERG waves and the amplitude density of the P1 wave in the 2nd to 5th rings of mfERG were decreased (all P < 0.05). ffERG and mfERG can be used for differential diagnosis of fundus disease (all P < 0.05), while PVEP has no significant diagnostic value for fundus disease (all P > 0.05). In the group without fundus disease, the amplitude of the PVEP 15′ P100 wave and the amplitude of dark-adapted (DA) 0.01 b-wave, DA 3.0 a-wave, and DA 10.0 a-wave were negatively correlated with postoperative logMAR BCVA (all P < 0.05). In the group with fundus disease, the amplitude of PVEP and ffERG and the amplitude density of mfERG were negatively correlated with postoperative logMAR BCVA (all P < 0.05). In the eyes of cortical cataracts, some parameters of PVEP, ffERG, and mfERG were significantly different before and after surgery. In the eyes of nuclear cataracts, some parameters of ffERG and mfERG were significantly different before and after surgery. In the eyes of posterior subcapsular cataracts, some parameters of PVEP and ffERG were significantly different before and after surgery. Conclusions. ffERG and mfERG can be used to detect fundus disease in mature cataract patients. The preoperative visual electrophysiological examination has high clinical value in predicting postoperative vision of mature cataract patients with fundus disease. Different types of cataracts have different effects on electrophysiological examination results. When interpreting the electrophysiological report, it is necessary to consider the existence of cataracts. This trial is registered with 2019-K068. [ABSTRACT FROM AUTHOR]

Nutraceuticals are natural substances whose anti-oxidant and anti-inflammatory properties may be used to treat retinal pathologies. Their efficacy is limited by poor bioavailability, which could be improved using nanocarriers. Lisosan G (LG), a fermented powder from whole grains, protects the retina from diabetic retinopathy (DR)-induced damage. For this study, we tested whether the encapsulation of LG in liposomes (LipoLG) may increase its protective effects. Diabetes was induced in mice via streptozotocin administration, and the mice were allowed to freely drink water or a water dispersion of two different doses of LG or of LipoLG. Electroretinographic recordings after 6 weeks showed that only the highest dose of LG could partially protect the retina from diabetes-induced functional deficits, while both doses of LipoLG were effective. An evaluation of molecular markers of oxidative stress, inflammation, apoptosis, vascular endothelial growth factor, and the blood–retinal barrier confirmed that the highest dose of LG only partially protected the retina from DR-induced changes, while virtually complete prevention was obtained with either dose of LipoLG. These data indicate that the efficacy of LG in contrasting DR is greatly enhanced by its encapsulation in liposomes and may lay the ground for new dietary supplements with improved therapeutic effects against DR. [ABSTRACT FROM AUTHOR]

The kallikrein-kinin system (KKS) contributes to vascular inflammation and neovascularization in age-related macular degeneration (AMD), particularly via the kinin B1 receptor (B1R). The aim of the present study was to determine the protective effects of the topical administration of the B1R antagonist (R-954) on inflammation, neovascularization, and retinal dysfunction in a murine model of neovascular AMD. Choroidal neovascularization (CNV) was induced in C57BL6 mice using an argon laser. A treatment with ocular drops of R-954 (100 μg/15 μL, twice daily in both eyes), or vehicle, was started immediately on day 0, for 7, 14, or 21 days. CNV, invasive microglia, and B1R immunoreactive glial cells, as well as electroretinography alterations, were observed within the retina and choroid of the CNV group but not in the control group. The staining of B1R was abolished by R-954 treatment as well as the proliferation of microglia. R-954 treatment prevented the CNV development (volume: 20 ± 2 vs. 152 ± 5 × 104 µm3 in R-954 vs. saline treatment). R-954 also significantly decreased photoreceptor and bipolar cell dysfunction (a-wave amplitude: −47 ± 20 vs. −34 ± 14 µV and b-wave amplitude: 101 ± 27 vs. 64 ± 17 µV in R-954 vs. saline treatment, day 7) as well as angiogenesis tufts in the retina. These results suggest that self-administration of R-954 by eye-drop treatment could be a promising therapy in AMD to preserve retinal health and vision. [ABSTRACT FROM AUTHOR]

In this report, we present a case of an ocular syphilis who presented with findings similar to acute zonal occult outer retinopathy. Ocular syphilis may present with keratitis, uveitis, retinal vasculitis, scleritis, optic neuropathy and, rarely, acute zonal occult outer retinopathy. It should be kept in mind that syphilis is a mimicry disease, may cause atypical clinical findings and can be treated with penicillin. [ABSTRACT FROM AUTHOR]

We aimed to report the early results of transcorneal electrical stimulation (TES) therapy in three patients with cone dystrophy. A detailed ophthalmic examination including ishihara color vision test, electroretinography (ERG), multifocal ERG (mf-ERG), optical coherence tomography and the quality of life (QoL) of low-vision patients questionnaire was performed before and after the TES therapy. After the TES therapy, favorable outcomes were obtained from the patients. Increase in visual acuity and color vision levels, improvement in photopic ERG and mf-ERG responses were noted. Furthermore, the QoL questionnaire scores increased remarkable in all patients. Objective and subjective promising results obtained with TES in these patients suggest that TES therapy may be a new treatment method in retinal dystrophy cases. [ABSTRACT FROM AUTHOR]

Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar cells in the retina. Electroretinography (ERG) is a diagnostic tool that measures the electrical activity of the retina in response to light stimuli, and it can help to determine the function of these cells. A normal ERG response consists of two waves, the a-wave and the b-wave, which reflect the activity of the photoreceptor cells and the bipolar and Muller cells, respectively. Despite the growing availability of next-generation sequencing (NGS) technology, identifying the precise genetic mutation causing an IRD can be challenging and costly. However, certain types of IRDs present with unique ERG features that can help guide genetic testing. By combining these ERG findings with other clinical information, such as on family history and retinal imaging, physicians can effectively narrow down the list of candidate genes to be sequenced, thereby reducing the cost of genetic testing. This review article focuses on certain types of IRDs with unique ERG features. We will discuss the pathophysiology and clinical presentation of, and ERG findings on, these disorders, emphasizing the unique role ERG plays in their diagnosis and genetic testing. [ABSTRACT FROM AUTHOR]

PURPOSE: Achromatopsia is a rare stationary retinal disorder that primarily affects the cone photoreceptors. Individuals with achromatopsia present with photophobia, nystagmus, reduced visual acuity (VA), and color blindness. Multiple genes responsible for achromatopsia have been identified (e.g. cyclic nucleotide-gated channel subunit alpha 3 [CNGA3] and activating transcription factor 6). Studies have assessed the role of gene therapy in achromatopsia. Therefore, for treatment and prevention, the identification of phenotypes and genotypes is crucial. Here, we described the clinical manifestations and genetic mutations associated with achromatopsia in patients from Saudi Arabia. METHODS: This case series study included 15 patients with clinical presentations, suggestive of achromatopsia, who underwent ophthalmological and systemic evaluations. Patients with typical achromatopsia phenotype underwent genetic evaluation using whole-exome testing. RESULTS: All patients had nystagmus (n = 15) and 93.3% had photophobia (n = 14). In addition, all patients (n = 15) had poor VA. Hyperopia with astigmatism was observed in 93.3% (n = 14) and complete color blindness in 93.3% of the patients (n = 14). In the context of family history, both parents of all patients (n = 15) were genetic carriers, with a high consanguinity rate (82%, n = 9 families). Electroretinography showed cone dysfunction with normal rods in 66.7% (n = 10) and both cone–rod dysfunction in 33.3% (n = 5) patients. Regarding the genotypic features, 93% of patients had variants in CNGA3 (n = 14) categorized as pathogenic Class 1 (86.7%, n = 13). Further, 66.7% (n = 10) of patients also harbored the c.661C>T DNA variant. Further, the patients were homozygous for these mutations. Three other variants were also identified: c.1768G>A (13.3%, n = 2), c.830G>A (6.6%, n = 1), and c. 822G >T (6.6%, n = 1). CONCLUSION: Consanguinity and belonging to the same tribe are major risk factors for disease inheritance. The most common genotype was CNGA3 with the c.661C>T DNA variant. We recommend raising awareness among families and providing genetic counseling for this highly debilitating disease. [ABSTRACT FROM AUTHOR]

Background: We investigated whether the photopic negative response (PhNR) in the electroretinogram (ERG) was affected in Parkinson's disease (PD) patients and whether it was associated with retinal changes on optical coherence tomography (OCT). Methods: Thirty-two patients with PD and 31 age and sex-matched healthy controls from a single tertiary centre were included in the study. Hoehn and Yahr scale scores and the presence of REM sleep behaviour were recorded. PhNR, a-wave and b-wave responses in photopic ERG (red on blue background) and retinal layer thicknesses in OCT were obtained. Results: The mean age was 61 ± 10.4 in the PD group (female/male: 18/14) and 60.9 ± 7 in the control group (female/male: 18/13). The amplitudes of the PhNR, a- and b-waves in the ERG were significantly decreased in the PD group, but the implicit times were not significantly different. BCVA was significantly correlated with Hoehn and Yahr scores (p < 0.001, r = − 0.596). There was a significant correlation between BCVA and a-wave amplitude (p = 0.047, r = − 0.251). On OCT analysis, the thickness of the nasal INL was increased, and the temporal and inferior OPL and temporal peripapillary RNFL were decreased in the PD group compared to healthy controls (p = 0.032, p = 0.002, p = 0.016 and p = 0.012, respectively). Conclusion: This study demonstrated reduced a-wave, b-wave and PhNR-wave amplitudes on ERG measurements in PD patients. These findings suggest that the whole ERG response, not just the PhNR, is attenuated in patient with PD, suggesting a possible involvement of the visual system in the disease. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA. Methods: Four experimental groups were studied in male rats: Naturally born rats as controls (CTL), naturally born rats injected s.c. with 50 µL of 330 nmols/L zr17-2 (ZR), animals that were exposed to PA for 20 min at 37°C (PA), and rats that were exposed to PA and injected with zr17-2 (PA-ZR). Forty-five days after treatment, animals were subjected to electroretinography. In addition, morphological techniques (TUNEL, H&E, multiple immunofluorescence) were applied to the retinas. Results: A reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram (ERG) was detected in PA animals. Treatment with zr17-2 resulted in a significant amelioration of these parameters (p < 0.01). In PA animals, a large number of apoptotic cells was found in the GCL. This number was significantly reduced by treatment with the small molecule (p < 0.0001). In a similar way, the thickness of the inner retina and the intensity of GFAP immunoreactivity (gliosis) increased in PA retinas (p < 0.0001). These parameters were corrected by the administration of zr17-2 (p < 0.0001). Furthermore, injection of the small molecule in the absence of PA did not modify the ERG nor the morphological parameters studied, suggesting a lack of toxicity. Discussion: In conclusion, our results indicate that a single s.c. injection of zr17-2 in asphyctic neonates may provide a novel and efficacious method to prevent the visual sequelae of PA. [ABSTRACT FROM AUTHOR]

Background: Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug. Objectives: To identify structural or functional changes in the retina and optic nerve in patients on chronic amiodarone therapy without visual complaints. Methods: This observational study included 15 eyes of 15 patients with cardiac arrythmia on chronic amiodarone treatment and 15 healthy matched subjects as a control group. All subjects underwent electrophysiological tests [pattern visual evoked potential (PVEP), pattern electroretinogram (PERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) and angiography (OCTA)]. Results: There were no statistically significant differences between the two groups regarding the PVEP, PERG, and the mfERG parameters. Macular and optic nerve head OCT and OCTA have not shown statistically significant differences except for the morphological parameters of the optic disc (p = 0.008 for the horizontal and p = 0.013 for vertical cup/disc ratio and p = 0.045 for rim area). Conclusion: Patients on chronic amiodarone therapy have not shown evident structural or functional changes in the retinal or optic nerve as demonstrated by electrophysiological tests, OCT, and OCTA results compared to controls. [ABSTRACT FROM AUTHOR]

The complex nature of rod and cone photoreceptors and the light-evoked responsivity of bipolar cells in the mature rodent retina have been well characterized. However, little is known about the emergent light-evoked response properties of the mouse retina and the role light plays in shaping these emergent responses.We have previously demonstrated that the outer retina is responsive to green light as early as postnatal day 8 (P8). Here, we characterize the progression of both photoreceptors (rods and cones) and bipolar cell responses during development and into adulthood using ex vivo electroretinogram recordings. Our data show that the majority of photoreceptor response at P8 originates from cones and that these outputs drive second-order bipolar cell responses as early as P9. We find that the magnitude of the photoresponse increases concurrently with each passing day of postnatal development and that many functional properties of these responses, as well as the relative rod/cone contributions to the total light-evoked response, are age dependent.We compare these responses at eye opening and maturity to age-matched animals raised in darkness and found that the absence of light diminishes emergent and mature cone-to-bipolar cell signaling. Furthermore, we found cone-evoked responses to be significantly slower in dark-reared retinas. Together, this work characterizes the developmental photoresponsivity of the mouse retina while highlighting the importance of properly timed sensory input for the maturation of the first visual system synapse. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the electrophysiological effects of hyperbaric oxygen treatment (HBOT) on the retina after ten sessions in healthy eyes. This prospective, interventional study evaluated forty eyes of twenty patients who were treated with HBOT of ten sessions with the diagnosis of an extraocular health problem. All patients underwent a complete ophthalmologic examination, including assessments of best-corrected visual acuity (BCVA), slit-lamp and pupil-dilated fundus examinations, full-field electroretinography (ffERG) measurements before and after HBOT within 24 h of the 10th session. The ffERG was recorded according to the International Society for Clinical Electrophysiology of Vision protocol using the RETI-port system. The mean age of patients was 40.5 years ranging from 20 to 59 years. Thirteen patients were administered HBOT for avascular necrosis, six patients for sudden hearing loss, and one patient for chronic osteomyelitis of the vertebra. BCVA acuity was 20/20 in all eyes. The mean spherical refractive was 0.56 dioptre (D), and the mean cylindrical refractive error was 0.75 D. Dark-adapted b-wave amplitude in 3.0 ERG was the only variable for the b-wave that showed a statistically significant decrease (p = 0.017). The amplitude of the a-waves in dark-adapted 10.0 ERG and light-adapted 3.0 ERG reduced significantly (p = 0.024, p = 0.025). The amplitude of N 1-P 1 in light-adapted 30 Hz Flicker ERG also demonstrated a statistically significant decrease (p = 0.011). Implicit times did not differ significantly in any of the ffERG data (p > 0.05). HBOT caused the deterioration of a-wave and b-wave amplitudes in ffERG after ten treatment sessions. The results showed that photoreceptors were adversely affected in the short term after HBOT treatment. [ABSTRACT FROM AUTHOR]

To understand RS1 gene interaction networks in the X-linked retinoschisis (XLRS) mouse retina (Rs1-/y), we analyzed the transcriptome by RNA sequencing before and after in vivo expression of exogenous retinoschisin (RS1) gene delivered by AAV8. RS1 is a secreted cell adhesion protein that is critical for maintaining structural lamination and synaptic integrity of the neural retina. RS1 loss-of-function mutations cause XLRS disease in young boys and men, with splitting ("schisis") of retinal layers and synaptic dysfunction that cause progressive vision loss with age. Analysis of differential gene expression profiles and pathway enrichment analysis of Rs1-KO (Rs1-/y) retina identified cell surface receptor signaling and positive regulation of cell adhesion as potential RS1 gene interaction networks. Most importantly, it also showed massive dysregulation of immune response genes at early age, with characteristics of a microglia-driven proinflammatory state. Delivery of AAV8-RS1 primed the Rs1-KO retina toward structural and functional recovery. The disease transcriptome transitioned toward a recovery phase with upregulation of genes implicated in wound healing, anatomical structure (camera type eye) development, metabolic pathways, and collagen IV networks that provide mechanical stability to basement membrane. AAV8-RS1 expression also attenuated the microglia gene signatures to low levels toward immune quiescence. This study is among the first to identify RS1 gene interaction networks that underlie retinal structural and functional recovery after RS1 gene therapy. Significantly, it also shows that providing wild-type RS1 gene function caused the retina immune status to transition from a degenerative inflammatory phenotype toward immune quiescence, even though the transgene is not directly linked to microglia function. This study indicates that inhibition of microglial proinflammatory responses is an integral part of therapeutic rescue in XLRS gene therapy, and gene therapy might realize its full potential if delivered before microglia activation and photoreceptor cell death. Clinical Trials. gov Identifier NTC 02317887.

CB-5083 is an inhibitor of p97/valosin-containing protein (VCP), for which phase I trials for cancer were terminated because of adverse effects on vision, such as photophobia and dyschromatopsia. Lower dose CB-5083 could combat inclusion body myopathy with early-onset Paget disease and frontotemporal dementia or multisystem proteinopathy caused by gain-of-function mutations in VCP. We hypothesized that the visual impairment in the cancer trial was due to CB-5083's inhibition of phosphodiesterase (PDE)-6, which mediates signal transduction in photoreceptors. To test our hypothesis, we used in vivo and ex vivo electroretinography (ERG) in mice and a PDE6 activity assay of bovine rod outer segment (ROS) extracts. Additionally, histology and optical coherence tomography were used to assess CB-5083's long-term ocular toxicity. A single administration of CB-5083 led to robust ERG signal deterioration, specifically in photoresponse kinetics. Similar recordings with known PDE inhibitors sildenafil, tadalafil, vardenafil, and zaprinast showed that only vardenafil had as strong an effect on the ERG signal in vivo as did CB-5083. In the biochemical assay, CB-5083 inhibited PDE6 activity with a potency higher than sildenafil but lower than that of vardenafil. Ex vivo ERG revealed a PDE6 inhibition constant of 80 nM for CB-5083, which is 7-fold smaller than that for sildenafil. Finally, we showed that the inhibitory effect of CB-5083 on visual function is reversible, and its chronic administration does not cause permanent retinal anomalies in aged VCP-disease model mice. Our results warrant re-evaluation of CB-5083 as a clinical therapeutic agent. We recommend preclinical ERG recordings as a routine drug safety screen. SIGNIFICANCE STATEMENT: This report supports the use of a valosin-containing protein (VCP) inhibitor drug, CB-5083, for the treatment of neuromuscular VCP disease despite CB-5083's initial clinical failure for cancer treatment due to side effects on vision. The data show that CB-5083 displays a dose-dependent but reversible inhibitory action on phosphodiesterase-6, an essential enzyme in retinal photoreceptor function, but no long-term consequences on retinal function or structure.

PurposeTo investigate ON-pathway versus OFF-pathway dysfunction in glaucoma using handheld electroretinography (ERG) with a temporally modulated sinusoidal flicker stimulus.DesignCross-sectional study.ParticipantsFifty-nine participants accounting for 104 eyes, comprised of 19 control eyes, 26 glaucoma suspect eyes, and 59 glaucoma eyes.MethodsParticipants underwent portable ERG testing, which included the photopic flash, photopic flicker, photopic negative response stimulus, ON-OFF stimulus, and a custom-written sinusoidal flicker stimulus that was modulated from 50 to 0.3 Hz.Main outcome and measuresThe ERG response amplitudes were measured by the handheld ERG. For the custom-written sinusoidal flicker stimulus, we derived and compared the log10 first harmonic frequency response amplitudes. Patient discomfort and fatigue after ERG testing were rated on a scale from 1 to 5.ResultsBaseline demographics were not significantly different between groups, except for ocular characteristics. Analysis was performed adjusting for participant age, sex, race, and dilation status, and the sinusoidal frequency responses were stratified at 10 Hz because higher frequencies are associated with the OFF-pathway, whereas lower frequencies are associated with the ON-pathway. After stratification, glaucoma eyes showed an adjusted decrease of 32.1% at frequencies of more than 10 Hz (95% confidence interval [CI], -51.8% to -4.1%; P = 0.03). For 10 Hz stimulus frequencies or less, an adjusted 11.5% reduction was found (95% CI, -39.5% to 29.1%; P = 0.50). Glaucoma suspect eyes did show a decreased response, but this was not significant at either frequency range. When comparing handheld ERG with traditional visual field assessments, participants found the handheld ERG to result in much less discomfort and fatigue.ConclusionsOur finding that glaucoma participants showed greater decreases in ERG response at higher frequencies supports the hypothesis that the OFF-pathway may be more vulnerable in human glaucoma. Using a handheld ERG device with a sinusoidal flicker stimulus may provide an objective assessment of visual function in glaucoma.

PurposeTo determine the range of normal ocular biometry and perform advanced retinal imaging and functional assessment of the rhesus macaque eye.MethodsWe performed ocular phenotyping on rhesus macaques at the California National Primate Research Center. This process consisted of anterior and posterior segment eye examination by ophthalmologists, advanced retinal imaging, and functional retinal electrophysiology.ResultsFull eye examinations were performed on 142 animals, consisting of pupillary light reflex, tonometry, external examination and photography, anterior slit lamp examination, and posterior segment examination by indirect ophthalmoscopy. Ages of the rhesus macaques ranged from 0.7 to 29 years (mean, 16.4 ± 7.5 years). Anterior segment measurements such as intraocular pressure (n = 142), corneal thickness (n = 84), lens thickness (n = 114), and axial length (n = 114) were acquired. Advanced retinal imaging in the form of fundus photography (n = 78), optical coherence tomography (n = 60), and quantitative autofluorescence (n = 44) was obtained. Electroretinography (n = 75) was used to assay retinal function. Quantitative analyses of the macular structure, retinal layer segmentation, and rod and cone photoreceptor electrical responses are reported. Quantitative assessments were made and variations between sexes were analyzed to compare with established sex changes in human eyes.ConclusionsThe rhesus macaque has an ocular structure and function very similar to that of the human eye. In particular macular structure and retinal function is very similar to humans, making this species particularly useful for the study of macular biology and development of therapies for cone photoreceptor disorders.Translational relevanceRhesus macaques are an ideal model for future vision science studies of human eye diseases.

PurposeThe purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.MethodsPatients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Haplotype reconstruction was performed in families harboring the same missense variant.ResultsTen individuals from 8 unrelated families with biallelic candidate variants in FDXR were identified. In addition to bilateral optic atrophy and variable extra-ocular findings, 7 of 10 individuals manifested retinal dystrophy comprising dysfunction and degeneration of both rod and cone photoreceptors. Five of 10 subjects had sensorineural hearing loss. The previously unreported missense variant (c.1115C > A, p.(Pro372His)) was found in 5 of 8 (62.5%) study families. Haplotype reconstruction using WGS data demonstrated a likely ancestral haplotype.ConclusionsFDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations.

Rod photoreceptors can be saturated by exposure to bright background light, so that no flash superimposed on the background can elicit a detectable response. This phenomenon, called increment saturation, was first demonstrated psychophysically by Aguilar and Stiles and has since been shown in many studies to occur in single rods. Recent experiments indicate, however, that rods may be able to avoid saturation under some conditions of illumination. We now show in ex vivo electroretinogram and single-cell recordings that in continuous and prolonged exposure even to very bright light, the rods of mice from both sexes recover as much as 15% of their dark current and that responses can persist for hours. In parallel to recovery of outer segment current is an ∼10-fold increase in the sensitivity of rod photoresponses. This recovery is decreased in transgenic mice with reduced light-dependent translocation of the G protein transducin. The reduction in outer-segment transducin together with a novel mechanism of visual-pigment regeneration within the rod itself enable rods to remain responsive over the whole of the physiological range of vision. In this way, rods are able to avoid an extended period of transduction channel closure, which is known to cause photoreceptor degeneration.SIGNIFICANCE STATEMENT Rods are initially saturated in bright light so that no flash superimposed on the background can elicit a detectable response. Frederiksen and colleagues show in whole retina and single-cell recordings that, if the background light is prolonged, rods slowly recover and can continue to produce significant responses over the entire physiological range of vision. Response recovery occurs by translocation of the G protein transducin from the rod outer to the inner segment, together with a novel mechanism of visual-pigment regeneration within the rod itself. Avoidance of saturation in bright light may be one of the principal mechanisms the retina uses to keep rod outer-segment channels from ever closing for too long a time, which is known to produce photoreceptor degeneration.

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimers disease (AD), as classified by cerebral spinal fluid (CSF) Aβ42/Tau ratio. Individuals with normal retinal morphology ascertained by spectral-domain optical coherence tomography were enrolled. Full-field ERG, pattern PERG, and photopic negative response (PhNR) were performed in 29 adult participants (58 eyes). Amplitude and implicit times of the ERG wave components were analyzed. Preclinical AD participants showed marked retinal ganglion cell dysfunction relative to controls. The PhNR was significantly diminished in preclinical AD relative to controls. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity. These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. Retinal ganglion cell dysfunction, as detected by ERG, may be a clinically useful, non-invasive in vivo biomarker for early disease detection, which is necessary for ultimately pursuing early intervention.

This article published the materials of the round table “Bioengineering in ophthalmology” (OphthalmicBioengineering), held on May 13, 2021 as part of the international conference Ural Symposium on Biomedical Engineering, Radioelectronics and Information Technology (USBEREIT). USBEREIT is held under the auspices of the IEEE Engineering in Medicine and Biology Society. The article presents reports on: metrological aspects of registration of tonometric and electrophysiological signals in ophthalmic diagnostics; approaches to modeling the processes of pulse blood filling of the eye with the determination of hemodynamic parameters; retinotoxicity based on electrophysiological signals; analysis of electrophysiological signals in the frequency-time domain and its application in clinical practice; extraction and analysis of specialized data obtained from the electrophysiological medical device; as well as diagnosing retinal diseases based on optical coherence tomography using machine learning.

Electroretinography is a method of electrophysiological testing, which allows diagnosing diseases associated with disorders of the vascular structures of the retina. The classical analysis of the electroretinogram is based on assessing four parameters of the amplitude-time representation and often needs to be specified further using alternative diagnostic methods. This study proposes the use of an original physician decision support algorithm for diagnosing retinal dystrophy. The proposed algorithm is based on machine learning methods and uses parameters extracted from the wavelet scalogram of pediatric and adult electroretinogram signals. The study also uses a labeled database of pediatric and adult electroretinogram signals recorded using a computerized electrophysiological workstation EP-1000 (Tomey GmbH) at the IRTC Eye Microsurgery Ekaterinburg Center. The scientific novelty of this study consists in the development of special mathematical and algorithmic software for analyzing a procedure for extracting wavelet scalogram parameters of the electroretinogram signal using the cwt function of the PyWT. The basis function is a Gaussian wavelet of order 8. Also, the scientific novelty includes the development of an algorithm for analyzing electroretinogram signals that implements the classification of adult (pediatric) electroretinogram signals 19 (20) percent more accurately than classical analysis.

Ploysai Rujkorakarn,1– 3 Michael J Margolis,1,2 Diana Morvey,1,2 Yujia Zhou,1,2 C Stephen Foster1,2,4 1Massachusetts Eye Research and Surgery Institution, Waltham, MA, USA; 2The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA; 3Suddhavej Hospital Department of Ophthalmology, Mahasarakham University, Maha Sarakham, Thailand; 4Department of Ophthalmology, Harvard Medical School, Cambridge, MA, USACorrespondence: C Stephen Foster, Massachusetts Eye Research and Surgery Institution, 1440 Main St. &num;201, Waltham, MA, 02451, USA, Tel +1 781 891-6377, Fax +1 781 647-1430, Email sfoster@mersi.comPurpose: To assess the possible correlation of anti-retinal antibody titers and number of anti-retinal antibodies with outcome measurements including visual acuity, subjective vision loss, visual field, and electroretinography in patients with autoimmune retinopathy.Design: Single-center, retrospective cross-sectional study.Patients and Methods: Patients with autoimmune retinopathy who underwent anti-retinal antibody testing at least twice during their follow-up were enrolled. Anti-retinal antibody titers and numbers were grouped as improved, stable, or worsened. Outcomes included Snellen visual acuity, patient-reported vision loss, Humphrey visual field mean deviations, and electroretinography parameters.Results: Thirty-one eyes among 16 patients with autoimmune retinopathy were included. Between-group analyses of visual acuity, subjective vision loss, visual field, and electroretinography outcomes did not reveal any significant differences by anti-retinal antibody titer or number group at a 95% confidence interval.Conclusion: Changes in anti-retinal antibody titers or numbers were not associated with any vision outcome. Repeated anti-retinal antibody testing may be unnecessary after diagnosis of autoimmune retinopathy and detection of an anti-retinal antibody.Keywords: autoimmune retinopathy, anti-retinal antibody, visual field, electroretinography, outcome measurements

Excitotoxicity has been linked to the pathogenesis of several serious degenerative ocular diseases. Long-term overactivation of the NMDA receptor by glutamate in retinal ganglion cells (RGCs) results in degeneration, apoptosis and loss of function leading to blindness. NMDA receptor antagonists have been proposed as a pharmacological blockage of glutamate excitotoxicity. However, an inhibition of the pathway activated by glutamate receptors has intolerable side effects. An interesting pharmacological alternative would be the use of antiapoptotic compounds as RGCs’ neuroprotective active substances. Several mechanisms have been proposed to explain neuroprotection, including anti-inflammatory and scavenging activities. Here, the role of dexamethasone in neuroprotection was studied. For this purpose, original controlled release systems composed of microparticles containing dexamethasone with or without vitamin E and human serum albumin (HSA) were designed. The particles were prepared by the solid-in-oil-in-water (S/O/W) emulsion–evaporation technique. After properly characterization of the particles, they were intravitreally injected into an rat model of acute ocular excitotoxicity injury. The functionality of the retina was determined by electroretinography and RGCs were counted after cell immunohistochemistry. These microparticulate systems showed the ability to maintain normal electroretinal activity and promoted significant protection of RGCs. Through this proof of concept, we demonstrated that dexamethasone could be a useful anti-inflammatory agent to avoid the progression of degenerative ocular diseases. Furthermore, when administered in controlled release systems that provide low concentrations during prolonged periods of time, not only can the patient’s comfort be increased but the cytotoxicity of the drugs can also be avoided.

IntroductionMuch interest has been addressed to antioxidant dietary supplements that are known to lower the risk of developing glaucoma or delay its progression. Among them, niacin and citicoline protect retinal ganglion cells (RGCs) from degeneration by targeting mitochondria, though at different levels. A well-established mouse model of RGC degeneration induced by experimental intraocular pressure (IOP) elevation was used to investigate whether a novel combination of niacin/citicoline has better efficacy over each single component in preserving RGC health in response to IOP increase.MethodsOcular hypertension was induced by an intracameral injection of methylcellulose that clogs the trabecular meshwork. Electroretinography and immunohistochemistry were used to evaluate RGC function and density. Oxidative, inflammatory and apoptotic markers were evaluated by Western blot analysis.ResultsThe present results support an optimal efficacy of niacin with citicoline at their best dosage in preventing RGC loss. In fact, about 50% of RGCs were spared from death leading to improved electroretinographic responses to flash and pattern stimulation. Upregulated levels of oxidative stress and inflammatory markers were also consistently reduced by almost 50% after niacin with citicoline thus providing a significant strength to the validity of their combination.ConclusionNiacin combined with citicoline is highly effective in restoring RGC physiology but its therapeutic potential needs to be further explored. In fact, the translation of the present compound to humans is limited by several factors including the mouse modeling, the higher doses of the supplements that are necessary to demonstrate their efficacy over a short follow up period and the scarce knowledge of their transport to the bloodstream and to the eventual target tissues in the eye.

The visual function of diabetic eyes was assessed to evaluate spatial-sweep steady-state pattern electroretinography (swpPERG) as a potential high-sensitivity analysis method. Data from 24 control eyes, 28 diabetic eyes without diabetic retinopathy (DR), and 30 diabetic eyes with DR (all with best-corrected visual acuity [BCVA] better than logMAR 0.05; median age, 51) in response to spatial-patterned and contrast-reversed stimuli of sizes 1 (thickest) to 6 were converted into the frequency domain using a Fourier transform and expressed as signal-to-noise ratios (SNRs). SNRs of diabetic eyes, both with and without DR, were lower than those of controls (P < 0.05), and those of DR eyes were lower than those of diabetic eyes without DR (P < 0.05). The SNRs were correlated with ganglion cell layer volume measured using optical coherence tomography (OCT) and foveal vascular length density at the superficial retinal layer measured using OCT angiography (P < 0.05 or < 0.01, according to stimulus size). Therefore, swpPERG SNRs could detect fine reductions in visual function in diabetic eyes and were particularly low in DR eyes. Moreover, SNRs were correlated with inner retinal morphological changes in diabetic eyes, both with and without DR. swpPERG may therefore be useful for detecting fine fluctuations in visual function in diabetic eyes. [ABSTRACT FROM AUTHOR]

(1) Background: mfERG testing is used to study the function of cone photoreceptors in the central retina. Various filters including "smoothing" (Smooth) and "adaptive data filtering" (Adapt) are used to simplify raw data. This study will seek to characterize the effect of data modification on raw patient data. (2) Methods: This was a retrospective study of patients with mfERG results at our institution. For each patient, raw mfERG data without filtering, with smooth level 4 modifier applied, and with adapt level 4 applied were collected and compared. (4) Conclusions: In all patients, smoothing and adaptive filter modifiers create statistically significant differences in both P1 latency and P1 amplitude values when compared to raw data. The impacts of these filters demonstrated in this study should impact physicians' decision making when interpreting mfERG results. [ABSTRACT FROM AUTHOR]

Background: In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In these various pursuits, the role of vision plays a crucial role. Electroretinography is the most used test to diagnose diseases of the retinal outer segment. There is a wide variety of devices to perform the electroretinography differing one from each other in the corneal electrode and the light stimulation. The Koijman electrode has been tested in dogs but not in horses. The main purpose of this study was to compare electroretinography parameters from horses sedated with detomidine alone or in combination with butorphanol, during a standardized protocol using the Koijman electrode and RETI-port® system. Seven mares were allocated to the detomidine and detomidine plus butorphanol group in a randomised, controlled, crossover study. Friedman and Willcoxon-signed ranked tests were used to compare the electroretinogram parameters. A Student's t-test was used to compare differences in the number of artefacts to valid values ratio obtained under both sedation protocols. Results: Dark adaptation peaked after 16 min under scotopic conditions in both groups. No significant differences in electroretinogram parameters between groups were observed. During the mixed rod and cone response evaluation under scotopic conditions, all mares made a movement of the head resulting in a high number of artefacts. The detomidine plus butorphanol group showed a non-significant tendency to have fewer artefacts and a longer duration of sedation compared to the detomidine group. Conclusions: Detomidine alone or combined with butorphanol may be suitable to use Koijman electrode and the RETI-port® to perform a standardized long protocol in horses with some adaptations. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 µM or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV–ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies. [ABSTRACT FROM AUTHOR]

To report a case of cone dystrophy, associated with autosomal recessive homozygote POC1B gene variant, mimicking autoimmune retinopathy. A 45-year-old female presented with a complaint of decreased vision in both eyes. Her best corrected visual acuity was 20/32 in the right eye and 20/50 in the left eye. Anterior segment and dilated fundus examinations were unremarkable. Spectral domain optical coherence tomography showed a subfoveal blurred dome-shaped ellipsoid zone and an extinguished interdigitation zone affecting the entire macula. Full field electroretinography revealed reduced cone responses. The differential diagnosis included inflammatory chorioretinopathies, autoimmune retinopathies (paraneoplastic or nonparaneoplastic), and hereditary retinal dystrophies. No remarkable finding was observed on combined fluorescein and indocyanine green angiographies. Paraneoplastic autoimmune antibody panel revealed nothing; however, aldolase, enolase, pyruvate kinase M2, and glyceraldehyde-3-phosphate dehydrogenase antibodies were positive on autoimmune retinopathy panel. To exclude hereditary retinal dystrophies, whole-exome sequencing (WES) was applied. WES identified an autosomal recessive homozygote POC1B gene variant (c.680A>G, p.His227Arg). Cone dystrophy diagnosis was given. Cone dystrophy associated with POC1B gene variant may present without visible fundus abnormalities. It should be kept in mind that retinal autoantibodies may be positive in such a hereditary dystrophy case due to long-term exposure of the immune system to self-antigens. Therefore, autoimmune retinopathy is a diagnosis of exclusion and should not be diagnosed until all other causes, including hereditary dystrophies, have been ruled out. [ABSTRACT FROM AUTHOR]

To describe a patient with retinoblastoma and subsequent maculopathy unrelated to the tumor but related to intra-arterial melphalan documented by pattern electroretinography. Comprehensive ophthalmic evaluation, treatment with intra-arterial chemotherapy and subsequent follow-up including electroretinography to assess for macular dysfunction. A 3-year-old child was evaluated with electrophysiological investigations following treatment of unilateral Group D retinoblastoma with intra-arterial and intravitreal chemotherapy with melphalan. Pattern reversal visual evoked potential amplitude and P100 latency were normal in the left eye, but abnormal and delayed in the right eye. Pattern electroretinograms (pERGs) were abnormal on the right eye. Flash electroretinograms (fERGs) were normal on both eyes. Visual acuity dysfunction of 20/50 attributed to melphalan was seen on the right eye vs 20/40 on the left eye. Our case report demonstrates that pERG rather than fERG should be used to monitor baseline macular function and potential toxicity in children undergoing chemotherapy for retinoblastoma using skin electrodes when corneal electrodes are not tolerated. [ABSTRACT FROM AUTHOR]

Purpose: Biallelic variants in POC1B are rare causes of autosomal recessive cone dystrophy associated with generalized cone system dysfunction. In this report, we describe the clinical characteristics of a Japanese male patient with POC1B-associated retinopathy with relatively preserved cone system function. Methods: We performed whole-exome sequencing (WES) to identify the disease-causing variants and a comprehensive ophthalmic examination, including full-field and multifocal electroretinography (ffERG and mfERG). Results: Our WES analysis identified novel compound heterozygous POC1B variants (p.Arg106Gln and p.Arg452Ter) in the patient. His unaffected mother carried the p.Arg452Ter variant heterozygously. The patient experienced decreased visual acuity in his 50s. At the age of 63, his corrected visual acuity was 20/22 in the right and 20/20 in the left eye. Fundus and fundus autofluorescence images for each eye showed no remarkable finding, except for a subtle hyperautofluorescent spot in the fovea of the left eye. Cross-sectional optical coherence tomography demonstrated blurred but a relatively preserved ellipsoid zone. The ffERG showed that amplitudes of rod and standard-flash responses were within the reference range, whereas the cone and light-adapted 30-Hz flicker amplitudes were close to, or slightly below, the reference range. The mfERG revealed substantially reduced responses with relative preservation of central function. Conclusions: We reported the case of an older patient with POC1B-associated retinopathy, demonstrating late-onset visual decrease, good visual acuity, and relatively preserved cone system function. The disease condition was much milder than previously reported in patients with POC1B-associated retinopathy. [ABSTRACT FROM AUTHOR]

The electroretinogram (ERG) measures the electrical activity of retinal neurons and glial cells in response to a light stimulus. Amongst other techniques, clinicians utilize the ERG to diagnose various eye diseases, including inherited conditions such as cone-rod dystrophy, rod-cone dystrophy, retinitis pigmentosa and Usher syndrome, and to assess overall retinal health. An ERG measures the scotopic and photopic systems separately and mainly consists of an a-wave and a b-wave. The other major components of the dark-adapted ERG response include the oscillatory potentials, c-wave, and d-wave. The dark-adapted a-wave is the initial corneal negative wave that arises from the outer segments of the rod and cone photoreceptors hyperpolarizing in response to a light stimulus. This is followed by the slower, positive, and prolonged b-wave, whose origins remain elusive. Despite a large body of work, there remains controversy around the mechanisms involved in the generation of the b-wave. Several hypotheses attribute the origins of the b-wave to bipolar or Müller glial cells or a dual contribution from both cell types. This review will discuss the current hypothesis for the cellular origins of the dark-adapted ERG, with a focus on the b-wave. [ABSTRACT FROM AUTHOR]

The continuous advancements in healthcare technology have empowered the discovery, diagnosis, and prediction of diseases, revolutionizing the field. Artificial intelligence (AI) is expected to play a pivotal role in achieving the goals of precision medicine, particularly in disease prevention, detection, and personalized treatment. This study aims to determine the optimal combination of the mother wavelet and AI model for the analysis of pediatric electroretinogram (ERG) signals. The dataset, consisting of signals and corresponding diagnoses, undergoes Continuous Wavelet Transform (CWT) using commonly used wavelets to obtain a time-frequency representation. Wavelet images were used for the training of five widely used deep learning models: VGG-11, ResNet-50, DensNet-121, ResNext-50, and Vision Transformer, to evaluate their accuracy in classifying healthy and unhealthy patients. The findings demonstrate that the combination of Ricker Wavelet and Vision Transformer consistently yields the highest median accuracy values for ERG analysis, as evidenced by the upper and lower quartile values. The median balanced accuracy of the obtained combination of the three considered types of ERG signals in the article are 0.83, 0.85, and 0.88. However, other wavelet types also achieved high accuracy levels, indicating the importance of carefully selecting the mother wavelet for accurate classification. The study provides valuable insights into the effectiveness of different combinations of wavelets and models in classifying ERG wavelet scalograms. [ABSTRACT FROM AUTHOR]

Hypertension is a major health problem in both developing and developed countries. Hypertension causes retinal structural and functional impairment within the ganglion cell layer. Pattern electroretinogram (PERG) offers an objective simple tool for assessment of retinal ganglion cell function. Aim of the work: To assess retinal dysfunction in hypertensive patients with or without signs of retinopathy using PERG. This is a case control study, including ninety-eight eyes. Twenty-eight eyes of healthy subjects served as a control group (group I) and seventy eyes of patients with systemic hypertension, who were further subdivided into group II including 39 eyes of hypertensive patients with normal fundus and group III including 31 eyes of patients with signs of hypertensive retinopathy. All subjects were subjected to ophthalmological examination and electrophysiological assessment using PERG. PERG implicit times were significantly prolonged and amplitudes were significantly reduced in patients with established hypertensive retinopathy. PERG abnormalities were detected in 96.8% of hypertensive retinopathy patients and 79.5% of hypertensive patients with normal fundus. PERG can objectively assess retinal dysfunction in hypertensive patients and may be considered a promising tool for early detection of hypertensive retinopathy. [ABSTRACT FROM AUTHOR]

Background: To perform a multimodal assessment of the ectopic inner foveal layers' (EIFL) prognostic role on idiopathic epiretinal membrane (ERM) surgery. Methods: We retrospectively followed-up for 12 months 27 patients who underwent ERM surgery and stratified them based on EIFL presence (group 1) or absence (group 2) at baseline. Central Retinal Thickness (CRT) and best-corrected visual acuity (BCVA) were compared pre- and post-operatively at 1, 4 and 12 months, whereas fixation stability (FS), macular sensitivity (MS) and multifocal electroretinogram (mfERG) responses were confronted at baseline and 12 months. Results: In group 1, BCVA improved at 4 and 12 months (MD = 0.14 (SE = 0.04); MD = 0.13 (SE = 0.05), respectively) as well as in group 2 (MD = 0.31 (SE = 0.07); MD = 0.41 (SE = 0.08), respectively). CRT did not change in group 1, whereas it decreased in group 2 at 4 and 12 months (MD = −73.13; SE = 23.56; MD = −76.20; SE = 23.56). MS showed no changes in both groups after surgery. FS did not change in group 1, whereas group 2 improved FS 2° (+8.91 ± 13.97) and FS 4° (+4.33 ± 3.84). MfERG P1 wave did not change in group 1, while in group 2 αP1-2, αP1-3 and αP1-4 improved postoperatively (27.97 ± 27.62; 12.51 ± 17.36; 10.49 ± 17.19, respectively). Conclusions: Multimodal assessment confirmed that EIFL negatively affected ERM surgery outcomes. [ABSTRACT FROM AUTHOR]

Nonparaneoplastic autoimmune retinopathy is a rare, potentially blinding retinal disease which can present as pericentral retinal degeneration or may be secondary to retinal damage from retinal degeneration. Treatment with IV immunoglobulin can be effective in these patients. Purpose: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy. Methods: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia. Results: Dilated fundoscopy demonstrated confluent yellow–white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina. Conclusion: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study describes the medical approach to a severe ocular disease impairing the vision of two young sea turtles rescued in the Tyrrhenian Sea. Proper diagnosis and treatment of ocular diseases in these animals is necessary because their sight is extremely important for their survival. Clinical examination of the eyes showed a bilateral lens opacity (cataract). The two turtles underwent an instrumental examination for accurate diagnosis. Ultrasonography was performed to study the anatomical features. Electroretinography was necessary to obtain functional data on the eyes' ability to translate the light signal perceived by the retina into a nerve signal to be transmitted to the brain. Only after verifying that there were no other eye impairments besides the cataracts, we decided to proceed to remove them surgically. The surgery was performed by phacoemulsification under a microscope. After surgery, both turtles were treated with antibiotics and anti-inflammatory drugs, both parenterally and topically. After 10 months of follow up, the two turtles are able to feed normally and to interact with obstacles. Clinically, all four eyes appear to be healthy. Bilateral cataracts were diagnosed in two rescued juvenile, immature loggerhead sea turtles (Caretta caretta), weighing 1.65 and 1.7 kg. Both animals showed vision impairment and difficulty in feeding without assistance. In fact, they did not notice the presence of the food in the tank unless it was brought close to touching the mouth. Ocular ultrasonography and electroretinography showed no lesions of the vitreal body and retinal layer, therefore, both animals were candidates for bilateral cataract surgery. Topical administration of tropicamide + phenylephrine alternating with rocuronium resulted in only minimal mydriasis. Administration of intracameral rocuronium did not improve mydriasis. Phacoemulsification using a one-handed technique was performed bilaterally with a phacoemulsification device (Sovereign, AMO (Abbott Medical Optics®). After surgery, the systemic anti-inflammatory drug (dexamethasone 0.2 mg/kg, IM daily for one week) and antibiotics (enrofloxacin 10 mg/kg IM q 72 h, for 4 weeks; ceftazidime 20 mg/kg IM q 72 h for 3 weeks) were administered. Topical ofloxacin, flurbiprofen and tobramycin/dexamethasone were instilled TID for 4 weeks. Both turtles regained vision in both eyes. Results at a 10-month follow-up were satisfactory. This is the first report of cataracts in turtles rescued in the Mediterranean Sea and the first description of surgical treatment of cataracts in loggerhead turtles so young. [ABSTRACT FROM AUTHOR]

Background: The electroretinogram is a clinical test used to assess the function of the photoreceptors and retinal circuits of various cells in the eye, with the recorded waveform being the result of the summated response of neural generators across the retina. Methods: The present investigation involved an analysis of the electroretinogram waveform in both the time and time–frequency domains through the utilization of the discrete wavelet transform and continuous wavelet transform techniques. The primary aim of this study was to monitor and evaluate the effects of treatment in a New Zealand rabbit model of endophthalmitis via electroretinogram waveform analysis and to compare these with normal human electroretinograms. Results: The wavelet scalograms were analyzed using various mother wavelets, including the Daubechies, Ricker, Wavelet Biorthogonal 3.1 (bior3.1), Morlet, Haar, and Gaussian wavelets. Distinctive variances were identified in the wavelet scalograms between rabbit and human electroretinograms. The wavelet scalograms in the rabbit model of endophthalmitis showed recovery with treatment in parallel with the time-domain features. Conclusions: The study compared adult, child, and rabbit electroretinogram responses using DWT and CWT, finding that adult signals had higher power than child signals, and that rabbit signals showed differences in the a-wave and b-wave depending on the type of response tested, while the Haar wavelet was found to be superior in visualizing frequency components in electrophysiological signals for following the treatment of endophthalmitis and may give additional outcome measures for the management of retinal disease. [ABSTRACT FROM AUTHOR]

PurposeTo report baseline visual fields in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.DesignCross-sectional study within a natural history study.MethodsSetting: multicenter, international.Study populationUsher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A.Observation proceduresRepeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intraclass correlation coefficients (ICCs). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t tests.Main outcome measuresVTOT (SP) and III4e isopter area (KP).ResultsUSH2 participants had more severe visual field loss than ARRP participants (P < .001, adjusting for disease duration, age of enrollment). Mean VTOT measures among 3 repeat tests were 32.7 ± 24.1, 31.2 ± 23.4, and 31.7 ± 23.9 decibel-steradians (intraclass correlation coefficient [ICC] = 0.96). Better VA, greater photopic ERG 30-Hz flicker amplitudes, higher mean microperimetry sensitivity, higher central subfield thickness, absence of macular cysts, and higher III4e seeing area were associated with higher VTOT (all r > .48; P < .05). Mean III4e isopter areas for left (4561 ± 4426 squared degrees) and right eyes (4215 ± 4300 squared degrees) were concordant (ICC = 0.94).ConclusionsUSH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration.

In multipolar vertebrate neurons, action potentials (APs) initiate close to the soma, at the axonal initial segment. Invertebrate neurons are typically unipolar with dendrites integrating directly into the axon. Where APs are initiated in the axons of invertebrate neurons is unclear. Voltage-gated sodium (NaV) channels are a functional hallmark of the axonal initial segment in vertebrates. We used an intronic Minos-Mediated Integration Cassette to determine the endogenous gene expression and subcellular localization of the sole NaV channel in both male and female Drosophila, para Despite being the only NaV channel in the fly, we show that only 23 ± 1% of neurons in the embryonic and larval CNS express para, while in the adult CNS para is broadly expressed. We generated a single-cell transcriptomic atlas of the whole third instar larval brain to identify para expressing neurons and show that it positively correlates with markers of differentiated, actively firing neurons. Therefore, only 23 ± 1% of larval neurons may be capable of firing NaV-dependent APs. We then show that Para is enriched in an axonal segment, distal to the site of dendritic integration into the axon, which we named the distal axonal segment (DAS). The DAS is present in multiple neuron classes in both the third instar larval and adult CNS. Whole cell patch clamp electrophysiological recordings of adult CNS fly neurons are consistent with the interpretation that Nav-dependent APs originate in the DAS. Identification of the distal NaV localization in fly neurons will enable more accurate interpretation of electrophysiological recordings in invertebrates.SIGNIFICANCE STATEMENT The site of action potential (AP) initiation in invertebrates is unknown. We tagged the sole voltage-gated sodium (NaV) channel in the fly, para, and identified that Para is enriched at a distal axonal segment. The distal axonal segment is located distal to where dendrites impinge on axons and is the likely site of AP initiation. Understanding where APs are initiated improves our ability to model neuronal activity and our interpretation of electrophysiological data. Additionally, para is only expressed in 23 ± 1% of third instar larval neurons but is broadly expressed in adults. Single-cell RNA sequencing of the third instar larval brain shows that para expression correlates with the expression of active, differentiated neuronal markers. Therefore, only 23 ± 1% of third instar larval neurons may be able to actively fire NaV-dependent APs.

Members of the arrestin superfamily have great propensity of self-association, but the physiological significance of this phenomenon is unclear. To determine the biological role of visual arrestin-1 oligomerization in rod photoreceptors, we expressed mutant arrestin-1 with severely impaired self-association in mouse rods and analyzed mice of both sexes. We show that the oligomerization-deficient mutant is capable of quenching rhodopsin signaling normally, as judged by electroretinography and single-cell recording. Like wild type, mutant arrestin-1 is largely excluded from the outer segments in the dark, proving that the normal intracellular localization is not due the size exclusion of arrestin-1 oligomers. In contrast to wild type, supraphysiological expression of the mutant causes shortening of the outer segments and photoreceptor death. Thus, oligomerization reduces the cytotoxicity of arrestin-1 monomer, ensuring long-term photoreceptor survival.SIGNIFICANCE STATEMENT Visual arrestin-1 forms dimers and tetramers. The biological role of its oligomerization is unclear. To test the role of arrestin-1 self-association, we expressed oligomerization-deficient mutant in arrestin-1 knock-out mice. The mutant quenches light-induced rhodopsin signaling like wild type, demonstrating that in vivo monomeric arrestin-1 is necessary and sufficient for this function. In rods, arrestin-1 moves from the inner segments and cell bodies in the dark to the outer segments in the light. Nonoligomerizing mutant undergoes the same translocation, demonstrating that the size of the oligomers is not the reason for arrestin-1 exclusion from the outer segments in the dark. High expression of oligomerization-deficient arrestin-1 resulted in rod death. Thus, oligomerization reduces the cytotoxicity of high levels of arrestin-1 monomer.