Search

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

PURPOSE: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses. METHODS: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data. Novel features include extended use of spectrum analysis, reduction of errors due to known sources, and a comprehensive statistical assessment using three different tests. The method was applied to ERG recordings from seven patients with RD and two patients with CNGB3 achromatopsia. RESULTS: The method was implemented as a Windows application to processes raw data obtained from a commercial ERG system, and it features a computational toolkit for statistical assessment of ERG recordings with amplitudes as low as 1 µV, commonly found in advanced RD patients. When recorded using conditions specific for eliciting cone responses, none of the CNGB3 patients had a CxC validated response, indicating that no signal artifacts were present with our recording conditions. A comparison of the presented method with conventional 30 Hz ERG was performed. Bland-Altman plots indicated good agreement (mean difference, -0.045 µV; limits of agreement, 0.193 to -0.282 µV) between the resulting amplitudes. Within-session test-retest variability was 15%, comparing favorably to the variability of standard ERG amplitudes. CONCLUSIONS: This novel method extracts highly reliable clinical recordings of low-amplitude flicker ERGs and effectively detects artifactual responses. It has potential value both as a cone outcome variable and planning tool in clinical trials on natural history and treatment of advanced RDs.

Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury. • Photoreceptor and bipolar cell function decline in middle aged mice. • Compensatory increase in bipolar cell sensitivity to light occurs in 12-month-old mice. • Increase inner retinal gain (ganglion cell function) up to 12 months of age. • Age-related functional differences can differ in transgenic mice. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether more stable electroretinography parameters could be obtained in younger children using skin electrodes placed at the inner canthus and ears compared to using contact lens electrodes. The study included three Japanese patients (two girls and one boy) who presented with epileptic spasms before the age of 3 years. We compared the electroretinography parameters obtained with skin electrodes and contact lens electrodes. We could record reproducible results using skin ERG with a montage of electrodes placed at the inner canthus and the ear in children. Moreover, standard data for younger children were created, enabling the evaluation of electroretinography parameters recorded with skin electrodes in individual pediatric patients. The skin electroretinography using the new montage may be stable parameters for evaluating retinal function in younger children. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionThis study aimed to assess and compare the retinal toxicity associated with silicone oil (SO) and perfluoropropane (C3F8) tamponade following vitreoretinal surgery for fresh rhegmatogenous retinal detachment (RRD), utilizing the office-based Diopsys® NOVA™ system for evaluation.Patients who underwent vitreoretinal surgery for fresh RRD and had SO (group 1) or C3F8 (group 2) tamponade were included in a prospective analysis. Flicker full field electroretinography (ffERG) and pattern electroretinography (PERG) tests were performed at 6 months postoperatively.Postoperative best corrected visual acuity (logMAR) was significantly different in group 1 and group 2 patients, 0.48 ± 0.3 and 0.30 ± 0.2, respectively. No significant disparities were found in demographic variables. Flicker ffERG and PERG recordings revealed notable alterations in retinal function parameters in the group 1 compared to the group 2.Our findings suggest a correlation between SO tamponade and retinal dysfunction, evidenced by office-based ERG measurements. The Diopsys® NOVA™ protocol offers clinical ease in assessing retinal function. Further controlled studies are essential to validate these findings and guide clinical practice effectively. [ABSTRACT FROM AUTHOR]

Visual electrophysiology measurements are crucial in ophthalmology as they are frequently used for diagnosing and treating numerous ocular diseases. Therefore, optically transparent and flexible electrodes with high sensitivity at localized regions are in high demand. Here, it is aimed to develop a soft, transparent, multi‐electrode system assembled on commercially available soft contact lenses and assess its application in measuring Electroretinography (ERG) responses in rabbits. A biocompatible multi‐electrode system on commercial disposable soft contact lenses is successfully constructed, showing 95% cell viability, 82% optical transparency over the visible range, and good flexibility at 10% strain. Direct current (DC) voltage is used to produce a highly resistive overoxidized poly(3,4‐ethylenedioxythiophene) (PEDOT) layer that covers all parts of the electrodes except the sensing region, which, owing to its high conductivity, can accurately measure electrical signals from local regions of the cornea. Spatially resolved ERG recordings of rabbits are obtained with superior signal quality using this multi‐electrode system. Thus, this device is expected to be used in ophthalmic diagnosis in the future. [ABSTRACT FROM AUTHOR]

Retinitis Pigmentosa is a leading cause of severe vision loss. Retinitis Pigmentosa can present with a broad range of phenotypes impacted by disease age of onset, severity, and progression. This variation is influenced both by different gene mutations as well as unique variants within the same gene. Mutations in the nuclear hormone receptor 2 family e, member 3 are associated with several forms of retinal degeneration, including Retinitis Pigmentosa. In our previous studies we demonstrated that subretinal administration of one Nr2e3 dose attenuated retinal degeneration in rd7 mice for at least 3 months. Here we expand the studies to evaluate the efficacy and longitudinal impact of the NR2E3 therapeutic by examining three different doses administered at early or intermediate stages of retinal degeneration in the rd7 mice. Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. Similarly, photoreceptor function was significantly improved in the early stage for all doses and intermediate stage low and mid dose groups 6 months post treatment. This study demonstrated efficacy in multiple doses of NR2E3 therapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the effects of intramuscular (IM) administration of alfaxalone with or without dexmedetomidine on short electroretinography (ERG), ocular parameters and cardiorespiratory in healthy cats. Methods: Eight healthy female spayed cats were treated with three sedation protocols: IM administration of 5 µg/kg dexmedetomidine (DEX), 5 mg/kg alfaxalone (ALF), and 5 µg/kg dexmedetomidine plus 5 mg/kg alfaxalone (DEX + ALF). The washout period after each treatment was 2 weeks. Physiological parameters, time metrics, intraocular pressure (IOP), Schirmer tear test 1 (STT-1) and a short ERG protocol were recorded. For age data, weight data, time metrics and ERG data, one-way ANOVA with Bonferroni posterior comparisons were performed. For physiological parameters, IOP and STT-1 data, twoway repeated measures ANOVA with Bonferroni posterior comparisons were performed. Statistical significance was set at a p-value <0.05. Results: IOPs were increased in all three groups compared to baseline and showed no significant differences among three groups at any time point. STT-1 values were decreased significantly during the process. Significant differences were noticed between a-wave amplitude in the dark-adapted response between DEX and ALF, and a-wave amplitude in light-adapted response between ALF and DEX + ALF. Conclusion: This study demonstrates the feasibility of three sedation protocols for short ERG recording in cats. All these treatments resulted in increased IOP values and reduced STT-1 values. But baseline data of ERG was not obtained as a blank control in cats. [ABSTRACT FROM AUTHOR]

Summary Hypersomnia spectrum disorders are underdiagnosed and poorly treated due to their heterogeneity and absence of biomarkers. The electroretinography has been proposed as a proxy of central dysfunction and has proved to be valuable to differentiate certain psychiatric disorders. Hypersomnolence is a shared core feature in central hypersomnia and psychiatric disorders. We therefore aimed to identify biomarkers by studying the electroretinography profile in patients with narcolepsy type 1, idiopathic hypersomnia and in controls. Cone, rod and retinal ganglion cells electrical activity were recorded with flash‐electroretinography in non‐dilated eye of 31 patients with idiopathic hypersomnia (women 84%, 26.6 ± 5.9 years), 19 patients with narcolepsy type 1 (women 63%, 36.6 ± 12.7 years) and 43 controls (women 58%, 30.6 ± 9.3 years). Reduced cone a‐wave amplitude (p = 0.039) and prolonged cone (p = 0.022) and rod b‐wave (p = 0.009) latencies were observed in patients with narcolepsy type 1 as compared with controls, while prolonged photopic negative response‐wave latency (retinal ganglion cells activity) was observed in patients with idiopathic hypersomnia as compared with controls (p = 0.033). The rod and cone b‐wave latency clearly distinguished narcolepsy type 1 from idiopathic hypersomnia and controls (area under the curve > 0.70), and the photopic negative response‐wave latency distinguished idiopathic hypersomnia and narcolepsy type 1 from controls with an area under the curve > 0.68. This first original study shows electroretinography anomalies observed in patients with hypersomnia. Narcolepsy type 1 is associated with impaired cone and rod responses, whereas idiopathic hypersomnia is associated with impaired retinal ganglion cells response, suggesting different phototransduction alterations in both hypersomnias. Although these results need to be confirmed with a larger sample size, the electroretinography may be a promising tool for clinicians to differentiate hypersomnia subtypes. [ABSTRACT FROM AUTHOR]

Purpose: Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Methods: Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9--39 weeks. Charge balanced, biphasic, current pulses (100 μA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3--34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. Therewas no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Conclusion: Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation. [ABSTRACT FROM AUTHOR]

Purpose: To assess the utility of electroretinogram (ERG) as a screening tool for vigabatrin-induced retinal toxicity in children with infantile spasms. Methods: This was an observational cohort study including children with infantile spasms receiving treatment with vigabatrin. A 30-Hz flicker potential ERG, using the RETeval system (LKC Technologies), was done at baseline before starting vigabatrin at 6 months and 1 year. The amplitudes were recorded. Results: Eleven children were included in the study. The most common etiologic factor for infantile spasms was tuberous sclerosis (36.4%) followed by West syndrome (27.3%). The mean age of the children was 7.14 ± 2.9 months, with a range of 3 to 16 months. The mean difference in amplitude was 3.21 ± 2.45 and 5.72 ± 4.18 µV at 6 and 12 months follow-up, respectively (P <.001). Eight of the 11 children (72.7%) showed vigabatrin-induced retinal toxicity, and all 8 children were receiving vigabatrin for more than 6 months. Conclusions: ERG can be used for vigabatrin-induced retinal toxicity monitoring in children with infantile spasms. Vigabatrin-induced retinal toxicity is related to the duration of treatment rather than cumulative dosage. [J Pediatr Ophthalmol Strabismus. 2024;61(4):273–278.] [ABSTRACT FROM AUTHOR]

Abstract Retinitis Pigmentosa is a leading cause of severe vision loss. Retinitis Pigmentosa can present with a broad range of phenotypes impacted by disease age of onset, severity, and progression. This variation is influenced both by different gene mutations as well as unique variants within the same gene. Mutations in the nuclear hormone receptor 2 family e, member 3 are associated with several forms of retinal degeneration, including Retinitis Pigmentosa. In our previous studies we demonstrated that subretinal administration of one Nr2e3 dose attenuated retinal degeneration in rd7 mice for at least 3 months. Here we expand the studies to evaluate the efficacy and longitudinal impact of the NR2E3 therapeutic by examining three different doses administered at early or intermediate stages of retinal degeneration in the rd7 mice. Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. Similarly, photoreceptor function was significantly improved in the early stage for all doses and intermediate stage low and mid dose groups 6 months post treatment. This study demonstrated efficacy in multiple doses of NR2E3 therapy.

BACKGROUND/AIMS: To evaluate the electroretinographic (ERG) changes in the early postoperative period following glaucoma filtration surgery, and its relationship with choroidal detachment (CD). METHODS: This retrospective observational single-centre study included 57 consecutive patients with primary open-angle glaucoma who underwent unilateral glaucoma filtration surgery. The patients were divided into two groups according to the presence or absence of CD. ERG components, including the photopic negative response (PhNR), a-wave and b-wave were compared before and after surgery using skin electrodes. RESULTS: There were 46 patients in the non-CD group and 11 in the CD group. ERG was recorded within 5.1 (2.1 to 8.1) (mean (95% CI)) days after surgery. In the non-CD group, the PhNR amplitude, PhNR/b-wave amplitude ratio and PhNR implicit time improved significantly after surgery (p=0.008, 0.002 and 0.039, respectively). In the CD group, the amplitude of the PhNR, a-wave and b-wave were significantly deteriorated after surgery (p=0.002, 0.001 and 0.001, respectively). Postoperative intraocular pressure (IOP) (p=0.031) and postoperative CD (p

Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens—voluntary (recreational-type) and forced (high-intensity)—on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations. [ABSTRACT FROM AUTHOR]

Abstract In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5–6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P

Koki Sakata, Takeshi Katsumoto, Tomoyuki Kumagai, Kei Shinoda Department of Ophthalmology, Saitama Medical University, Saitama, JapanCorrespondence: Kei Shinoda, Department of Ophthalmology, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan, Tel +81-4-9276-1250, Fax +81-4-9295-8002, Email shinok@saitama-med.ac.jpPurpose: To determine whether 0.025% povidone-iodine (0.025% PI) in the irrigation solution during vitrectomy for endophthalmitis is safe.Methods: Two cases of bleb-associated endophthalmitis were treated with vitrectomy using 0.025% PI in the irrigation solution. The RETevel electroretinographic (ERG) system with skin electrodes was used to assess the physiology of the retina pre- and postoperatively.Case: Case 1 was a 46-year-old man who had atopic keratoconjunctivitis and underwent trabeculectomy with the creation of a bleb after there was a rise in the intraocular pressure. One month postoperatively, a mild filtering bleb-associated endophthalmitis developed, and the eye was treated with intravitreal and subconjunctival injections of vancomycin (VCM) and ceftazidime (CAZ). After three days, the fundus was not visible and B-mode echography showed an area of high brightness in the retina. Vitrectomy with irrigation with VCM and CAZ, and 0.025% PI was performed successfully. Pre- and postoperative ERGs showed an improvement in both the a- and b-wave amplitudes and the b/a ratio was stable at 2.0. Case 2 was a 63-year-old man who had undergone trabeculectomy for glaucoma. Five years later, the eye developed blebitis which was treated with topical and subconjunctival injections of VCM and CAZ. Three days later, vitreous opacities appeared and a high brightness area was seen in the B-mode echographic images. Vitrectomy with VCM and CAZ, and 0.025% PI irrigation was successfully performed. Comparisons of the pre- and postoperative ERGs found that the a- and b- wave amplitudes of the ERGs increased and the b/a ratio was stable at approximately 1.5.Conclusion: Vitrectomy with 0.025% PI irrigation is safe and ERG recordings with skin electrodes can be used to evaluate the pre- and postoperative retinal physiology safely.Plain Language Summary: We report our findings in two cases of bleb-related endophthalmitis that underwent pars plana vitrectomy (PPV) with irrigation with 0.025% povidone-iodine (PI)-Balanced Salt Solution (BSS) PLUS (Alcon Laboratories, Fort Worth, TX). The retinal function was evaluated by full-field electroretinograms (ERGs) recorded with skin electrodes before and after the vitrectomy.At present, there is no consensus on whether patients with bleb-related endophthalmitis should be treated with PPV or treated solely by intravitreal antibiotics. It was recently reported that vitrectomy using an irrigation solution containing 0.025% PI followed by postoperative antibiotics was effective and safe for the treatment of endogenous endophthalmitis and postoperative endophthalmitis. However, iodine is known to be retinotoxic depending on its concentration.Electroretinography is a useful method to evaluate the safety of medications because it represents the physiology of the entire retina. However, conventional recording procedures with contact lens electrodes cannot be used in eyes with bleb associated endophthalmitis. Therefore, we performed ERG using skin electrodes which were introduced relatively recently. As a result, electroretinographic response showed that retinal function was not altered after surgery in these two cases.Keywords: blebitis, electroretinography, bleb-related endophthalmitis, povidone iodine irrigation, vitrectomy

Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-a-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rodbipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. Methods: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. Results: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. Conclusions: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment. [ABSTRACT FROM AUTHOR]

The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG). The study was performed on 13 mixed breed dogs affected by retinal atrophy (11 males and 2 females that were 1.5–14 years old). Depending on the advancement of RA, SD-OCT examinations identified retinal abnormalities ranging from layer disorganisation to advanced atrophy. The most advanced RA occurred ventral to the optic disc. Total retinal thickness in both eyes (mean ± SD) was lower in dogs with RA compared to controls dorsally (77.7 ± 39.5 μm vs 173.5 ± 13.3 μm), ventrally (33.4 ± 29.9 μm vs 139.5 ± 10.8 μm), nasally (65.0 ± 34.5 μm vs 163.9 ± 11.0 μm) and temporally (61.8 ± 41.7 μm vs 171.9 ± 11.1 μm) to the optic disc. In dogs with locally normal architecture of inner retina, loss of definition of outer retinal layers occurred in many regions. Dark and light-adapted ERGs were reduced in 2 dogs with RA and were unrecordable in 11 dogs. Lesions evident in SD-OCT scans of mixed breed dogs affected with retinal atrophy initially appear ventrally to the optic disc and ventro-dorsally in advanced RA. In all mixed breed dogs with retinal atrophy, clinical signs and SD-OCT results correlate with ERG findings. [ABSTRACT FROM AUTHOR]

Purpose: To identify the ophthalmic causes of congenital nystagmus with normal eye examination by electroretinography (ERG). Study design: Retrospective observational study. Methods: We reviewed the medical records of patients younger than 6 months of age who presented between June 2008 and November 2011 with nystagmus and no other neurological signs following an otherwise normal eye examination. A complete ophthalmic examination and ERG (Nicolet Bravo system; Nicolet Biomedial & RETIscan; Roland Instruments), fundus photography, and Ishihara color test were performed to identify any ophthalmic causes of congenital nystagmus. Results: Thirty-three patients met the criteria. Rod dysfunction was diagnosed in 4 patients (12.1%), cone dysfunction in 2 patients (6.1%), and cone-rod dysfunction in 1 patient (3.0%). The results of ERG were negative in 2 patients (6.1%). Idiopathic infantile nystagmus was diagnosed in the remaining 24 patients (72.7%) based on their normal ERG examination. Conclusions: In Korean congenital nystagmus patients with a normal fundus examination, achromatopsia and Leber's congenital amaurosis are uncommon causes. ERG is needed to make a definite diagnosis and provide prognostic information in congenital idiopathic nystagmus patients with a normal fundus examination. [ABSTRACT FROM AUTHOR]

Purpose: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. Methods: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan–Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. Results: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20–60 years), 65 converted to perimetric glaucoma during follow-up (0.5–23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per μV amplitude decrease. Conclusions: PERG helps to estimate glaucoma suspects' risk for visual field defects. [ABSTRACT FROM AUTHOR]

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development. [ABSTRACT FROM AUTHOR]

Introduction: Platelet-activating factor (PAF), PAF receptor (PAFR), and PAF-synthesis/degradation systems are involved in essential CNS processes such as neuroblast proliferation, diffferentiation, migration, and synapticmodulation. The retina is an important central nervous system (CNS) tissue for visual information processing. During retinal development, the balance between Retinal Progenitor Cell (RPC) proliferation and differentiation is crucial for proper cell determination and retinogenesis. Despite its importance in retinal development, the effects of PAFR deletion on RPC dynamics are still unknown. Methods: We compared PAFR knockout mice (PAFR-/-) retinal postnatal development proliferation and differentiation aspects with control animals. Electrophysiological responses were analyzed by electroretinography (ERG). Results and discussion: In this study, we demonstrate that PAFR-/- mice increased proliferation during postnatal retinogenesis and altered the expression of specific differentiation markers. The retinas of postnatal PAFR-/- animals decreased neuronal differentiation and synaptic transmissionmarkers, leading to differential responses to light stimulimeasured by ERG. Our findings suggest that PAFR signaling plays a critical role in regulating postnatal RPC cell differentiation dynamics during retinal development, cell organization, and neuronal circuitry formation. [ABSTRACT FROM AUTHOR]

Renal coloboma syndrome (RCS) and dominant optic atrophy are mainly caused by heterozygous mutations in PAX2 and OPA1, respectively. We describe a patient with digenic mutations in PAX2 and OPA1. A female infant was born without perinatal abnormalities. Magnetic resonance imaging at 4 months of age showed bilateral microphthalmia and optic nerve hypoplasia. Appropriate body size was present at 2 years of age, and mental development was favorable. Color fundus photography revealed severe retinal atrophy in both eyes. Electroretinography showed slight responses in the right eye, but no responses in the left eye, suggesting a high risk of blindness. Urinalysis results were normal, creatinine-based estimated glomerular filtration rate was 63.5 mL/min/1.73 m2, and ultrasonography showed bilateral hypoplastic kidneys. Whole exome sequencing revealed de novo frameshift mutations in PAX2 and OPA1. Both variants were classified as pathogenic (PVS1, PS2, PM2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Genetic testing for ocular diseases should be considered for patients with suspected RCS and a high risk of total blindness. [ABSTRACT FROM AUTHOR]

Background. Worldwide, more than 67 million people suffer from glaucoma. In Russia, this number exceeds 1.08 million people. Annually, the number of primary cases increases by 3–4%. The increasing prevalence of glaucoma intensifies the search for neuroprotectants that can reduce the loss of retinal ganglion cells, thereby impeding the progression of the disease. Objective. To study of the pharmacological activity of mGLUR4 agonist, ZC64-0001 substance, on a model of primary open-angle glaucoma. Methods. The conducted preclinical study involved 60 sexually mature male Wistar rats, weighing 180–220 g. The observation period was 73 days. The animals were divided into 6 groups with 10 animals in each. Group 1 included intact animals (without any manipulations); Group 2 included negative control animals with the water injected in the anterior chamber of the eye; in Group 3–6, primary open-angle glaucoma was modelled by injecting 1% hyaluronic acid solution into the anterior chamber of the eye once every 7 days from day 1 to day 62 of the study. Animals in Group 4 were treated intragastrically with H-[(4-chlorophenyl)methyl]-1,6-dihydro-4-methoxy-1-(2-methylphenyl)-6-oxo-3-pyridazinecarboxamide under the laboratory code of ZC64-0001 at a dose of 10 mg/kg. Animals in Group 5 received Mexidol as a comparison drug intramuscularly at a dose of 25.7 mg/kg. Animals in Group 6 were treated with a Timolol instillation at a dose of 0.009 ml/kg. The studied compounds were administered from day 63 of the study once a day for 10 days. The evaluated indicators included the level of microcirculation in the retina, the amplitude of a-wave and b-wave of the electroretinogram, and the number of retinal ganglionic layer nuclei in the setting of the conducted treatment. Statistical processing of the data was performed using the Statistica 10.0 software (StatSoft, USA). Differences were determined at the significance level of p ˂ 0.05. Results. ZC64-0001 increased the level of microcirculation relative to the group with modelled glaucoma by 11.5%, with this indicator being statistically significantly different from that both in the group with modelled glaucoma and the intact group ( р < 0.05). In the group of animals receiving ZC64-0001, the amplitude of a-wave increased relative to the primary glaucoma group by 17.7%, with this index being statistically different from the groups of intact animals and negative control (р < 0.05). The b-wave amplitude increased by 34.4% relative to the group with modelled glaucoma, being statistically different from the intact group, negative control group, pathology modelled group, and comparison drug groups ( р < 0.05). Administration of ZC64-0001 increased the number of retinal ganglion cell nuclei relative to the group with modelled glaucoma by 41.0%, which had a statistically significant difference from all the studied groups ( р < 0.05). Conclusion. The ZC64-0001 compound demonstrated high neuroprotective properties in a model of primary open-angle glaucoma, leading to an improvement in retinal microcirculation, an increase in the wave amplitude according to the conducted electrophysiological study, and an increase in the number of ganglion cell nuclei.

Variation of multifocal electroretinogram (mfERG) data presentation in existing scientific publications is a challenge for eye care practitioners to apply the scientific information for evidence-based practice in patient management. This review offers an overview of the mfERG data presentation types. Eight types of data presentation in the form of a table, scatter plot, line graph, bar graph/box plot, single waveform/a group of waveforms, trace array topography, three-dimensional topography, and two-dimensional topography are identified. The table format is used to provide the exact values. Line graphs, scatter, and box plots offer information about the relationship of mfERG values. Waveforms are helpful for comparison between groups or conditions. Topographies outline the retinal, especially the specific localized retinal abnormalities. An infographic of fundamental mfERG electrical response with definitions and clinical indications is provided to bridge the gap between researchers and clinicians to facilitate efficient clinical application.

BackgroundInherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5. Examination of these patients included funduscopic evaluation, spectral-domain optical coherence tomography, short-wavelength autofluorescence, and full-field electroretinography (ffERG). Genetic diagnoses were confirmed using whole exome capture. Protein modeling of the identified variants was performed to explore potential genotype-phenotype correlations.ResultsGenetic testing revealed five novel variants in TTLL5 in three unrelated patients with retinal dystrophy. Clinical imaging demonstrated features of sectoral cone-rod dystrophy and cone dystrophy, with phenotypic variability seen across all three patients. One patient also developed high-frequency hearing loss during a similar time period as the onset of retinal disease, potentially suggestive of a syndromic disorder. Retinal structure findings were corroborated with functional measures including ffERG findings that supported these diagnoses. Modeling of the five variants suggest that they cause different effects on protein function, providing a potential reason for genotype-phenotype correlation in these patients.ConclusionsThe authors report retinal phenotypic findings in three unrelated patients with novel mutations causing autosomal recessive TTLL5-mediated retinal dystrophy. These findings broaden the understanding of the phenotypes associated with TTLL5-mediated retinal disease and suggest that mutations in TTLL5 should be considered as a potential cause of sectoral retinal dystrophy in addition to cone-rod and cone dystrophies.

PurposeLoss of retinoschisin (RS1) function underlies X-linked retinoschisis (XLRS) pathology. In the retina, both photoreceptor inner segments and bipolar cells express RS1. However, the loss of RS1 function causes schisis primarily in the inner retina. To understand these cell type-specific phenotypes, we decoupled RS1 effects in bipolar cells from that in photoreceptors.MethodsBipolar cell transgene RS1 expression was achieved using two inner retina-specific promoters: (1) a minimal promoter engineered from glutamate receptor, metabotropic glutamate receptor 6 gene (mini-mGluR6/ Grm6) and (2) MiniPromoter (Ple155). Adeno-associated virus vectors encoding RS1 gene under either the mini-mGluR6 or Ple-155 promoter were delivered to the XLRS mouse retina through intravitreal or subretinal injection on postnatal day 14. Retinal structure and function were assessed 5 weeks later: immunohistochemistry for morphological characterization, optical coherence tomography and electroretinography (ERG) for structural and functional evaluation.ResultsImmunohistochemical analysis of RS1expression showed that expression with the MiniPromoter (Ple155) was heavily enriched in bipolar cells. Despite variations in vector penetrance and gene transfer efficiency across the injected retinas, those retinal areas with robust bipolar cell RS1 expression showed tightly packed bipolar cells with fewer cavities and marked improvement in inner retinal structure and synaptic function as judged by optical coherence tomography and electroretinography, respectively.ConclusionsThese results demonstrate that RS1 gene expression primarily in bipolar cells of the XLRS mouse retina, independent of photoreceptor expression, can ameliorate retinoschisis structural pathology and provide further evidence of RS1 role in cell adhesion.

Purpose. The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). Materials and Methods. This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Results. Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. Conclusions. ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression. [ABSTRACT FROM AUTHOR]

Purpose. The aim of the study is to describe the genotype and phenotype of a Mexican cohort with PCARE-related retinal disease. Methods. The study included 14 patients from 11 unrelated pedigrees with retinal dystrophies who were demonstrated to carry biallelic pathogenic variants in PCARE. Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field test, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed either by gene panel sequencing or by exome sequencing. Results. According to the results of multimodal imaging and functional tests, all 14 patients were diagnosed with cone-rod dystrophy. Six different PCARE pathogenic alleles were identified in our cohort, including three novel mutations: c.3048_3049del (p.Tyr1016 ∗), c.3314_3315del (p.Ser1105 ∗), and c.551A > G (p.His184Arg). Notably, alleles p.His184Arg, p.Arg613 ∗ , and p.Arg984 ∗ were present in 18 of the 22 (82%) PCARE alleles from probands in our cohort. Conclusion. Our work expands the PCARE mutational profile by identifying three novel pathogenic variants causing retinal dystrophy. While phenotypic variations occurred among patients, a cone-rod dystrophy pattern was observed in all affected individuals. [ABSTRACT FROM AUTHOR]

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (β = − 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (β = − 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). Methods: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 patients with type 1 diabetes (T1DM); the control group included 23 age-matched healthy subjects. pERG and pVEP were assessed using the RETI-port/scan21 recording software (version 1021.3.0.0). Results: Mean age was 48 ± 9.77 years for the diabetic group and 51.7 ± 4.75 years for the control group. The mean duration of diabetes was 28.88 ± 8.04 years. The mean HbA1c value was 7.29 ± 0.89%. There were no differences in the age or sex distribution. Regarding the pERG, T1DM patients exhibited a significant decrease in the amplitude of the P50 and N95 waves compared to the control group (p = 0.018 and p = 0.035, respectively), with no differences in the peak time of each component. pVEP showed no significant changes in either peak time or amplitude of the different components. Conclusions: Long-term T1DM patients without DR showed changes in the amplitude of pERG waves with preserved peak times. We did not observe modifications in pVEP. pERG may serve as a subclinical marker of ganglion cell damage in long-term T1DM patients. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Applied Ecology / Yingyong Shengtai Xuebao is the property of Chinese Journal of Applied Ecology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Flash visual evoked potential (FVEP) is a critical method for monitoring intraoperative visual function during neurosurgery. A new benzodiazepine drug called remimazolam has recently been used for general anesthesia. However, the impact of remimazolam on FVEP remains unclear. Therefore, we aimed to investigate how remimazolam, in comparison to propofol, when combined with 0.6% sevoflurane anesthesia, affects the FVEP waveform during pituitary adenoma resection. Methods: Overall, 36 patients undergoing pituitary adenoma resection under general anesthesia were randomly assigned to either the remimazolam group (Group R) or the propofol group (Group P) in a prospective, randomized, controlled, non-inferiority trial. For anesthesia induction, a bolus of 0.2 mg/kg remimazolam or 2 mg/kg propofol was intravenously infused for approximately one minute. The anesthesia was maintained by continuous infusion of either remimazolam (0.7-1.0 mg/kg/h) or propofol (4–6 mg/kg/h), in combination with 0.6% sevoflurane, aimed at sustaining the bispectral index (BIS) within the range of 40–60. The primary outcome was the N75-P100 amplitude of FVEP recorded at approximately 20 min after intubation (T0). 10% of the amplitude at T0 in group P was defined as the non-inferiority margin (δ). Confidence interval testing was used to evaluate the non-inferiority hypothesis. The secondary outcomes covered the P100 latency of FVEP, electroretinogram (ERG) b wave amplitude, demographic characteristics, hemodynamics, and occurrence of adverse events. Results: The BIS index during anesthesia was comparable between the groups at the same measured time points (P > 0.05). The N75-P100 amplitude at T0 in group R was 7.64 ± 1.36 µV, while it was 6.96 ± 0.95 µV in group P (P = 0.09), with a mean difference of 0.68 µV (95% CI, -0.11 µV to 1.48 µV). The δ was set at 0.7 and the lower limit of the 95% CI exceeded the -δ. Both remimazolam and propofol had little effect on ERG b-wave amplitudes. At the designated time points, FVEP amplitude and P100 latency displayed no appreciable variation between the two groups (P > 0.05). Furthermore, there were no significant differences in the incidence of adverse events related to anesthesia, needle electrodes, or surgery between the two groups (P > 0.05). Conclusion: Our findings suggest that remimazolam-0.6% sevoflurane is non-inferior to propofol-0.6% sevoflurane for general anesthesia, based on the FVEP N75-P100 amplitude. The electrophysiological data obtained in both groups indicate that reproducible and stable FVEP and ERG waveforms can be acquired at set time points. Therefore, for reliable FVEP monitoring, remimazolam-0.6% sevoflurane appears to be a safe and effective protocol in general anesthesia. Trials registration: This study was registered on chictr.org.cn (ChiCTR2200056803, 17/02/2022). [ABSTRACT FROM AUTHOR]

Introduction: This study tested whether multiple traumatic brain injuries (TBIs) alter the structure of the Henle fiber layer (HFL) and degrade cell-specific function in the retinas of human participants. Methods: A cohort of case participants with multiple TBIs and a cohort of pairmatched control participants were prospectively recruited. Directional optical coherence tomography and scanning laser polarimetry measured HFL thickness and phase retardation, respectively. Full-field flash electroretinography (fERG) assessed retinal function under light-adapted (LA) 3.0, LA 30 Hz, dark-adapted (DA) 0.01, DA 3.0, and DA 10 conditions. Retinal imaging and fERG outcomes were averaged between both eyes, and paired t-tests or Wilcoxon signed-rank tests analyzed inter-cohort differences. Results: Global HFL thickness was significantly (p = 0.02) greater in cases (8.4 ± 0.9 pixels) than in controls (7.7 ± 1.1 pixels). There was no statistically significant difference (p = 0.91) between the cohorts for global HFL phase retardation. For fERG, LA 3.0 a-wave amplitude was significantly reduced (p = 0.02) in cases (23.5 ± 4.2 µV) compared to controls (29.0 ± 8.0 µV). There were no other statistically significant fERG outcomes between the cohorts. Discussion: In summary, the HFL thickens after multiple TBIs, but phase retardation remains unaltered in the macula. Multiple TBIs may also impair retinal function, indicated by a reduction in a-wave amplitude. These results support the potential of the retina as a site to detect TBI-associated pathology. [ABSTRACT FROM AUTHOR]

Objective: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram. Methods: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG). Results: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy. Conclusion: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Quercetin has therapeutic effects on retinopathy induced by hyperglycemia. • Quercetin protects against retinopathy by regulating gut-retina axis. • Quercetin can enhance the antioxidant capacity in the retina. Hyperglycemia-related retinopathy is a disease with a high blindness rate. Recent reports indicate that many flavonol compounds have the potential to prevent the occurrence of disease in the retina by regulating the gut–retina axis. Here, we hypothesized that quercetin could alleviate the symptoms of retinopathy. To clarify the mechanism, Sprague Dawley rats were fed a high-fat diet containing quercetin for 12 weeks and injected with streptozotocin in the ninth week. Additionally, neomycin and ampicillin were used to establish a pseudo-sterile rat model. Afterward, changes in the retina were investigated by using electroretinogram and optical coherence tomography. Blood and tissue samples were collected and biochemical components were analyzed. The extent of intestinal injury was determined via hematoxylin-eosin staining. Microbial community structure was analyzed by using 16S ribosomal RNA sequencing. Finally, the expression of genes was analyzed using real-time polymerase chain reaction. The results showed that quercetin reduced the decline in electroretinography amplitude and outer nuclear layer thickness, increased the activities of antioxidant enzymes, decreased the contents of proinflammatory factors and blood glucose, enhanced the concentration of insulin, and inhibited intestinal dysbiosis and improved gut morphology. Importantly, the underexpression of nuclear factor erythroid-2 related factor 2 in the retina was reversed by quercetin. However, trend changes were no longer significant in most of the indicators after antibiotic treatment. In summary, quercetin has therapeutic effects on retinopathy by regulating the gut–retina axis and nuclear factor erythroid-2 related factor 2 pathway, and the presence of gut microbiota helps quercetin exert its effects on the retina. Quercetin has therapeutic effects on hyperglycemia-induced retinopathy. It increases antioxidant capacity of the retina, decreases the contents of pro-inflammatory factors and the concentration of blood sugar, and restores the gut microbial composition. After the use of broad-spectrum antibiotics, the protective effects of quercetin on retinopathy are no longer significant. Red arrows indicate decreased trend, green arrows indicate increased trend, and purple circles indicate no changes. [Display omitted] [ABSTRACT FROM AUTHOR]

Alcohol is the most widely consumed addictive substance around the world and have deleterious effect on the central nervous system. Alcohol consumption affect the balance of certain neurotransmitters like GABA, glutamate and dopamine. The retina provides an easy means of investigating dysfunctions of synaptic transmission in the brain. The purpose of this study is to assess the impact of alcohol consumption on retinal function using pattern electroretinogram (PERG) and flash electroretinogram (fERG). We recorded PERG and fERG under scotopic and photopic condition in 20 patients with alcohol use disorder and 20 controls. Implicit time and amplitude of numerous parameters were evaluated: a- and b-waves for fERG, OP3 and OP4 for dark-adapted 3.0 oscillatory potentials fERG, P50 and N95 for PERG. Patients with alcohol use disorder showed a significant increase in N95 implicit time without a significant change in the amplitudes of oscillatory potentials. The results of our study reflect the impact of alcohol use on ganglion cell function and could highlight alterations in glutamatergic neurotransmission inside the retina. We believe that ERG could be used as an early marker of alcohol consumption. [ABSTRACT FROM AUTHOR]

Objectives: The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. Materials and Methods: The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. Results: The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on fullfield ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. Conclusion: The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG. [ABSTRACT FROM AUTHOR]

Glaucoma is characterized by cupping of the optic disc, apoptotic degeneration of retinal ganglion cells (RGCs) and their axons, and thinning of the retinal nerve fiber layer, with patchy loss of vision. Elevated intraocular pressure (IOP) is a major risk factor for hypertensive glaucoma and the only modifiable one. There is a need to find novel compounds that counteract other risk factors contributing to RGC degeneration. The oil derived from the wild olive tree (Olea europaea var. sylvestris), also called Acebuche (ACE), shows powerful anti-inflammatory, antioxidant and retinoprotective effects. We evaluated whether ACE oil could counteract glaucoma-related detrimental effects. To this aim, we fed mice either a regular or an ACE oil-enriched diet and then induced IOP elevation through intraocular injection of methylcellulose. An ACE oil-enriched diet suppressed glaucoma-dependent retinal glia reactivity and inflammation. The redox status of the glaucomatous retinas was restored to a control-like situation, and ischemia was alleviated by an ACE oil-enriched diet. Notably, retinal apoptosis was suppressed in the glaucomatous animals fed ACE oil. Furthermore, as shown by electroretinogram analyses, RGC electrophysiological functions were almost completely preserved by the ACE oil-enriched diet. These ameliorative effects were IOP-independent and might depend on ACE oil's peculiar composition. Although additional studies are needed, nutritional supplementation with ACE oil might represent an adjuvant in the management of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system. To investigate the dark-adapted cone-driven waveform in healthy individuals, we delivered flashes on a dim blue background, designed to saturate the rods, but minimally adapt the cones. Methods: ERGs were recorded, using conductive fibre electrodes, in adults from the TwinsUK cohort. Responses to 13 cd m−2 s white xenon flashes (similar to the standard DA 10 flash), delivered on a blue background, were analysed. Photopic and scotopic strengths of the background were 1.3 and 30 cd m−2, respectively; through a dilated pupil, this is expected to largely saturate the rods, but adapt the cones much less than the standard ISCEV background. Results: Mean (SD) participant age was 62.5 (11.3) years (93% female). ERGs from 203 right and 204 left eyes were included, with mean (SD) b/a ratios of 1.22 (0.28) and 1.18 (0.28), respectively (medians, 1.19 and 1.17). Proportions with negative waveforms were 23 and 26%, respectively. Right and left eye b/a ratios were strongly correlated (correlation coefficient 0.74, p < 0.0001). We found no significant correlation of b/a ratio with age. Conclusions: Over 20% of eyes showed b/a ratios less than 1, consistent with the notion that dark-adapted cone-driven responses to standard bright flashes can have negative waveforms. The majority had ratios greater than 1. Thus, whilst selective loss of rod function can yield a negative waveform (with reduced a-wave) in some, our findings also suggest that loss of rod function can occur without necessarily yielding a negative ERG. One potential limitation is possible mild cone system adaptation by the background. [ABSTRACT FROM AUTHOR]

Targeted electric signal use for disease diagnostics and treatment is emerging as a healthcare game-changer. Besides arrhythmias, treatment-resistant epilepsy and chronic pain, blindness, and perhaps soon vision loss, could be among the pathologies that benefit from bioelectronic medicine. The electroretinogram (ERG) technique has long demonstrated its role in diagnosing eye diseases and early stages of neurodegenerative diseases. Conspicuously, ERG applications are all based on light-induced responses. However, spontaneous, intrinsic activity also originates in retinal cells. It is a hallmark of degenerated retinas and its alterations accompany obesity and diabetes. To the extent that variables extracted from the resting activity of the retina measured by ERG allow the predictive diagnosis of risk factors for type 2 diabetes. Here, we provided a comparison of the baseline characteristics of intrinsic oscillatory activity recorded by ERGs in mice, rats, and humans, as well as in several rat strains, and explore whether zebrafish exhibit comparable activity. Their pattern was altered in neurodegenerative models including the cuprizone-induced demyelination model in mice as well as in the Royal College of Surgeons (RCS-/-) rats. We also discuss how the study of their properties may pave the way for future research directions and treatment approaches for retinopathies, among others. [ABSTRACT FROM AUTHOR]

Background: Despite the marked increase in the anatomical success rates of macula-off rhegmatogenous retinal detachment (RRD) surgery, patients may still complain about unsatisfactory visual outcome. This study aims to correlate the postoperative corrected distance visual acuity (CDVA) with the mf-ERG (multifocal electroretinogram) and OCT (optical coherence tomography) findings following vitrectomy surgery for RRD. Patients and methods: This retrospective observational study included 40 eyes of 40 patients who underwent successful vitrectomy surgery for macula-off RRD. CDVA, mf-ERG amplitudes, mf-ERG latencies, the central macular thickness (CMT) and the integrity of the inner segment/outer segment (IS/OS) junction assessed by OCT, were evaluated 6 months postoperatively. The correlations between CDVA with mf-ERG amplitudes, mf-ERG latencies, central macular thickness, and IS/OS junction integrity were analyzed. Results: There was a statistically significant moderate positive correlation between CDVA of the studied eyes with mf-ERG amplitudes of N1, P1 and N2 in ring 1 (P = 0.008; P < 0.001 and P = 0.004, respectively), CMT (P < 0.001), and the integrity of IS/OS junction (P < 0.001). There was no significant correlation between CDVA and mf-ERG latencies in ring 1 (P > 0.05). Linear regression analysis revealed that CDVA was significantly associated with mf-ERG amplitudes and the IS/OS junction integrity. In addition, there was a strong positive correlation between mf-ERG amplitudes in ring 1 and the IS/OS junction integrity. Conclusions: The integrated interpretation of postoperative CDVA, multifocal ERG parameters, and OCT findings provides useful information about functional visual recovery and retinal microstructural changes following vitrectomy for macula-off RRD surgery. The positive correlation between the IS/OS junction integrity and the mf-ERG amplitudes was stronger than the correlation between the IS/OS junction integrity and CDVA suggesting that mf-ERG may be superior to CDVA in reflecting the extent of microstructural damage in the photoreceptor layer. Trial Registration: Clinicaltrials.gov, NCT05993208. Registered 15 August 2023 - Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT05993208. [ABSTRACT FROM AUTHOR]

Background: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation. Objective: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing. Methods: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls. Results: PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time. Conclusions: We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD. [ABSTRACT FROM AUTHOR]

Variation of multifocal electroretinogram (mfERG) data presentation in existing scientific publications is a challenge for eye care practitioners to apply the scientific information for evidence-based practice in patient management. This review offers an overview of the mfERG data presentation types. Eight types of data presentation in the form of a table, scatter plot, line graph, bar graph/box plot, single waveform/a group of waveforms, trace array topography, three-dimensional topography, and two-dimensional topography are identified. The table format is used to provide the exact values. Line graphs, scatter, and box plots offer information about the relationship of mfERG values. Waveforms are helpful for comparison between groups or conditions. Topographies outline the retinal, especially the specific localized retinal abnormalities. An infographic of fundamental mfERG electrical response with definitions and clinical indications is provided to bridge the gap between researchers and clinicians to facilitate efficient clinical application. [ABSTRACT FROM AUTHOR]

Fundus Albipunctatus (FA) is one of the rare forms of persistent night blindness. Common white or pale yellow spots are present on the fundus. Given its clinical findings; FA is also considered in the group of diseases (retinitis punctata albescens, fundus flavimaculatus, familial drusen, flecked retina of Kandori) termed flecked retina syndromes. In order to ensure an accurate diagnosis of FA, it is important to be aware of the multimodal retinal imaging characteristics and appropriate electroretinographic findings for this disorder. In this manuscript, we aimed to present multimodal retinal images and disease-specific electroretinography findings in two patients diagnosed with FA in our clinic. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) is frequently prescribed for managing rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, prolonged use of HCQ has been linked to retinal toxicity. Objective: To assess retinal changes in patients receiving HCQ treatment using multifocal electroretinogram (mfERG). Methods: This cross-sectional study included forty Egyptian patients with a history of one year or more of HCQ intake for conditions like systemic lupus erythematosus or rheumatoid arthritis. Patients underwent complete ophthalmic examinations and were subsequently evaluated using multifocal electroretinogram. Results: There was no statistically significant difference in multifocal ERG abnormalities concerning the age distribution among the studied patients (P>0.05). However, a statistically significant difference was observed between mfERG abnormalities and the duration of HCQ treatment (P<0.05). Notably, patients with paracentral depression had the longest treatment duration. Conclusions: The study findings indicate that multifocal ERG serves as a valuable screening tool for early detection of HCQ retinopathy, detecting signal depression, primarily in the paracentral region, in patients treated with HCQ for over 5 years. Importantly, even visually asymptomatic patients with no fundus abnormalities may exhibit abnormal results on mfERG. [ABSTRACT FROM AUTHOR]