Metrics details The Pattern Electroretinogram (PERG) is an essential tool in ophthalmic electrophysiology providing an objective assessment of the central retinal function It quantifies the activity of cells in the macula and the ganglion cells of the retina assisting in the differentiation of macular and optic nerve conditions an extensive collection of 1354 transient PERG responses accessible on the PhysioNet repository These recordings were conducted at the Institute of Applied Ophthalmobiology (IOBA) at University of Valladolid over an extended period spanning nearly two decades The dataset thoughtfully includes demographic and clinical data This comprehensive dataset fills a gap in ocular electrophysiological repositories Researchers can explore a broad range of eye-related conditions and diseases and a deeper understanding of ocular electrophysiology This specific area of the retina is responsible for central vision and fine-detail visual tasks therefore it plays a critical role in our daily lives The importance of PERG lies in its ability to identify early signs of macular disorders and conditions that affects the optic nerve even before substantial loss of visual field occurs PERG serves as a valuable tool for long-term monitoring of the progress of these disorders allowing healthcare professionals to assess the effectiveness of treatment strategies and make necessary adjustments when needed Beyond its role in early detection and monitoring PERG can be employed for differential diagnoses In situations where retinal disorders present similar symptoms but originate from diverse underlying causes specific focus on macular function helps provide more accurate diagnoses PERG extends beyond the boundaries of clinical practice and is frequently used in clinical research and trials related to retinal and optic nerve diseases Its ability to offer precise data on macular function makes it a useful tool for evaluating the efficacy of new treatments and interventions generated at temporal rates less than 6 pattern reversals per second (rps) generated at temporal rates higher than 10 rps PERG signal datasets are not currently available in public repositories Access to datasets generated and analyzed in various studies can often be obtained from the corresponding author upon request it is frequently presented in the form of summarized component wave amplitudes and their corresponding implicit times we present a extensive transiet PERG dataset It is comprised of 1354 signals gathered from 304 participants enrolled at the Institute of Applied Ophthalmobiology (IOBA) a University of Valladolid-affiliated institution in Spain Throughout this elongated recruitment period 23 individuals participated in multiple visits As a part of the routine clinical assessment subjects provided detailed clinical information and between 1 and 3 diagnoses by ophthalmology specialists this dataset ensures access to at least one PERG signal for each eye facilitating research into patterns and variations in ocular responses The dataset described in this paper was compiled for a project focused on the automated analysis of electrical signals obtained through ocular electrophysiology tests which received approval from the IOBA research committee (approval 2021/47) The rigorous approval process guarantees strict adherence to ethical and research standards Following IOBA’s standard clinical practice all patients were informed about the procedures and benefits of the ocular electrophysiological tests they were made aware of the potential use of their de-identified data for research purposes All participants signed an informed consent form indicating their agreement and acknowledging their understanding of the information provided a total of 336 ocular electrophysiology visits were conducted at IOBA a research institute affiliated with the University of Valladolid in Spain These visits involved the measurement of transiet PERG signals from a diverse group of 304 subjects or participants involved in eye-related research As a result of these visits a substantial collection of 1354 transient PERG signals was collected The dataset encompasses all individuals who underwent transient PERG testing in the Retina Unit at IOBA during this period ensuring comprehensive inclusion without selective exclusion criteria Transient PERG was primarily used to assess visual prognosis in patients with retinal diseases who retained some vision It is generally not indicated for patients with a logMAR visual acuity exceeding 1.0 which corresponds to the threshold for legal blindness as its results are often expected to be flat PERG may be useful in cases where the cause of vision loss is unclear in patients with normal ocular fundus although such scenarios are relatively uncommon Data were compiled during routine checkups The results were reviewed and analyzed by a specialized ophthalmologist belonging to the Retina Unit who conducted comprehensive clinical evaluations and diagnoses The ISCEV guidelines involves a standardized and well-defined procedure to guarantee a high degree of consistency and reliability in measurements there was only one hardware and software upgrade This upgrade is unlikely to have had a major impact on data consistency the ISCEV PERG standards have been updated to reflect advancements in technology and a deeper understanding of electrophysiological testing Key changes include more flexible stimulus parameters updated recording conditions with a preference for binocular recordings These adjustments improve the accuracy and consistency of PERG recordings without fundamentally altering the basic principles of the protocol described bellow A binocular recording was carried out using single-use conveniently sterilized electrodes with their integrity verified before insertion A recording gold electrode was accurately positioned on the corneal surface while a separate reference electrode was placed on the skin near the outer canthus of each eye on the same side (ipsilateral) a surface electrode was placed on he forehead and connected to the amplifier to “ground input” The subjects were meticulously prepared for the examination ensuring they were in a comfortable and relaxed state throughout the process with their heads in a stable position against a head-rest the PERG signals were recorded without dilatation of the pupils and with the necessary optical correction for an optimal visual acuity This correction was initially based on the participants’ current refractive prescriptions if these prescription did not provide 20/20 vision the refraction was manually reassessed during the visit and the optical correction was adjusted accordingly dark room at a distance of 1 m from the monitor with the screen occupying 12o vertically and 16o horizontally of the visual field Explicit instructions were provided to the participants directing them to fixate on a central target in the stimulator (0.5o with an emphasis on minimizing any unnecessary eye and/or face movements The lighting conditions in the testing room were thoughtfully controlled maintaining a subdued ambient light environment before presenting the visual stimuli to the subjects These conditions remained constant throughout all recordings A black and white reversing checkerboard pattern was employed The stimulus was displayed on a cathode-ray tube (CRT) monitor to mitigate flash artifacts that can occur during pattern reversals The checkerboard pattern featured a check size of 1.0o with white areas exhibited a photopic luminance exceeding 80 candela per square meter and the contrast between the black and white squares was maximized a frame rate of 75 Hz was utilized to present the stimuli with precision Each eye was subjected to an average of 230 pattern reversal stimuli was set at 150 milliseconds with 250 milliseconds intervals between reversals a higher sampling rate of 1700 Hz was employed during PERG recording PERG signals were recorded using amplification systems and electrodes and the raw data was collected in digital form The signal processing adhered to the clinical standards integrated into the used devices This encompassed a series of essential steps These steps collectively aimed to elevate data quality while eliminating any unwanted noise a series of preprocessing steps were carried out encompassing crucial procedures such as filtering and baseline correction The recorded signals were filtered within a 1–100 Hz band to isolate the relevant frequency components and remove noise outside this range with each segment corresponding to a single stimulus presentation These segments underwent meticulous artifact detection procedures to maintain data integrity Computerized algorithms analyzed the data to detect abnormal data points often stemming from sources like eye blinks were identified by the algorithms through predefined threshold values A fast rejection threshold of 8 μV was applied to eliminate data points with high-amplitude fluctuations while a slow rejection threshold of 50 μV was used to filter out slower artifacts that could affect the signal Any data point exceeding these established thresholds was flagged as a potential artifact Flagged data points were replaced with interpolated values effectively eradicating their influence on the final data Signal averaging emerges as a fundamental step in PERG signal processing due to their typically low amplitude This process is instrumental in augmenting the signal-to-noise ratio thereby enabling the extraction of meaningful insights from the data A minimum of 100 artifact-free sweeps were acquired and then subjected to averaging In cases where the PERG response exhibited small amplitude or was overshadowed by significant background noise a higher number of sweeps became imperative to yield reliable results To safeguard the confidentiality and privacy of the subjects involved all protected health information has been meticulously removed from the dataset and a comprehensive de-identification process was applied The anonymization process began with the identification of personal information which was categorized into direct and indirect identifiers Clinical history references were replaced with a unique four-digit codes generated randomly to preserve data utility while ensuring confidentiality were handled through generalization and random offset techniques birthdates were replaced with only the age of participants (in years) acquisition dates were subtly shifted by a random offset preserving chronological order but obscuring specific dates These measures ensure the protection of individual privacy while maintaining the value of the dataset for research purposes with each record corresponding to a single visit and it encompasses a total of 1354 PERG signals Each record in the dataset guarantees the presence of at least one PERG signal for each eye The PERG signal data are presented in comma-separated value (CSV) format These files adhere to a standardized naming convention featuring a four-digit unique identifier that has been exclusively designed for this collection this unique identifier is entirely independent of any information found in the participants’ medical records All CSV files include a TIME column and at least one PERG signal data for each eye identified as RE_1 and LE_1 for the right and left eye The time is encoded as YYYY-MM-DD hh:mm:ss.ms To accommodate cases where the test is repeated during the same visit are included to encompass multiple signals collected for each eye to provide temporal information for the repeated tests are incorporated into the CSV records whenever applicable In total, there are 1354 PERG signals distributed across 336 records, with a number of signals per record ranging from 2 to 10. A detailed breakdown regarding the number of signals per record is presented in Table 1 Note that the number of PERG signals is always a multiple of 2 as data from both eyes are consistently incorporated Metadata for all PERG records are provided in CSV format, organized within the file participants_info.csv containing 12 columns. Table 2 gives an overview of the variables included in this table The color scheme differentiates between diagnostic classes Distribution of PERG-IOBA records within diagnostic categories and subcategories: (a) Diagnostic classes and (c) Subclasses of neuro-ophthalmic disorders Demographic data comprises information on age and sex, with 47.6% being male and 52.4% female. The age refers to the subjects’s age at the time of the PERG recording. The age distribution for the complete dataset and segregated by gender is presented in Table 3 The variable rep_record is designed to aggregate record identifiers belonging to the same individual Each entry in this variable follows the format id:XXXX where XXXX represents the specific record identifier Different records are separated by hyphens (-) Distribution of the average visual acuity between eyes within diagnostic subcategories more frequent evaluations were carried out when necessary to promptly address any deviations and maintain consistent performance Specific equipment calibration parameters were meticulously maintained These parameters include adjusting stimulus luminance of white areas within the range of 100 to 500 cd/m2 80 to 100 cd/m2 and a mean luminance of 45–50 cd/m2 constant overall screen luminance during checkerboard reversals was verified Other parameters include maintaining a sampling frequency of 1700 Hz calibrating stimulus voltage levels to prevent saturation while ensuring adequate response setting system response time typically between 1 to 10 ms post-stimulus precise alignment of visual stimuli on the monitor maintaining background noise levels below 5 μV and ensuring electrode impedance remains below 5 kΩ Calibration also involves setting amplifier gain to amplify signals without distortion can be greatly affected by background noise This noise can originate from various sources such as electronic components or inherent limitations in the measurement or transmission process emphasizing the crucial role of signal averaging in the acquisition process is essential for mitigating the impact of background noise averaging involves combining multiple repetitions of the same stimulus presentation which remains consistent across repetitions contributing to enhancing the signal-to-noise ratio The presence of noise in signals is often characterized by rapid and random changes in amplitude from point to point within the signal the signal amplitudes typically exhibit a smoother the use of smoothing techniques can be useful for evaluating the presence of high-frequency variations or noise in a signal In terms of the frequency components of a signal a smoothing operation serves as a low-pass filter reducing high-frequency components while preserving low-frequency components This results in a naturally smoother signal characterized by a slower step response to signal changes In this section we use smoothing to assess the presence of noise in the signals of the PERG-IOBA dataset Note that this smoothing process has not been applied to the actual signals available in the dataset Decomposition of PERG data into signal and noise components from three illustrative recordings exhibiting different levels of background noise To assess the predictive performance of the smoothed signal the coefficient of determination (R2) can be used as a measure of goodness of fit Distribution of the 1 − R2 across diagnostic subcategories The weakened signal becomes more susceptible to interference from various sources The PERG-IOBA dataset was created for the primary objective of developing and assessment of automated diagnostic algorithms relying on PERG signals In a field where repositories of ocular electrophysiological signals are limited this extensive dataset stands as a valuable resource holding the potential to drive substantial progress in the realm of ophthalmology research Its accessibility opens up fresh avenues for the exploration of a wide range of eye-related conditions and diseases facilitates the advancement of diagnostic techniques and a more profound comprehension of ocular electrophysiology To download and explore this dataset, users can visit the following url: https://physionet.org/content/perg-ioba-dataset/1.0.0/ provided that appropriate attribution is given to the original data owner No custom code was generated for this work Kremers, J., McKeefry, D. J., Murray, I. J. & Parry, N. R. Developments in non-invasive visual electrophysiology. Vision Research 174, 50–56, https://doi.org/10.1016/j.visres.2020.05.003 (2020) Mahroo, O. A. Visual electrophysiology and “the potential of the potentials”. Eye 37, 2399–2408, https://doi.org/10.1038/s41433-023-02491-2 (2023) Yu, M., Creel, D. J. & Iannaccone, A. Handbook of Clinical Electrophysiology of Vision, https://doi.org/10.1007/978-3-030-30417-1 (Springer Parisi, V. et al. Morphological and functional retinal impairment in alzheimer’s disease patients. Clinical Neurophysiology 112, 1860–1867, https://doi.org/10.1016/S1388-2457(01)00620-4 (2001) Nightingale, S., Mitchell, K. & Howe, J. Visual evoked cortical potentials and pattern electroretinograms in parkinson’s disease and control subjects. Journal of Neurology, Neurosurgery & Psychiatry 49, 1280–1287, https://doi.org/10.1136/jnnp.49.11.1280 (1986) Barton, J. L., Garber, J. Y., Klistorner, A. & Barnett, M. H. The electrophysiological assessment of visual function in multiple sclerosis. Clinical Neurophysiology Practice 4, 90–96, https://doi.org/10.1016/j.cnp.2019.03.002 (2019) The electrophysiological characteristics and monitoring of ethambutol toxicity Investigative Ophthalmology & Visual Science 55 Silverstein, S. M., Demmin, D. L., Schallek, J. B. & Fradkin, S. I. Measures of retinal structure and function as biomarkers in neurology and psychiatry. Biomarkers in Neuropsychiatry 2, 100018, https://doi.org/10.1016/j.bionps.2020.100018 (2020) Holder, G. E. Pattern electroretinography (PERG) and an integrated approach to visual pathway diagnosis. Progress in Retinal and Eye Research 20, 531–561, https://doi.org/10.1016/S1350-9462(00)00030-6 (2001) Bach, M. et al. ISCEV standard for clinical pattern electroretinography (PERG): 2012 update. Documenta Ophthalmologica 126, 1–7, https://doi.org/10.1007/s10633-012-9353-y (2013) ISCEV standard for clinical pattern electroretinography-2007 update Holder, G. Electrophysiological assessment of optic nerve disease. Eye 18, 1133–1143, https://doi.org/10.1038/sj.eye.6701573 (2004) ISCEV standard for clinical pattern electroretinography (2024 update) Canedo, C., Fernández, I., Coco, R. M., Cuadrado, R. & Rueda, C. Novel modeling proposals for the analysis of pattern electroretinogram signals. In Statistical Methods at the Forefront of Biomedical Advances, 255–273, https://doi.org/10.1007/978-3-031-32729-2_11 (Springer Fernández, I., Cuadrado Asensio, R., Larriba, Y., Rueda, C. & Coco Martín, R. M. A comprehensive dataset of pattern electroretinograms for ocular electrophysiology research: The PERG-IOBA dataset (version 1.0.0), https://doi.org/10.13026/d24m-w054 (2024) Goldberger, A. L. et al. PhysioBank, PhysioToolkit, and PhysioNet: Components of a new research resource for complex physiologic signals. Circulation 101, e215–e220, https://doi.org/10.1161/01.CIR.101.23.e215 (2000) Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision McCulloch, D. L. et al. ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update). Documenta Ophthalmologica 1–12, https://doi.org/10.1007/s10633-023-09932-z (2023) Bubl, E. et al. Elevated background noise in adult attention deficit hyperactivity disorder is associated with inattention. PLoS One 10, e0118271, https://doi.org/10.1371/journal.pone.0118271 (2015) Download references This work was supported by a biomedical research grant from the Eugenio Rodriguez Pascual Foundation Department of Statistics and Operations Research Institute of Applied Ophthalmobiology (IOBA) Biomedical Research Networking Center in Bioengineering Mathematics Research Institute of the University of Valladolid (IMUVA) and R.C.-M.; Creation and maintenance of the dataset: I.F and Y.L.; Verified PERG signal quality: R.C.-A and R.C-M.; Diagnosis and classification assignment: R.C.-A and R.C.-M.; Supervision of the project: I.F. and R.C.-M.; Manuscript preparation: I.F.; Critical comments and revision of manuscript: all authors The authors declare no competing interests The funder had no role in the design of the study; in the collection of the data; in the writing of the manuscript Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41597-024-03857-1 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Use el menú superior o el formulario de búsqueda para encontrar otros contenidos información y entendimiento entre culturas The UK's Walker Guidelines for Disclosure and Transparency in Private Equity (the "Guidelines") have been updated, and a feedback statement was published by the BVCA on 18 December 2024.  The revised Guidelines will take effect for financial years that end after April 2025 and will be used for the Private Equity Reporting Group's (PERG) 2026 review The first version of the Guidelines was issued in 2007 to increase transparency of the activities of large private equity-backed companies and to demonstrate the private equity industry's contribution to the UK economy although compliance is required by the BVCA for BVCA member firms The original 2007 guidelines were reviewed and updated in 2014 and 2022 to incorporate new reporting requirements and improve public access to the published information the semi-independent body which oversees the Guidelines have been consulting on a more fundamental update of the Guidelines since July 2024 That consultation closed on 30 September and a new version of the Guidelines has now been published The definition of a private equity firm will be clarified to make it clearer that the Guidelines are only intended to apply to firms whose strategies focus on acquiring controlling stakes in companies Refining the scope of relevant transactions UK portfolio companies were within scope of the Guidelines if a majority of equity or control was acquired by one or more private equity firms and there will now be a single threshold test for both public to private and private to private deals The revised Guidelines focus on the enterprise value at the time of the transaction and have increased the threshold to £500 million.  In addition the company must either (i) have more than £200 million of revenue at least 50% of which is generated in the UK or (ii) employ more than 1,000 full time equivalent employees in the UK The BVCA says that the increased threshold is driven by the significant increase in size of comparable listed companies since 2007 while the addition of a minimum revenue test of £200 million is designed to exclude companies which do not have a significant economic impact and were never intended to be caught by the Guidelines PERG is planning to introduce a mechanism that will allow companies that increase or decrease in size during the private equity firm's period of ownership to join or leave the Walker population.  Further work is being undertaken on this aspect of the Guidelines and more details will be announced next year.  The revised Guidelines also include some small changes to the criteria for determining whether infrastructure assets are in scope.  In an update to the reporting requirements for portfolio companies that fall into scope the revised Guidelines have added or enhanced portfolio company disclosure requirements in three main areas: principal risks and uncertainties; environmental matters; and diversity the portfolio company will now be expected to explain how the board "promotes the long-term sustainable success of the company by identifying opportunities to create and preserve value and establishes oversight for the identified and mitigation of risks"  This narrative report should also cover risk management objectives and policies in light of the principal risks and uncertainties facing the company including those relating to leverage.  the revised Guidelines include new requirements for climate disclosures including on greenhouse gas (GHG) emissions and on transition planning.  Many large private companies are already required to disclose some of this information under existing UK law but the Guidelines now mandate it for companies in scope and go beyond the legal requirements in certain areas.  Walker companies will be required to disclose information on whether they have established a clear DEI policy aligned with their overall business strategy and include details of that policy.  There are also requirements to include some demographic data on gender and to state whether the company is a signatory to any DEI initiatives.  Portfolio companies will be permitted to cross reference to other publicly available disclosures that contain the relevant information about sustainability performance and risks and opportunities; for example Appropriate caveats should accompany references to third-party sources.  PERG reports that 90% (81 of 90) companies within scope of the Guidelines complied It also publicly names the non-compliant companies none of which were owned by a BVCA member firm NEWSLETTER SIGN UP In the opinion of camera industry veteran Harry Box the primary purpose of a good trade association “is to identify areas where there is difficulty or problems that affect everyone and address them as a service to the whole industry.” Box ought to know – he has served for over ten years as manager of the Production Equipment Rental Group (PERG) at ESTA (the Entertainment Services and Technology Association) Particularly considering challenges posed by the pandemic-ravaged last 12-plus months Box suggests there are few entertainment sectors that need such support more than the equipment rental industry Reception before PERG’ General Membership Meeting at NAB PERG evolved a little over a decade ago out of the former Professional Equipment Rental Association (PERA) – an independent trade organisation specifically for rental companies in the motion picture and television space PERA was absorbed into ESTA as one of several programmes that the association supervises “ESTA is an international trade association for all entertainment categories,” Box says “Film and television is largely the same equipment manufacturers and a lot of the same interests as other entertainment sectors like event rigging and at that point we became a programme within ESTA known as PERG.” Camera prep at Daufenbach Camera (Chicago) Box says PERG has about 90 member companies ranging from large players such as Panavision Keslow Camera and others to “all the premiere brands” and a wide range of smaller companies across the United States but the goal is the same – to figure out what kind of needs are universal to all of them?” Along those lines, in terms of recent events, the organisation’s response to the Covid-19 pandemic serves as an example of addressing important needs impacting the equipment rental community. Box explains that the wider entertainment industry produced a template for production-related Covid protocols with the 2020 White Paper published by an industry-wide task force last summer and there have been other solid efforts in various sectors “there needed to be a similar thing for vendors specifically.” PERG therefore put together four specific working groups – one for sound stages since lots of rental companies own-and-operate vehicles The organisation asked them to come up with vendor-oriented Covid protocols that would be compliant with CDC and OSHA guidelines “We had to take that [wider] guidance and interpret it,” Box relates “How does it apply to equipment like lighting stands delicate pieces of equipment made of all kinds of different materials We came up with guidelines and released them last April as a public review document The resulting document – PERG Safe Return To Work Guidelines –“was something the industry needed protocols and industry-wide dialogue on a wide range of issues that are of particular importance to equipment vendors – including sometimes in partnership with other important industry entities In particular, Box says, in recent years PERG got together with the Association Of Independent Commercial Producers (AICP) to address particular challenges that vendors run into when negotiating rental contracts with production companies and large studios “It’s a perennial problem that big studios not agreeing to certain things or demanding changes “Principals and owners of companies spend hours and hours having to re-negotiate the same basic rental contract they previously used over and over again we formed a joint committee with AICP to try and come up with terms-and-conditions on major and we offered that as a resource to the industry.” Check desk a the Camera Division (Los Angeles) with input from the insurance industry and direct contact with major production companies basic agreement on many points was achieved production companies didn’t understand why it takes so long to produce a list of missing and damaged equipment after a job is returned,” he adds brought them over and had them observe technicians going over equipment from a recent job That’s how those companies understood why it takes more than two hours to produce a loss-and-damage report Heather Williams (RED Digital Cinema) and Leigh Blicher (Videofax As a result, the AICP-ESTA Terms & Conditions document was produced which has essentially been making life a bit less complicated for rental companies ever since Box says PERG has on its agenda the hope of next bringing the usefulness of this initiative to a wider clientele – the major studios PERG’s relationship with ESTA has also allowed the organisation to join its parent’s fraud-and-theft prevention programme, known as Rental Guard That is essentially a five-year-old international network/database for rental companies to list missing or stolen equipment serial numbers and share information about how thefts are happening and file reports on theft issues across the rental industry Masks and signage at camera prep at the Camera Division “Rental Guard has grown every year in terms of the number of people registering for it and using it,” Box says “There has long been an international problem regarding theft We have done lots of outreach to rental companies and others to educate them about the nature of equipment theft in the modern era people are using Rental Guard as a tool to recover their equipment if you have a website where people can look up serial numbers of stolen equipment people are going to start being a lot more careful and the theft marketplace becomes less free-flowing.” newer issues on the horizon that PERG is also hoping to work with major studios on inclusion) challenges in the rental industry – the fact that in the US there are not a large number of minority-owned rental companies He says PERG “is working with studios right now to encourage actionable ways to address this issue going forward.” Rental Manager behind plexiglass at the Camera Division Box suggests that PERG’s greatest contribution may be in the area of communication and interaction across the rental industry our members want to talk to each other and learn from each other,” he says four major yearly live events were routinely held across the US specifically for the purpose of bringing members together and Box expects those to resume in some form once the Covid crisis abates where members could discuss things like insurance problems they have with clients and how they deal with those issues,” he explains “We also started doing a breakfast at NAB and at Cine Gear and we would host a New York-based collaborative party with AICP and we were doing a similar Cinco de Mayo based event in Los Angeles The idea was that bringing rental houses together with each other and with clients was a huge benefit to members.” Harry Box (center) with Kristin Wilcha (AICP) and another guest at the PERG/AICP Oktoberfest Party in New York Although the pandemic took live events off the table over the course of the last year Box adds that a silver lining has emerged in the sense that the organisation has realised remote communication technology can help connect members more frequently made up of 12 member companies that are the steering council for everything we do and we had to book a space and then try to get everyone together for meetings while they were trying to cover the trade show we are doing one-hour meetings on a monthly basis via Zoom An audience of rental company principals listens to a panel discussion about evolving technologies at the 2019 PERG General Memberhip Meeting at NAB Kees Van Oostrum ASC NSC (formerly ASC president) and Michael Cioni (then at Panavision/Loght Iron) and moderator Noah Kadner PERG has also started holding remote one-hour “Coffee Break” events in which experts in some areas of interest can give a talk to interested members via Zoom And Box expects more such innovative remote programming to develop in the coming months PERG Council Member Paul Royalty (LiteGear) hosts an online event with Lori Rubinstein (Executive Director of the Behind the Scenes charity) and Taryn Longo (somatic trauma therapist) speaking about the BTS Mental Health and Suicide Prevention Initiative this technology lets us get the membership together without them ever leaving their office,” he relates “So that is something we will definitely be pursuing.”   A landmark new pilot study from ScreenSkills and 4Skills has provided a first of its kind detailed look at the British Screen.. The International Cinematographers Guild (ICG IATSE Local 600) has announced the tentative results of its 2025 national election The Production Guild of Great Britain (PGGB) has confirmed that Kaye Elliott will join as its new CEO commencing 16th July 2025 Necessary cookies are required to enable the basic features of this site such as providing secure log-in or adjusting your consent preferences These cookies do not store any personally identifiable data Functional cookies help perform certain functionalities like sharing the content of the website on social media platforms Analytical cookies are used to understand how visitors interact with the website These cookies help provide information on metrics such as the number of visitors Performance cookies are used to understand and analyse the key performance indexes of the website which helps in delivering a better user experience for the visitors Advertisement cookies are used to provide visitors with customised advertisements based on the pages you visited previously and to analyse the effectiveness of the ad campaigns Download PDF Prompt therapeutic intervention is important in preventing visual loss in glaucoma yet standard diagnostic tools fail to catch retinal ganglion cell (RGC) damage at the ear­liest stages does not detect RGC damage until about 25% to 35% of the RGCs have been lost.1 Would earlier detection of RGC dysfunction improve the management of glaucoma Another technology—pattern electroretinography (PERG)—which has been used experimentally for years to identify early glaucoma damage to RGCs commercial devices—Diopsys’ Nova and Argos Vision Testing Systems and Konan Medical’s EvokeDx—have become available These machines are equipped with PERG and visual evoked potential (VEP) software; the Diopsys also includes full-field electroretinog­raphy Early adopters of these devices discuss whether this technology might have clinical usefulness The pattern electroretinogram measures the electrical activity of the retina in response to a test stimulus and objective method for assessing RGC function Studies with lab-based PERG devices have shown its usefulness in detecting early RGC damage in glaucoma suspects.2-6 Commercially available PERG technol­ogy takes the principles of laboratory-based electrophysiology and places it a more user-friendly format at the Doheny Eye Institute in Los Angeles Although office-based technology does not completely take the place of laboratory-based electrophysiology testing it overcomes the impracticality of re­ferring glaucoma patients for extensive laboratory tests In-office machines can serve as adjuncts to the tools that ophthalmologists already have available at the Icahn School of Medicine at Mount Sinai Although he relies chiefly on the clinical exam­ination when evaluating patients for glaucoma can be particularly helpful for patients who present a diagnostic dilemma Panarelli noted that advances in technology over the years have greatly improved ophthalmologists’ ability to diagnose glaucoma “Optical coherence tomography [OCT] has been a huge help to the glaucoma specialist,” he said “Though many of us carefully evaluate the optic nerve there are times when the OCT ‘sees’ some­thing that we do not.” He noted that an OCT image of an anom­alous nerve coupled with borderline intraocular pressures (IOPs) might not provide enough information for a glau­coma diagnosis Although visual field testing can be used in this situation and some patients need to repeat the test multiple times before the results are reliable “This is where these clinic-based [PERG] devic­es come in—they provide an objective way to evaluate the [functional status of the] visual pathway.” “PERG can help identify pathology even before structural lesions are evident and therefore before they are detectable using OCT or visual field testing,” said Dr Whom to test. Dr. Francis uses PERG for patients in whom he sus­pects glaucoma but the clinical picture is unclear or the visual field testing unreliable. “PERG can help improve differentiation of the diagnosis in these patients, where the data don’t add up,” he said. (See “Case Report,” below.) Francis also uses PERG in patients diagnosed with glaucoma to monitor their response to medical He said PERG is useful for most patients with mild glaucoma because the technology allows him to establish a baseline for later PERG testing during treatment follow-up “Diopsys is a patient-friendly device because testing sessions are noninvasive,” said Dr Electrodes on sticky pads are placed on the patient’s forehead and around the eyes He said that the entire procedure—including preparation—takes about 15 to 20 minutes and the actual testing takes less than 5 minutes it requires less time than a visual field test “and the patient doesn’t have to do anything except look at the stimulus and pay attention.” Panarelli said that very little technical expertise or training is needed to use the EvokeDx machine most of these tests are performed by technicians or medical students they can learn how to properly place the electrodes and how to instruct the patient to accurately complete the test Panarelli noted that patients find clinic-based PERG easier than visual field testing Francis ac­knowledged that there are no estab­lished guidelines for PERG testing in­tervals I repeat PERG testing if something triggers the need for it—for example if I’m going to be doing a specific treatment or if IOP is high and I need to step up treatment or if I feel the patient is getting worse but I’m not seeing evidence of worsen­ing on visual field testing or OCT.” Francis discussed use of PERG in a 66-year-old woman a visiting assistant scientific research­er at UCLA he determined that the patient had high myopia in the left eye and mild to moderate myopia in the right eye “Visual field abnormality was also found in the left eye.” In cases like this Francis stressed that OCT results may be unreliable because of the long axial length associated with high myopia because “all objective signs were suggestive of glaucoma but we were unsure as to whether it was actually glaucoma or myopia.” This is exactly the type of situation in which PERG is useful [PERG] was normal [symmetrical] in both eyes so I was comfortable making a diagnosis of suspected glaucoma and observing this patient avoid­ing unnecessary treatment.” Even though clinic-based PERG testing is simple to admin­ister PERG is not as easy to evaluate as a visual field test or OCT “It’s more neurology than ophthalmology and clinicians need to be sure they understand what the test entails before using the device,” he explained Panarelli said that he spent a few weeks reviewing medical literature on PERG and re-learning the pathology of neuro­nal loss After speaking extensively with representatives from the device manufacturer he devoted further time to learning how to perform the test on patients as well as on himself the Diopsys and EvokeDx devices are somewhat lacking in sensitivity and specificity Francis added that the test may not be particularly useful in patients with very poor vision Patients must take the test with their best-cor­rected vision “so high myopes must wear either their glasses or contact lenses while doing the test,” he said “Artefacts also occur if the patient is blinking or not paying attention.” “The in-office technology will im­prove in time,” said Dr “This is the first generation of this Diopsys device The first generation of OCT was nowhere near what we have today.” In particular he believes the sensitivity and specificity of the technology will improve resulting in less variation between tests and fewer artefacts Panarelli noted that while the EvokeDx device seems to be particu­larly useful to help assess central vision and evaluate damage to magnocellular axons it does not appear to be as useful for mapping specific structural changes or peripheral defects “A multifocal visual evoked potential would be better to evaluate such changes or defects,” he said saying that the Diopsys system does not perform a multifocal electroretinogram which would be required to detect localized damage this in-office tool does not appear to be useful in providing the kind of detailed clini­cal information that ophthalmologists have come to expect from visual field testing and OCT noted that a maximum signal-to-noise ratio is desired for any test that is used for glaucoma and it may be so narrow that it significantly limits its usefulness,” he said Dr. Panarelli agreed, and he high­lighted this as one of the reasons why these clinic-based devices require fur­ther research (which he is conducting, see “Clinical study under way,” below) “We need to keep investigating the lim­itations of these testing modalities and see where their strengths lie.” Panarelli also emphasized that the current lack of guidelines or diagnostic algorithms makes it challenging for ophthalmologists to apply data from these devices to clinical practice “We may obtain data telling us there is a re­duced signal we don’t really have enough literature to help us accu­rately interpret this and tell us what it really means for the patient comparing data output from one eye to the other can be helpful to see if the comparison fits with everything else we see clinically.” Quigley questioned whether the typical ophthalmologist would find it useful to spend money on a PERG device and ophthalmologists need more information before they consider buying it to use in their own glaucoma practice “They would want to be sure that it is somehow better than something we do now or is highly additive to something we do now,” he emphasized “This has not yet been shown with this in-office device in a way that has been peer reviewed and is analyzable.” Register online at aao.org/2017 Given the lack of data for these clinic-based devices Panarelli is using EvokeDx mostly for diagnostic purposes “I don’t know yet whether it will be useful to monitor glaucoma progression,” he said “Will this test ultimately be able to just tell us ‘disease’ or ‘no disease,’ or will it also prove use­ful to determine glaucoma severity and to track progression of disease?” He added that it remains to be seen who will ultimately adopt these mo­dalities in practice: “Will these devices have more general use by optometrists and general ophthalmologists or will they occupy more of a niche market for glaucoma specialists and neuro-ophthalmologists?” New tools and treatments in glaucoma may enhance clinicians’ ability to provide better care “but we have to understand that they all have limitations and we need to understand these limitations before we widely adopt them.” Panarelli is performing a clinical study with the EvokeDx device in 150+ patients including those who are glau­coma suspects and those who have glaucoma with varying degrees of visual field loss “The aim is to see if the EvokeDx can be used to reliably separate patients into these groups We want to see how sensitive and specific this test is at picking up different de­grees of damage.” By using EvokeDx to examine patients with different severities of glaucoma Panarelli hopes to deter­mine whether any differences exist in their test results (the evoked potentials) based on visual field loss “I’m particu­larly interested in comparing patients who are glaucoma suspects to those with preperimetric glaucoma I would like to see if this modality really can help us to pick up glaucoma earlier,” he said I want to use the test in patients who are diagnostic challeng­es to help me make better treatment decisions Medical therapy is costly and can be a life-long burden to patients.” Panarelli said these diagnostic challenges may include patients who have normal-tension glaucoma pa­tients who have anomalous discs (high myopia) and certain high-risk patients in whom medical therapy may or may not be needed (pigment dispersion syndrome) “If I had a test that would allow me to examine a patient and then tell them ‘This looks like glaucoma and it’s not just your myopia’ Francis is professor of clinical ophthalmol­ogy the Rupert and Gertrude Steiger Chair in Glaucoma and Director of Glaucoma Services at the Doheny Eye Institute Relevant financial disclosures: Diopsys: S Panarelli is assistant professor of ophthal­mology Icahn School of Medicine at Mount Si­nai Relevant financial disclosures: None.  Edward Maumenee Professor of Ophthalmology For full disclosures and the disclosure key This section includes both patient details and details regarding the test settings the test is typically run with a 15% contrast stimulus (7.5% depth of modulation) and the stimulus is presented at a frequency of 10 Hz easy-to-read significance measurement as well as the mean values for amplitude and phase of a response are plotted as “+” points on the readout The circle surround­ing the dot indicates the noise level and represents the 95% confidence interval for a given response If this noise radius overlaps with the origin SNR <1 and the response is non-sig­nificant at the p=0.05 level Note in the control example that the trials are tightly clus­tered and the noise radius does not include the origin responses are spread among the four quadrants SNR ≥1 indicates a significant response to the stimulus The small yellow area corresponds to 0.85 ≤SNR <1; insignificant at p <0.05 SNR is calculated by dividing the mean amplitude by the noise radius Note the stark contrast in SNR between the control eye (3.60) and the glaucoma eye (0.41) This section estimates how well the response tracks with the stimulus presentation 10 Hz represents the first harmonic for standard icVEP re­cording; harmonic number 2 represents 20 Hz The response of interest is that which is provided by the test stimulus (10 Hz) Responses above the green line indicate significance at a p <0.05 level Note the high coherence of the 10 Hz response in the control eye compared to all other frequency bands and the relatively low response in the glaucoma eye Also worth not­ing is harmonic number 6—this corresponds to 60 Hz which is the frequency of electronic background noise from the surrounding environment The waveform is reconstructed from fre­quency components of the response the waveform for a healthy observer should also appear sinusoidal the waveform does not appear sinusoidal (multiple peaks periods of insignificant response to the stimulus) Response to the stimulus before mathemat­ical transformation In order to confirm that a test doesn’t have excessive noise interference it is best that the ampli­tude of the raw data is <10 μV The amplitude is below this threshold in both the healthy and glaucoma eyes This section includes amplitude and phase responses for different frequency levels note that the amplitude and phase value correspond to the amplitude and phase value listed and plotted in section 2 the 10 Hz frequency band is much larg­er than that of the frequencies >10 Hz while in the glaucoma patient the amplitudes are more comparable Download PDF Whom to test. Dr. Francis uses PERG for patients in whom he sus­pects glaucoma but the clinical picture is unclear or the visual field testing unreliable. “PERG can help improve differentiation of the diagnosis in these patients, where the data don’t add up,” he said. (See “Case Report,” below.) Dr. Panarelli agreed, and he high­lighted this as one of the reasons why these clinic-based devices require fur­ther research (which he is conducting, see “Clinical study under way,” below) Register online at aao.org/2017 All content on the Academy’s website is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy All content on the Academy\'s website is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy Metrics details A Correction to this article was published on 13 October 2021 This article has been updated Clinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG) Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma The disease groups discussed include hereditary inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed as are their applications in clinical diagnosis of disease monitoring progression and response to novel therapies PhNR) 以及其他更专业的技术可以进行视神经和视网膜神经节细胞功能的临床电生理评估。本文中 我们描述了这些电生理技术及其在除青光眼以外的影响视神经和视网膜神经节细胞疾病中的应用。讨论的疾病组包括遗传性、应力性、毒性/营养性、外伤性、血管性、炎性和颅内原因导致的视神经或视网膜神经节细胞功能障碍。本文讨论了客观的、电生理测量视网膜神经节细胞和视神经的优势 The optic nerve and retinal ganglion cells (RGCs) are essential in the transmission of visual information through the intracranial pathway to the striate/primary visual (V1) cortex Diseases of the optic nerve and RGCs therefore can lead to significant visual impairment and may be a primary pathology or secondary consequence of other conditions Whilst ophthalmic imaging and psychophysical tests can provide insight into structural and behavioural sequelae of optic nerve dysfunction functional assessments through electrophysiology provide an objective and quantitative approach to characterise these deficits directly at the level of optic nerve and RGCs The electrophysiology of the optic nerve and RGCs has been well established through the Visual Evoked Potential (VEP) and Pattern Electroretinogram (PERG) and more recently with the Photopic Negative Response (PhNR) alongside other specialised techniques like the multifocal electroretinogram mfVEP) to provide a more detailed evaluation of the retinal locus and spatial extent of cellular dysfunction These prospects are promising in the phenotyping and characterisation of optic nerve disease where other clinical information may not provide sufficient information we discuss the electrophysiological basis of optic nerve and RGC disease and its role in investigating the site and extent of dysfunction to complement structural and psychophysical findings in disease followed by a description of the main electrophysiological techniques used to assess the optic nerve and RGCs including their stimulus and recording parameters We then discuss the clinical applications of these techniques to diseases or conditions affecting the optic nerve and RGCs lastly concluding with diagnostic aids and dilemmas commonly encountered in ophthalmic and neuro-ophthalmic practice A comprehensive search of literature on Medline (PubMed) the Cochrane Library was performed by the authors Search terms included respective diagnostic tests and their related terms or abbreviations (i.e Visual* evoked potential OR VEP OR Visual* evoked response) against the clinical condition of interest (i.e Optic neuritis OR demyelin* OR papillitis OR multiple sclerosis) Broad search terms were used to capture a wide range of literature In circumstances where standard search terms retrieved few results search terms were broadened to include more general electrophysiological terms (i.e electrophysio* OR electroret* or electrodiag*) No limits were applied in relation to publication dates but only articles available in the English language were reviewed Each article had a full-text review and was critically appraised by the authors Additional review of references within qualifying publications was also undertaken in search of any further published works relevant to this review The main interests to this review were studies employing electrophysiological techniques within the main clinical conditions from which the authors used their clinical experience to determine the most relevant and clinically useful findings to this review Animal studies were generally excluded unless of particular importance to underpinning science or methodology The VEP is an important clinical test for assessing the functional integrity of the visual pathway from the retina to the striate cortex (primary visual cortex or V1) this test has been extensively used in the evaluation of ophthalmic The VEP is produced from activation of cortical neurons in response to afferent pathway stimulation which is recorded with electrodes placed over the occiput VEPs are recorded to a high contrast pattern or diffuse flash stimuli a checkerboard or grating stimulus is reversed in contrast over time whilst maintaining a constant mean luminance (PR-VEP) or alternatively the checkerboard appears and disappears on a background with the same mean luminance known as the pattern onset-offset VEP (PO-VEP) which provide information regarding the function of the macular pathways Flash VEPs (F-VEP) are typically recorded to a strobe or LED flash stimulator and is useful in the examination of the generalised visual pathway function particularly in eyes with poor optical quality where retinal image contrast is degraded relative amplitudes are observed in the top right The left most panel shows the transient pattern electroretinogram (PERG) following the stimulus (red arrow) an initial N35 negativity is seen followed by the main positivity (P50) and large later negativity (N95) The photopic negative response (PhNR) is next seen recorded to a diffuse flash stimulus (red arrow) The a- and b-waves of the ERG are seen of the typical flash ERG followed by the late negativity known as the PhNR In the central panel the pattern reversal VEP (PR-VEP) is seen The pattern onset-offset VEP (PO-VEP) response is seen to a longer stimulus (red bar) the initial response comprises the onset VEP of C1-C3 components later followed by the offset VEP C4-C6 components Lastly the flash VEP (F-VEP) is seen to a diffuse flash stimulus (red arrow) followed by a series of positive-negative deflections Interpretation of VEPs should rarely be used in isolation as this could lead to misdiagnosis even in suspected neurological dysfunction an abnormality of a P-VEP is not specific to optic nerve disease as the response is subject to good macular integrity and therefore assesses the visual pathway from the macula to striate cortex and should be explored with the PERG where abnormal The P50 component should therefore not be extinguished unless there is concomitant dysfunction anterior to the RGCs (i.e A normal PERG but abnormal PR-VEP localises dysfunction to outside of the central RGCs or posteriorly along the visual pathway This figure illustrates the full-field nature of the PhNR (red circle) being a pan-retinal response whereas the PERG is recorded to a central stimulus subtending 30° (grey box) or 15° (black box) of the central retina respectively This technique is commonly referred to as the multifocal VEP (mfVEP) and allows topographical analysis of the VEP through the detection of regional changes in amplitude and waveform delay that may not be reflected in the gross potentials measured with conventional VEP recording The STR reflects a combination of RGC and amacrine cell responses mediated by the rod pathway This ERG measure has not gained clinical utility mainly due to dark-adaptation requirements These findings highlight the importance of using focal stimulation for optimal electrophysiological testing of ADOA patients who typically demonstrate central visual field defects to demonstrate the normal findings of the photopic negative response (PhNR) pattern electroretinogram (PERG) (to 30° and 15° fields) pattern reversal visual evoked potential (PR-VEP) (to 50′ and 12.5′ check widths) and flash visual evoked potential (F-VEP) LHON: The PERG demonstrates normal P50 components but markedly abnormal N95 components which do not fall below the baseline to the 15° field the P50 is also reduced with early peak-time The PR-VEP is severely degraded to both check widths with only a small response to large check widths with the F-VEP broad and slightly low amplitude but preserved this indicates marked bilateral retinal ganglion cell (RGC) and optic nerve dysfunction with some preservation of peripheral RGC function Optic neuritis: The PERG shows normal P50 components but mildly reduced N95 components to both field sizes The PR-VEP is atypically delayed but with preserved amplitude The PhNR is markedly reduced with normal a- and b-waves this indicates some optic nerve dysfunction with some level of retrograde degeneration to the RGCs centrally Macular dystrophy: The PERG P50 to a 30° field is well defined but that to a 15° field is absent indicating marked macular dysfunction localised to the central 15° field The PR-VEP to 50′ check widths is of normal peak-time but borderline amplitude with loss of the PR-VEP to small check widths this indicates localised macular dysfunction affecting the 15° field with preservation of the surrounding 15–30° field The preserved N95:P50 ratio and PhNR indicating normal RGC and optic nerve function in conditions such as EAST syndrome when the PhNR amplitude reduction can be prone to more than one interpretation additional tests such as the PERG and VEP will be useful to assess the full extent of RGC and optic nerve function Compressive optic neuropathies or those secondary to space occupying lesions can cause significant disruption to optic nerve and RGC physiology Intracranial tumours may affect any portion of the visual pathway and the VEP is well suited to provide assessment in localising the pathway lesion and information of pathway integrity Whilst this review focuses on conditions affecting the optic nerve and RGC’s it is prudent to discuss lesions affecting the entire visual pathway to the striate cortex which may later inflict dysfunction of the optic nerve or RGCs for example due to retrograde degeneration of RGCs VEPs are a useful tool in the examination of the intracranial visual pathway especially when used in conjunction with the PERG and/or PhNR Selective stimulation of the right- or left-hemifield can isolate the visual pathway contributions and allow localisation of the pathway dysfunction site for example a bi-temporal hemifield loss in the PR-VEP would suggest chiasmal dysfunction whereas a homonymous left hemifield loss would indicate a right hemisphere dysfunction the benefits of multichannel VEPs in the investigation of intracranial pathway abnormalities are encouraged and are discussed elsewhere within this issue particularly of benefits in patients unable to undertake visual field examination the MRI is shown and checkerboard stimuli demonstrating the presentation of the pattern stimulus respectively The occipital VEP responses are shown at the bottom from the left A No reproducible PR-VEP is evident to left eye stimulation B A reproducible PR-VEP is seen at the occiput to full-field PR-VEP stimulation of the right eye however this is best defined over the left- and mid-occiput (red arrow) and attenuated over the right occiput (red asterisk) C Selective right half-field stimulation for the right eye demonstrates a reduced ipsilateral positivity expected (red asterisk) D Selective left half-field stimulation of the left eye demonstrates a preserved positivity (red arrow) similar to the full-field PR-VEP PR-VEPs indicate profound macular pathway dysfunction affecting the LE and RE crossing fibres but relatively preserved RE non-crossing fibres subserving the left half-field These authors also remarked how the PhNR recording was achievable in all children whereas OCT examination was not possible in one-third of their cohort due to motion artefacts or scan quality which is a valuable concern for paediatric practice The value of the PERG and PhNR in assessing RGC function in traumatic optic neuropathy has seldom been explored PERG and PhNR have been employed extensively in studies of Glaucoma in the clinical setting for evaluation of RGC dysfunction and death and this information is covered elsewhere in this issue The type of PVEP abnormality may in some instances characterise some of these pathologies but often demands the additional use of a PERG to further aid diagnosis As the PERG N95 loss in optic neuritis typically occurs after the acute phase of vision loss a reduced PERG N95 during acute presentation suggests other primary RGC disease such as LHOA or other optic nerve pathology the technical demands of a mfVEP and its accessibility have limited its widespread use to date differentiation of optic disc oedema from rICP and from optic neuropathies the comparative normality of the focal-PhNR compared to the abnormal PERG in the same patients are curious perhaps reflecting differences between each stimulus modality and their relative origins find a relatively low sensitivity of the PERG in IIH (45.5%) perhaps reflecting differences between the transient and steady-state PERG and the influence of different spatial frequencies These findings overall suggest that the PhNR and PERG are useful indicators of optic nerve and RGC function in rICP but to date have not been directly associated with ICP measurements as a surrogate marker The reader can follow the different scenarios whereby the PVEP to ascertain what clinical conclusions may be drawn from these findings that this algorithm should be interpreted in the clinical context and not all diseases or patterns of optic nerve or retinal ganglion cell dysfunction conform to these patterns genetic or other laboratory testing may be necessary to aid diagnosis Visual electrophysiology is a key diagnostic tool in the assessment of conditions affecting RGCs and the optic nerve In this review we have discussed the role of the PERG PhNR in characterising visual function in RGC and optic nerve disease The benefits of electrophysiology are to provide functional data of the visual system to complement structural data and the clinical examination At the advent of the genomic era and beginning of new exciting therapies for optic nerve disease functional measurements will be essential for measuring safety the objective nature of electrophysiology testing means information about the visual system can be gained from patients unable to complete subjective tests The ability to assess RGC and optic nerve function quantitatively and through different but complementary tests builds a diagnostic platform for phenotyping of disease A Correction to this paper has been published: https://doi.org/10.1038/s41433-021-01798-2 The changing shape of the ISCEV standard 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evoked potentials Pattern electroretinograms become abnormal when background diabetic retinopathy deteriorates to a preproliferative stage: possible use as a screening test Electrophysiological discrimination between retinal and optic nerve disorders Steady-state pattern electroretinogram in insulin-dependent diabetics with no or minimal retinopathy Electrophysiological and pupillometric measures of inner retina function in nonproliferative diabetic retinopathy Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy The photopic negative response of flash ERG in nonproliferative diabetic retinopathy Clinical applications of photopic negative response (PhNR) for the treatment of glaucoma and diabetic retinopathy Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes The scotopic threshold response in diabetic retinopathy Predominant loss of the photopic negative response in central retinal artery occlusion The photopic negative response of the flash electroretinogram in retinal vein occlusion Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion Photopic negative response reflects severity of ocular circulatory damage after central retinal artery occlusion High correlation of scotopic and photopic electroretinogram components with severity of central retinal artery occlusion Focal macular electroretinogram in macular edema secondary to central retinal vein occlusion Evaluation of macular function using focal macular electroretinography in eyes with macular edema associated with branch retinal vein occlusion Morphological and electrophysiological outcome in prospective intravitreal bevacizumab treatment of macular edema secondary to central retinal vein occlusion Photopic negative response in branch retinal vein occlusion with macular edema Macular function following intravitreal ranibizumab for macular edema associated with branch retinal vein occlusion: 12-month results Macular function following intravitreal ranibizumab for macular edema associated with branch retinal vein occlusion Correlation of electroretinography components with visual function and prognosis of central retinal artery occlusion Visual-evoked response differentiation of ischemic optic neuritis from the optic neuritis of multiple sclerosis The comparison of small-size rectangle and checkerboard stimulation for the evaluation of delayed visual evoked responses in patients suspected of multiple sclerosis Neurophysiological investigation in optic nerve disease: combined assessment of the visual evoked response and electroretinogram and acuity changes in chronic non-arteritic ischemic optic neuropathy Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy Electrophysiology in acute anterior ischaemic optic neuropathy A correlative clinical and visual evoked potential study of 18 patients Neuropathies of the optic nerve and visual evoked potentials with special reference to color vision and differential light threshold measured with the computer perimeter OCTOPUS The Visual Evoked Potential in Ischaemic Optic Neuropathy Documenta Ophthalmologica Proceedings Series Visual Evoked Potential and Pupillary Signs: a Comparison in Optic Nerve Disease Pattern electroretinography and visual evoked potentials in optic nerve diseases Electrophysiological findings in patients with nonarteritic anterior ischemic optic neuropathy Use of pattern electroretinography to differentiate acute optic neuritis from acute anterior ischemic optic neuropathy Photopic negative response of full-field and focal macular electroretinograms in patients with optic nerve atrophy Significant correlations between photopic negative response and mean defects of visual fields in asymmetric optic nerve disorders Electrophysiological findings in anterior 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neuritis measured with the multifocal VEP Normalisation of visual evoked potentials after optic neuritis Optic neuritis in children - Clinical and electrophysiological follow-up The incidence of abnormal pattern electroretinography in optic nerve demyelination The pattern electroretinogram: a long-term study in acute optic neuropathy The pattern electroretinogram: N95 amplitudes in normal subjects and optic neuritis patients Correlation between Morphological and Functional Retinal Impairment in Multiple Sclerosis Patients Electrophysiologic evaluation of the visual pathway in patients with multiple sclerosis Pattern electroretinograms in optic neuritis during the acute stage and after remission The photopic negative response of the flash electroretinogram in multiple sclerosis Selective Loss of the Photopic Negative Response in Patients with Optic Nerve Atrophy Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic neuritis Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: a review Pathogenesis of optic disc edema in raised intracranial pressure Assessment of visual function in idiopathic intracranial hypertension Further studies with a noninvasive method of intracranial pressure estimation Relationship between visual evoked potentials and intracranial pressure intracranial pressure and ventricular size in hydrocephalus Ophthalmologic prognosis in Benign Intracranial Hypertension Visual Evoked Potentials in Pseudotumor Cerebri Visual evoked potentials follow-up in idiopathic intracranial hypertension Visual evoked potentials in idiopathic intracranial hypertension Visual Evoked Potential in Idiopathic Intracranial Hypertension Clinical and Neuro-ophthalmologic Predictors of Visual Outcome in Idiopathic Intracranial Hypertension Prevalence of abnormal pattern reversal visual evoked potentials in craniosynostosis Visually-Evoked Potentials for the Assessment of Visual Function in Patients with Craniosynostosis Serial Visual Evoked Potentials in Patients with Craniosynostosis and Invasive Intracranial Pressure Monitoring Monitoring visual function in children with syndromic craniosynostosis: a comparison of 3 methods Pattern electroretinograms and visual evoked potentials in idiopathic intracranial hypertension Profound contrast adaptation early in the visual pathway Contrast adaptation in human retina and cortex Relationship between pattern electroretinogram and automated perimetry in chronic papilledema from pseudotumor cerebri syndrome The photopic negative response in idiopathic intracranial hypertension Electroretinography in idiopathic intracranial hypertension: comparison of the pattern ERG and the photopic negative response Download references Clinical and Academic Department of Ophthalmology Both OM and SV were responsible for designing the review strategy OM and SV were responsible for writing of the study paper and generation of figures Both authors approve to the final version of the paper The original online version of this article was revised: Figure 1 illustration had an error - in the second panel (the PhNR waveform) the ‘a’ and ‘b’ labels were the wrong way around Download citation DOI: https://doi.org/10.1038/s41433-021-01614-x 2022 3 pm Eastern | 2pm Central | 1pm Mountain | 12pm Pacific REGISTER FOR THIS EVENT Join PERG for an informative Coffee Break and dive into current zoom lens trends in cinema The event will also cover topics of discussion such as best practices in zoom lens quality control procedures will share insights on the range of applications which drive rental demand for cinema zoom lenses who serves as director of cinema sales for Zeiss The presentation will include an interactive audience Q&A so bring your questions and share a cup of coffee This event is presented by PERG (part of ESTA) and is open to non-members as well as members Metrics details It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG) recorded during 4-min presentation of patterned stimuli are reduced in glaucoma suspects and patients compared to normal subjects Our study aims at testing the hypothesis that adaptive changes of SS-PERG recorded using the novel optimized Next Generation PERG (PERGx) protocol differ between glaucoma patients and controls we included 28 glaucoma patients and 17 age-matched normal subjects Both patients and controls underwent a full ophthalmologic examination The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects PERGx amplitude and phase data showed declining trends in both groups PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01) whereas phase angular dispersion was greater in patients but not significantly different between the two groups The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients presumably due to the loss of functional retinal ganglion cell autoregulation might be helpful in the identification and diagnosis of early glaucomatous dysfunction dubbed Next Generation PERG (PERGx as a contraction of PERGnext) whose parameters strictly correlated with those of PERGLA so allowing to be proposed as a promising source of further clinical information about RGC function in optic nerve diseases The aim of this study was to test the hypothesis that adaptive changes of the SS-PERG differ between glaucoma patients and normal subjects A cross-sectional study was performed on consecutive patients presenting to the Glaucoma Service at the Fondazione Policlinico Universitario A Gemelli IRCCS - Università Cattolica del Sacro Cuore of Roma The study protocol (ID 3934) was approved by the Ethics Committee of the aforementioned institution and carried out in accordance with the tenets of the Declaration of Helsinki Written informed consent was obtained from all subjects following an explanation of the nature and intent of the study The study population included a group of 28 glaucoma patients consisting of pre-perimetric early and moderate stage patients (64.3% women and 35.7% men; mean age ± standard deviation [SD]: 58.64 ± 14.04 years whose sex and age distribution were comparable with those of patients were also enrolled into the study as a control group including best-corrected Snellen visual acuity measurement slit-lamp biomicroscopy of the ocular anterior segment and fundus central corneal pachymetry by the digital ultrasonic pachymeter Pachmate DGH55 (DGH Technology computerized white-on-white 30–2 visual field testing by Humphrey Field Analyzer 750i (HFA; Carl Zeiss Meditec SS-PERG with adaptation paradigm recording by Retimax (CSO and measurement of both peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell/inner plexiform layer (GCIPL) thicknesses by spectral-domain Cirrus HD-OCT (model 5000 and OCT analyses were obtained for each subject within 1 week of each other as well as normal visual field for pre-perimetric glaucoma In pre-perimetric glaucoma eyes (60.71%) MD ± SD was 0.64 ± 1.14 dB in early glaucoma eyes (32.14%) MD ± SD was − 1.58 ± 2.08 dB and in moderate glaucoma eyes (7.14%) MD ± SD was − 10.95 ± 0.94 dB and T.S.) observed and defined the damage to the optic nerve head as detected by fundus examination The inter-observer agreement coefficient was 91.7% (95% confidence interval = 83.7–99.7) In case of disagreement the specialists discussed together sometimes by matching their clinical judgment with OCT analysis mainly from RNFL thickness and deviation maps until they eventually obtained a consensus as for Cirrus HD-OCT classification by the average RNFL thickness parameter 68.75% of eyes were “outside normal limits” (thinner than all but 1% of normative database) 18.75% of eyes were “suspect” (thinner than all but 5% of normative database) and 12.50% of eyes were “within normal limits” but in presence of a focal narrow defect at RNFL thickness and/or deviation map 88.89% of eyes were “outside normal limits” and 11.11% of eyes were “suspect” All patients were under treatment with one or more topical hypotensive drugs (β-blockers and α2-agonists) providing a stable IOP lower than 21 mmHg Exclusion criteria were as follows: corrected Snellen visual acuity < 20/25 refractive errors equal to or more than 2 D of myopia or hyperopia and 1 D of astigmatism cataract surgery or changes in the IOP-lowering and/or neuroprotectant therapies within the 3 months before patient recruitment and morpho-functional assessment and ophthalmologic or neurologic diseases which may affect visual function and exam execution The study can be considered as a diagnostic accuracy study according to STARD guidelines22 where the gold target condition was glaucoma diagnosis the clinical reference standards were the clinical tests for glaucoma diagnosis (see below) and the index test was the PERG adaptation paradigm (PERGx) Data collection was planned before the reference standard tests and after the index tests were performed Controls and patients participating in the study formed a random series and E.D.S.) performing the index test were masked as to the clinical diagnosis and the reference standard tests with one or more of the following alterations: Glaucoma Hemifield Test outside normal limits pattern standard deviation (PSD) with p < 5% not contiguous with the field borders nor the blind spot in the upper and/or lower hemifield of the total and pattern deviation plots with p < 5% the two global indices of field sensitivity OCT imaging was performed using the Cirrus HD-OCT on both peripapillary RNFL and macular GCIPL The OCT lens was adjusted for the refractive error The subject was instructed to stare at the internal fixation target with the eye under examination to enable the optic disc and the macula to subsequently come into the appropriate windows and to be centered The scan protocols were the Optic Disc Cube 200 × 200 and Macular Cube 512 × 128 for the study of peripapillary RNFL and macular GCIPL three separate scans were obtained per eye by each protocol during the same session and the best one with optimal signal strength (> 6/10) and scan image centering no movements during scans or anomalous internal/external boundary definition was used for the analysis Average RNFL and GCIPL thicknesses were collected The PERG was acquired simultaneously from both eyes with standard skin surface electrodes (Grass gold 10 mm diameter) taped on the lower eyelids (active) and central forehead (ground) using the Retimax system Subjects fixated at the center of the stimulating field (size 60° width × 50° height) with natural pupils 3.5 ± 1.0 mm) at a viewing distance of 57 cm wearing full refractive correction No statistically significant differences in pupil size were observed between patients and normal subjects Fixation was monitored by a trained observer 100 µV AC range) and averaged in synchronism with stimulus onset were automatically rejected to minimize amplitude bias PERGx was recorded similarly to a published protocol19 SS-PERG was elicited by black-and-white horizontal gratings of 0.8 cycles/degree spatial frequency and 95% contrast (mean luminance: 35 cd/m2) modulated in counterphase at 7.5 Hz (15 reversals/s) Stimulus was electronically generated on a high-resolution organic light-emitting diode television (OLED TV) monitor and administered continuously over nearly 2 min The response was recorded as a sequence of 10 partial averages (packets) each one (10 s average duration) obtained summing up to 60 cycles.18 The first packet was obtained with the patient exposed to a uniform gray stimulus equiluminant with the pattern stimulus Two replications of the entire adaptation paradigm and an appropriate time interval between replications was chosen to avoid residual adaptive effects The following PERGx parameters were chosen as the primary outcome measures of the study: average scalar amplitude and phase for each packet; amplitude slope and phase angular dispersion as measures of adaptive PERGx changes; and grand-average vector amplitude and phase as surrogates of ordinary non-adapted SS-PERG The secondary outcomes were the OCT morphometric parameters of peripapillary and macular retina Statistical analysis was performed using SPSS 17.0 for Windows (IBM SPSS Alpha and beta error were established at 5% and 20% The following variables were considered as continuous quantitative variables: age; IOP measurement; perimetric MD and PSD indices; OCT RNFL and GCIPL thicknesses; PERGx amplitude slope phase angular dispersion and grand-average vector phase Assimilability to normal distribution was evaluated using the Kolmogorov–Smirnov test The electrophysiological 9 signal packets were separately analyzed and PERGx amplitude and phase were initially studied as individual temporal series and then averaged across subjects and plotted as a function of the single sequential packets Linear regression analyses were applied to the amplitude and phase data in order to evaluate the presence of an adaptive behavior Univariate comparison between the two groups’ parameters was performed using the two-tailed Student’s t-test for independent groups A Bonferroni corrected p value < 0.05 was considered to establish the statistical significance of the results Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters (i.e their ability to differentiate between unhealthy and healthy eyes) by evaluating the area under the curve (AUC) with an AUC of 0.5 indicating no discrimination ability and an AUC of 1.0 indicating maximal discrimination ability Eleven right early to moderate glaucoma eyes (39.29%) and 17 right pre-perimetric glaucoma eyes (60.71%) were considered Results from the descriptive analysis of the study groups are summarized in Table 1 No statistically significant differences between the 2 groups were detected in terms of age With regard to the visual field test parameters the patient group showed significantly (p < 0.05) different MD and PSD values compared to control group the 2P signal component of PERGx was sufficiently above the noise level (signal/noise > 2.5 with the noise level at the 2P frequency ranging from 0.07 to 0.12 µV) Representative examples of sequential PERGx samples recorded in two random subjects from control group (A top left panel) and patient group (B top left panel) The black waveform represents the noise recorded during an initial 10-s presentation of a grey uniform background whereas the 9 coloured superimposed waveforms correspond to the responses obtained by high-contrast reversing black-and-white gratings Data represent successive averages of 60 epochs each (~ 10 s sampling time) Top right graphs show PERGx vector changes over the recording time in the control subject (A top right panel) and the patient (B top right panel) The bottom graphs display how the PERGx amplitude and phase of successive samples (filled coloured symbols) change over time in the control (A) and in the patient (B) Scatter plots of scalar 2P amplitude (A) and phase (B) averaged across all subjects of both control (open circles) and patient (filled circles) groups as a function of packet number The linear regression (R and p values are shown) applied to the amplitude and phase data shows a steeper decline (i.e more negative slope) in controls compared with patients median and 25–75% percentiles of PERGx parameters with whiskers and cross symbols representing the 5–95% and 1–99% percentiles The statistical significance (p-value) of t-test comparisons between group parameters is shown As for the secondary morphometric measurements the patient group revealed lower average RNFL and GCIPL thicknesses compared to controls reaching the statistical significance (p < 0.05) only in RNFL values Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) calculated for (A) PERGx amplitude slope (solid line; AUC = 0.87) and grand-average vector amplitude (densely dashed line; AUC = 0.76) and for (B) PERGx grand-average vector phase (solid line; AUC = 0.87) and phase angular dispersion (densely dashed line; AUC = 0.62) The dashed diagonal line serves as an imaginary reference line representing a non-discriminatory test The present study was designed to compare the adaptive SS-PERG changes as recorded by using an optimized paradigm called PERGx between glaucoma patients and normal subjects we wanted to determine if this tool was sufficiently accurate in discriminating patients from controls the study of PERG adaptation dynamics in already diagnosed glaucoma patients is more important for assessing the physiological status of RGCs This amplitude difference may be explained by the so-called energy budget model according to which under steady state stimulus conditions (that is higher temporal frequencies) the metabolic demand of neurons may be greater than the available supply (energy budget) The current protocol is specifically intended to explore the pathophysiology of RGC adaptation in glaucoma habituation PERG represents an interesting source of additional biological information about RGC function in glaucoma patients To the best of our knowledge, Porciatti et al.18 were the only ones to study the adaptation of SS-PERG in glaucoma they demonstrated that adaptive PERG changes differed from standard SS-PERG responses (corresponding to the grand-average amplitude and phase measures) in glaucoma patients maybe involving different functional dynamics and so providing further contribution to the study of impaired RGC activity they found that adaptive PERG phase changes significantly decreased with increasing severity of disease whereas adaptive PERG amplitude changes were similar among glaucoma patients and control subjects as for the PERG grand-average values (amplitude and phase average across the sequential response packets from each subject) the amplitude decreased with increasing severity of disease whereas the phase was not different among the three groups As for adaptive PERGx changes, the present results agree with those reported by Porciatti et al.18 indicating a reduction of adaptive PERG changes in glaucoma and hence a possible loss of functional RGC autoregulation we found a significantly lower amplitude slope in patients compared to controls as well as similar phase angular dispersion between the two groups This discrepancy of our results compared to those from Porciatti et al may be due to some differences in patient characteristics and recording protocol conceived and used the first PERG habituation protocol with longer presentation of the stimulus which created more stressful and energy consuming conditions for RGCs The current protocol is an abbreviated and optimized tool designed to provide an easier clinical application along with adequate diagnostic accuracy reliably distinguishing glaucoma eyes from normal eyes PERGx might be helpful in the detection and diagnosis of glaucomatous or pre-glaucomatous dysfunction If the adaptive abnormalities are expression of a dysfunctional state and do not reflect a loss in the number of RGCs then appropriate hypotensive or neuroprotective treatments might be able to rescue injured RGCs and restore adaptive PERG changes Clinical pilot trials investigating the short-term effect of neuroprotection on adaptive PERG changes as an outcome variable will appropriately address this question Present and new treatment strategies in the management of glaucoma Electrophysiological assessment of retinal ganglion cell function Retinal ganglion cell functional plasticity and optic neuropathy: A comprehensive model Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma The coma in glaucoma: Retinal ganglion cell dysfunction and recovery The physiological basis of the pattern electroretinogram Pattern electroretinogram detects localized glaucoma defects Pattern electroretinogram abnormality and glaucoma Pattern electroretinogram progression in glaucoma suspects Normative data for a user-friendly paradigm for pattern electroretinogram recording Habituation of retinal ganglion cell activity in response to steady state pattern visual stimuli in normal subjects Lack of habituation in the light adapted flicker electroretinogram of normal subjects : A comparison with pattern electroretinogram Reduced habituation of the retinal ganglion cell response to sustained pattern stimulation in multiple sclerosis patients Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina Adaptation of the steady-state PERG in early glaucoma Next generation PERG method: Expanding the response dynamic range and capturing response adaptation Clinical Decisions in Glaucoma 52–61 (The C STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies Evidence-based criteria for assessment of visual field reliability Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study ISCEV standard for clinical pattern electroretinography—2007 update Structure–function relationship in ocular hypertension and glaucoma: Interindividual and interocular analysis by OCT and pattern ERG Pattern ERG as an early glaucoma indicator in ocular hypertension: A long-term Electrophysiological approaches for early detection of glaucoma Modeling retinal ganglion cell dysfunction in optic neuropathies Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? Regulation of optic nerve head blood flow in normal tension glaucoma patients Download references Gemelli IRCCS - Università Cattolica del Sacro Cuore Dysmetabolic and Aging-Associated Diseases National Centre of Services and Research for the Prevention of Blindness and Rehabilitation of Low Vision Patients and A.F.); data analysis and interpretation (F.B. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-021-02048-x Neuroscience and Behavioral Physiology (2024) Metrics details 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 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 The smaller/larger HF N95 amplitude ratio did not significantly change with age (β =  − 0.005 whereas the full-field N95 amplitude showed a negative correlation with age (β =  − 0.081 HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma the present investigation focused on hemifield (HF) PERG amplitude and its ratio to determine if it could be used to detect early functional defects in glaucoma patients we compared PERG parameters in PPG patients and normal subjects and evaluated the diagnostic utility of HF-based analysis of PERG parameters we aim to contribute to the refinement of diagnostic strategies for detecting glaucoma at its incipient stages The data were evaluated for 33 eyes of 33 PPG patients who had met the inclusion criteria and 32 eyes of 32 normal subjects. Table 1 compares the demographics and clinical characteristics of the PPG patients with those of the normal controls There was no statistically significant difference in the two groups’ age The IOP value of the PPG group was lower than that of the normal controls and this might have been due to the fact that 12 PPG patients (36.4%) were taking topical glaucoma medications The PPG group showed significantly thinner RNFL and ganglion cell-inner plexiform layer (GCIPL) thickness compared with the normal controls (both P < 0.001) and there were no significant intergroup differences in the SAP parameters The PPG group showed significantly lower thinner/thicker HF RNFL and GCIPL thickness ratios compared with the control group (0.85 ± 0.11 vs The smaller/larger HF N95 amplitude ratio of PERG was significantly lower among the PPG group (0.74 ± 0.21) than among the control group (0.86 ± 0.12; P = 0.007) the affected/unaffected HF N95 amplitude ratio was 0.89 ± 0.39 Scatterplots showing correlation between age and spectral-domain optical coherence tomography (SD-OCT) hemifield parameters Entire study subjects showed a negative correlation between age and the thinner/thicker hemifield (HF) retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL) thickness ratios (r =  − 0.252 there was no age correlation seen in the thinner/thicker HF thickness ratio for RNFL and GCIPL parameters in the subgroup analyses for the PPG and control groups (all P > 0.05 (A) Normal control case of 48-year-old woman (B) Preperimetric glaucoma (PPG) case of 51-year-old woman (A) Stereoscopic disc photography (SDP) revealed no glaucomatous optic disc rim change in the normal eye of a 48-year-old female control and optical coherence tomography (OCT) thickness maps revealed no ganglion cell inner plexiform layer (GCIPL) or retinal nerve fiber layer (RNFL) thinning with normal visual field (B) SDP revealed optic disc rim loss in the superotemporal area and OCT exhibited thinning in the superior region of the RNFL and GCIPL thickness maps with normal visual field test findings The PPG case showed decreased PERG N95 amplitudes in the full field (FF) The smaller/larger HF N95 amplitude ratio was 0.60 in the PPG case and was lower than the value for the normal control (0.96) there were statistically significant decreases in the FF and LF PERG N95 amplitudes and smaller/larger HF N95 amplitude ratio relative to the normal control group (FF smaller/larger HF N95 amplitude ratio: P = 0.007) The average GCIPL thickness was positively correlated with the FF PERG N95 amplitude and smaller/larger HF N95 amplitude ratio (r = 0.382 as was the affected HF average GCIPL thickness (r = 0.442 the N95 amplitude should be more sensitive for glaucoma patients we investigated its applicability to PPG patients in this study This method may be useful in measuring the topographic distribution of damage as well as the disease course PERG certainly has the potential to serve as a valuable biomarker for glaucoma progression as well as for long-term monitoring of glaucoma in large-scale prospective studies It is apparent that the conclusions of these earlier investigations are consistent with those of the current study the PERG N95 amplitude-related parameters performed better in this study than the SAP parameters Comparison of the SD-OCT-derived structural parameters with the PERG parameters indicated that the former still showed strong diagnostic abilities This might be an intrinsic restriction of PERG or it could be surmounted by controlling the variables influencing PERG variability This concern might be addressed in the future by further studies employing progression analysis and lowering PERG variability while adjusting for a number of other factors such as IOP and others Fixation shifts and stray light effects during stimulation might occur even though the subject’s fixation is monitored by a trained observer Testing time tends to vary from 10 to 25 min PPG patients taking medicine to lower their IOP were included in this study and those lower IOP values may also have impacted the outcomes as this study was of cross-sectional design including examination of conversion from PPG to perimetric glaucoma PERG N95 amplitude and the HF ratio of N95 amplitude may offer useful information in terms of the functional evaluation of PPG This study served to highlight the benefits of HF analysis in addition to the use of PERG N95 amplitude it is proposed herein that combining those two could be a more effective diagnostic strategy The Institutional Review Board of Seoul National University Hospital authorized the protocol for this prospective cross-sectional study (IRB no and all of the pertinent investigations and procedures followed the principles of the Declaration of Helsinki Informed consent was obtained from all of the subjects the clinical data were gathered from glaucoma patients who had visited the Seoul National University Glaucoma Clinic between October 2022 and January 2023 The normal controls were volunteers who had come to the clinic in response to an advertisement Patients who had glaucomatous optic discs (e.g. focal notching) or RNFL defects without any abnormal VF defect were allocated to the PPG group Glaucomatous VF defect was defined as (1) glaucoma hemifield test values outside the normal limits or (2) three or more abnormal contiguous points with a probability of P < 0.05 of which at least one point has a probability of P < 0.01 on a pattern deviation plot or (3) a pattern standard deviation (PSD) of P < 0.05 The additional inclusion requirements were as follows: (1) BCVA of 20/30 or better (3) open anterior chamber angle on gonioscopy Patients with any history of retinal degeneration If both eyes met the criteria for inclusion computer-based random selection of one eye per person was performed The normal control group was defined as subjects having an IOP ≤ 21 mmHg Every participant had undergone complete ophthalmologic examinations IOP measurements by Goldmann applanation tonometry (Haag-Streit refractive error measurements with an autorefractor (KR-890; Topcon Corporation corneal pachymetry (Pocket II Pachymeter Echo Graph; Quantel Medical red-free RNFL photography (Visucam 524; Carl Zeiss Meditec AXL measurements (Axis II PR; Quantel Medical SAP with the Swedish interactive threshold algorithm according to the central 24-2 standard program (Humphrey Field Analyzer II; Carl Zeiss Meditec) Cirrus SD-OCT version 6.0 (Carl Zeiss Meditec) and PERG (Neuro- electroretinogram (ERG); Neurosoft the RNFL thickness was determined in the optic Disc Cube 200 × 200 scan mode and the GCIPL thicknesses were evaluated using GCA software (Carl Zeiss Meditec) and macular cube scanning Only images with signal strengths greater than 6 were included The average of the HF RNFL thickness was determined from the thickness values obtained from clock-hour sectors Data from the 3 and 9 o’clock sectors were not taken into account because they were not related to a single horizontal HF and inferotemporal) thicknesses of the GCIPL were measured in an elliptical annulus around the fovea The average of superior HF GCIPL thicknesses was determined in the macular cube scan mode from the superotemporal The inferior HF values were obtained in the same way The aberrant glaucomatous optic disc changes included conspicuous neuroretinal rim thinning or notching on SDP There were no cases of bilateral HF involvement In accordance with the average thickness value acquired from SD-OCT the HF with a thinner or thicker RNFL or GCIPL also was identified Patients with non-dilated pupils were seated in a dimly-lit room and four electrodes were applied—two 35-mm Ag/AgCl skin electrodes to the lower eyelids with two ground electrodes at both earlobes—for stimulation Black and white reversing checkerboards with 0.8° checks were presented on a 24-inch liquid crystal display (LCD) monitor at a 35° × 30° visual angle and a distance of 60 cm Because LCD monitor brightness might fluctuate care was taken when selecting the viewing angle The positioning of each subject was carefully observed as issues may arise if the individual’s eye level is not adjusted to the center of the screen The contrast between the black and white squares was 98% and the mean luminance of the checkerboards was 100 cd/m2 The checkerboards used reversal rates of 4 reversals per second The participants focused on a target at a red fixed point in the middle of the monitor after having their refractive error properly corrected Signals were band-pass filtered (1–50 Hz) and sampled at 10,000 Hz Computerized artifact rejection was employed and traces exceeding 100 μV were automatically rejected as artifacts which correspond to a positive peak at 50 ms (P50) and a slow broad negative component at about 95 ms (N95) The N35 amplitude trough (a modest initial negative component with a peak time of about 35 ms) to the P50 peak is used to calculate the P50 amplitude by calculating the distance between the P50 peak and the N95 trough The PERG test was performed binocularly and continuously in the order of FF and the unstimulated field was kept dark gray and LF values were automatically reported separately following HF exams the data from the study will be available by the corresponding author Pattern electroretinogram or pattern electroretinography Area under the receiver operating characteristic curves Spectral-domain optical coherence tomography International Society of Clinical Electrophysiology and Vision Imaging retinal ganglion cell death and dysfunction in glaucoma The structure and function relationship in glaucoma: Implications for detection of progression and measurement of rates of change The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma Clinical and experimental evidence that the pattern electroretinogram (PERG) is generated in more proximal retinal layers than the focal electroretinogram (FERG) Significance of abnormal pattern electroretinography in anterior visual pathway dysfunction Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects Clinical ability of pattern electroretinograms and visual evoked potentials in detecting visual dysfunction in ocular hypertension and glaucoma Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons Pattern electroretinograms in preperimetric and perimetric glaucoma Pattern electroretinogram in glaucoma suspects: New findings from a longitudinal study Electrophysiology and glaucoma: Current status and future challenges Update on the pattern electroretinogram in glaucoma Diagnostic accuracy of pattern electroretinogram optimized for glaucoma detection Photopic negative response versus pattern electroretinogram in early glaucoma Pattern electroretinogram and psychophysical tests of visual function for discriminating between healthy and glaucoma eyes and spectral-domain optical coherence tomography Pattern electroretinography changes in patients with established or suspected primary open angle glaucoma Pattern electroretinogram and automated perimetry in patients with glaucoma and ocular hypertension The pattern electroretinogram in glaucoma and ocular hypertension Hemifield pattern electroretinogram in ocular hypertension: Comparison with frequency doubling technology and optical coherence tomography to detect early optic neuropathy Pattern electroretinograms from hemifields in normal subjects and patients with glaucoma The effects of ageing on the pattern electroretinogram and visual evoked potential in humans Ventura, L. M., Feuer, W. J. & Porciatti, V. Progressive loss of retinal ganglion cell function is hindered with IOP-lowering treatment in early glaucoma. Invest. Ophthalmol. Vis. Sci. 53, 659–663. https://doi.org/10.1167/iovs.11-8525 (2012) Gallo Afflitto, G. et al. Pattern electroretinogram in ocular hypertension, glaucoma suspect and early manifest glaucoma eyes: A systematic review and meta-analysis. Ophthalmol. Sci. 3, 100322. https://doi.org/10.1016/j.xops.2023.100322 (2023) Long-term PERG monitoring of untreated and treated glaucoma suspects Relationship between N95 amplitude of pattern electroretinogram and optical coherence tomography angiography in open-angle glaucoma Macular blood flow and pattern electroretinogram in normal tension glaucoma Attenuated amplitude of pattern electroretinogram in glaucoma patients with choroidal parapapillary microvasculature dropout Porciatti, V. et al. Head-down posture in glaucoma suspects induces changes in IOP, systemic pressure, and PERG that predict future loss of optic nerve tissue. J. Glaucoma 26, 459–465. https://doi.org/10.1097/ijg.0000000000000648 (2017) Porciatti, V. & Chou, T. H. Modeling retinal ganglion cell dysfunction in optic neuropathies. Cells 10, 1456. https://doi.org/10.3390/cells10061398 (2021) Moroto, N. et al. Use of multifocal electroretinograms to determine stage of glaucoma. PLoS One 18, e0278234. https://doi.org/10.1371/journal.pone.0278234 (2023) Sugiyama, K. et al. Localized wedge-shaped defects of retinal nerve fiber layer and disc hemorrhage in glaucoma. Ophthalmology 106, 1762–1767. https://doi.org/10.1016/s0161-6420(99)90347-0 (1999) Bach, M. et al. ISCEV standard for clinical pattern electroretinography (PERG): 2012 update. Doc. Ophthalmol. 126, 1–7. https://doi.org/10.1007/s10633-012-9353-y (2013) Download references These authors contributed equally: Eun Jung Ahn and Young In Shin Seoul National University College of Medicine and Y.I.S.; drafting of the manuscript and final approval of the version: all authors; revision of the manuscript for important intellectual content: all authors Download citation DOI: https://doi.org/10.1038/s41598-024-55601-9 Metrics details Retinal ganglion cells are distributed disproportionately with retinal eccentricity Pattern electroretinogram (PERG) stimuli resulted in reduced responses with more eccentric stimuli we investigated whether PERG amplitude is associated with the location of visual field (VF) defect in primary open-angle glaucoma Data from Twenty-nine glaucoma patients with a parafoveal scotoma (PFS) within the central 10° of fixation 23 glaucoma patients with a peripheral nasal step (PNS) and 27 normal control subjects were analyzed in this study Electroretinograms (ERGs) were obtained using a commercial ERG stimulator (Neuro-ERG) The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using spectral-domain optical coherence tomography A lower N95 amplitude was observed in both PFS and PNS compared to the normal control (Both P < 0.001) The N95 amplitude of the PFS group was significantly lower than that of the PNS group (P = 0.034) Average GCIPL thickness correlated positively with N95 amplitude (r = 0.368 but did not correlate significantly with global mean sensitivity (r = 0.228 P = 0.073) or mean deviation on 24-2 standard automated perimetry (r = 0.173 parafoveal VF defects were associated with the lower PERG amplitude it is necessary to take into account the location of VF defects in evaluating PERGs of glaucoma patients It has not been extensively studied whether PERG parameters differ depending on the location of VF defects in glaucoma patients even though conventional PERGs have been regarded as a central vision test stimulating the macula a PERG response may differ with subjects with parafoveal scotoma (PFS) compared to those with peripheral nasal step (PNS) quantitatively and qualitatively we compared the PERG results between glaucoma patients with PNS and PFS This cross-sectional study was approved by the Institutional Review Board of the Catholic University of Korea and followed the tenets of the Declaration of Helsinki Informed consent was obtained from all the patients Glaucoma patients who met the inclusion criteria were consecutively included from all patients the glaucoma clinic of Seoul St Mary’s Hospital between October 2017 and November 2017 Inclusion criteria were: best-corrected visual acuity ≥20/40 Patients with diseases that might affect the parapapillary or macular areas one eye per individual was randomly selected for the study All patients underwent a complete ophthalmic examination Stereoscopic optic disc photography was also performed on all subjects A glaucomatous VF defect was defined as a cluster of 3 or more points with a P-value < 5% one of which had a P-value of < 1% for the pattern deviation plot or retinal nerve fiber layer defect with corresponding glaucomatous VF damage Ganglion cell analysis software was used to measure the average and inferonasal) GCIPL thicknesses in a 14.13 mm2 elliptical annulus with vertical inner and outer radii of 0.5 and 2.0 mm and horizontal inner and outer radii of 0.6 and 2.4 mm Retinal nerve fiber layer (RNFL) thickness was determined using the optic Disc Cube 200 × 200 scan mode Poor-quality images with signal strength <6 were discarded All patients underwent SAP 24-2 with a Humphrey field analyzer (Carl Zeiss Meditec Goldmann size III targets were used with the Swedish interactive threshold algorithm (SITA) standard program The mean deviation (MD) and pattern standard deviation (PSD) were evaluated Mean sensitivity (MS) was evaluated on threshold printout in VF tests VF sensitivity was evaluated using the logarithmic decibel (dB) [10 × log(1/Lambert)] scale Reliable tests were defined as those with <15% fixation losses A second VF test was conducted if the first one was not reliable Pattern deviation plot divided into two subfields of the Humphrey visual field The parafoveal scotoma group included abnormal points within 12 points of a central 10° radius (dashed line) The peripheral nasal step group had abnormal points within 12 nasal peripheral points (dotted line) in one hemifield ERG was performed using a commercial ERG stimulator (Neuro- ERG a device that complies with the standards set by the International Society of Clinical Electrophysiology and Vision (ISCEV) A total of 4 electrodes were applied for stimulation Two 35 mm Ag/AgCl skin electrodes were taped to the lower lids with two ground electrodes at both earlobes Black and white checkerboards with a check size of 1.81° were presented on a 24 inch-monitor with 48° × 33° visual angle Stimuli were modulated in counterphase at 4 Hz The checkerboards had a mean luminance of 105 cd/m² Participants fixed their views at the center of the monitor where a red-colored fixed point was placed The PERG was measured as binocular recordings with an appropriate refractive correction provided through undilated pupils Responses were band-pass filtered (1-50 Hz) At least 100 readings were recorded and averaged To investigate the reproducibility of the ERG parameters test-retest variability was measured with 34 randomly selected measurements The P50 amplitude was estimated from the trough of N35 to the peak of P50 The N95 amplitude was defined as being from the peak of P50 to the trough of N95 and N95 was measured from the onset of checkerboard reversal to the peak of each component Differences between the PFS and PNS groups were analyzed by the Student’s t test for continuous parameters and by the chi-square test for categorical parameters Correlations between RNFL or GCIPL thickness and PERG amplitudes or SAP MD or MS were evaluated based on Pearson correlation coefficients P < 0.05 was taken to indicate statistical significance Glaucoma patients with PFS or PNS were found to have a thinner average RNFL than the control group (All P < 0.001, Table 2) There was no difference in average RNFL thickness between the PFS and PNS groups (P = 0.503) and superotemporal GCIPL were thinner in the PFS group than in the PNS or control groups (P < 0.05 for all) There was no significant difference in optic disc parameters between the PFS and PNS group (All P > 0.05) The ERG measurements were found to have excellent reproducibility for the N95 amplitude (ICC = 0.827 and 95% CI = 0.645–0.910; Table 3) while the reproducibility for the P50 amplitude was moderate (ICC = 0.705 and 95% CI = 0.476–0.844) ICC values were moderate for the implicit times of N35 Comparison of the P50 and N95 pattern electroretinogram amplitudes in normal control subjects and glaucoma patients with parafoveal scotoma (PFS) or peripheral nasal step (PNS) *Statistically significant difference between groups Scatterplots showing the relationship between average retinal nerve fiber layer (RNFL) thickness or average ganglion cell-inner plexiform layer (GCIPL) thickness and pattern electroretinogram (PERG) N95 amplitude or standard automated perimetry (SAP) mean sensitivity (MS) or SAP mean deviation P50 amplitude did not correlate with RNFL thickness, but did positively correlate with average, minimum, superonasal, inferonasal, inferior, inferotemporal, and superotemporal GCIPL thickness (0.269 < r < 0.472, P < 0.030; Table 5) Representative cases with parafoveal scotoma (PFS) or peripheral nasal step (PNS) were displayed in Fig. 4 (A: PFS, B: PNS). In two cases, MD was −1.34 dB in the A case and −2.21 dB in the B case. The N95 amplitude was lower in the patient with PFS (4.76 µV) than the patient with PNS (6.38 µV). Representative cases with parafoveal scotoma (PFS) or peripheral nasal step (PNS) (A) A 58-year-old-woman with PFS: mean deviation (MD) −1.34 dB; pattern standard deviation (PSD) 6.37 dB; N95 amplitude 4.76 µV; P50 amplitude 3.46 µV (B) A 58-year-old-woman with PNS: mean deviation (MD) −2.21 dB; pattern standard deviation (PSD) We demonstrated that the PERG amplitudes of glaucoma patients with PFS or PNS were lower than those of normal control subjects the PFS group had a lower N95 PERG amplitude than the PNS group even though both groups had a similar MD and PSD Average GCIPL thickness was related to PERG N95 amplitude Damage of RGCs in the central region can contribute the substantial loss of PERG response the PFS group might show greater loss of PERG response because of the RGC loss in more central regions The finding that the PFS group had a lower N95 PERG amplitude than the PNS group does not indicate that PERG amplitudes are able to discriminate between the patients with different types of VF defect such as PFS and PNS We only found that parafoveal scotoma was associated with lower N95 PERG amplitude We just recommend that we need to consider the location of VF defects in evaluating the PERGs of glaucoma patients patients with early stage glaucoma were included: Mean MD was determined to be −2.8 dB in the PFS group and −2.6 dB in the PNS group PERG amplitude seemed to reflect functional glaucomatous damage on the macula better than SAP 24-2 in early-stage glaucoma That could be the reason for the finding that P50 amplitude had a significant correlation with GCIPL thickness parameters but not with RNFL thickness This difference may result from the use of different instruments or glaucoma severity The reproducibility of implicit time was relatively lower than that of amplitude parameters One limitation of this study is the relatively small sample size in each group this is the first study to evaluate the relationship between VF location and PERG with extended visual angle Larger and more carefully controlled prospective studies are needed to confirm the results obtained here Our results cannot be applied to the conventional PERG with the narrower visual angle which does not cover the peripheral VF Another limitation is that the 48° horizontal visual angle of PERG is smaller than the 54° horizontal visual angle of SAP 24-2 because SAP 24-2 examines visual field from 30° nasally Visual function measured using PERG may be underestimated in patients with PNS than those with PFS the difference between the PERG and SAP 24-2 horizontal visual angles is very small we found that the location of VF defects in glaucoma patients affected the PERG amplitude Lack of familiarity with PERG hampers its widespread use in clinical practice despite its great potential as an objective assessment Our results will increase the general understanding of the nature of PERG indicating that there is a need to consider the location of VF defects in evaluating the PERGs of glaucoma patients our investigation of visual function in the paracentral retinal region is significant because of the clinical importance of central visual function GCIPL thickness was positively related to PERG amplitude may be clinically helpful in the functional evaluation of early glaucoma patients with paracentral scotoma Will Perimetry Be Performed to Monitor Glaucoma in 2025 Electrophysiology and glaucoma: current status and future challenges Predictive value of the pattern electroretinogram in high-risk ocular hypertension Pattern-reversal electroretinograms and high-pass resolution perimetry in suspected or early glaucoma Measurement of macular structure-function relationships using spectral domain-optical coherence tomography (SD-OCT) and pattern electroretinograms (PERG) Progressive color visual field loss in glaucoma Parafoveal scotoma progression in glaucoma: Humphrey 10-2 versus 24-2 visual field analysis The Nature of Macular Damage in Glaucoma as Revealed by Averaging Optical Coherence Tomography Data Macular ganglion cell-inner plexiform layer: automated detection and thickness reproducibility with spectral domain-optical coherence tomography in glaucoma Comparative study of macular ganglion cell-inner plexiform layer and peripapillary retinal nerve fiber layer measurement: structure-function analysis The design and Analysis of Clinical Experiments Structure-function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG Correlation between optical coherence tomography and visual evoked potentials in open-angle glaucoma patients Reproducibility of pattern electroretinogram in glaucoma patients with a range of severity of disease with the new glaucoma paradigm Repeatability of pattern electroretinogram measurements using a new paradigm optimized for glaucoma detection Pattern electroretinogram to detect glaucoma: comparing the PERGLA and the PERG Ratio protocols Download references This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare Republic of Korea (grant number: HI15C1940) The authors declare that no competing interests exist with the funder K.I.J); conduct of study (K.I.J.); data collection (S.J. K.I.J); analysis and interpretation of data (K.I.J. K.I.J.); writing the article (K.I.J.); and critical revision of the article (C.K.P.) Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-019-39948-y Metrics details Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina Little is known about flicker-induced changes of activity of retinal neurons themselves We non-invasively investigated flicker-induced changes of retinal ganglion cell (RGC) function in common inbred mouse strains using the pattern electroretinogram (PERG) Flicker was superimposed on the pattern stimulus at frequencies that did not generate measurable flicker-ERG and alter the PERG response Transition from flicker at 101 Hz (control) to flicker at 11 Hz (test) at constant mean luminance induced a slow reduction of PERG amplitude to a minimum (39% loss in C57BL/6J mice and 52% loss in DBA/2J mice) 4–5 minutes after 11 Hz flicker onset followed by a slow recovery to baseline over 20 minutes Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease The non-contact flicker-PERG method opens the possibility of combined assessment of neural and vascular response dynamics Little is known about the magnitude and temporal dynamics of retinal neurons themselves in response to flicker Here we non-invasively investigate flicker-induced changes of RGC function in common inbred mouse strains 13 C57BL/6J (B6) mice and 13 DBA/2J (D2) mice 4 months old purchased from Jackson Labs (Bar Harbor All procedures were performed in compliance with the Association for Research in Vision and Ophthalmology (ARVO) statement for use of animals in ophthalmic and vision research The experimental protocol was approved by the Animal Care and Use Committee of the University of Miami All mice were maintained in a cyclic light environment (12 h light: 50 lux – 12 h: dark) and fed with Grain Based Diet (Lab Diet: 500 All procedures and testing were performed under anesthesia by means of intraperitoneal injections (0.5–0.7 ml/kg) of a mixture of ketamine (42.8 mg/ml) and xylazine (8.6 mg/ml) Representative examples of the effect of flicker on ERG (A) 1 Hz Flicker (50% duty cycle) generates robust light-adapted ERG responses at both light onset and offset (B) 101 Hz Flicker does not generate a signal distinguishable from noise (dotted line) (F) 11 Hz flicker also does not generate a measurable signal due to interference between onset and offset ERGs (E) Simulation of interference between onset and offset ERGs by superimposing onset and offset ERGs shown in A at 11 Hz frequency (C,G) Fluorescein angiography images obtained with superimposition of flicker at either 101 Hz (C) or 11 Hz (G) (D,H) PERG recorded with superimposition of flicker at either 101 Hz (D) or 11 Hz (H) noise response were obtained by averaging even and odd epochs in counterphase In panels (D,H) noise response were obtained with the pattern contrast set to zero (uniform mean luminance) the PERG at 0% contrast was at noise level and the PERG at 100% contrast had no visible distortions due to flicker ERG contamination results of this experiment provide the necessary framework for studying the effect of flicker on PERG As the results were similar in the two eyes the results of the left eye only will be presented 11 Hz flicker induced a noticeable vasodilation compared to 101 Hz flicker To analyze flicker-induced PERG changes over time (PERG #1,2,3,4) the method of Generalized Estimating Equations (GEE) was used (IBM SPSS statistics Ver GEE is an unbiased non-parametric method to analyze longitudinal correlated data PERG amplitude was the dependent variable and test period (PERG #1,2,3,4) and strain (B6 strain) and interaction between test period and strain were computed as well as pairwise combinations between period and strain Effect of flicker on PERG in different mouse strains (A,B) Representative examples of PERGs sequentially recorded in C57BL/6J mice (A) or DBA/2J mice (B) with superimposition of flicker at either 101 Hz or 11 Hz (C,D) Distribution of PERG amplitudes sequentially recorded in individual mice (C) DBA/2J with superimposition of flicker at either 101 Hz or 11 Hz Time course of PERG amplitude change upon superimposition of flicker at either 101 Hz or 11 Hz in C57BL/6J mice and DBA/2J mice Each sequential PERG (average of 372 epochs) was sampled off-line in 12 subaverages of 31 epochs of 0.52 minutes for a total of 48 samples (25 minutes) Each data point represents the group average of C57BL/6J mice (N = 13) and DBA/2J mice (N = 13) To facilitate visualization of time-dependent changes data were smoothed by running average of three contiguous data points (continuous lines) Better understanding of flicker-induced neurovascular/neurometabolic coupling in the retina requires quantification of the temporal dynamics of inner retinal neurons themselves If flicker-induced neural activity substantially changes over time then this will be inevitably be reflected on the temporal dynamics of neurovascular/neurometabolic coupling The stimulus and the recording conditions were designed in such a way as not to generate measurable flicker-ERG which could have distorted the PERG waveform The peak-to-trough PERG amplitude was measured in an automated manner Data analysis was conducted to account for nonspecific changes of PERG amplitude over time As glaucoma progression in individual mice is variable an altered PERG response to flicker may identify susceptible individuals and help predict development of disease Testing this hypothesis was beyond the scope of this study it is conceivable that an instrument can be built that allows simultaneous assessment of flicker-induced neural and vascular dynamics under identical conditions This would allow a better insight on the neurovascular interactions in health and disease combined assessment of flicker-induced neural and vascular dynamics is possible by adapting available imaging instruments Transition from flicker at 101 Hz to flicker at 11 Hz at constant mean luminance induces reduction of the RGC functional response whose magnitude and temporal dynamics can be non-invasively assessed with PERG in the mouse This provides a means for investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease Newman, E. 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Transl Vis Sci Technol 6, 5, https://doi.org/10.1167/tvst.6.3.5 (2017) Download references unrestricted grant to Bascom Palmer Eye Institute from Research to Prevent Blindness University of Miami Miller School of Medicine is the producer of the PERG system used in this study He developed hardware and software for the specific needs of this study Download citation DOI: https://doi.org/10.1038/s41598-019-54930-4 visual electrophysiology testing has been considered the last test to turn to when a patient presents with unexplained vision loss the increased accessibility of electroretinogram (ERG) and visual-evoked potential (VEP) testing and our improved understanding of how to apply it in our clinics shows us that these tests are valuable for diagnosing evaluating and managing a large variety of ocular disease states Electrophysiology can objectively illustrate how the retina and visual system are working and identify functional abnormalities in the cells prior to cell death Clinicians are then able to track disease progression and tailor treatment to improve that function Pattern electroretinography (PERG) is an objective test of retinal ganglion cell function While optical coherence tomography looks at the structure of the eye PERG looks at how well the cells in the eye are functioning This test is particularly valuable in the early detection of glaucoma It has been shown that functional abnormalities stemming from glaucoma can be detected up to 8 years earlier with PERG than with traditional structural tests (Banitt et al.) a stronger or weaker signal is measured from electrically active retinal ganglion cells Dysfunctional cells producing a weaker signal can improve with therapy and the increase in function can be seen on subsequent PERG test results leads to the ability to preserve healthy cells through earlier treatment which can slow the progression of the disease Clinical diagnosis of glaucoma has typically focused on elevated intraocular pressure and visual field and retinal nerve fiber layer defects these are often insufficient due to the nature of the disease IOP is not always elevated enough to raise concern allowing the disease to progress unchecked once the disease has reached the stage where the optic nerve has cupped or a defect is seen on a visual field or OCT PERG enables cell dysfunction to be identified in time to instigate early intervention and treatment PERG testing is beneficial for diabetic retinopathy (DR) suspects as it is often possible to detect electrophysiological abnormalities of the retina prior to the development of any obvious clinical retinopathy The fact that dysfunction in the retina and visual pathways occurs well before structural changes are typically identified has been extensively documented such as OCT or intravenous fluorescein angiography PERG is not only more efficient in detecting abnormalities earlier (Caputo et al test results can also demonstrate treatment efficacy (Ozkiri and Ozkiri et al.) Sanofi-Aventis) is used to treat malaria and inflammatory disorders such as rheumatoid arthritis and lupus This drug has also been known to damage the structure of the outer retina and retinal pigment epithelium According to the American Academy of Ophthalmology the preferred tests to evaluate patients with potential macular toxicity are OCT visual field and multifocal electroretinography Early detection is the key to minimizing this damage and PERG has proven to be a valuable tool in identifying toxic retinopathy (Neubauer et al.) Testing can be repeated after the agent has been discontinued to track further progression is helpful when assessing retinal dysfunction such as in retinal vascular occlusions and DR This test measures generalized dysfunction in response to stimulus of the entire retina with flicker ffERG particularly inciting a response from the cone cells ffERG is especially helpful in monitoring disease progression and treatment efficacy in moderate to severe retinopathies This test is also beneficial for patients with media opacities as the full field light stimulus is able to penetrate through to the retina ffERG is a useful tool for optometrists managing patients with dense cataract The technology can be used prior to surgery and after the procedure to monitor healing and vision improvement Visual evoked potential (VEP) measures the electrical activity in the entire vision system from the patient’s retina to the visual cortex Latency (peak time) is the first important measure which indicates the response time along the visual pathway Amplitude is the second important measure and indicates the strength of the signal amblyopia or neurological diseases such as optic neuritis due to multiple sclerosis can be signified by delayed response time or reduced signal strength A delayed latency confirms that the visual pathway is dysfunctional Early identification of these abnormalities allows for earlier intervention it is also ideal for nonverbal patients such as children or those with communication issues as it does not necessitate a response from the patient Optic neuritis is often associated with multiple sclerosis Useful clinical and subclinical information can be provided by OCT; however especially in identifying subtle past optic neuritis (Naismith et al.) VEP is also more efficient than visual acuity or optic nerve appearance in determining optic pathway damage (Kelly et al.) Treatment of any pathology is significantly improved with early detection as the underlying potential of vision improvement is an essential element in establishing a treatment arc for this population VEP is especially beneficial in diagnosing and projecting treatment plans for these patients because it identifies abnormal changes along the entire visual pathway Amplitude increases on pattern VEP test results reflect vision improvement over the course of treatment Traumatic brain injury (TBI) can cause ophthalmic issues such as blurry vision reading impairment and posttraumatic vision syndrome which optometrists can address with vision therapy VEP is especially beneficial in not only diagnosing and projecting treatment courses for TBI patients but also in tracking the efficacy of vision therapy As the test results are obtained objectively patients cannot inadvertently skew results allowing for accurate readings of ocular and visual dysfunctions ERG and VEP tests allow optometrists to treat a wide variety of patients many of whom may have been difficult to examine in the past Disclosures: González García is employed by Diopsys Lighthizer reported he is a consultant for Aerie Pharmaceuticals Get the latest news and education delivered to your inbox The email address associated with your Healio account is: If you would like to edit or change the email address that your subscriptions and alerts are sent to You'll receive reminders to complete your saved activities from Healio CME Metrics details The electrophysiological findings in optic nerve and primary ganglion cell dysfunction are reviewed The value of the pattern reversal visual-evoked potential (VEP) in the diagnosis of optic nerve disease and the pattern appearance VEP in the demonstration of the intracranial misrouting associated with albinism The pattern electroretinogram (PERG) is used in the direct assessment of ganglion cell function The use of PERG or multifocal electroretinography (mfERG) to enable the distinction between VEP delay due to optic nerve disease and that due to macular dysfunction The visual-evoked cortical potential (VEP) is an important electrophysiological test in the investigation of suspected optic nerve disease The stimulus for diagnostic VEP is usually a reversing black and white checkerboard or grating (PVEP) but an appearance stimulus (onset/offset) can also be used The latter stimulus is of particular value in demonstrating the misrouting of optic nerve and chiasmal fibres that occurs in ocular or oculocutaneous albinism but the flash VEP (FVEP) is less sensitive to the effects of disease than the pattern VEP and is highly variable across a population due to its low interocular or interhemispheric asymmetry in a normal subject the FVEP may detect interocular or interhemispheric asymmetry within an individual patient Delayed VEPs 7 months following left optic neuritis in a 39-year-old male Note that the delay is present in both pattern and flash VEPs and that there is selective reduction in the N95 component from the affected eye in keeping with retrograde degeneration to the retinal ganglion cells Right eye findings show no significant abnormality the P50 component is ‘driven’ by the macular photoreceptors and can thus be used as an index of macular function A ‘steady state’ waveform is obtained if a rapid (>3.5 Hz) stimulus rate is used; however this does not allow measurement of individual components and ISCEV recommends the transient PERG for routine diagnostic work and a ‘Standard; mixed rod–cone response to a bright white flash under dark adaptation This latter response is dominated by rod function A recent recommendation is an additional response to a brighter flash The maximal ERGs shown below utilise this stimulus better to demonstrate the a-wave Photopic ERGs are recorded both to a single flash (with adequate photopic adaptation and a rod-suppressing background) and to a 30 Hz flicker stimulus; rods are unable to respond to a 30 Hz stimulus due to poor temporal resolution The ERG is a mass response and is therefore normal when dysfunction is confined to small retinal areas This also applies to macular dysfunction; despite the high photoreceptor density an eye with purely macular disease has a normal ERG This 37-year-old female complained of blurred vision in her left eye following exercise or a hot bath Other than questionable pallor of the left optic disc The symptomatic left eye shows VEP evidence of marked optic nerve conduction delay; here is also reduction in the left eye PERG N95 component with shortening of P50 component latency Note the marked subclinical delay in right optic nerve conduction presumably explaining the lack of a relative afferent pupillary defect in relation to the left eye prior to the development of computerised tomographic scanning (CT) or magnetic resonance imaging (MRI) invasive neuroradiology such as myelography was the investigation of choice for patients presenting with spinal cord lesions The ability of the VEP to detect subclinical optic nerve demyelination thus had a profound impact on the management of such patients the demonstration of optic nerve conduction delay obviating the need for myelography by identifying dissemination of lesions referrals for VEP in patients with suspected multiple sclerosis reduced as it is now apparent that the specificity of the changes on MRI may be less than originally anticipated the VEP continues to be of value in the diagnosis of demyelination P50 latency increase is not a feature of optic nerve or retinal ganglion cell disease it was noted the only two eyes not to regain 6/12 acuity or better at follow-up had PERG P50 amplitudes of <0.5 μV at presentation (normal >2.0 μV) A larger series is necessary before firm prognostic conclusions can be drawn but with an elegant stimulus design such that separate responses were recorded during the same session to stimulation of central They concluded that central fibres were most affected by demyelination They emphasised the difficulties in accurate component identification with a single midline recording channel and a large stimulus field (eg 15° radius) reporting both phase and amplitude abnormalities contralateral to the stimulated eye VEP and PERG findings from three patients with dominantly inherited optic atrophy Patient A (VA 6/18) has a markedly abnormal PERG with clear N95 component reduction and shortening of P50 component latency but a VEP that falls within the normal range PERG shows loss of N95 with shortening of P50 latency and additional P50 amplitude abnormality (<2 μV) it is often a symmetrical and marked reduction in the N95 component that suggests primary ganglion cell dysfunction rather than dysfunction consequent upon an optic nerve insult and usually occurs only in severe disease accompanied by shortening of latency or severe reduction unaccompanied by P50 latency shortening the PERG may be normal in optic nerve disease or may show amplitude reduction confined to N95 an almost invariably present observation in primary ganglion cell dysfunction Electrophysiological investigation is a powerful tool in the objective evaluation of optic nerve and intracranial visual pathway function it is used alongside the structural information provided by neuroradiological investigation to give a more complete assessment in an individual patient and can demonstrate optic nerve demyelination unaccompanied by signs or symptoms and an adjunctive test of macular function is required before a delayed or otherwise abnormal VEP in a patient with visual symptoms can be assumed to reflect optic nerve rather than macular dysfunction but the objective assessment of retinal ganglion cell dysfunction directly provided by the N95 component of the PERG and the fact that the PERG is elicited by a stimulus directly comparable to that used for the pattern VEP suggests that the PERG is the more appropriate parameter The pattern electroretinogram and an integrated approach to visual pathway diagnosis Electrophysiologic Testing in Disorders of the Retina The Foundation of the American Academy of Ophthalmology: San Francisco and some observations on associated fundus autofluorescence imaging in inherited maculopathy The significance of abnormal pattern electroretinography in anterior visual pathway dysfunction The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity Invest Ophthalmol Vis Sci 2000; 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13: 79–84 Optic disc pallor: a false localizing sign Afferent pupillary defect in macular degeneration Visual function abnormalities in central serous retinopathy Download references Reprints and permissions Download citation DOI: https://doi.org/10.1038/sj.eye.6701573 Verpasse nicht die neuesten Inhalte von diesem Profil: Melde dich an um neue Inhalte von Profilen und Bezirken zu deinen persönlichen Favoriten hinzufügen zu können Tatjana wurde in Berlin als Kind eines Österreichers und einer Baltendeutschen geboren wobei ihr viele Steine in den Weg gelegt wurden Die Familie ihres ersten Mannes schirmte die beiden gemeinsamen Kinder völlig von ihr ab Ein Wiedersehen sollte es erst Jahrzehnte später geben In Wien schloss Tatjana ein Studium an der Grafischen Lehranstalt ab Gegen Kriegsende wurde sie zur Zwangsarbeit in einer Rüstungsfabrik verpflichtet später malte sie im Tiergarten Schönbrunn Schilder Um ihr drittes Kind kämpfte Tatjana erfolgreich Eine drohende Entführung durch den bulgarischen Vater konnte sie mit Hilfe ihrer Mutter verhindern Mit ihrem Mann Werner Gamerith trat eine glückliche Wende in Tatjanas Leben ein wo die beiden ein altes Bauernhaus kauften Die Liebe zur Natur spiegelt sich in ihren Bildern wider ein Gegensatz zu ihrem oft harten und entbehrungsreichen Lebensweg Trotz fortschreitendem Verlust des Augenlichts erlosch ihr Talent nicht Auch die künstlerische Eingebung blieb lange wach Im September 2018 erlitt Tatjana einen Schlaganfall Im Jänner 2019 trat sie trotzdem den langen Weg von Waldhausen nach Linz ins Krankenhaus der Elisabethinen an Unzählige Freunde und Bewunderer ihrer Kunst besuchten die Eröffnung und standen Schlange um der Jubilarin persönlich zu gratulieren "Ihre Bilder preisen die Schönheit und den Lebensreichtum der Schöpfung Sie werden noch lange ihren Betrachtern vom Glück erzählen das uns eine liebevolle Begegnung mit der Natur schenkt" um diesen Inhalt mit «Gefällt mir» zu markieren Werde Regionaut! 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